Asymmetries in unimanual and bimanual coordination...

Asymmetries in unimanual and bimanual coordination: Evidence from

behavioural and transcranial magnetic stimulation studies.

Deborah Faulkner, B.Sc., B.A. (Honours)

This thesis is presented for the degree of Doctor of Philosophy and partial fulfilment of

Master of Psychology (Clinical Neuropsychology) of The University of Western

Australia

School of Psychology and Centre for Neuromuscular and Neurological Disorders, The

University of Western Australia

2009

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ABSTRACT

The issue of the laterality of control during unimanual and bimanual coordination was

addressed in this thesis. Two tasks were used throughout: a repetitive discrete response

task (finger tapping) and a continuous task (circle-drawing). Different mechanisms have

been implicated in the temporal control of repetitive discrete movements and continuous

movements. The tasks also differ in the degree of spatiotemporal coordination required

which might have important implications in the question of laterality of control.

The first section of the thesis examined between-hand differences in the dynamics of

performance during unimanual and bimanual coordination. During tapping, the

dominant hand was faster and less temporally variable than the nondominant hand.

During circle drawing the dominant hand was faster, more accurate, less temporally and

spatially variable, and produced smoother trajectories than the nondominant hand.

During bimanual coordination, several of these asymmetries were attenuated: the rate of

movement of the two hands became equivalent (the hands became temporally coupled),

the asymmetry in temporal variability during tapping was reduced, and the asymmetry

in trajectory smoothness during circle drawing was reduced.

The second section of the thesis examined the effects of disrupting motor processes with

transcranial magnetic stimulation (TMS) over the left or right primary motor cortex

(M1) on the ongoing performance of the hands. In the first study, TMS over left or right

M1 during unimanual tapping caused large disruptions to tapping with the contralateral

hand but had little effect on the ipsilateral hand. In contrast, for a subset of trials during

bimanual tapping, two lateralized effects of stimulation were seen: the effect of TMS on

the contralateral hand was greater after stimulation over left M1 than after stimulation

over right M1, and prolonged changes in inter-tap interval were observed in the left

hand regardless of the side of stimulation. In the second study, TMS over left M1 during

circle drawing decreased the accuracy of drawing with both the contralateral and

ipsilateral hand, whereas TMS over right M1 decreased accuracy of drawing only with

the contralateral hand. This lateralized effect was not limited to the bimanual case, but

was also apparent during unimanual drawing.

The final chapter addressed issues in bimanual motor control after unilateral stroke.

Performance of the affected limb was examined during unimanual and bimanual

coordination in a group of stroke patients with varying levels of impairment. The results

indicated an improvement in the performance of the affected limb for some patients

with mild to moderate, but not severe upper limb motor deficits during bimanual

movement. The improvements were limited to the patients who showed evidence of

temporal coupling between the hands.

These findings support the hypothesis that the dominant motor cortex has a role in the

control of both hands during bimanual coordination. In addition, the dominant

hemisphere appears to play a role in controlling both hands during unimanual

movements which require a greater degree of spatiotemporal coordination. The final

study suggests that temporal coupling between the limbs is crucial for the facilitation of

performance of the affected limb during bimanual coordination, which has both

theoretical and practical implications.

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CONTENTS

Abstract......................................................................................................................iii

Declaration of authorship.......................................................................................... ix

Chapter 1. Introduction.............................................................................................. 1

Neural substrates of interlimb coordination ....................................................................................... 2 Laterality of bimanual control ............................................................................................................. 6 Outline of thesis ................................................................................................................................ 10

Chapter 2. Unimanual and bimanual finger tapping. ............................................. 13

2.1 Method ............................................................................................................................................ 14 Participants........................................................................................................................................ 14 Procedure .......................................................................................................................................... 14 Data analysis...................................................................................................................................... 15

2.2 Results.............................................................................................................................................. 16 Comfortable-pace tapping................................................................................................................. 16 Rapid tapping..................................................................................................................................... 19

2.3 Discussion......................................................................................................................................... 22

Chapter 3. Unimanual and bimanual circle drawing. ............................................. 29

3.1 Method ............................................................................................................................................ 31 Participants........................................................................................................................................ 31 Procedure .......................................................................................................................................... 31 Data analysis...................................................................................................................................... 32

3.2 Results.............................................................................................................................................. 35 Accuracy of drawing .......................................................................................................................... 35 Rate of drawing ................................................................................................................................. 38 Spatial variability ............................................................................................................................... 40 Rate variability................................................................................................................................... 41 Smoothness of drawing..................................................................................................................... 43 Pressure............................................................................................................................................. 45

3.3 Discussion......................................................................................................................................... 46 Bimanual versus unimanual drawing ................................................................................................ 47 Large- versus small-circle drawing .................................................................................................... 49 Left-right asymmetries in performance ............................................................................................ 50

Chapter 4. TMS-induced disruption of motor performance................................... 55

Transient and Sustained Effects of TMS within M1........................................................................... 55 TMS-induced disruption of motor performance ............................................................................... 57

Chapter 5. TMS-induced disruption of unimanual and bimanual finger tapping . 67

5.1 Method ............................................................................................................................................ 69 Participants........................................................................................................................................ 69

TMS ................................................................................................................................................... 69 Procedure.......................................................................................................................................... 69 Data analysis ..................................................................................................................................... 71

5.2 Results ............................................................................................................................................. 73 Baseline (pre-TMS) performance...................................................................................................... 73 Motor threshold and silent period duration..................................................................................... 73 TMS-induced disruption to unimanual tapping ................................................................................ 74 TMS-induced disruption of bimanual tapping .................................................................................. 83

5.3 Discussion ........................................................................................................................................ 96 General effects of TMS on the contralateral hand ........................................................................... 96 Contralateral and ipsilateral effects of TMS during unimanual tapping........................................... 98 Contralateral and ipsilateral effects of TMS during bimanual tapping ............................................. 99

Chapter 6. Disruption of unimanual and bimanual circle drawing with TMS .... 105

6.1 Method .......................................................................................................................................... 108 Participants ..................................................................................................................................... 108 TMS ................................................................................................................................................. 109 Procedure........................................................................................................................................ 109 Data analysis ................................................................................................................................... 111

6.2 Results ........................................................................................................................................... 113 Baseline (pre-TMS) performance.................................................................................................... 113 TMS at 10% above threshold .......................................................................................................... 115 TMS at threshold............................................................................................................................. 130 TMS at 10% below threshold .......................................................................................................... 136

6.3 Discussion ...................................................................................................................................... 142

Chapter 7. Unimanual and bimanual performance after unilateral stroke.......... 151

7.1 Method .......................................................................................................................................... 156 Participants ..................................................................................................................................... 156 Procedure........................................................................................................................................ 157

7.2 Results ........................................................................................................................................... 159 Unimanual and bimanual tapping................................................................................................... 160 Unimanual and bimanual circle-drawing ........................................................................................ 165

7.3 Discussion ...................................................................................................................................... 177 Interlimb coupling........................................................................................................................... 180 Mechanisms of facilitation of performance with the impaired limb .............................................. 181

General Discussion.................................................................................................. 185

References ............................................................................................................... 195

Appendix A.............................................................................................................. 211

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Acknowledgements

I extend a warm thank you to my supervisors Geoff Hammond, who provided

invaluable advice, astute insights, and kind criticisms, and Gary Thickbroom, who also

provided enormously useful advice, technical expertise, and encouragement just when it

was needed. Thank you both for your support and patience.

Michelle Byrnes supported me in accessing patients and provided technical expertise,

without which this thesis would not have been possible. A warm thank you also to all of

the patients and other participants who generously gave their time.

Many friends supported me throughout, and I especially want to thank Tim Perich who

was always there (despite moving to Japan then Sydney!) with an encouraging word or

motivational thought to lift my confidence; Tim Booth for his steady support, friends

and colleagues at CCRN for their support and patience, and my fellow PhD students,

who were inspirational.

Finally, my family. My dad, Bob Faulkner, who passed away suddenly in the middle of

all of this, my inspirational mum, my brother, and my step father; where would I be

without your faith in me?

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DECLARATION OF AUTHORSHIP

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CHAPTER 1. INTRODUCTION

Bimanual movements constitute the majority of our daily activities. Yet for the most

part, our ability to execute precisely coordinated actions with our hands goes unnoticed;

little (if any) conscious thought goes into tying shoelaces, pouring a glass of wine, using

a knife and fork. These tasks appear easy, even effortless, unless our motor system

becomes compromised by injury or disease at which time the importance of these

abilities is brought into sharp focus.

Despite the apparent effortlessness of the task of bimanual coordination, bimanual skills

are anything but a simple task for the central nervous system to execute; bimanual

coordination is the result of a finely tuned orchestration of activity within a widely

distributed network of brain areas (Debaere et al., 2001; Swinnen, 2002). However,

many aspects of this neural organization remain unclear. One aspect of motor control

which is largely unresolved is the issue of laterality in the control of bimanual

coordination, which forms the basis of the present thesis.

There is a natural tendency, when coordinating two different effectors, to move them

synchronously, so that when the two hands are used together, movements tend to be

coupled in time. Two patterns of bimanual synchronization are relatively easy to

produce: in-phase (symmetrical), and anti-phase (asymmetrical) movements. Of the two

modes, in-phase coordination is more stable, so that above a critical frequency of

tapping, there is a tendency to flip from an anti-phase to an in-phase mode (Kelso,

1984). The two hands also tend to be tightly temporally coupled when moving through

space, for example, initiation and termination of bimanual aiming movements occurs

almost simultaneously even when the two hands aim to targets at different distances

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(Kelso, Southard, & Goodman, 1979). Tight temporal coupling is also observed during

other bimanual movements such as drawing circles or lines concurrently (Franz,

Zelaznik, & McCabe, 1991; Semjen, Summers, & Cattaert, 1995) and during more

natural goal-oriented behaviours such as opening a drawer and retrieving an object

(Kazennikov et al., 1994; Perrig, Kazennikov, & Wiesendanger, 1999) or pouring liquid

from a bottle into a glass (Weiss & Jeannerod, 1998).

Bimanual movements are coupled spatially as well as temporally. If two tasks which

differ in a spatial dimension are executed simultaneously, an integration of features of

the motor response of one limb into the motor response of the other limb is seen (e.g.

consider patting your head while rubbing your stomach). When aiming movements are

made with the two hands simultaneously to targets at different distances, each

movement becomes more like the other; the shorter amplitude movement tends to be

overshot, and the longer amplitude movement tends to be undershot (Marteniuk,

MacKenzie, & Baba, 1984; Sherwood, 1990). In more complex tasks, such as drawing

two different figures concurrently, the assimilation becomes more obvious. For

example, when drawing lines with one hand and circles with the other, both shapes take

on characteristics of the other and become elliptical (Franz, 1997; Franz, Zelaznik, &

McCabe, 1991).

Neural substrates of interlimb coordination

The emerging consensus is that bimanual coordination is the result of tightly

coordinated activity within a distributed network of brain areas (Debaere et al., 2001;

Swinnen, 2002). Neuroimaging, neurophysiological, and lesion studies with humans

and non-human primates have revealed the major areas responsible for interlimb

coordination include the supplementary motor area (SMA), primary motor cortex (M1),

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premotor cortex, corpus callosum, and cerebellum (see Swinnen & Wenderoth, 2004 for

a recent review).

A series of studies on patients with callosal agenesis and patients who have undergone

callosal resection for intractable epilepsy highlights the importance of interhemispheric

transfer of motor information during bimanual coordination. After callosotomy,

temporal coupling between the limbs is preserved (Franz, Eliassen, Ivry, & Gazzaniga,

1996) or even enhanced (Tuller & Kelso, 1989) for tasks requiring production of

discrete bimanual movements whereas timing between the hands is decoupled in these

patients during a continuous bimanual oscillation task (Kennerley, Diedrichsen,

Hazeltine, Semjen, & Ivry, 2002). The finding that temporal coupling of the hands in a

discrete coordination task does not depend on interhemispheric transfer of information,

but coupling of the hands in a continuous task does depend on such transfer suggests a

different neural origin for the processes governing timing during repetitive discrete and

continuous bimanual movements (Zelaznik, Spencer, & Ivry, 2002; Zelaznik et al.,

2005). In contrast, patients with cerebellar lesion exhibit disruptions in the timing of

discrete but not continuous movements (Spencer, Zelaznik, Diedrichsen, & Ivry, 2003),

implicating this structure in the representation of explicit temporal information.

Split brain patients have an advantage in decoupling spatial aspects of movements, and

are able to produce two different shapes with little interference between the hands

(Franz, Eliassen, Ivry, & Gazzaniga, 1996). Similarly, force coupling between the limbs

is attenuated in individuals with callosal agenesis compared to normal controls

(Diedrichsen, Hazeltine, Nurss, & Ivry, 2003). These findings suggest that both spatial

coupling and force coupling observed during bimanual coordination is largely cortical

in origin, mediated by interhemispheric transfer of direction and force information.

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Recent work by Carson and colleagues in unimpaired individuals (Carson, Smethurst,

Oytam, & de Rugy, 2007) suggests that corticomotor excitability is modulated by the

recruitment of muscles on the other side of the body and that this mediates interactions

between the limbs; furthermore, the authors concluded that modulation of excitability

occurs via interhemispheric interactions between motor cortices (Carson et al., 2004).

The SMA has long been considered important for bimanual motor control. The SMA

has interconnections via the corpus callosum, which makes it particularly well suited to

the task of interlimb coordination (Rouiller et al., 1994). Several lines of research

converge to implicate SMA in bimanual coordination; in non-human primates bimanual

movement is associated with SMA neural activity (Donchin, Gribova, Steinberg,

Bergman, & Vaadia, 1998; Tanji & Kurata, 1982), unilateral lesions to SMA in

monkeys leads to unwanted mirror movements during bimanual coordination (C.

Brinkman, 1984), repetitive transcranial magnetic stimulation over SMA degrades

bimanual coupling (Steyvers et al., 2003) and neuroimaging studies show activation of

SMA during bimanual coordination (Sadato, Yonekura, Waki, Yamada, & Ishii, 1997;

Stephan et al., 1999; Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). However, the

role of SMA as a coordinating structure specifically responsible for interlimb

coordination has been challenged. Contrary to Brinkman’s (1984) findings, Kazennikov

and colleagues reported that unilateral lesions in SMA in monkeys led to a delay in

movement initiation in the contralateral limb, but did not lead to deficits in bimanual

goal directed task performance (Kazennikov et al., 1998). Furthermore, equivalent SMA

activation has been found during repetitive unimanual and in-phase bimanual hand

movements, suggesting that SMA activity is not specific for bimanual movements

(Stephan, Binkofski, Posse, Seitz, & Freund, 1999). These authors found that SMA

activity increased during anti-phase bimanual movements, and concluded that activity in

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SMA is related to temporal aspects of coordination and the complexity of a task rather

than its bimanual nature. Consistent with a role for SMA in complex coordination tasks

is the report of a large increase in SMA activation when musicians tapped a complex

polyrhythmic bimanual sequence compared to a simple in-phase bimanual sequence (W.

Lang, Obrig, Lindinger, Cheyne, & Deecke, 1990).

Recordings from neurons within SMA and M1 in monkeys suggest that each area plays

an important a role in interlimb coordination. Surprisingly, the proportion of “bimanual

neurons”1 in M1 is equivalent to the proportion in SMA (Kermadi, Liu, Tempini,

Calciati, & Rouiller, 1998), suggesting a crucial role for both areas in interlimb

coordination. Furthermore, Donchin and colleagues found bimanual-related activity in

M1 that was in addition to the neural activity seen during unimanual movements

(Donchin, Gribova, Steinberg, Bergman, & Vaadia, 1998). Similar to the results of the

previous study, the amount of bimanual-related activity in M1 was comparable to the

amount of bimanual-related activity in SMA, challenging the conventional view of M1

as a simple output area and SMA as the coordinating structure during bimanual

coordination. These results are consistent with the emerging view that M1 codes not

only for the dynamics of movement generation by the contralateral limb but also for

more complex aspects of movement control. For example, M1 neurons show

anticipatory activity for upcoming elements in a sequence of movements (Ben-Shaul et

al., 2004; Lu & Ashe, 2005). Neuroimaging results in humans also show an increase in

M1 and SMA activation during bimanual compared to unimanual coordination

(Toyokura, Muro, Komiya, & Obara, 1999) suggesting that both areas are critical for

the control of bimanual coordination.

1 Bimanual neurons were defined as those whose discharge patterns were specifically associated with bimanual movement during a sequential bimanual coordination task (not predicted from their discharge patterns during equivalent unimanual movements).

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Laterality of bimanual control

The issue of laterality in bimanual motor control has been gaining support in recent

years. We have a natural asymmetry in motor control which is reflected in handedness,

characterized by the dominant hand being more adept at fast, precisely controlled

movements (Peters, 1976; Peters & Durding, 1979) and producing smoother movements

with more consistent temporal and spatial features (Phillips, Gallucci, & Bradshaw,

1999) than the nondominant hand. These performance asymmetries are also obvious

during bimanual coordination when the two hands perform the same task concurrently

(e.g.`, Byblow, Carson, & Goodman, 1994; Carson, Thomas, Summers, Walters, &

Semjen, 1997; Helmuth & Ivry, 1996), and in the natural roles adopted by each hand;

the nondominant hand usually performs a stabilizing and orienting role and the

dominant hand performs precise manipulations (Guiard, 1987).

Several lines of evidence point to a possible role of the dominant hemisphere in the

coordination of the hands during bimanual performance. Liepman (1908`, 1920`, cited

in Goble & Brown, 2008) was the first to suggest asymmetric processing for motor

control after observing that fine motor control was affected in both left and right upper

limb movements after left-sided lesions, but only in left limb movements after right-

sided lesions, a finding confirmed in subsequent studies (Wyke, 1971). Left parietal and

premotor areas are associated with planning complex sequences of movements

performed with either hand in normal controls (Haaland, Elsinger, Mayer, Durgerian, &

Rao, 2004). Lesion studies highlight the importance of the left hemisphere in

sequencing with both hands (Haaland & Harrington, 1994), preparation of movement

(Haaland & Harrington, 1989) and complex goal directed behaviour (Haaland,

Harrington, & Knight, 2000).

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There is also evidence for the importance of the left hemisphere in control of interlimb

coordination. Some support for lateralized control of interlimb coordination comes from

behavioural data in normal individuals. Despite the abundance of evidence that the

motor system synchronizes the hands during bimanual coordination, the

synchronization is not perfect; the dominant hand usually leads the nondominant hand

by around 20 ms during continuous and discrete bimanual movements (Stucchi &

Viviani, 1993; Swinnen, Jardin, & Meulenbroek, 1996). This observation has led to the

hypothesis that some aspects of motor control are specified in the dominant hemisphere

and transferred to the nondominant hemisphere during bimanual coordination. An

important addendum to this finding is that the asynchrony is unlikely to reflect an

attentional bias towards the dominant hand since directing one’s attention towards the

dominant or nondominant hand modifies the magnitude of the asynchrony but does not

abolish it (Swinnen, Jardin, & Meulenbroek, 1996). It has been suggested that the

asynchrony between the hands reflects temporal control by the dominant hemisphere;

the lag resulting from the time for interhemispheric transfer of timing information from

the dominant to the nondominant hemisphere (Stucchi & Viviani, 1993; Viviani, Perani,

Grassi, Bettinardi, & Fazio, 1998). However, this idea is not without contention; the

hand that leads during bimanual coordination might depend in part on task

requirements. Although some studies on hand asynchrony during bimanual circle

drawing have found a right-hand lead during symmetrical and asymmetrical drawing

(Semjen, Summers, & Cattaert, 1995; Stucchi & Viviani, 1993), others have found that

mode of coordination affects which hand leads. During asymmetrical circle drawing,

Franz and colleagues found that in right-handers the right hand leads when both hands

circle in a clockwise direction, and the left hand leads when both hands circle in a

counter-clockwise direction (Franz, Rowse, & Ballantine, 2002). Nevertheless, at least

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in the symmetrical mode of coordination, the finding that the dominant hand tends to

lead has been found in most studies.

Further behavioural evidence for dominant hemispheric control of bimanual

coordination comes from temporal and spatial interactions between the limbs during

bimanual coordination. Both spontaneous and intentional transitions from asymmetric

to symmetric modes of coordination are more often generated by the nondominant limb

falling into phase with the dominant limb than vice versa (Byblow, Carson, &

Goodman, 1994; de Poel, Peper, & Beek, 2006; de Poel, Peper, & Beek, 2007; Semjen,

Summers, & Cattaert, 1995). The tendency for these transitions to be initiated by

changes in the nondominant limb’s trajectory has been attributed to an asymmetry in

interlimb coupling strength (the dominant hemisphere exerts a stronger coupling

strength on the nondominant hemisphere than the reverse). It has been argued that phase

transitions from the asymmetric to the symmetric mode of bimanual coordination are

due to uncrossed (ipsilateral) descending pathways; individuals in whom ipsilateral

responses could be elicited after transcranial magnetic stimulation over M1 showed

greater spatial and temporal error than those for whom such responses could not be

elicited (Kagerer, Summers, & Semjen, 2003). Furthermore, larger ipsilateral responses

were elicited after stimulation over the dominant than the nondominant hemisphere,

which suggests a greater proportion of these fibres originate in the dominant than the

nondominant hemisphere. This could account for a greater instability in the

coordination of the nondominant than the dominant hand, and could explain the

tendency for phase transitions to be initiated by the nondominant hand. Transcallosal

motor connections may also be important; temporal coupling between the hands is

disrupted in callosotomy patients during continuous bimanual coordination (Kennerley,

Diedrichsen, Hazeltine, Semjen, & Ivry, 2002). Spatial interactions between the hands

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are also asymmetric; the nondominant hand is more affected by the spatial trajectory of

the dominant hand than vice versa (Byblow, Lewis, Stinear, Austin, & Lynch, 2000;

Marteniuk, MacKenzie, & Baba, 1984; Sherwood, 1994), which also suggests left

hemispheric dominance of bimanual motor control.

Neuroimaging results, however, are equivocal with respect to a lateralized role of M1 in

interlimb coordination. Bimanual sequential finger-thumb movements were associated

with greater left than right hemisphere activation, although no distinction was made in

the report between M1 and premotor areas (Jäncke et al., 1998), and bimanual ellipse

drawing was associated with greater left than right hemisphere activation in both M1

and premotor areas (Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). However,

during a simpler bimanual task (in-phase finger tapping), similar loci of neuromagnetic

sources were seen in the left and right sensorimotor cortices suggesting that the neural

control of bimanual coordination is not lateralized for these movements (Pollok, Muller,

Aschersleben, Schnitzler, & Prinz, 2004). The authors speculated that task complexity

rather whether a task is bimanual may determine the amount of left hemispheric

involvement. However, in a study using a more complex anti-phase bimanual tapping

task, no asymmetry in M1 activation was observed (Toyokura, Muro, Komiya, &

Obara, 1999). Similarly, when the tapping rates required of each hand are different (one

hand tapping at double the pace of the other), levels of left and right sensorimotor cortex

activation during bimanual tapping were equivalent to the levels of activation during

unimanual tapping, although there was greater left than right SMA activation during

bimanual coordination (Jäncke et al., 2000).

Koeneke and colleagues (2004) also addressed the issue of task complexity. The authors

noted that most imaging studies of bimanual coordination have not used a unimanual

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task that adequately controls for the level of difficulty of the bimanual task (bimanual

tasks usually require coordination of two effectors, whereas the comparison unimanual

task requires movement of a single effector). When a complex visuospatial tracking task

was performed by moving a cursor with either two fingers on different hands or two

adjacent fingers on the same hand, no asymmetry in M1 activation was observed during

the bimanual task. In fact, the authors reported less left M1 activation during the

bimanual tasks than during the left-hand unimanual task, and interpreted this as

evidence that the participants may have found the nondominant unimanual task more

difficult than the bimanual task. Furthermore, although greater left SMA activity was

observed during the bimanual task, a similar asymmetry in SMA activity was seen

during left and right unimanual tasks, and these authors also suggested that the degree

lateralized activation of motor areas depends on task difficulty rather than the bimanual

nature of a task.

An EEG coherence study during unimanual and bimanual cyclical flexion-extension

movements showed that whereas unimanual movements showed greater coherence from

the contralateral hemisphere, coupled bimanual movements were associated with greater

coherence from the dominant to the nondominant sensorimotor cortex, suggesting

greater drive from the dominant than nondominant hemisphere during bimanual

movements (Serrien, Cassidy, & Brown, 2003). The coherence decreased when the

bimanual movements became uncoupled by perturbation, suggesting that direct

transmission of drive between sensorimotor areas is responsible for bimanual coupling.

Outline of thesis

The physiological mechanisms underlying interlimb coordination remain unclear. In

this thesis, the question of the laterality of control during unimanual and bimanual

11

coordination is addressed. Two tasks were chosen: tapping, and circle-drawing. As

discussed earlier, there is evidence that these tasks represent two fundamentally

different types of bimanual coordination: different mechanisms have been implicated in

the temporal control of repetitive discrete events versus continuous coordination (Ivry &

Richardson, 2002). The first section of the thesis (Chapters 2 and 3) examine between-

hand differences in dynamics of performance during unimanual and bimanual

coordination.

The second section of the thesis examines the effects of disrupting cortical processing

with TMS over the left or right M1 on the ongoing coordination patterns between the

hands. Chapter 4 reviews the literature on the effects of TMS on unimanual and

bimanual performance. The studies reported in Chapters 5 and 6 used TMS to examine

the contribution of left and right M1 to the control of bimanual movements. The first

study examined the effects of TMS on unimanual and bimanual repetitive finger tapping

and the second study examined the effects of TMS on unimanual and bimanual circle

drawing. The circle-drawing task requires a larger degree of spatiotemporal

coordination than the repetitive tapping task. While both tasks are accomplished by the

sequential activation of different muscles, in the tapping task the raising and lowering of

the finger around a single joint is accomplished by of the reciprocal activation of flexor

and extensor muscles, whereas the circle-drawing task is a multi-joint coordination task,

which requires a more complex pattern of activation of multiple muscles in order to

produce the required trajectory with pen on paper. The differences in complexity of

sequential muscle activation between the tasks may have important consequences for

the issue of laterality of control (Pollok, Muller, Aschersleben, Schnitzler, & Prinz,

2004).

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The final chapter addresses issues in bimanual motor control after unilateral stroke.

There is evidence that performance with the affected limb after stroke is enhanced

during bimanual coupling (Cunningham, Phillips Stoykov, & Walter, 2002; McCombe

Waller, Harris-Love, Liu, & Whitall, 2006). Neuroimaging data showed that, in stroke

patients, greater activation of the affected hemisphere was seen during bilateral

movement than during unilateral movement (Staines, McIlroy, Graham, & Black,

2001). In addition, rehabilitation strategies which emphasize the use of both hands have

been shown to have beneficial outcomes (Stewart, Cauraugh, & Summers, 2006;

Whitall, McCombe Waller, Silver, & Macko, 2000). In chapter 7, the performance of

the affected limb during bimanual and unimanual coordination are presented for three

groups of patients with varying levels of deficit.

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CHAPTER 2. UNIMANUAL AND BIMANUAL FINGER TAPPING.

There is evidence that repetitive discrete, and continuous tasks represent two

fundamentally different types of bimanual coordination: different mechanisms have

been implicated in the temporal control of repetitive discrete events versus continuous

coordination (Ivry & Richardson, 2002; Kennerley, Diedrichsen, Hazeltine, Semjen, &

Ivry, 2002). Previous studies of the repetitive, discrete type of bimanual coordination

have examined inter-limb coordination during finger tapping or wrist flexion-extension.

These studies have usually employed either a synchronization task or a synchronization-

continuation task in which participants synchronize their taps to the beat of a

metronome, and continue this rhythm in the continuation phase, with both hands

moving either at the same rate (Drewing & Aschersleben, 2003; Glencross, Piek, &

Barrett, 1995; Helmuth & Ivry, 1996; Pollok, Muller, Aschersleben, Schnitzler, &

Prinz, 2004) or different rates (Peters, 1981, , 1985; Ullen, Forssberg, & Ehrsson, 2003).

It is assumed that in the continuation phase of the synchronization-continuation task the

timing of events is based on an internal representation of the temporal interval formed

in the synchronization phase, and response initiation is contingent on this internal

representation (Ivry & Richardson, 2002). The current study used a more naturalistic,

un-paced tapping task to measure speed and temporal regularity of unimanual and

bimanual tapping at two rates; at a comfortable (submaximal) rate or as rapidly as

possible, with either hand alone, or both hands together. This study extends previous

studies which have shown a bimanual advantage in temporal variability during

synchronization-continuation tasks (Helmuth & Ivry, 1996) to un-paced tapping.

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2.1 Method

Participants

Ten right-handed adults, 6 females and 4 males, with ages ranging from 21 to 58 years

(median age 30 years) participated. Handedness, measured as the laterality quotient

from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 70 to 100

(median 95). The procedure for this study (and all subsequent studies in this thesis) was

approved by The University of Western Australia’s Human Research Ethics Committee,

and informed consent was obtained from all participants.

Procedure

Participants sat comfortably with their elbows flexed at approximately 90 degrees and

both hands resting on a desk surface (palm down). Participants were instructed to tap at

a comfortable pace or at a rapid pace (as fast as possible) for ten seconds with their left

hand alone, with their right hand alone, or with both hands together, by extending and

flexing their index finger(s) around the metacarpal-phalangeal joint, keeping their hand

and other fingers flat on the table. Finger movement was measured with a miniature

accelerometer mounted in a resin block, attached over the index finger of each hand

(Figure 2.1). Output from the accelerometers was sampled from the audio input of a

computer at 44 kHz.

Figure 2.1. Participant set-up showing mounted accelerometer attached over right index finger.

15

Participants self-initiated each trial, and the timing of a trial began when the

accelerometer signal exceeded a predetermined threshold, indicating that the participant

had started tapping, and ended after ten seconds. Two blocks of 9 trials were performed

(one block at each tapping rate); each block consisted of three trials each of left

unimanual, right unimanual and bimanual tapping. The order of trials were determined

by Latin square.

Data analysis

Figure 2.2 shows 2.5 s of accelerometer output from a typical trial. Large vertical spikes

in accelerometer output indicate the sudden change in acceleration that occurred when

the participant’s finger contacted the table. The time of each contact was stored for later

analysis. Inter-tap intervals (ITIs) were determined as the time between successive

contacts. Asynchrony of left and right hand contacts was calculated (a positive

asynchrony indicated that the right hand led). Coefficients of variation (CV) of the ITIs

were calculated as a measure of tapping variability as the standard deviation of ITIs on

each trial divided by mean trial ITI and expressed as a percentage.

Time (ms)

Figure 2.2. Signal output from an accelerometer during tapping. Long vertical spikes in the signal indicate the rapid deceleration which occurred when the participant’s finger contacted the table. Inter-tap intervals (ITIs) were calculated as the time between successive contacts. The dashed horizontal line indicates the amplitude threshold for identifying a tap.

0 500 1000 1500 2000 2500

16

Autocorrelations of ITIs (correlations between ITIs within a trial) were calculated at

lags 1 to 8 for each hand during unimanual and bimanual tapping. Fisher’s r-to-z

transforms were applied to the correlation coefficients to allow averaging and statistical

analyses (Guilford, 1965). The correlation coefficients presented here are back-

transformed values.

Statistical analyses. ITIs and CV of ITIs were analysed using two-way repeated

measures ANOVAs with Hand (left and right) and Mode (unimanual and bimanual) as

within-subject factors. Systematically negative ITI autocorrelations at lag 1 (correlations

between adjacent intervals) were of particular interest (Wing & Kristofferson, 1973),

and significance of the difference of each z-transformed autocorrelation from zero were

calculated using t-tests.

2.2 Results

Comfortable-pace tapping

Table 2.1 shows mean ITI for the left and right hands during unimanual and bimanual

tapping at a comfortable rate. Mean ITI was approximately the same for the left and

right hands during both unimanual tapping and bimanual tapping. Tapping was slightly

slower with the right hand than the left hand during unimanual tapping, and equal for

the hands when tapping bimanually. The effect sizes for Hand (partial η2 = .28) and for

the interaction between Hand and Mode (partial η2 = .30) were fairly substantial

however neither effect was significant (F(1,9) = 3.57, p = .09 and F(1,9) = 3.85, p = .08,

respectively). There was no significant effect of Mode (F(1,9) = 0.12, p = .73, partial η2 =

.01).

17

Table 2.1.

Mean inter-tap-interval (ms) for each hand in unimanual and bimanual tapping at a comfortable rate. Standard deviations are in parentheses.

Mode Left Right Mean

Unimanual 411 (87) 421 (96) 416 (89) Bimanual 425 (72) 425 (72) 425 (70)

Mean 418 (79) 423 (84) 420 (79)

Table 2.2 shows mean CV for the left and right hands during unimanual and bimanual

tapping. Tapping was more variable with the left hand than the right hand during both

unimanual and bimanual tapping, and there was a significant effect of Hand (F(1,9) =

6.37, p = .03, partial η2 = .41). There was no marked difference between the variability

of each hand during unimanual and bimanual tapping, and no significant effect of

Mode (F(1,9) = 0.37, p = .56, partial η2 = .04) or interaction between Hand and Mode

(F(1,9) = 0.30, p = .60, partial η2 = .03).

Table 2.2.

Mean coefficient of variation for each hand during unimanual and bimanual tapping at a comfortable rate. Standard deviations are in parentheses.


Unimanual 5.1 (1.6) 4.0 (0.6) 4.6 (1.3) Bimanual 5.2 (1.7) 4.3 (0.8) 4.7 (1.4)

Mean 5.2 (1.6) 4.2 (0.7) 4.7 (1.3)

The mean asynchrony between left and right hand taps during self-paced bimanual

tapping was 4.0 ms (SD = 4.7 ms). Examining the asynchrony data within each trial

revealed that for all participants, the hand which led was highly variable, even within a

single trial. All but one participant tended to lead with the right hand. With this

18

participant excluded, mean asynchrony was 5.2 ms (SD = 3.6 ms). For the participants

who tended to lead with their right hand, the mean proportion of taps in which the right

hand led was 0.66 (SD = 0.12), and for the participant who tended to lead with her left

hand, the proportion of taps in which the right hand led was 0.38.

Autocorrelations of ITIs at lags from 1 to 8 for each hand during unimanual and

bimanual tapping are shown in Figure 2.3. During unimanual tapping, autocorrelations

were close to zero for all lags, and there was no systematic difference between the

hands. Autocorrelations at lag 1 (correlations between adjacent inter-tap intervals) were

not significantly different from zero for either hand during unimanual tapping (left, t(9) =

0.68, p = .35; right, t(9) = 1.11, p = .29). During bimanual tapping, negative

autocorrelations were seen for both hands at lag 1 (a significant deviation from zero for

the left hand, t(9) = 2.79, p = .02, but not the right hand, t(9) = 1.81, p = .10) and

autocorrelations at all other lags were close to zero.

Figure 2.3. Mean ITI autocorrelations at lags 1 to 8 of inter-tap interval during unimanual and bimanual tapping at a comfortable pace with the left ( ) and right ( ) hands. Error bars are ± 1 standard error of the mean. Points of left and right data sets are slightly offset on the x-axis for clarity.

Unimanual Bimanual

Lag Lag

CO

RR

ELA

TIO

N C

OE

FF

ICIE

NT

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 2 4 6 8

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 2 4 6 8

19

Rapid tapping

Table 2.3 shows mean ITI for the two hands during unimanual and bimanual rapid

tapping. Tapping was faster with the right hand than the left hand during unimanual

tapping and during bimanual tapping the rates of the two hands were the same. There

was a significant effect of Hand (F(1,9) = 23.47, p = .001, partial η2 = .72), but no

significant effect of Mode (F(1,9) = 0.50, p = .83, partial η2 = .01). There was a

significant interaction between Hand and Mode (F(1,9) = 23.58, p = .001, partial η2 =

.72), reflecting the slower rate of the right hand during bimanual than unimanual

tapping and the faster rate of the left hand during bimanual than unimanual tapping.

Table 2.3.

Mean inter-tap-interval (ms) for each hand during unimanual and bimanual tapping at a rapid rate. Standard deviations are in parentheses.



Mean 198 (25) 193 (25) 196 (25)

Table 2.4 shows mean CV for the left and right hands during unimanual and bimanual

rapid tapping. Tapping was more variable with the left hand than the right hand during

both unimanual and bimanual tapping, reflected by a significant effect of Hand (F(1,9) =

4.85, p = .05, partial η2 = .35). Although tapping was less variable for both hands

during bimanual than unimanual tapping, the main effect of Mode was not significant

(F(1,9) = 1.28, p = .29, partial η2 = .12). The difference between unimanual and

bimanual tapping variability was greater fro the left hand than the right, and the effect

size for the interaction between Hand and Mode was .27, however this effect was not

significant (F(1,9) = 3.37, p = .10).

20

Table 2.4.

Mean coefficient of variation for each hand during rapid unimanual and bimanual tapping. Standard deviations are in parentheses.


Unimanual 10.4 (5.1) 6.5 (3.8) 8.4 (4.8) Bimanual 7.4 (2.2) 6.4 (4.1) 6.9 (3.2)

Mean 8.9 (4.1) 6.4 (3.8) 7.7 (4.1)

The mean asynchrony between the left and right hand during rapid bimanual tapping

was 13.5 ms (SD = 16.5 ms). All but two participant tended to lead with the right hand

(as indicated by positive asynchronies). One led more often with his left hand and one

led inconsistently with either her left or right hand (mean asynchrony close to zero).

With these two participants excluded, the mean asynchrony was 19.2 ms (SD = 13.6).

For the participants who tended to lead with their right hand, the proportion of taps in

which the right hand led was fairly consistent (mean = 0.87, SD = 0.21). For the

participant who led with his left hand, the proportion of taps led by the right hand was

0.33, and for the participant who had an inconsistent lead-hand, the proportion of taps

led by the right hand was 0.56.

Autocorrelations of ITI at lags from 1 to 8 for each hand during unimanual and

bimanual tapping are shown in Figure 2.4. During unimanual tapping, small positive

autocorrelations were seen at all lags, and there was no systematic difference between

the hands. During bimanual tapping, a negative autocorrelation was seen for the left

hand and a positive autocorrelation for the right hand at lag 1, autocorrelations at most

other lags were close to zero. Autocorrelations at lag 1 were not significantly different

from zero for either hand during unimanual tapping (left, t(9) = 1.31, p = .22 right, t(9) =

1.47, p = .18), was significantly less than zero for the left hand (t(9) = 2.33, p = .04), and

greater than zero for the right hand (t(9) = 3.26, p = .01) during bimanual tapping.

21

Figure 2.4. Mean ITI autocorrelations at lags 1 to 8 of inter-tap interval during rapid unimanual and bimanual tapping with the left ( ) and right ( ) hands. Error bars are ± 1 standard error of the mean. Points of left and right data sets are slightly offset on the x-axis for clarity. Negative autocorrelations at lag 1 were due to a tendency to alternate between relatively

large and small ITIs whereas positive autocorrelations were due to a progressive

decrease (or increase) in ITI across a trial (Figure 2.5).

Figure 2.5. Illustrative trials from two participants showing the pattern of ITIs resulting in a negative autocorrelation at lag 1 (r = -.49; left panel) and positive autocorrelation at lag 1 (r = .49; right panel).

100

120

140

160

180

200

220

240

1 50

100

120

140

160

180

200

220

240

1 50

Lag Lag

ITI (

ms)

C

OR

RE

LAT

ION

CO

EF

FIC

IEN

T

Response number Response number

Unimanual Bimanual

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 2 4 6 8

-0.4

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 2 4 6 8

22

2.3 Discussion

The main findings of this study were: 1) tapping was faster with the right than left hand

during fast but not comfortably paced unimanual tapping and tapping rates of the hands

equalized during bimanual tapping, 2) the right hand was less temporally variable than

the left hand at both paces and this asymmetry was maintained though attenuated

during bimanual tapping, 3) a trend to lower temporal variability during bimanual than

unimanual tapping was observed for the left but not right hand during rapid but not

during comfortably paced tapping, and 4) right hand taps preceded left hand taps

during fast bimanual tapping and less consistently during comfortably paced bimanual

tapping. These findings will be discussed in turn.

Tapping rates were faster with the right hand than the left hand during rapid unimanual

tapping and were equivalent during slow (comfortably paced) unimanual tapping. Not

surprisingly, the rates of tapping with two hands were identical during bimanual

tapping at either rate. The faster rate of the dominant hand during rapid unimanual

tapping is a replication of a consistently found performance asymmetry (Hammond,

Bolton, Plant, & Manning, 1988; Peters, 1980; Schmidt, Oliveira, Krahe, & Filgueiras,

2000; Todor & Kyprie, 1980). Peters (1980) demonstrated that this performance

difference between the hands is largely attributable to a faster and less variable

transition between movement directions by the dominant than nondominant hand and

suggested that this is due to a greater precision in specification of timing and

magnitude of excitatory outflow to muscles of the dominant hand than the

nondominant hand.

Tapping with the right hand was consistently less variable than tapping with the left

hand regardless of speed of performance. This is also a robust asymmetry between the

23

hands (Todor & Kyprie, 1980; Truman & Hammond, 1990), which persists, as in this

study, during bimanual tapping (Drewing & Aschersleben, 2003; Helmuth & Ivry,

1996). The greater precision of force modulation which was proposed as the source of

the dominant hand’s speed advantage during rapid tapping is also responsible for the

smaller variability in timing with the dominant than nondominant hand. Heuer (2007)

found greater co-contractions of antagonist muscles in the nondominant hand than in

the dominant hand during fast rhythmical finger oscillations. Heuer reported that

movements were characterized by faster and less variable cycle durations when

performed with the dominant hand than the nondominant hand, similar to the result

during rapid finger tapping in the current study. A critical finding was that activation

patterns in the dominant hand were characterized by sharply defined, non-overlapping

contractions of antagonist muscles, indicating a more precise control of their reciprocal

activation. Furthermore, the greater variability in timing of movement oscillations with

the non-dominant hand was associated with greater variability in the relative timing of

antagonist muscle activity. These findings suggest that a more precise control of

reciprocal activation in the dominant hand results in smaller variability in timing of

movements with the dominant hand.

Previous research has shown that the variability in both hands is reduced during

bimanual tapping compared to unimanual tapping (Drewing & Aschersleben, 2003;

Helmuth & Ivry, 1996; Yamanishi, Kawato, & Suzuki, 1980). In the current study, no

benefit of bimanual tapping on temporal variability was observed during slow tapping.

During rapid tapping, temporal variability was smaller for the left hand during the

bimanual task than during the unimanual task, although this difference was not

statistically significant. Helmuth and Ivry attributed the smaller variability during

bimanual tapping to the integration of the outputs of two separate timing mechanisms

24

(from each hemisphere), leading to reduced temporal variability in movements with

both hands. Drewing and Aschersleben showed that variability of both unimanual and

bimanual tapping was reduced by providing auditory feedback and attributed at least

part of the bimanual advantage (less variable tapping bimanually than unimanually) to

the additional sensory reafference associated with bimanual movements compared to

unimanual movements. Important methodological differences between this study and

prior research may explain the differences. Most research on temporal variability has

employed a synchronization-continuation task in which participants tap in synchrony

with an auditory timing stimulus for some time then attempt to continue to tap at the

same frequency in the absence of the auditory stimulus (performance variability is

assessed during the continuation period). In addition to the synchronization phase,

which establishes a consistent response, explicit instructions are given to maintain the

tapping pace during the continuation phase. In contrast, in the current study, which was

more naturalistic and less contrived, timing was not an explicit goal for the participants,

nor was consistency of tapping emphasised. This difference in methodology might

explain the differences between the current study and previous findings. Nevertheless,

the improvement in tapping variability with the left hand when paired with the right

hand during fast tapping requires an explanation. It is possible that during fast tapping,

the dominant hemisphere plays a role in controlling the left hand. This is consistent with

the finding that during rhythmical bimanual wrist movements there is greater

interhemispheric coherence from the dominant to the nondominant sensorimotor cortex

than vice versa, suggesting greater cortical drive from the dominant than from the

nondominant hemisphere during bimanual movements (Serrien, Cassidy, & Brown,

2003).

25

It has been argued that different timing mechanisms are responsible for temporal

precision of rapid and slow tapping (Peters, 1989). In particular, Peters proposed that

short intervals are produced as automatic movements and longer intervals as controlled

movements, the transition between automatic and controlled mechanisms occurring in

the range of 300 ms. Other evidence supports a distinction between two different

modes of tapping; preferred rates of tapping have been found to form a bimodal

distribution, with modes at 272 ms and 450 ms (Collyer, Broadbent, & Church, 1994).

The intervals produced during fast and comfortably paced tapping in the current study

clearly fell on either side of this division. Although Peters’ distinction originally

applied to synchronization tasks, two findings in the current study support a similar

distinction between slow and fast tapping in un-paced modes. Firstly, the trend to a

bimanual advantage (less variable bimanual than unimanual tapping) for the left hand

was seen during fast paced but not comfortably paced tapping. In addition, there was a

difference between the asynchrony data the two tapping rates. During bimanual

coordination, asynchronies in the timing of movements are commonly observed

between the limbs (Stucchi & Viviani, 1993; Swinnen, Jardin, & Meulenbroek, 1996).

In the current study, the asynchrony between the hands was inconsistent during slow

bimanual tapping (although 9/10 participants tended to lead with their right hand, the

right hand led in only 66% of taps, and the mean asynchrony was small, around 5 ms).

In contrast, the asynchrony during rapid tapping was more consistently associated with

a right-hand lead (in the 8/10 participants who showed a consistent right-hand lead, 87

percent of taps were led by the right hand). The magnitude of the mean asynchrony

during rapid tapping (19 ms) was comparable to that reported previously of around 20

to 25 ms (Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). As discussed in the

introduction, a proposed explanation for the asynchrony between the hands is that it

reflects temporal control of both hands by the dominant hemisphere; the lag is

26

proposed to result from the time for interhemispheric transfer of timing information

from the dominant to the non-dominant hemisphere. It is possible that during bimanual

tapping at the fast rate, which according to Peters’ distinction represents a type of

automatic movement, the asynchrony data is a good reflection of left hemispheric

control of the two hands. At longer intervals, other processes may be involved in

maintaining the tapping rate (such as attentional processes), which could add to the

variability of tapping with each hand, and might obscure the expression of

asymmetrical control through the asynchrony data.

A final note concerns the inconsistent patterns of autocorrelations seen during fast and

comfortably-paced tapping. The clock model of motor control proposed by Wing and

Kristofferson (1973) predicts that adjacent inter-tap intervals should be negatively

correlated (according to the model, a long delay for the completion of one inter-tap

interval will tend to shorten the next interval and vice versa) and that inter-response

intervals separated by one or more intervals should have correlations close to zero. In

the current study, correlations between adjacent inter-tap intervals (lag 1

autocorrelations) did not consistently reflect this prediction. The lack of a metronome

paced segment of each trial or explicit instructions to maintain a stable rhythm might

account for this negative finding, and the strong positive correlations between adjacent

taps which were sometimes observed indicate that there was drift in tapping rates

within trials. It was only during bimanual tapping that the lag 1 autocorrelations

significantly deviated from zero. It is possible that additional sensory reafference

associated with bimanual movements provided an additional “comparison” interval for

each hand in a similar way to the pacing by a metronome in other studies. However,

caution should be used in interpreting these findings because the total duration of

tapping in the current study was not long compared to previous work, and therefore

27

may not have provided a large enough sample of ITIs to make a reliable estimate of the

autocorrelations.

In summary, a superiority of the dominant hand in terms of speed and variability of

tapping was shown in the current study. In contrast to previous research, a bimanual

advantage for tapping variability with both hands was not seen, possibly due to the less

constrained nature of the current study. A bimanual advantage was seen for the left

hand during rapid tapping implicating the left hemisphere in control of bimanual

movements. Finally, several findings point to differences in the mechanisms of

movement control during slow-paced and rapid tapping.

29

CHAPTER 3. UNIMANUAL AND BIMANUAL CIRCLE DRAWING.

Naturally occurring bimanual movements typically require multi-joint coordination.

Whereas early work on bimanual coordination employed simple, single joint

coordination tasks such as finger tapping or wrist flexion-extension, a growing body of

research has employed multi-joint tasks; one such task is the continuous production of

circles. Previous work using this task has primarily focused on interactions between the

hands during two modes of bimanual coordination: symmetric coordination in which the

two hands cycle in different directions (one clockwise and one counter-clockwise)

which maintains symmetry with respect to the body mid-line, and asymmetric in which

the two hands cycle in the same direction, resulting in movements which are not

symmetrical with respect to the body mid-line. A major finding is that both modes of

coordination can be produced easily but symmetric coordination patterns are more

stable and produced more accurately than asymmetric patterns. The relative stability of

symmetric movements compared to asymmetric movements becomes obvious at high

frequencies of movement when transitions occur from the asymmetric to the symmetric

mode, but not in the reverse direction (Byblow, Lewis, Stinear, Austin, & Lynch, 2000;

Carson, Thomas, Summers, Walters, & Semjen, 1997; Semjen, Summers, & Cattaert,

1995). These transitions are mostly due to reversals in the direction of the non-preferred

hand, indicating an unequal interaction between the hands. Several possible

explanations for this finding have been forwarded including: conflict between

contralateral and ipsilateral descending pathways, interhemispheric interactions, and

attentional asymmetries during bimanual coordination.

30

There is evidence from the studies mentioned above that the dominant hand produces

more accurate and temporally consistent circles than the non-dominant hand, however,

because most previous work has focused on inter-limb dynamics there is little

information on the kinematic differences between the hands during unimanual and

bimanual circle-drawing. Phillips characterized differences between the hands in a

hand-writing task (the drawing of repetitive cursive letter ls and their mirror inverse)

and found that the dominant hand of right-handers produced faster, smoother

trajectories, of more consistent duration, length, and peak velocity than the non-

dominant hand (Phillips, Gallucci, & Bradshaw, 1999). The current study extends this

work to examine the kinematic profile of the left and right hand of right-handers during

unimanual and bimanual continuous circle-drawing. Furthermore, while previous work

has compared unimanual and bimanual drawing of large circles, this study extends the

comparison to the more dexterous task of drawing of small circles, which is arguably

more like the handwriting task employed by Phillips and colleagues than the large-circle

drawing tasks employed thus far. Biomechanical requirements are different for small-

and large-circle drawing; large circles are drawn with movements of proximal effectors

and small circles are drawn with proportionately greater involvement of distal effectors.

A series of recent studies by Buchanan and Ryu varied circle size to determine the

effect of joint amplitude on stability of drawing (Buchanan & Ryu, 2005; Ryu &

Buchanan, 2004). The authors found that spatial variability varied directly with circle

diameter. In these studies similar effectors were used to draw each circle size, whereas

in the current study two sizes of circles were used to encourage the use of distal and

proximal effectors in small and large circle drawing, respectively. Byblow and

colleagues studied interlimb coordination dynamics during circle-drawing with distal

and proximal musculature (Byblow, Lewis, Stinear, Austin, & Lynch, 2000).

Participants intentionally reversed the direction of drawing and the authors found that

31

unintentional disruptions in the contralateral limb trajectories were equivalent for distal

and proximal postures, and concluded that these disruptions are unlikely to arise from

ipsilateral pathways (if this was the case, the authors predicted greater disruption in the

proximal than distal posture because of greater ipsilateral control during proximal than

distal movements). The primary focus of the current study is to characterize the

kinematics of circle-production by the left and right hands during unimanual and

bimanual drawing with proximal and distal musculature. Given the predominantly

contralateral control of distal musculature and bilateral control of proximal musculature

(Kuypers, 1981), it was predicted that interlimb differences in accuracy of circle

production would be larger for the small circles (executed by distal musculature) than

the large circles (executed by proximal musculature).

3.1 Method

Participants

Thirty two right-handed subjects, 23 females and 9 males, with ages ranging from 20 to

69 years (median age 31.5 years) participated. Handedness, measured as the Laterality

Quotient from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 60 to

100 (median 88).

Procedure

Participants traced the contours of two circles (either 15-mm or 70-mm diameter),

centres 120 mm apart, on a digitizing tablet (WACOM Intuos 2 Graphics Tablet, Model

No. XD-1212-U) continuously for 10 seconds, at a comfortable and individually

determined pace. Circles were drawn in the clockwise direction with the left hand and in

the counter-clockwise direction with the right hand to maintain biomechanical

equivalence. For the small circle targets, drawing was performed with the forearm

32

resting on the surface of the graphics tablet, which was the position adopted naturally by

participants using their right hand. Subjects were instructed to adopt this position with

the left hand to eliminate the tendency to use the whole arm during left-hand drawing,

thus limiting proximal movements and promoting distal movements, and ensuring task

equivalence across the hands. For the large circle targets, participants were free to adopt

a comfortable drawing position. Each trial began when force was detected from one pen

(for unimanual drawing) or two pens (for bimanual drawing) on the graphics tablet,

indicating that the subject had begun drawing. Each participant completed four trials of

three tasks: unimanual left, unimanual right, and bimanual circle-drawing, for each

circle size. Task order was partially counter-balanced across participants by Latin

square arrangement.

Data analysis

For each trial, time, X and Y coordinates of pen positions, and pen pressure on the

digitizing tablet were sampled at 100 Hz with a computer, and stored for later analysis.

The DC components of the X and Y waveforms were removed and the data were dual

band-pass filtered with the low cut-off frequency determined as half the average peak

frequency from the power spectra of X and Y waveforms and the high cut-off

determined using the method described by Winter (2005, p. 45). The purpose of the dual

filtering process (filtering once in the forward and once in the reverse direction) was to

correct the phase shift otherwise introduced by a single filtering process. The linear

excursion of the pen was calculated from consecutive X-Y coordinate pairs. The data

were separated into cycles, which were defined by every second zero crossing in the Y

dimension. Accuracy, rate, variability, and smoothness of drawing were assessed using

the following measures (calculated for each cycle):

33

Rate of drawing. Period (time to complete one cycle in seconds), mean linear speed, and

peak speed, for each cycle, calculated as the first derivative of linear distance with

respect to time, were calculated.

Accuracy. X- and Y-amplitude (calculated as the maximum minus minimum X- or Y-

value for each cycle), and circularity (defined below) were used to assess accuracy of

drawing. To enable comparison of accuracy in X- and Y-dimensions between different

target sizes, X-amplitude ratio and Y-amplitude ratio were calculated as the X- or Y-

amplitude of each cycle divided by the diameter of the template circle (15 mm or 70

mm). Because the shapes drawn in the present study were often more complex than

simple ellipses (e.g., small circles drawn with the left hand often took on a triangular

appearance; see Figure 3.1), a simple aspect ratio of minor to major axes would not

have sufficiently captured the complexity of the figures. The circularity ratio defined

below has been used in geography to describe the degree of “compactness” of complex

land regions (a circle being the most “compact” two-dimensional shape), and also more

recently in the bio-medical field to describe tumour shapes (Boyce & Clark, 1964;

Iwano, Nakamura, Kamioka, & Ishigaki, 2005).

Circularity was calculated:

drawnshapeofperimeterwithcircleofArea

drawnshapeofAreayCircularit =

2

4

Perimeter

Area⋅⋅= π

Circularity as defined above ranges from 0 to 1 (with a straight line scoring 0 and a

perfect circle scoring 1). Circularity can be calculated for any shape; as examples, an

equilateral triangle scores 0.60 and a square scores 0.79.

34

Variability. Spatial variability was measured by coefficient of variation (CV) of X- and

Y-diameters and temporal variability was measured by CV of period, CV of speed, and

CV of peak speed measured.

Smoothness of drawing. Number of cycles of acceleration-deceleration, and RMS jerk

were calculated as measures of drawing smoothness. The number of cycles of

acceleration and deceleration per drawing stroke has been used as a measure of drawing

efficiency; lower values indicate more efficient stroke production (Hogan & Flash,

1987). This measure has been used previously to quantify differences in efficiency

between the left and right hands (Phillips, Gallucci, & Bradshaw, 1999). Acceleration

was calculated as the second derivative of linear distance with respect to time. Number

of cycles of acceleration-deceleration were calculated by counting the number of Y-zero

crossings in the acceleration function during each cycle.

A related measure, jerk (change in acceleration), is also smaller in smooth movements

(Flash & Hogan, 1985), and has been shown to be larger in patients with Parkinson’s

disease than in normal controls (Teulings, Contreras-Vidal, Stelmach, & Adler, 1997).

Jerk was calculated as the third derivative of linear distance with respect to time.

Statistical analyses. All measures were analysed using three-way repeated-measures

ANOVAs with Hand (left and right), Mode (unimanual and bimanual), and Size (small

and large) as within-subject factors. An alpha-level of 0.05 was used for all statistical

tests. Partial eta squared (η2) values are presented as estimates of effect size.

35

3.2 Results

Figure 3.1 shows unimanual and bimanual tracings of small and large circles with the

left and right hands from a typical participant. Drawings made with the left hand appear

more spatially variable than those made with the right hand and this difference is

particularly noticeable for the small shapes. Small circles drawn with the left hand

appeared more “segmented” than those drawn with the right hand, often appearing

almost triangular (as is the case for this participant). Differences between the hands

were less obvious for large circles.

Accuracy of drawing

Figure 3.2 shows X-amplitude ratio (X-amplitude/ template diameter; panel A), Y-

amplitude ratio (Y-amplitude/template diameter; panel B), and circularity (panel C) of

shapes drawn with the left and right hands during unimanual and bimanual drawing of

small and large circles. Amplitude ratios were used to enable comparisons between

small and large circle-drawings. Table 3.1 shows the results of three-way repeated

measures ANOVAs for these measures with Hand (left and right), Mode (unimanual

and bimanual), and Size (large and small) as within-subjects factors.

A comparison of X- and Y-amplitude ratios (Figure 3.2, panels A and B, respectively)

shows that shapes were slightly elliptical; they were drawn with a smaller X amplitude

than Y amplitude for all conditions. Mean X-amplitudes were smaller than the template

diameter (the dashed line indicates equivalence of drawing and template diameters) and

mean Y-amplitudes were larger than the template diameter.

36

Figure 3.1. Example of a typical participant’s responses during unimanual and bimanual drawing of small (template diameter = 15 mm), and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/deceleration (Ac/Dec) are shown for each trial.

Right Hand Left Hand

Unimanual

Bimanual

10 mm

Small Circles

Large Circles

20 mm

Right Hand Left Hand

Unimanual

Bimanual

Circ: 0.90 Per: 0.60

X: 15.2 Y: 17.4

Ac/Dec: 2.8

Circ: 0.98 Per: 0.53

X: 13.8 Y: 14.3

Ac/Dec: 2.6

Circ: 0.92 Per: 0.53

X: 15.3 Y: 15.9

Ac/Dec: 2.4

Circ: 0.93 Per: 0.53

X: 11.4 Y: 13.3

Ac/Dec: 1.9

Circ: 0.94 Per: 1.89

X: 59.1 Y: 62.2

Ac/Dec: 5.5

Circ: 0.97 Per: 1.89

X: 64.1 Y: 62.4

Ac/Dec: 4.9

Circ: 0.98 Per: 1.19

X: 66.1 Y: 69.7

Ac/Dec: 3.3

Circ: 0.99 Per: 1.05

X: 69.1 Y: 67.5

Ac/Dec: 3.3

37

0.80

0.85

0.90

0.95

1.00

Table 3.1. Three-Way Repeated-Measures ANOVA for X-Amplitude Ratio, Y-Amplitude Ratio, and Circularity, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.

X-Amplitude ratio Y-Amplitude ratio Circularity Source F p Partial η2 F p Partial η2 F p Partial η2

Hand (H) 10.72 .003 .26 22.13 <.001 .42 87.12 <.001 .74 Mode (M) 0.08 .782 <.01 0.01 .912 <.01 3.78 .061 .11 Size (S) 28.61 <.001 .48 50.91 <.001 .62 47.55 <.001 .61 H x M 3.06 .090 .09 4.44 .043 .12 0.54 .468 .02 H x S 8.49 .007 .22 11.82 .002 .18 41.17 <.001 .57 M x S 21.45 <.001 .41 3.56 .069 .10 0.92 .344 .03 H x M x S 2.26 .143 .07 2.67 .112 .08 0.60 .446 .02

Figure 3.2. Spatial measures: Mean X- and Y-amplitude ratios (A and B) and mean circularity (C) of small and large circles drawn with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual circle-drawing. X- and Y- amplitude ratios were calculated as the X- and Y-amplitude of the shape drawn divided by the diameter of the template circle. Dashed horizontal lines in panels A and B indicate accurate amplitude reproduction. Error bars are ±1 standard error of the mean.

0.7

0.8

0.9

1.0

1.1

1.2

1.3

Large Small Unimanual Unimanual Bimanual Bimanual


A B

C

Circ

ular

ity

X-A

mpl

itude

rat

io

0.7

0.8

0.9

1.0

1.1

1.2

1.3

Y-A

mpl

itude

rat

io

38

Circles were slightly larger when drawn with the left hand than with the right hand, in

both the X-dimension and Y-dimension. The largest differences between the hands in

X- and Y-amplitude ratios were seen when drawing small circles.

Shapes were more circular when drawn with the right hand than with the left hand

(Figure 3.2, panel C). Mean circularities with the right hand were equivalent for small

and large circles. In contrast, with the left hand, circularity was smaller for small circles

than large circles. Mode of drawing had no effect on circularity; for each hand shapes

were equally circular when drawn in unimanual and bimanual modes.

Rate of drawing

Figure 3.3 shows mean period (panel A), speed (panel B), and peak speed (Panel C) of

the left and right hands during unimanual and bimanual drawing of small and large

circles. Table 3.2 shows the results of three-way repeated measures ANOVAs for these

measures with Hand (left and right), Mode (unimanual and bimanual), and Size (large

and small) as within-subjects factors.

The most obvious differences in period of circle drawing were between small- and

large-circle drawing (Figure 3.3, panel A). As expected, mean period of circle drawing

was longer for large circles than for small circles. Although period of circle drawing

was significantly shorter with the right hand than the left hand overall, this difference

was almost entirely due to a difference between the period of left and right hands when

they drew small circles in the unimanual mode (mean period with left hand 0.86, SD

0.26, and right hand 0.68, SD 0.20). During all other tasks, the period of circle drawing

was similar for the left and right hands. The significant Hand by Mode by Size

interaction (Table 3.2) reflected this observation.

39

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

0

50

100

150

200

250

0

50

100

150

200

250

300

Table 3.2. Three-Way Repeated-Measures ANOVA for Period (s) and Speed (mm.s-1), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.

Period Speed Peak Speed Source F p Partial η2 F p Partial η2 F p Partial η2

Hand (H) 17.66 <.001 .36 0.01 .925 <.01 6.50 .016 .17Mode (M) 4.161 .050 .12 5.28 .029 .14 4.68 .038 .13Size (S) 155.41 <.001 .83 345.76 <.001 .92 355.48 <.001 .92H x M 16.70 <.001 .35 12.53 .001 .29 10.54 .003 .25H x S 22.81 <.001 .42 4.79 .036 .13 0.10 .756 >.01M x S 0.60 .446 .02 0.34 .564 .01 >0.01 .982 >.01H x M x S 22.44 <.001 .42 6.73 .014 .18 2.69 .111 .08

Figure 3.3. Mean period (A), speed (B), and peak speed (C) of drawing large and small shapes with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual circle-drawing. Error bars are ±1 standard error of the mean.

PE

RIO

D (

s)

Bimanual

Large Small Unimanual Unimanual Bimanual

PE

AK

SP

EE

D (

mm

.s-1

)


SP

EE

D (

mm

.s-1

)

A

B C

L R L R

L R L R

L R L R

L R L R

40

Although it took less time to draw small circles than large circles (Figure 3.3, panel A),

mean linear speed was slower for small circles than for large circles (panel B). The left

hand was faster than the right hand (although the differences were not great) for all

conditions except when small circles were drawn in the unimanual mode; in this

condition, speed of drawing with the right hand was greater than speed of the left hand.

This is reflected in a significant Hand by Mode by Size interaction.

Peak speed was also slower for small circles than large circles (Figure 3.3, panel C).

The peak speed of drawing was faster with the left hand than with the right hand. The

largest difference in peak speed between the hands was observed in the bimanual mode,

reflected in a significant Hand by Mode interaction.

Spatial variability

Figure 3.4 shows mean between-cycle variability of X amplitude (CV of X-amplitude;

panel A) and Y-amplitude (CV of Y-amplitude; panel B) for the left and right hands

during unimanual and bimanual drawing of large and small circles. Table 3.3 shows the

results of three-way repeated measures ANOVAs for these measures with Hand (left

and right), Mode (unimanual and bimanual), and Size (large and small) as within-

subjects factors.

Amplitudes were more variable for small circles than large circles in the X-dimension

(Figure 3.4, panel A) and in the Y-dimension (panel B). Circles produced with left hand

were more variable than circles produced with the right hand in the X-dimension (panel

A), and in the Y-dimension (panel B), and the greatest differences between the hands in

spatial variability were seen when participants drew small circles; this was reflected in

significant interactions between Hand and Size in both the CV of X- and CV of Y-

41

0

2

4

6

8

10

12

0

2

4

6

8

10

12

amplitude data. Bimanual drawing was also associated with more variability in X- and

Y-amplitudes than unimanual drawing.

Table 3.3. Three-Way Repeated-Measures ANOVA for CV of X-Amplitude and CV of Y-Amplitude, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.

CV of X-amplitude CV of Y-amplitude Source F p Partial η2 F p Partial η2

Hand (H) 19.63 <.001 .39 21.01 <.001 .40 Mode (M) 47.14 <.001 .60 25.29 <.001 .45 Size (S) 38.58 <.001 .55 66.77 <.001 .68 H x M 0.29 .592 .01 0.06 .811 <.01 H x S 14.34 .001 .32 13.58 .001 .30 M x S 3.40 .075 .10 2.06 .162 .06 H x M x S 0.92 .344 .03 2.67 .113 .08

Figure 3.4. Mean CV of X-amplitude (A) and mean CV of Y-amplitude (B) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.

Rate variability

Figure 3.5 shows mean between-cycle variability of period of drawing (CV of period,

panel A), speed (CV of speed, panel B) and peak speed (CV of peak speed, panel C) for


Bimanual

CV

X-A

mpl

itude


CV

Y-A

mpl

itude


L R

L R

L R

L R

L R

L R

L R

L R

A B

42

0

1

2

3

4

5

6

7

8

0

2

4

6

8

10

12

0

2

4

6

8

10

12

14

circles. Table 3.4 shows the results of three-way repeated measures ANOVAs for these

measures.

Table 3.4. Three-Way Repeated-Measures ANOVA for CV of Period, CV of Speed and CV of Peak Speed, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.

CV of Period CV of Speed CV of Peak Speed Source F p Partial η2 F p Partial η2 F p Partial η2

Hand (H) 0.36 .553 .01 1.08 .307 .03 12.56 .001 .29 Mode (M) 0.75 .393 .02 3.49 .071 .10 7.23 .011 .19 Size (S) 2.57 .119 .08 8.75 .006 .22 27.59 <.001 .47 H x M 2.24 .144 .07 0.04 .836 <.01 0.02 .887 <.01 H x S 5.40 .027 .15 12.60 .001 .29 15.29 <.001 .33 M x S 0.20 .655 .01 3.10 .088 .09 1.76 .195 .05 H x M x S 6.69 .015 .18 0.94 .341 .03 0.96 .334 .03

Figure 3.5. Mean CV of period (A), CV of speed (B), and CV of peak speed (C) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.

There was no systematic difference in the between-cycle variability of period between

the small and large circles (Figure 3.5, panel A). Neither was there a systematic

Bimanual



CV

Spe

ed

CV

Pea

k S

peed

CV

Per

iod

A

B C

L R

L R

L R

L R

L R L R L R L R

43

difference between the hands in the variability of period. However, the variability of

period tended to be larger with the left hand than the right hand in all conditions except

when large circles were drawn in the unimanual mode; in this condition, CV of period

was larger with the right hand than the left hand. This is reflected in a significant Hand

by Mode by Size interaction.

Overall, small circles were drawn with more variable speed than large circles (Figure

3.5, panel B). When drawing small circles, the variability of speed was larger for the left

hand than the right hand. In contrast, when drawing large circles, the differences

between the hands were flipped; variability of speed was slightly larger for the right

hand than the left hand and this was reflected in a significant Hand by Size interaction.

There was no systematic difference between unimanual and bimanual modes of drawing

in variability of speed.

The variability of peak speed data (Figure 3.5, panel C) were similar to the variability of

speed data (panel B). Variability of peak speed was larger for the left hand than the right

hand when drawing small circles, and approximately equal for the left and right hands

when drawing large circles. Variability of peak drawing was slightly greater overall

during bimanual than unimanual drawing.

Smoothness of drawing

Figure 3.6 shows mean the mean number of cycles of acceleration-deceleration per

cycle (panel A) and RMS jerk (panel B) for the left and right hands during unimanual

and bimanual drawing of small and large circles. Table 3.5 shows the results of three-

way repeated measures ANOVAs for these measures.

44

0

1

2

3

4

5

0

200

400

600

800

1000

1200

1400

1600

1800

Table 3.5. Three-Way Repeated-Measures ANOVA for Cycles of Acceleration-Deceleration and RMS Jerk (mm.s-3), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subject Factors. Values in Bold are Significant at p<.05.

Acceleration-Deceleration RMS Jerk (mm.s-3) Source F p Partial η2 F p Partial η2

Hand (H) 22.39 <.001 .42 84.96 <.001 .73 Mode (M) 2.20 .148 .07 1.05 .313 .03 Size (S) 10.99 .002 .26 33.53 <.001 .52 H x M 4.08 .052 .12 2.81 .104 .08 H x S 0.28 .602 .01 2.57 .119 .08 M x S 4.63 .039 .13 5.80 .022 .16 H x M x S 0.98 .330 .03 0.07 .794 <.01

Figure 3.6. Mean number of cycles of acceleration-deceleration per cycle (A) and RMS jerk (B) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.

There were fewer cycles of acceleration-deceleration per cycle with the right than the

left hand (panel A), indicating a smoother trajectory with the right hand than the left

hand. In addition, small circles were drawn with fewer cycles of acceleration-

deceleration than large circles. During small-circle drawing, the number of cycles of

acceleration-decelerations was larger for unimanual than bimanual drawing (indicating

smoother drawing in the bimanual mode). In contrast, during large-circle drawing, the

Bimanual

Large Small

Unimanual Unimanual Bimanual Bimanual

Large Small

Unimanual Unimanual Bimanual

RM

S J

erk

(mm

.s-3

)

Cyc

les

of A

c/D

ec

A

L R L R

L R

L R B

L R

L R

L R L R

45

number of cycles of acceleration-decelerations was larger for bimanual than unimanual

drawing (indicating smoother drawing in the unimanual mode).

RMS jerk (the third derivative of distance with respect to time) was smaller with the

right than the left hand (Figure 3.6, panel B). RMS jerk was also smaller during small-

circle drawing than large-circle drawing. Furthermore, during large-circle drawing,

RMS jerk was similar for unimanual and bimanual modes, but during small-circle

drawing, RMS jerk was smaller for the bimanual mode than the unimanual mode,

indicating smoother drawing with both hands during the unimanual mode.

Pressure

Figure 3.7 shows mean median pressure (in non-scaled pressure units) for the left and

right hands during unimanual and bimanual drawing of small and large circles. Table

3.6 shows the results of three-way repeated measures ANOVAs for pressure.

More pressure was used with the right hand than with the left hand during all drawing

conditions, which may be an indirect indicator of greater confidence of drawing with the

dominant than nondominant hand (LaRoque & Obrzut, 2006). Although significantly

more pressure was applied during unimanual than bimanual drawing, the difference was

small.

46

0

100

200

300

400

500

600

700

800

900

Table 3.6. Three-Way Repeated-Measures ANOVA for Pressure (in non-scaled pressure units), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.

Source F-value p-value Partial η2

Hand (H) 47.618 <.001 .61 Mode (M) 7.178 .012 .19 Size (S) 1.76 .195 .05 H x M 0.21 .648 .01 H x S 0.01 .920 <.01 M x S 0.11 .742 <.01 H x M x S 1.42 .242 .04

Figure 3.7. Mean pressure (in non-scaled pressure units) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean

3.3 Discussion

The main findings of this study were: 1) circles drawn with the right hand were more

spatially accurate, less spatially variable, had smoother trajectories and were drawn with

more pressure than circles drawn with the left hand, 2) large circles were drawn more

accurately than small circles with the left hand, but not with the right hand (the

circularity of large and small circles was equivalent with the right hand), 3) small circles

were more spatially and temporally variable than large circles, but were associated with

Bimanual

Large Small

Unimanual Unimanual Bimanual

Pre

ssur

e

L R L R L R L R

47

smoother trajectories than large circles and 4) bimanual drawing was associated with

greater spatial variability but smoother trajectories than unimanual drawing, whereas

accuracy of drawing was similar in unimanual and bimanual modes.

Bimanual versus unimanual drawing

There were no differences between unimanual and bimanual drawing in the accuracy of

the shapes drawn; circularity was equivalent and there were no systematic X- or Y-

amplitude differences between shapes drawn unimanually and bimanually. Although

previous research has shown reduced accuracy in bimanual drawing than unimanual

drawing (Carson, Thomas, Summers, Walters, & Semjen, 1997), differences in

methodology may account for the difference between this finding and the current

results. Carson and colleagues used a paced circle-drawing task and found that as rate of

drawing increased, accuracy decreased. In the current study, no temporal constraints

were imposed; participants were free to draw at their preferred pace. Consequently,

speed of drawing was slower during bimanual than unimanual drawing, which suggests

that in a trade-off between speed and accuracy, participants slowed their drawing to

preserve accuracy during the more demanding task of bimanual drawing. However,

more spatial variability was seen during bimanual than unimanual drawing. Given that

this was not associated with a reduction in accuracy of drawing, this finding may reflect

a reduced capacity to allocate attention to each hand during bimanual drawing.

Participants were free to direct their attention wherever they wished, which probably

resulted in attention being focused on the responding hand during unimanual drawing,

whereas during bimanual drawing they may have adopted a strategy of alternating their

attention between the hands.

48

There was an attenuation of the asymmetry between the hands in smoothness of circle

drawing (cycles of acceleration/deceleration) during bimanual coordination. This was

only seen during small-circle drawing, and it represented an improvement in the

performance of the nondominant hand, with no apparent change in the performance of

the dominant hand, which suggests an integration of features of the movement trajectory

of the dominant limb into the trajectory of the nondominant limb. A second measure of

trajectory smoothness (RMS jerk) was smaller for both hands during bimanual than

unimanual small circle drawing (although the absolute asymmetry between the hands

was the same during unimanual and bimanual coordination). The apparent discrepancy

between the two measures of movement smoothness might be due to a faster rate of

circling with the dominant hand during unimanual than bimanual modes which could

have contributed to its smaller jerk when coupled with the nondominant hand (i.e. the

smaller jerk is secondary to a decreased rate of movement). The rate of drawing with the

nondominant hand did not change markedly from unimanual to bimanual drawing (if

anything its rate was slightly faster in the bimanual mode) so this cannot explain the

smoother trajectories with the nondominant hand during bimanual movements.

The greater smoothness with the nondominant hand during bimanual than unimanual

drawing in the current study was not associated with a reduction in between-cycle

temporal variability, indeed, between-cycle amplitude and temporal variability was

greater during bimanual than unimanual drawing. Rather, the greater smoothness during

bimanual than unimanual drawing occurred within each cycle, reflecting greater within-

cycle precision in the spatiotemporal specification of muscle activity. A tentative

explanation for these findings is that the features of the movement trajectories of the

dominant limb become integrated into the motor response of the nondominant limb.

This has been shown to occur at a coarser level during the attempt to draw circles with

49

one hand and lines with the other, although in this case, the resulting figures both hands

become more elliptical (Franz, 1997; Franz, Zelaznik, & McCabe, 1991). The substrate

for the interaction between trajectories of the two hands may be interhemispheric

connections via the corpus callosum since callosotomy patients are able to produce

shapes which have different trajectories with each hand concurrently (Franz, Eliassen,

Ivry, & Gazzaniga, 1996). In the current study this effect was unidirectional (at least for

the acceleration/deceleration measure of smoothness), which suggests that the dominant

hemisphere has a role in the control of the nondominant hand during bimanual

movements for the task used in the current study. That greater smoothness during

bimanual than unimanual drawing was seen for small circles but not large circles may

be related to differences in the control of distal and proximal musculature, which is

explored further below.

Large- versus small-circle drawing

Large circles were drawn with less spatial and temporal variability than small circles

with both hands and period of drawing was smaller for small than large circles

indicating less time was required to produce each cycle during small- than large-circle

drawing. Despite a more variable performance during the production of small circles

than large circles, drawing small circles required fewer cycles of acceleration-

deceleration and was associated with less jerk than drawing large circles. This

represents greater efficiency of stroke production during small- than large-circle

drawing, which may be related to different neural control during the two tasks.

Biomechanical requirements were different for small- and large-circle drawing; large

circles were drawn with movements of more proximal effectors and small circles were

drawn with movements of proportionately greater involvement of distal effectors.

Corticomotoneuronal connections to motoneurons innervating distal muscles have been

50

proposed as the neural substrate for fine finger movements. In monkeys, intrinsic hand

muscles receive strong input from the dorsolateral corticospinal tract and the activity of

corticomotoneuronal cells is related to fractionated activity in hand muscles (Bennett &

Lemon, 1996). Furthermore, corticomotoneuronal projections, which originate almost

entirely in the primary motor cortex, are more numerous to motoneurons of distal

muscles than proximal muscles (Kuypers, 1981), and comparisons across different

primates indicates that an increased density of these monosynaptic connexions is related

to an increased capacity to perform independent finger movements (Heffner &

Masterton, 1983). Transcranial magnetic stimulation suggests that the projection of the

corticomotoneuronal system to the upper limb in humans follows a similar pattern to

that in monkeys, with greater distal than proximal innervation (Palmer & Ashby, 1992).

The smoother trajectories during small-circle drawing than during large-circle drawing

reflect an ability to more precisely modulate the activity of agonist-antagonist muscles

for distal than proximal effectors, which is possibly at least partly related to the greater

number of monosynaptic projections of cortico-motoneuronal cells onto motoneurons

innervating distal than proximal muscles.

Left-right asymmetries in performance

Drawing was more accurate, less spatially variable, and smoother with the right hand

than the left hand. Similar left-right asymmetries were found in a study which compared

handwriting with the left hand and right hand in right-handers (Phillips, Gallucci, &

Bradshaw, 1999). The authors found that the right hand was faster than the left hand,

writing strokes drawn with the right hand were less variable in length, duration, and

peak velocity, and the right hand produced more efficient strokes than the left hand

(there were fewer cycles of acceleration-deceleration with the right than left hand). In

the present study, the size of the small circle template was comparable to that of the

51

handwriting study. In this task, the rate of drawing with the right hand was greater than

the rate of drawing with the left hand (during unimanual drawing), and the right hand

was less spatially variable, less variable in rate, less variable in peak speed, and

produced more efficient strokes than the left hand. These between-hand differences

were also seen during large-circle drawing for all measures except variability of rate and

peak speed. However, the magnitude of the asymmetry between the hands was smaller

when drawing large than small circles. The left-right asymmetry differences between

large and small drawing tasks are particularly noticeable in Figure 3.1; the performances

of the left and right hands are not markedly different when drawing large circles, but

considerable distortions in the shapes and more cycle-to-cycle variability is obvious in

small circles drawn by the left than the right hand. Obvious submovements in the

trajectories of small circles drawn with the left but not the right hand, as seen in the

illustrative example, were common, whereas submovements were never obvious in the

drawings of large circles. Submovements have been shown to be more prevalent in the

initial stages of motor skill acquisition and become fewer and more blended with skill

development (von Hofsten, 1991), a finding mirrored during recovery from stroke

(Rohrer et al., 2004). The presence of less well blended submovements in left- than

right-hand trajectories during small-circle drawing in the current study may reflect less

precise control of agonist and antagonist muscle activity in the left hand than the right

hand. Furthermore, submovements in the nondominant hand appeared to become more

blended during bimanual coordination which suggests, similar to the point made above,

that aspects of the trajectory of the dominant hand become integrated into the trajectory

of the nondominant hand. This further supports the hypothesis that the dominant

hemisphere plays a role in managing the nondominant limb during bimanual

coordination.

52

The biomechanical difference between the tasks discussed above, coupled with a natural

tendency to control movements of the left limb by controlling more proximal joints

(compared to control of the right limb), might explain the larger between-hand

differences during small-circle drawing than during large-circle drawing. Right-handers

naturally use more proximal movements for writing with their left hand, and more distal

movements for writing with their right hand (Mack, Gonzalez Rothi, & Heilman, 1993),

which is accomplished by a greater “locking” of the more distal joints in the left than in

the right limb (Newell & Van Emmerik, 1989). In the current study, biomechanical

differences between the hands during small-circle drawing were minimized by

encouraging participants to adopt a similar drawing position with the left and right

hands (using the position naturally adopted with the right hand for both), forcing the use

of distal joints with both hands.

The basis for the greater asymmetries during small-circle than large-circle drawing may

be related to a difference in the control of distal and proximal effectors; distal muscles

are controlled predominantly by projections from the contralateral hemisphere, whereas

proximal muscles are controlled from both hemispheres (J. Brinkman & Kuypers,

1972). From this observation, it may be expected that hemispheric differences in motor

control would be reflected more in tasks that require distal control than in tasks that

require proximal control. Hore and colleagues (1996) found that inaccuracies in

throwing with the left arm were the result of variability in the control of distal effectors

(the fingers). The authors reported greater variability with the left limb than the right

limb in both proximal and distal joint movements, however the asymmetry was more

marked for distal joints, and it was the less precise control of distal joint rotations which

accounted for most of the variability in throwing with the left limb.

53

Representations of the forelimb muscles in monkeys extend over large areas of M1

(Donoghue, Leibovic, & Sanes, 1992) and the representation of each small finger

muscle in M1 has multiple foci that overlap with representations of other muscles (Sato

& Tanji, 1989). This pattern of overlapping muscle representation in M1 has been

proposed to form the basis for the control of muscle synergies, and may also allow for a

dynamic reorganization of interconnections between different muscle representations

during the learning a new skill (Donoghue, Leibovic, & Sanes, 1992). Furthermore, the

areas of digit representation are more widely distributed in dominant than nondominant

M1 (Volkmann, Schnitzler, Witte, & Freund, 1998), possibly reflecting use-dependent

plastic changes. Greater neuropil volume in dominant than nondominant M1 suggests

more profuse intracortical connections in the dominant than nondominant hemisphere

(Amunts et al., 1996) providing a neural substrate for these plastic changes. On this

note, it is likely that practice contributed to the performance asymmetries in the current

study given the more extensive exposure to dexterous tasks received by the right hand

than the left hand. Extensive practice can reduce the magnitude of left-right

asymmetries in tapping speed (Peters, 1976). Practice is also associated with reductions

in the spatial variability of movement trajectories (Georgopoulos, Kalaska, & Massey,

1981) and a reduction in the variability of motor unit discharge rate (Kornatz, Christou,

& Enoka, 2005). The more accurate, less variable, and more efficient movement

trajectories with the right hand than the left hand in the current study could, at least

partly, be the result of differences between the hands in exposure to related tasks. The

greater practice, combined with a neural substrate to capitalize on that practice (the

greater interconnections between movement representations in the dominant than

nondominant hemisphere) could explain a more effective control of movement

synergies with the dominant than the nondominant hand, reflected in the more precise

54

spatiotemporal control of fine finger movements and blending of submovements seen in

the current study.

In summary, the right hand produced more accurate, less variable, and more efficient

trajectories than the left hand. Others have shown greater accuracy and smaller temporal

and spatial variability with the dominant than non-dominant hand using a large-circle

drawing task (Carson, Thomas, Summers, Walters, & Semjen, 1997). This study

extended the findings to small-circle drawing, and showed greater asymmetries between

the hands during this task. Furthermore, although accuracy was not different between

unimanual and bimanual modes of drawing, circle trajectories were smoother during

bimanual than unimanual drawing despite showing more cycle-to-cycle spatial

variability. This last finding was observed during the small circle task but not the large

circle task, and was asymmetric; the nondominant hand benefited from bimanual

coupling but the nondominant hand did not. This may reflect an integration of features

of the movement trajectories of the dominant hand into the motor response of the

nondominant limb and provides support for the hypothesis that the dominant

hemisphere has a role in managing the nondominant hand during bimanual

coordination.

55

CHAPTER 4. TMS-INDUCED DISRUPTION OF MOTOR PERFORMANCE

Transcranial magnetic stimulation (TMS) can be used to temporarily disrupt ongoing

neural processes during the performance of motor tasks. In its single-pulse mode, a brief

intense magnetic field generated by an insulated coil held over the scalp passes virtually

unattenuated through the skin and skull and induces an electrical current in the

underlying cortex resulting in neural depolarisation (Barker, Jalinous, & Freeston,

1985). The delivery of single-pulse TMS can be precisely timed, the magnetic field

generated by the coil is brief (less than 1 ms`, Walsh & Rushworth, 1999), and its

effects have been extensively studied, making this mode of TMS delivery an ideal tool

for examining processes of voluntary movement control. The review which follows

briefly outlines the physiological effects of single-pulse TMS within the cortex, the

behavioural effects of TMS on motor performance, and the proposed mechanisms of

disruption to motor control.

Transient and Sustained Effects of TMS within M1

The immediate effect of TMS is a transient, trans-synaptic excitation of corticospinal

neurons, resulting in their depolarisation. When TMS is delivered over the hand area of

M1 at a sufficiently high intensity, the resulting corticospinal volley excites spinal

motoneurons which results in a motor evoked potential (MEP) in hand muscles

contralateral to the side of delivery.

Although the area of electrical current induced by the TMS pulse is relatively focal, the

area of the brain affected by TMS extends to regions outside the stimulated area through

spread of activation. Increased regional neural activity in ipsilateral and contralateral

56

motor cortex after single-pulse TMS have been demonstrated using functional magnetic

resonance imaging (Bohning et al., 2000). Additionally, electroencephalographic

recordings after TMS over M1 have shown spread of activation to anatomically

connected regions within the same hemisphere within 5 to 10 ms, and to homologous

regions in the contralateral hemisphere within 20 ms (Ilmoniemi et al., 1997).

Sustained effects of single-pulse TMS result from the activation of inhibitory neurons.

These sustained effects are very powerful, and in active muscle, result in a complete or

partial interruption of the voluntary cortical drive to a target muscle which can be

observed as a silent period (SP) in the EMG activity immediately following the MEP

induced by TMS. The SP lasts up to 250 ms and increases with increasing TMS

intensity (Inghilleri, Berardelli, Cruccu, & Manfredi, 1993). While the first 50 ms of the

SP may be largely due to spinal mechanisms, the final stage is cortical in origin, and

reflects a reduced outflow from M1 (Fuhr, Agostino, & Hallett, 1991). The cortical

effect is thought to be due to the activation of inhibitory interneurons. Like the

immediate effects of TMS, the sustained effects are not limited to the site of TMS

application; silent periods in muscles ipsilateral to the side of delivery have been

reported with high intensity TMS (Chiappa et al., 1995).

The output of the motor cortex is a function of the interplay between excitatory and

inhibitory input to corticospinal tract neurons. Rapidly acting excitatory and inhibitory

circuits are thought to shape motor output by the excitation of relevant output cells and

inhibition of irrelevant output cells (Liepert, Classen, Cohen, & Hallett, 1998; Zoghi,

Pearce, & Nordstrom, 2003). The functional significance of long-lasting inhibitory

circuits is less well understood, but these circuits may modulate ongoing motor output

(Rosenkranz & Rothwell, 2003). Asymmetries in both short- and long-lasting inhibitory

57

circuits have been reported, with more excitable circuitry for both in the dominant than

non-dominant hemisphere (Hammond, Faulkner, Byrnes, Mastaglia, & Thickbroom,

2004; Hammond & Garvey, 2006; Matsunaga, Uozumi, Tsuji, & Murai, 1998),

implicating them in fine motor control.

TMS introduces a non-physiological form of neural “noise” into the organised pattern

of neural firing by disrupting both intracortical excitatory and inhibitory processes and

hence interferes with the organized output from M1. TMS provides a powerful tool to

disrupt cortical processing during motor control, analogous to the classical lesion

studies in examining cortical functions, with the advantages of being reversible, and

having greater temporal resolution.

TMS-induced disruption of motor performance

Unimanual motor performance. TMS can either facilitate or lengthen RT, depending on

the intensity of the stimulus, its timing relative to the response, and the site of

stimulation. At subthreshold intensities, TMS applied at around the time of the response

signal (i.e. early in the response latency) shortened both simple RT (Hashimoto, Inaba,

Matsumura, & Naito, 2004; Pascual-Leone, Brasil-Neto, Valls-Solé, Cohen, & Hallett,

1992) and go/no-go RT (Sawaki, Okita, Fujiwara, & Mizuno, 1999). These effects were

similar in the contralateral and ipsilateral hands. When applied later in the response

latency (within 120 ms of an expected movement), subthreshold TMS had no effect on

RT in the ipsilateral hand, and shortened RT in the contralateral hand (Hashimoto,

Inaba, Matsumura, & Naito, 2004; Sawaki, Okita, Fujiwara, & Mizuno, 1999).

The facilitation of RT by subthreshold TMS is likely to result from at least two different

cortical processes. The facilitation observed when a stimulus is applied early in the

58

response latency is probably due to non-specific intersensory facilitation (conferred by

the loud auditory click associated with TMS discharge), since sham TMS, subthreshold

TMS, and suprathreshold TMS applied at around the time of the response signal all

shorten RT to a similar extent (Ziemann, Tergau, Netz, & Homberg, 1997). This

facilitation is similar to the facilitation of RT observed when an accessory stimulus,

conveying no information pertinent to the response to be performed, is presented at

around the time of a response signal (Nickerson, 1970). The facilitation of contralateral

RT by subthreshold stimulation later in the response latency results from a different

mechanism, since neither sham TMS nor ipsilateral TMS applied at this time affect RT

(Hashimoto, Inaba, Matsumura, & Naito, 2004). M1 excitability (measured as MEP

amplitude to a fixed stimulus intensity) increases gradually in the period preceding a

movement, starting around 100 ms before a self-paced movement and 80 ms before a

RT movement (R. Chen, Yaseen, Cohen, & Hallett, 1998). This increase in M1

excitability parallels an increase in the firing rate of cells in M1 just prior to a voluntary

movement (Evarts, 1966), which continues until a threshold is reached for discharging

spinal motoneurons. Subthreshold TMS applied late in the response latency may shorten

RT by increasing the pre-movement M1 excitability, bringing the M1 discharge rate

closer to the threshold for spinal motoneuron discharge.

In contrast, suprathreshold TMS applied over M1 during a critical time window of

approximately 120 ms prior to movement onset delays contralateral RT by up to 150

ms, whereas suprathreshold TMS applied earlier than this has little effect (Romaiguère,

Possamai, & Hasbroucq, 1997), or facilitates RT as discussed above. Furthermore, the

closer the application of TMS to the next expected movement, the longer the delay (Day

et al., 1989). The delay in RT increases with increasing TMS intensity (Taylor,

Wagener, & Colebatch, 1995; Ziemann, Tergau, Netz, & Homberg, 1997). Similarly,

59

RT in the hand ipsilateral to stimulation can be delayed by a very high intensity

stimulus (up to 2.1 times threshold) applied late in the response latency (Meyer & Voss,

2000). At a lower intensity (1.2 times threshold), TMS over ipsilateral M1 has no effect

on RT (Foltys et al., 2001).

The critical time window during which TMS can delay RT corresponds to the time of

increased discharge rate of contralateral M1 neurons prior to the execution of a

movement (Evarts, 1966), and suggests that TMS acts at the final motor output stage.

The TMS-induced delays in RT appear to be cortical in origin, since during the RT

delay after TMS over contralateral M1, spinal motoneurons are still accessible to

descending input (Day et al., 1989). The delay does not seem to be related to the

immediate excitatory effect of TMS, since the delay in RT is not related to the size of

the MEP (Wilson, Thickbroom, & Mastaglia, 1993), suggesting a different neural origin

of the two phenomena. Several studies implicate inhibitory processes within M1 in the

delay of voluntary movement. Firstly, in a simple RT task, the onset of movement

following TMS over the contralateral M1 was delayed until the end of the SP (Wilson,

Lockwood, Thickbroom, & Mastaglia, 1993). Furthermore, RT delays have been shown

to correlate with SP durations both within and between subjects (Burle, Bonnet, Vidal,

Possamai, & Hasbroucq, 2002; Ziemann, Tergau, Netz, & Homberg, 1997) and the

delay in RT increases linearly (with a slope of 1) as the time between TMS and

expected response onset decreases (Day et al., 1989). These findings suggest that,

during a critical period of motor preparation, TMS induces a relatively fixed period of

disruption to M1 processing, halting motor output for a similarly fixed period regardless

of when TMS is applied during the critical period, after which neural processing

resumes.

60

Two lines of evidence suggest that the pre-movement processing in M1 is temporarily

halted by TMS, but not abolished. Firstly, the increase in M1 excitability that occurs in

the final stage before a movement is executed is maintained during the period after TMS

is delivered, suggesting that the processes responsible for the pre-movement increase in

excitation in M1 continue unabated despite the reduced output from M1 (Palmer,

Cafarelli, & Ashby, 1994). Secondly, Day and colleagues (1989) found that although a

TMS pulse delivered over M1 during the response latency delayed simple RT in the

contralateral hand, the pattern of agonist and antagonist EMG bursts in the delayed

movement was unchanged. These authors reasoned that because the movement was

executed in an intact form immediately following the SP, the motor commands must be

held in a temporary buffer, probably upstream of M1, and were executed after the

temporary block of M1 output had lifted. TMS over M1 during this critical period

therefore seems to affect motor cortex output, by delaying, but not abolishing, pre-

movement processing. After a fixed period of disrupted processing, the motor cortex

seems to resume processing from the state it was in prior to the TMS disruption.

Delays in ipsilateral RT caused by suprathreshold TMS applied close to the onset of

movement are shorter than those seen in the contralateral hand (40 ms compared with

up to 150 ms`, respectively`, Day et al., 1989; Meyer & Voss, 2000), and almost

identical to the duration of the SP evoked by ipsilateral stimulation (Aranyi & Rosler,

2002). The ipsilateral RT delays are likely to be the result of transcallosally mediated

inhibition (Meyer & Voss, 2000).

Single-pulse TMS applied over secondary motor cortices can also affect motor

performance. Suprathreshold TMS applied over premotor cortex or SMA late in the

response latency has no effect on simple RT (Taylor, Wagener, & Colebatch, 1995).

61

However, stimulation over premotor cortex early in the response latency delays choice

RT, reflecting the role of the premotor cortex in the preparation of movements

(Schluter, Rushworth, Passingham, & Mills, 1998), and the earlier critical time window

for disruption of motor control by stimulation of areas cortically upstream of M1. This

is consistent with the time course of the onset of neuronal firing in the premotor and

SMA cortical areas relative to firing in M1 (Tanji & Kurata, 1982).

TMS over M1 also disrupts the performance of ongoing rhythmical motor tasks. TMS

applied over M1 during a sequence of finger flexion/extensions affected only the first

element of the sequence in the contralateral hand, whereas TMS over premotor cortex

and SMA lengthened movement time for elements later in the sequence (Amassian,

Cracco, Maccabee, Bigland-Ritchie, & Cracco, 1991). The effect of TMS over SMA

and premotor cortex on elements later in the sequence of movements is consistent with

a role of these areas in the preparation of sequential finger movements. The disruption

to only the first element in the sequence after TMS over M1 suggests a similar

mechanism of interference to that postulated for the delays in RT; a period of inhibition

during which there is reduced output from M1, followed by a resumption of M1 output

in an unchanged form. However, a recent study indicated that TMS applied over M1

during a critical window of approximately 100 ms prior to movement onset had two

distinct effects on repetitive tapping: 1) an immediate delay in tapping with the

contralateral hand which lasted a single tapping cycle, and 2) the introduction of

“implementation noise” observed as an increase in variability of tapping rate in intervals

after TMS application (Verstynen, Konkle, & Ivry, 2006). Furthermore, others have

shown a more sustained effect of TMS over M1 on repetitive rhythmical movements

when the task required more complex two-joint synergies, with effects persisting for

several cycles of movement (Latash, Danion, & Bonnard, 2003). This finding is

62

consistent with the view that M1 is not exclusively an output area, but also contributes

to movement preparation; single-cell recordings in M1 of the monkey have shown

activity associated with future elements in a sequence of movements (Lu & Ashe,

2005).

Very few studies have attempted to compare the contributions of left M1 and right M1

to unimanual motor control using single-pulse TMS as a tool to disrupt M1 activity.

Stimulation over left and right M1 has equivalent effects on simple RT with the

contralateral hand (Schluter, Rushworth, Passingham, & Mills, 1998) suggesting that

neither hemisphere is dominant in the control of simple finger movements. Similarly,

these authors found no differential effect on simple RT with the ipsilateral hand after

stimulation over left and right M1. In right-handers performing a continuous finger-

tapping task, contralateral finger tapping was disrupted more by TMS over left M1 than

by TMS over right M1 (J. T. Chen et al., 2005), presumably reflecting either a greater

number of corticomotoneuronal projections from dominant M1 than from non-dominant

M1 during this task, or a greater excitability of dominant than non-dominant M1

corticomotoneuronal cells. There was a small disruption to ipsilateral tapping, but no

difference between left- and right-sided stimulation on the ipsilateral effect, suggesting

that, in simple unimanual movements such as repetitive finger tapping, there is no

lateralized contribution of dominant M1 to ipsilateral movement control.

Bimanual motor performance. Few studies have utilized single-pulse TMS to disrupt

ongoing M1 processing during bimanual performance. Foltys et al. (2001) found that

the effects of TMS over M1 on simple RT were similar during unimanual and bimanual

tasks; during both tasks the ipsilateral hand was facilitated by stimulation early in the

response latency and responses were progressively delayed by stimulation later in the

63

response latency, while the contralateral hand was slightly facilitated or unaffected by

stimulation early in the response latency, and responses were delayed to a greater degree

by stimulation later in the response period. These effects were similar regardless of

hemisphere of stimulation. The similarity of the effects during unimanual and bimanual

responding suggests similar M1 engagement in simple unimanual and bimanual

movements. Similarly, during a bimanual in-phase finger-tapping task, TMS caused a

larger disruption of tapping with the contralateral hand than with the ipsilateral hand,

with similar results after TMS over left and right M1 (J. T. Chen et al., 2005). In this

last study, the hand ipsilateral to the side of stimulation was more affected during

bimanual than unimanual tapping, which may reflect a greater contribution of ipsilateral

M1 in the control of bimanual movements. Alternatively, the greater disruption to

ipsilateral tapping during the bimanual task may have been a behavioural consequence

of the disruption to tapping with the contralateral hand, that is, after a disruption to the

tapping of the contralateral hand, the most parsimonious solution to attain

resynchronization of the hands may be to alter the tapping rates with both the

contralateral hand and the ipsilateral hand. These authors quantified changes in

performance after TMS as “resetting index”2, which limited any detailed analysis of the

evolving change in tapping after TMS or of a detailed analysis of the relationship

between disruptions in each hand following stimulation.

The absence of a lateralized effect in these studies suggests that the left hemisphere does

not have a special role in the control of simple bimanual movements such as simple RT

2 Tap onset was defined by EMG burst onset. Phase resetting was calculated by determining the mean baseline inter-tap-interval (aveI), the time between TMS and the last EMG burst before TMS (as a proportion of the aveI, denoted as %I), and the interval between predicted EMG bursts after TMS and actual EMG bursts after TMS (as a proportion of aveI) for five tapping intervals after TMS (d1/aveI to d5/aveI). Resetting index was then calculated as the mean slope of the regression lines of %I against d(n)/aveI (mean of the slopes of five regression lines). Thus, resetting index indicates the (proportional) increase in inter-tap-interval with increasing time of TMS application from last EMG burst. A limitation of this method is that any evolution of the change in tapping over the five intervals post-TMS will be missed because of the averaging procedure.

64

and simple in-phase repetitive finger tapping. In contrast, growing evidence indicates a

greater contribution from left motor areas than right motor areas in the control of

complex motor behaviour. Clinical evidence from patients with unilateral cortical

lesions indicate left hemispheric dominance for control of complex motor behaviour,

with left sided cortical lesions causing both contralateral and ipsilateral deficits whereas

right-sided lesions cause only contralateral deficits (Wyke, 1971). Similarly patients

with left sided lesions produce more sequencing errors with the ipsilateral hand than

patients with right sided lesions (Haaland & Harrington, 1994). Functional imaging

studies have shown greater ipsilateral activation with left hand than right hand

movements, although the results are equivocal concerning the lateralized contribution of

M1. Some have shown no difference in the amount of ipsilateral M1 activation during

simple unimanual hand movements (Volkmann, Schnitzler, Witte, & Freund, 1998) or

during finger-thumb opposition movements (Jäncke et al., 1998). Others have found

greater left sided ipsilateral activation in pre-motor cortex (Singh et al., 1998) and

parietal areas during complex unimanual hand movements (Haaland, Elsinger, Mayer,

Durgerian, & Rao, 2004), but no lateralized activity in M1. Others, however, have

shown greater ipsilateral left M1 activation than ipsilateral right M1 activation during

unimanual sequential finger movements (Kansaku et al., 2005) and during finger-thumb

opposition movements (Kawashima et al., 1993; Kim et al., 1993), suggesting a greater

contribution of left M1 than right M1 in the control of sequential movements of both

hands. Repetitive TMS has also been shown to induce more ipsilateral timing errors in

sequential finger movements when delivered over left M1 than over right M1 (R. Chen,

Gerloff, Hallett, & Cohen, 1997). Several imaging studies have shown greater left M1

than right M1 activation during bimanual motor tasks (Jäncke et al., 1998; Viviani,

Perani, Grassi, Bettinardi, & Fazio, 1998), although others have found no such

asymmetry (Toyokura, Muro, Komiya, & Obara, 1999). The results are therefore

65

equivocal with respect to a lateralized role of M1 in bimanual coordination, although

some evidence suggests that the degree of asymmetry between left and right M1

contribution to bimanual control may be related to task complexity (Koeneke, Lutz,

Wustenberg, & Jäncke, 2004). When an adequate unimanual control was used for the

multi-effector bimanual coordination tasks, Koeneke and colleagues found a similar

network of activation during unimanual and bimanual coordination, suggesting that task

difficulty was a better predictor of cortical activation than mode of coordination per se.

However, the unimanual task (controlling a cursor with two fingers of the same hand)

may have been more difficult to perform than the bimanual task (controlling a cursor

with the left and right index fingers), limiting the interpretation of the results.

The studies reported in the next two chapters used TMS to examine the contribution of

left and right M1 to the control of bimanual movements. TMS was used to manipulate

neurophysiological processes during unimanual and bimanual repetitive finger tapping

and circle drawing; for both tasks, the behavioural consequences of TMS over left and

right M1 were measured during unimanual and bimanual coordination. As discussed in

the introduction, there is evidence that these two tasks represent two fundamentally

different types of bimanual coordination; different mechanisms have been implicated in

the temporal control of repetitive discrete movements versus continuous coordination

(Ivry & Richardson, 2002). Furthermore, the circle-drawing task requires a larger

degree of spatiotemporal coordination than the repetitive tapping task. While both tasks

are accomplished by the sequential activation of different muscles, in the tapping task

the raising and lowering of the finger around a single joint is accomplished by of the

reciprocal activation of flexor and extensor muscles, whereas the circle-drawing task is

a multi-joint coordination task, which requires a more complex pattern of activation of

multiple muscles in order to produce the required trajectory with pen on paper. The

66

differences in complexity of sequential muscle activation between the tasks may have

important consequences for the issue of laterality of control.

67

CHAPTER 5. TMS-INDUCED DISRUPTION OF UNIMANUAL AND

BIMANUAL FINGER TAPPING

Left hemispheric dominance for control of bimanual movements in right-handers is

suggested from several lines of evidence including behavioural (Byblow, Lewis,

Stinear, Austin, & Lynch, 2000; Marteniuk, MacKenzie, & Baba, 1984; Stucchi &

Viviani, 1993) and imaging (Jäncke et al., 1998; Viviani, Perani, Grassi, Bettinardi, &

Fazio, 1998) studies. However, during simple bimanual tasks (in-phase finger tapping),

no lateralization of loci of neuromagnetic sources were seen in sensorimotor cortices

suggesting that the neural control of bimanual coordination is not lateralized (Pollok,

Muller, Aschersleben, Schnitzler, & Prinz, 2004). Similarly, in a study using a more

complex anti-phase bimanual tapping task, no asymmetry in M1 activation was

observed (Toyokura, Muro, Komiya, & Obara, 1999). Furthermore, the absence of a

lateralized effect of TMS on bimanual reaction time and bimanual tapping suggests that

the left hemisphere does not have a special role in the control of simple bimanual

movements (J. T. Chen et al., 2005; Foltys et al., 2001). Some authors have posited that

task complexity rather than whether a task is bimanual may determine the amount of left

hemispheric involvement. However, an EEG coherence study during simple unimanual

and bimanual cyclical wrist flexion-extension movements showed that whereas

unimanual movements are largely controlled by the contralateral hemisphere, coupled

bimanual movements were associated with greater drive from the dominant to the non-

dominant sensorimotor cortex, indicating predominant control by the dominant

hemisphere (Serrien, Cassidy, & Brown, 2003). The issue of dominant control of

bimanual coordination remains a topic of debate.

68

This study extends the findings of the study by Chen et al. (2005) which showed no

lateralized effects of TMS over M1 on bimanual tapping. As discussed in the

introduction to this section, in the study by Chen and colleagues, changes in tapping

rates after TMS were averaged over five taps after TMS application, which limited a

detailed analysis of the evolving change in ITI after TMS. In addition, the authors

equated response onset with onset of EMG. Although this technique is not uncommon

in motor control research, a recent study showed more sharply defined EMG bursts for

dominant than nondominant hand movements (Heuer, 2007), adding a confound to any

comparison of movement onset if EMG is used for this purpose. The current study

calculated an ITI difference score for each tap interval after TMS was applied over left

and right M1 to examine both the pattern of changes in ITI over time in each hand and

the relationship between these changes.

TMS was delivered over left and right M1 at various times within the inter-tap interval

during ongoing unimanual and bimanual tapping. Based on previous studies, discussed

in the previous section, which showed that TMS applied over M1 during a critical time

window (approximately 120 ms) prior to movement onset delays contralateral RT but

TMS applied earlier than this has little effect, TMS was applied at three intervals before

an expected response onset: short (40 ms), medium (90 ms), and long (140 ms)

intervals. Changes in inter-tap interval after TMS was delivered were examined. Based

on neuroimaging and TMS data it was predicted that the effects of TMS over left and

right M1 would be similar. Specifically, during unimanual tapping, TMS over either

hemisphere was expected to disrupt tapping with the contralateral, but not the ipsilateral

hand. Similarly, during bimanual tapping, TMS over either hemisphere was expected to

cause an immediate, transient disruption to tapping with the contralateral but not the

ipsilateral hand. Given the strong tendency to couple the timing of taps with each hand

69

during bimanual tapping, disruptions to tapping with one hand may result in changes to

the inter-tap-intervals with both hands. Given the previous results which have shown

contralateral control for simple repetitive movements, the effects were expected to be

equivalent after left- and right-sided stimulation.

5.1 Method

Participants

Ten right-handed participants, 6 females and 4 males, with ages ranging from 21 to 58

years (median age 30 years) participated. Handedness, measured as the laterality quotient


(median 95). A brief screening questionnaire was administered to exclude individuals

who had previous or current neurological conditions, aneurism clips, pace makers,

cochlear implants, or who were taking drugs with psychoactive effects (Appendix A). If

participants responded in the affirmative on any item they were excluded from the study.

TMS

Magnetic stimuli were generated with a Magstim 200 stimulator and delivered through

a figure-of-eight coil (70-mm diameter). The coil was held manually and was aligned in

the para-sagittal plane with the handle posterior to the coil. Scalp sites were identified

on a snugly fitting cap with pre-marked sites at 1-cm spacings.

Procedure

Electromyographic (EMG) activity was recorded from the extensor indicis and flexor

digitorum superficialis muscles in the forearm using surface electrodes placed

approximately 2 cm apart. The EMG signal was amplified (1000x), filtered (high-pass

70

100 Hz; low-pass 2 kHz), and digitized at a frequency of 2 kHz for 500 ms following

stimulation. The optimal site for eliciting an MEP from the extensor muscle was

determined by systematically delivering four stimuli over 1-cm spaced adjacent scalp

sites at an intensity sufficient to produce an MEP discernible above background EMG in

active muscle. The scalp site with the largest mean MEP amplitude was selected as the

optimal site for stimulation of the extensor muscle. The intensity chosen for stimulation

during testing was the minimum intensity which consistently elicited a silent period

duration of at least 100 ms in the slightly contracted finger extensor. The motor

threshold (minimum intensity at which three of four successive stimulations elicited an

MEP) was also recorded. During determination of optimal site, threshold, and silent

period duration, subjects maintained a slight contraction of the extensor muscles by

extending their index finger to emulate the level of extensor activation during finger

tapping.

Task. Participants sat comfortably with their elbows flexed at approximately 90 degrees

and both hands resting on a desk surface (palm down). Participants were instructed to

tap at a comfortably rapid pace for five seconds by extending and flexing their index

finger around the metacarpal-phalangeal joint, keeping their hand and other fingers flat

on the table. Finger movement was measured with a miniature accelerometer mounted

in a resin block, attached over the index finger of each hand. Prior to testing,

participants tapped for 2.5 seconds with the left and right hands and an amplitude

threshold for identifying taps on the accelerometer output was set (Figure 5.1). EMG

activity and output from the accelerometers were sampled at 1.5 kHz with a computer.

Participants self-initiated each trial, and the timing of a trial began when the

accelerometer signal exceeded a predetermined threshold, indicating that the participant

71

had begun tapping, and ended after five seconds. TMS was applied over left or right M1

during each trial. For each trial, a mean ITI was calculated from the first 2 seconds of

tapping and was used to determine the timing of TMS delivery. TMS was timed to

occur at short (40 ms), medium (90 ms), and long (140 ms) intervals prior to the first

expected tap (TMS-tap interval) after 2.5 s of tapping had occurred. For bimanual trials,

the TMS-tap interval was based on the timing of taps with the hand contralateral to the

side of TMS delivery. Two sessions (one for each side of TMS) consisting of four

blocks of 9 trials were performed; each block consisted of one trial each of left

unimanual, right unimanual, and bimanual tapping at each of the three TMS-tap

intervals. Left and right M1 stimulation were performed in separate sessions at least 24

hours apart. Each session lasted approximately 80 minutes.

Data analysis

Figure 5.1 shows 2.5 s of accelerometer output from a typical trial. Large vertical spikes

in accelerometer output indicate the sudden change in acceleration that occurred when

the participant’s finger contacted the table. ITIs were determined as the time between

successive contacts. For each trial, ITI was measured prior to and after TMS delivery. A

difference score for each ITI after TMS delivery was calculated as ITI minus the mean

of the ITIs in the first 2.5 seconds of tapping.

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Time (ms)

Figure 5.1. Signal output from an accelerometer during tapping. Long vertical spikes in the signal indicate the rapid deceleration which occurred when the participant’s finger contacted the table. Inter-tap intervals (ITIs) were calculated as the time between successive contacts. The dashed horizontal line indicates the amplitude threshold for identifying a tap.

Statistical analyses. Baseline (pre-TMS) ITIs were analysed using a two-way repeated

measures ANOVA with Hand (left and right) and Task (unimanual and bimanual) as

within-subject factors.

Preliminary examination of the data indicated that the behavioural changes in tapping

occurred within six ITIs after TMS. Trend analyses were performed to identify any

systematic relationships between ITI and interval after TMS by performing one-way

repeated-measures ANOVAs with Interval (6 intervals post-TMS) as the within-subject

factor for each hand and each side of stimulation. To compare the effects of left- and

right-sided stimulation, two-way repeated-measures ANOVAs with Side of TMS and

Interval as within subject factors were conducted on ITI difference scores for ipsilateral

and contralateral hands separately. Linear, quadratic, and cubic trends are reported;

higher order trends are not reported. An alpha-level of 0.05 was used for all statistical

0 2500 500 1000 1500 2000

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tests, and partial eta squared (η2) values are presented as estimates of effect size.

5.2 Results

Baseline (pre-TMS) performance

Table 5.1 shows mean ITI for the left and right hands during unimanual and bimanual

tapping prior to TMS. Mean inter-tap interval was longer with the left than with the

right hand during unimanual tapping and during bimanual tapping the inter-tap interval

of the two hands was approximately equal, with the left hand matching the speed of the

right hand. There was a significant effect of Hand (F(1,9) = 6.8, p = .03, partial η2 = .43)

and Task (F(1,9) = 9.0, p = .02, partial η2 = .50) and a significant interaction between

Hand and Task (F(1,9) = 5.3, p = .05, partial η2 = .37). The mean ITI in this study was

slightly longer than the mean ITI for rapid tapping in Chapter 2 because participants

were instructed to tap at a comfortably rapid pace for this task, whereas in the previous

study they were instructed to tap as rapidly as possible. However, the pattern of results

was similar in each study.

Table 5.1.

Mean inter-tap-interval (ms) for each hand in unimanual and bimanual tapping. Standard deviations are in parentheses.

Task Left Right Mean


Mean 209 (11) 206 (10) 208 (10)

Motor threshold and silent period duration

Mean motor threshold was 45% of stimulator output (SD 12 %) for the left hemisphere

(right extensor) and 45% (SD 9%) for the right hemisphere (left extensor). Mean testing

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intensity was 60% (SD 12%) for left M1 stimulation, which during a slight contraction

evoked a silent period duration of 123 ms (SD 17 ms) in the right extensor, and 59%

(SD 10%) for right M1 stimulation, which evoked a silent period duration of 138 ms

(SD 28 ms) in the left extensor.

TMS-induced disruption to unimanual tapping

Figures 5.2, 5.3, and 5.4 show the accelerometer output and EMG signals from the limb

contralateral to the side of TMS delivery in typical unimanual trials after TMS timed to

occur at short, medium, and long intervals before an expected tap, respectively.

At the short TMS-tap interval (Figure 5.2), in this example, TMS was delivered after the

conclusion of the EMG activity of the extensor muscle, towards the end of or after the

burst of flexor activity. There was a delay in the EMG activity of the extensor muscle

before the next burst of activity, which was followed by a return of EMG activity in the

flexor muscle. The ITI that contained the TMS (ITI1) was not prolonged and the interval

after TMS delivery (ITI2) was prolonged.

At the medium TMS-tap interval (Figure 5.3) TMS was delivered after the conclusion

of EMG activity in the extensor muscle, during a period of EMG activity in the flexor

muscle. A silent period was observed in the flexor EMG before a return of activity. The

ITI that contained the TMS (ITI1) was not prolonged and the interval after TMS

delivery (ITI2) was prolonged.

At the long TMS-tap interval (Figure 5.4), TMS was delivered during a period of EMG

activity in the extensor and flexor muscles, resulting in a silent period in each muscle

before simultaneous return of EMG in the two muscles. The ITI that contained the TMS

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(ITI1) was prolonged relative to the mean baseline ITI.

Figure 5.5 shows mean ITI difference scores (ITI for each interval following TMS

minus the mean ITI from the first 2.5 s of tapping) for each hand after TMS over left

and right M1 at each TMS-tap interval. Trends (linear, quadratic and cubic) for these

data are presented in Table 5.2. The effects of TMS over left and right M1 on ITI were

compared using a two-way repeated measures ANOVA with Hand (left, right) and

Interval (1 to 5) as within subject variables (presented in Table 5.3).

76

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ITI 2 ITI 1

Time (ms)

Figure 5.2. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 40 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B), and EMG activity in flexor (C) muscles. The broken vertical line shows the time of TMS delivery and an MEP can be seen in both extensor and flexor activity after TMS delivery. The accelerometer signal shows no prolongation of the inter-tap interval that contained the TMS (ITI1) and a prolongation of the next interval (ITI2).

77

Figure 5.3. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 90 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B), and EMG activity in flexor (C) muscles. The broken vertical line shows time of TMS delivery. The accelerometer signal shows no prolongation of the inter-tap interval that contained the TMS (ITI1) and a prolongation of the next interval (ITI2). A silent period (SP) is observed in the EMG of the flexor muscle.

0.5 mV

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B

C

ITI 2 ITI 1

Time (ms)

SP

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Figure 5.4. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 140 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B) and EMG activity in flexor (C) muscles. The broken vertical line shows time of TMS delivery. The accelerometer signal shows a prolongation of the inter-tap interval that contained the TMS (ITI1). A silent period (SP) is observed in the EMG activity of the extensor muscle.

1600 1800 2000 2200 2400 2600 2800

0.5 mV

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B

C

ITI 2 ITI 1

Time (ms)

SP

79

At the short TMS-tap interval (Figure 5.5, top panel), there was no change in ITI for the

interval in which TMS was delivered after TMS over left and right M1. The greatest

change in ITI in the contralateral hand was seen in the following interval. TMS over left

and right M1 prolonged this interval in the contralateral hand to a similar extent. In the

ipsilateral hand, ITI difference scores were small after TMS over left and right M1,

although there were significant trends in the ipsilateral data for both hands (Table 5.2).

At the medium TMS-tap interval (Figure 5.5, middle panel), TMS over both left and

right M1 caused a small increase in ITI in the contralateral hand in the interval of TMS

delivery and a larger increase in the next interval. The magnitude of the change in ITI

difference scores was similar after TMS over left and right M1. ITI difference scores for

the ipsilateral hand were close to zero for all intervals after TMS over left and right M1.

At the long TMS-tap interval (Figure 5.5 bottom panel), TMS over both left M1 and

right M1 prolonged the ITI for the interval of TMS delivery in the contralateral hand.

The following ITI was also prolonged, although to a smaller extent. The magnitude of

the changes in contralateral ITI was similar after TMS over left and right M1. The

changes in ITI in the ipsilateral hand after TMS over left and right M1 were small.

The effects of TMS over left and right M1 during unimanual tapping were similar.

There were no significant effects of Side of TMS or interactions between Side of TMS

and Interval for either the contralateral or the ipsilateral hand at any of the TMS timings

(Table 5.3), indicating no lateralized effect of TMS on unimanual tapping.

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Interval

Figure 5.5. Mean difference in inter-tap interval (ITI difference) from baseline during unimanual tapping with the ipsilateral ( ) and contralateral ( ) hands after TMS to the left and right M1 at short, medium, and long TMS-expected tap intervals. Six intervals post-TMS are displayed (TMS was delivered during interval 1). Ipsilateral and contralateral data points are slightly offset on the x-axis for clarity. Errors are ±1 standard error of the mean.

Short TMS-tap interval

Medium TMS-tap interval

Long TMS-tap interval

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Table 5.2. Trend analyses: Results of One-way Repeated-Measures ANOVAs for ITI Difference Scores with Interval (6 intervals post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10 for all).

Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2

Short TMS-tap interval Contralateral hand Linear 17.98 .002 .67 25.53 .001 .74 Quadratic 3.79 .083 .30 5.01 .052 .36 Cubic 15.55 .003 .63 18.20 .002 .67 Ipsilateral hand Linear 1.56 .244 .15 13.53 .005 .60 Quadratic 5.03 .052 .35 9.40 .013 .51 Cubic 6.78 .029 .43 3.53 .093 .28

Medium TMS-tap interval Contralateral hand Linear 39.19 <.001 .81 24.84 .001 .73 Quadratic 0.11 .747 .01 1.12 .317 .11 Cubic 9.12 .014 .50 2.58 .142 .22 Ipsilateral hand Linear 0.34 .575 .04 1.46 .258 .14 Quadratic 5.34 .046 .37 2.85 .126 .24 Cubic 5.04 .051 .36 43.25 <.001 .83

Long TMS-tap interval Contralateral hand Linear 37.43 <.001 .81 16.60 .003 .65 Quadratic 11.79 .007 .57 7.46 .023 .45 Cubic 0.20 .665 .02 0.49 .502 .05 Ipsilateral hand Linear 0.29 .602 .03 3.94 .079 .30 Quadratic 2.24 .169 .20 6.18 .035 .41 Cubic 0.18 .678 .02 0.10 .762 .01

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Table 5.3. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands, With Side of TMS (Left, Right) and Interval (6 intervals after TMS) as Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10 for all).

* df = degrees of freedom for effect and error.

The mean differences in ITI from pre-TMS values in the contralateral hand for the

interval of stimulation and the following interval are summarised in Table 5.4. As the

TMS-tap interval increased, the interval of stimulation began to be prolonged; at the

short TMS-tap interval, there was no change in ITI in the interval of stimulation, and a

large increase in the following interval, at the medium interval there was a small

increase in ITI in the interval of stimulation and a large increase in the following

interval, and at the long TMS-tap interval, there was a large increase in ITI in the

interval of TMS delivery with a small increase in ITI in the following interval.

Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2

Short TMS-tap interval Side of TMS 1, 9 0.37 .558 .04 1, 9 0.24 .637 .03 Interval 5, 45 25.71 <.001 .74 5, 45 6.28 <.001 .41 Side x Interval 5, 45 0.86 .513 .09 5, 45 1.20 .324 .12

Medium TMS-tap interval Side of TMS 1, 9 0.28 .609 .03 1, 9 1.41 .265 .14 Interval 5, 45 13.38 <.001 .60 5, 45 3.82 .006 .30 Side x Interval 5, 45 0.99 .433 .10 5, 45 1.05 .402 .10

Long TMS-tap interval Side of TMS 1, 9 3.50 .094 .28 1, 9 0.04 .840 .01 Interval 5, 45 9.28 <.001 .51 5, 45 1.75 .142 .16 Side x Interval 5, 45 0.10 .991 .01 5, 45 0.49 .784 .05

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Table 5.4.

Mean Difference in ITI from Baseline (ms) for the Interval of TMS (Intl 1) and the Interval After TMS (Int 2) During Unimanual Tapping in the Contralateral Hand After TMS Over Left and Right M1 at Short, Medium, and Long TMS-Tap Intervals. Standard Deviations Are in Parentheses.

Short Medium Long Int 1 Int 2 Int 1 Int 2 Int 1 Int 2

Left TMS 6 (14) 105 (69) 18 (25) 84 (55) 51 (37) 24 (51)

Right TMS 9 (7) 94 (48) 34 (45) 69 (66) 59 (48) 28 (46)

In summary, TMS over left and right M1 increased ITI in the contralateral hand to a

similar extent. The timing of the effect changed systematically with TMS-tap interval

duration; at the shortest TMS-tap interval, the largest change in ITI occurred in the

interval after TMS, and as TMS-tap increased, the effect of TMS progressively shifted

toward the interval of stimulation, so that at the longest TMS-tap interval, the largest

change in ITI occurred in the interval of stimulation. There were small changes in ITI in

the hand ipsilateral to the side of TMS delivery after TMS over both left and right M1.

TMS-induced disruption of bimanual tapping

Figure 5.7 illustrates two distinct response types for an individual participant at the

short TMS-tap interval. Panels A and B of Figure 5.7 show the accelerometer output for

the ipsilateral and contralateral hands in a trial with fewer contralateral than ipsilateral

taps in the period after TMS. In this example, the second tap after TMS with the

contralateral hand coincided closely with the third tap of the ipsilateral hand.

Panels C and D of Figure 5.7 show the accelerometer output for ipsilateral and

contralateral hands in a trial with an equal number of ipsilateral and contralateral taps in

the period after TMS. These two distinct response types were identified at all TMS- tap

intervals; some trials had fewer contralateral taps than ipsilateral taps in the period

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Figure 5.7. Accelerometer output for the ipsilateral and contralateral hands during bimanual tapping before and after TMS delivered at the short TMS-tap interval. Two types of trial are illustrated; A and B show ipsilateral and contralateral hands respectively from a trial with an unequal number of ipsilateral and contralateral taps, C and D show ipsilateral and contralateral hands respectively from a trial with an equal number of ipsilateral and contralateral taps. Inter-tap intervals are marked for the hand

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B ITIc 2 ITIc 1

ITIi 2 ITIi 1

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85

ipsilateral (ITIi) and contralateral (ITIc) to side of stimulation. The broken vertical line indicates the timing of TMS. after TMS (the contralateral hand appeared to “skip” a tap) and other trials had equal

numbers of ipsilateral and contralateral taps.

The number of trials observed for the “unequal taps” response type for each participant

is displayed in Table 5.5 as a function of side of stimulation and TMS-tap interval (four

trials were performed at each TMS-tap interval, so “equal taps” can be determined by

subtracting the number of “unequal taps” from 4). Overall there were more “equal taps”

responses after TMS over left M1 (70%) and more “unequal taps” responses after TMS

over right M1 (64%); this pattern of results held true for all TMS-tap intervals. The

frequencies of equal taps trials and unequal taps trials after TMS over left and right M1

were significantly different (χ2 = 28.11, p < .001).

Table 5.5

Number of trials which had more ipsilateral than contralateral taps after TMS for each participant, out of a total of four, as a function of side of stimulation and TMS-tap interval.

TMS over Left M1 TMS over Right M1

Participant Short Medium Long Short Medium Long

1 2 2 3 3 3 1 2 2 1 0 4 0 3 3 2 0 0 3 2 3 4 0 1 0 3 4 4 5 2 0 2 4 4 4 6 1 2 3 3 3 1 7 4 0 1 4 4 4 8 4 1 3 3 4 2 9 0 0 0 1 0 0

10 0 0 0 2 1 0

Sum 17 7 12 30 25 22

Figure 5.8 shows mean ITI difference scores for each type of response (left panels show

86

trials with unequal numbers of ipsilateral and contralateral taps, right panels show trials

with equal numbers of taps) for each TMS-tap interval after TMS over left and right

M1. Trends for these data are presented in Table 5.6 (trials with unequal numbers of

ipsilateral and contralateral taps) and Table 5.8 (trials with equal numbers of taps).

In the trials with more ipsilateral than contralateral taps (Figure 5.8, left panel), the

effects of TMS over left and right M1 were similar at all TMS-tap intervals. At the short

TMS-tap interval (top panel), trials with fewer contralateral than ipsilateral taps were

characterized by a long delay in the contralateral hand in the interval after TMS. This

delay was almost equivalent to the mean ITI pre-TMS; mean ITI difference score in the

contralateral hand in the interval after TMS over left M1 was 200 ms (SD 32 ms) and

after TMS over right M1 was 163 ms (SD 44 ms), compared to mean pre-TMS ITIs for

the respective hands 204 ms (SD 8 ms) and 211 ms (SD 13 ms). Although small, the

difference in changes in ITI with the contralateral hand between left and right TMS was

significant (a larger effect after left TMS than after right TMS; Table 5.7 shows the

repeated-measures ANOVA results comparing the effects of left and right TMS on

contralateral and ipsilateral responses). In these trials ITI difference scores in the

ipsilateral hand were close to zero for all intervals after TMS.

Similarly, at the medium TMS-tap interval, for trials with fewer contralateral than

ipsilateral taps (Figure 5.8, middle left panel), TMS over left and right M1 caused large

increases in ITI in the contralateral hand in the interval after TMS delivery and little

change in the ipsilateral hand. At the long TMS-tap interval, for trials with fewer

contralateral than ipsilateral taps (bottom left panel), there was a large increase in ITI in

the contralateral hand in the interval of TMS delivery over left and right M1 and in the

following interval, and little change in ITI with the ipsilateral hand. At the medium and

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long TMS-tap intervals, there were no significant differences between left and right

TMS on either the contralateral hand or the ipsilateral hand.

A comparison of the ITI difference scores presented in the left panel of Figure 5.8 with

those presented in Figure 5.5 reveals a striking similarity; during bimanual tapping,

when the number of taps performed with the contralateral hand was fewer than the

number performed with the ipsilateral hand in the period after TMS (in other words,

when the contralateral hand appeared to “skip” a tap), the effects of TMS on the

contralateral and ipsilateral hand were very close to those observed during unimanual

tapping.

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Left M1 TMS Right M1 TMS Left M1 TMS Right M1 TMS

Figure 5.8. Mean difference in inter-tap interval (ITI difference) from baseline during bimanual tapping with the ipsilateral ( ) and contralateral ( ) hands after TMS to the left and right M1 at short, medium, and long TMS-expected tap intervals. Left panel shows trials in which one extra tap was performed by the hand ipsilateral to the side of TMS compared to the contralateral hand, right panel shows trials with equal taps with ipsilateral and contralateral hands. Six intervals post-TMS are displayed. The inset figures show individual contralateral responses at the short TMS-tap interval after TMS to left and right M1. Ipsilateral and contralateral data points are slightly offset on the x-axis for clarity. Errors are ±1 standard error of the mean.

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Long TMS-tap interval Long TMS-tap interval

Interval Interval

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Table 5.6. Trend Analyses in Trials with Fewer Contralateral than Ipsilateral Taps After TMS: Results of One-way Repeated-Measures ANOVAs with Interval (6 intervals post-TMS) as the Within-subject Factor. Values in bold are significant at alpha < .05.

Left TMS Right TMS df F-value p-value Partial η2 df F-value p-value Partial η2

Short TMS-tap interval Contralateral hand Linear 6 43.52 .001 .88 9 35.70 <.001 .80 Quadratic 6 5.16 .064 .46 9 22.49 .001 .71 Cubic 6 249.30 <.001 .98 9 87.98 <.001 .91 4th Order 6 214.18 <.001 .97 9 198.55 <.001 .96 Ipsilateral hand Linear 6 1.24 .309 .17 9 1.58 .240 .15 Quadratic 6 0.12 .744 .02 9 0.09 .767 .01 Cubic 6 0.86 .389 .13 9 0.26 .621 .03 4th Order 6 0.86 .390 .12 9 4.64 .060 .34

Medium TMS-tap interval Contralateral hand Linear 4 17.92 .013 .82 7 35.57 .001 .84 Quadratic 4 10.97 .030 .73 7 0.10 .757 .02 Cubic 4 30.87 .005 .88 7 20.98 .003 .75 4th Order 4 47.98 .002 .92 7 64.65 <.001 .90 Ipsilateral hand Linear 4 8.86 .041 .69 7 0.83 .391 .11 Quadratic 4 0.61 .478 .13 7 2.14 .187 .23 Cubic 4 1.59 .276 .28 7 7.24 .031 .51 4th Order 4 0.92 .392 .19 7 0.03 .859 .01

Long TMS-tap interval Contralateral hand Linear 4 70.91 .001 .95 7 85.98 <.001 .92 Quadratic 4 7.22 .055 .64 7 7.71 .027 .52 Cubic 4 0.08 .786 .02 7 0.24 .636 .03 4th Order 4 2.32 .202 .37 7 1.75 .227 .20 Ipsilateral hand Linear 4 3.19 .148 .44 7 4.90 .062 .41 Quadratic 4 0.30 .612 .07 7 2.66 .147 .28 Cubic 4 0.11 .759 .03 7 0.47 .514 .06 4th Order 4 0.01 .925 .01 7 0.64 .451 .08

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Table 5.7. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands in Trials with Fewer Contralateral than Ipsilateral Taps; Side of TMS (Left, Right) is a Between-Subjects Factor and Interval (6 intervals after TMS) is a Within-Subjects Factor. Values in Bold are Significant at alpha < .05.


The right panel of Figure 5.8 shows mean ITI difference scores in the contralateral and

ipsilateral hands for responses with equal numbers of ipsilateral and contralateral taps in

the period after TMS delivery, for each TMS-tap interval, after TMS over left and right

M1. The results of trend analyses for these data are presented in Table 5.8.

It can be seen from Figure 5.8 that in trials with an equal number of ipsilateral and

contralateral taps (right panel), the effect of TMS over left M1 on the contralateral hand

was attenuated as TMS-tap interval increased. The same was not true after TMS over

right M1; in these trials, after TMS over right M1, the effects were attenuated at all

TMS-tap intervals. The effects of TMS over left and right M1 at each TMS-tap interval

will be discussed in turn.

In the responses with an equal number of ipsilateral and contralateral taps at the short

TMS-tap interval (Figure 5.8, top right panel), TMS over left M1 increased the ITI in


Short TMS-tap interval Side of TMS 1, 15 2.51 .134 .14 1, 15 1.42 .252 .09 Interval 5, 75 172.21 <.001 .92 5, 75 1.11 .365 .07 Side x Interval 5, 75 2.38 .047 .14 5, 75 0.32 .898 .02

Medium TMS-tap interval

Side of TMS 1, 11 1.25 .287 .10 1, 11 1.46 .252 .12 Interval 5, 55 52.14 <.001 .83 5, 55 2.65 .032 .19 Side x Interval 5, 55 2.53 .039 .19 5, 55 1.06 .391 .09


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the contralateral hand in the interval after stimulation. After TMS over left M1, ITI in

the ipsilateral hand was greater than baseline from the second to the fifth interval. In

comparison, after TMS over right M1, the mean increase in ITI with the contralateral

hand in the interval after stimulation was smaller and there was a small decrease in ITI

in the following interval. After TMS over right M1, ITI difference scores with the

ipsilateral hand remained around zero. The changes in both contralateral and ipsilateral

ITI were greater after TMS over left M1 than after TMS over right M1 (Table 5.9 shows

the repeated-measures ANOVA results comparing the effects of left and right TMS on

contralateral and ipsilateral responses). On closer inspection of the data, contralateral

responses after TMS over right M1 varied greatly between individuals (shown in the

small right-hand insert in Figure 5.8); three individuals showed a sizeable increase in

ITI, one a small decrease in ITI, and the remainder showed no marked change in ITI

after TMS over right M1. In contrast, the individual responses after TMS over left M1

were consistent and large (shown in the small left-hand insert in Figure 5.8).

At the medium TMS-tap interval, in responses with equal numbers of ipsilateral and

contralateral taps, TMS over left M1 increased the ITI with the contralateral hand in the

interval after TMS delivery. ITI with the ipsilateral hand increased in the interval after

TMS and the following interval, and returned to baseline over the following two

intervals. The changes in ITI with the contralateral and ipsilateral hand after TMS over

right M1 were small. However, as for the short TMS-tap interval, contralateral

responses after TMS over right M1 varied across individuals (individual data not

shown).

At the long TMS-tap interval, in trials with equal numbers of ipsilateral and

contralateral taps, TMS over left M1 delayed the response in the contralateral hand in

the interval of TMS delivery. Contralateral ITI remained slightly above baseline in the

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following interval before returning to baseline. ITI increased in the ipsilateral hand after

TMS over left M1 in the interval of TMS and remained elevated for the following

interval. After TMS over right M1 there was an increase in ITI in the contralateral hand

in the interval of TMS followed by a decrease in ITI in the following two intervals. The

changes in ITI in the ipsilateral hand after TMS over right M1 were small.

Table 5.8. Trend Analyses in Trials With Equal Numbers of Ipsilateral and Contralateral Taps After TMS: Results of One-way Repeated-measures ANOVAs with Interval (6 intervals post-TMS) as the Within-subject Factor for Each Hand and Each Side of Stimulation. Values in bold are significant at alpha < .05.

Left TMS Right TMS df F-value p-value Partial η2 df F-value p-value Partial η2

Short TMS-tap interval Contralateral hand Linear 8 9.13 .017 .53 6 0.09 .772 .02 Quadratic 8 0.33 .582 .04 6 0.99 .357 .14 Cubic 8 14.26 .005 .64 6 <0.01 .985 .01 4th Order 8 21.94 .002 .73 6 12.30 .013 .67 Ipsilateral hand Linear 8 0.04 .849 .01 6 3.36 .116 .36 Quadratic 8 11.78 .009 .60 6 1.68 .242 .22 Cubic 8 0.11 .746 .01 6 2.00 .207 .25 4th Order 8 3.29 .107 .29 6 0.41 .547 .06

Medium TMS-tap interval Contralateral hand Linear 9 26.34 .001 .74 5 0.59 .476 .11 Quadratic 9 0.13 .728 .01 5 0.68 .449 .12 Cubic 9 5.07 .051 .36 5 0.10 .767 .02 4th Order 9 11.59 .008 .56 5 0.70 .440 .12 Ipsilateral hand Linear 9 7.38 .024 .45 5 0.64 .460 .11 Quadratic 9 11.66 .008 .56 5 0.02 .895 .01 Cubic 9 11.28 .008 .56 5 0.37 .569 .07 4th Order 9 0.36 .561 .04 5 0.92 .382 .16

Long TMS-tap interval Contralateral hand Linear 9 11.87 .007 .57 6 16.74 .006 .74 Quadratic 9 4.46 .064 .33 6 61.02 <.001 .91 Cubic 9 0.40 .541 .04 6 27.17 .002 .82 4th Order 9 0.27 .616 .03 6 2.47 .167 .29 Ipsilateral hand Linear 9 6.05 .036 .40 6 0.45 .528 .07 Quadratic 9 3.72 .086 .29 6 1.94 .213 .24 Cubic 9 0.26 .620 .03 6 1.34 .292 .18 4th Order 9 0.37 .556 .04 6 1.60 .253 .21

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Table 5.9. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands in Trials with an Equal Number of Ipsilateral and Contralateral Taps, With Side of TMS (Left, Right) as a Between Subjects Factor and Interval (6 intervals after TMS) as a Within-Subjects Factor. Values in Bold are Significant at alpha < .05 (N=10 for all).


In trials with an equal number of ipsilateral and contralateral taps, the larger and more

consistent contralateral effect after TMS over left M1 than right M1 was not related to a

difference in excitability of M1 at the time of stimulation as measured by the MEP.

Mean MEP amplitude after TMS over left M1 was 2.3 mV (SD = 1.3 mV) and 2.2 mV

after TMS over right M1 (SD = 0.8 mV), t(9) = 0.10, p = .92 (collapsed across TMS-tap

interval because there were no significant differences across the TMS-tap intervals).

Neither is a longer SP duration likely to explain the larger contralateral effect after TMS

over left M1; although SP was not measured during tapping, when measured prior to

testing, the SP after left TMS (M 123 ms, SD 17 ms) was shorter than the SP after right

TMS (M 138 ms, SD 28 ms), although this difference was not significant (t(9) = 1.74, p =

.12).


Short TMS-tap interval Side of TMS 1, 14 7.83 .014 .36 1, 14 9.23 .009 .40 Interval 5, 70 13.80 <.001 .50 5, 70 3.96 .003 .22 Side x Interval 5, 70 5.34 <.001 .28 5, 70 1.47 .211 .10

Medium TMS-tap interval Side of TMS 1, 14 6.26 .025 .31 1, 14 3.20 .095 .38 Interval 5, 70 4.98 .001 .26 5, 70 2.13 .072 .13 Side x Interval 5, 70 1.43 .222 .09 5, 70 1.85 .114 .12


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The mean difference in ITI from baseline in the contralateral hand for the interval of

stimulation (ITI1) and the following interval (ITI2) are summarised in Table 5.10 after

TMS over left and right M1 for the two trials types, and for all trials combined. For

trials with more ipsilateral than contralateral taps (unequal taps), as the TMS-tap

interval increased, the delay in the contralateral response in the interval of stimulation

became progressively larger; at the short TMS-tap interval, there was no change in ITI

in the interval of stimulation, and a large increase in the following interval, at the

medium interval there was a small increase in ITI in the interval of stimulation and a

large increase in the following interval (although there was a small decrease in the

interval of stimulation after left-sided stimulation), and at the long TMS-tap interval, the

greater increase in ITI occurred during the interval of TMS delivery with a smaller

increase in ITI in the following interval. This pattern of results is similar to those for

unimanual tapping (Table 5.4). The changes in ITI in the contralateral hand were

slightly larger during bimanual than unimanual tapping after TMS over both left and

right M1 for these trials. The pattern was similar although attenuated for the trials with

an equal number of ipsilateral and contralateral taps after TMS over left M1 and greatly

attenuated after TMS over right M1 (as discussed above, the attenuation of the response

after TMS over right M1 was due to a large variability in individual response patterns).

The changes in ITI in the contralateral hand for all trials combined were of a similar

magnitude to those for unimanual tapping (after TMS over both left and right M1).

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Table 5.10.

Mean Difference in ITI from Baseline (ms) for the Interval of TMS (Intl 1) and the Interval After TMS (Int 2) During Bimanual Tapping in the Contralateral Hand After TMS Over Left and Right M1 at Short, Medium, and Long TMS-Tap Intervals. Standard Deviations Are in Parentheses.

Short Medium Long Int 1 Int 2 Int 1 Int 2 Int 1 Int 2

Unequal taps:

Left TMS 8 (16) 194 (42) -11 (14) 128 (45) 116 (56) 79 (53)

Right TMS 0 (15) 164 (46) 36 (39) 123 (34) 95 (55) 79 (39)

Equal taps:

Left TMS 0 (6) 89 (69) 7 (7) 69 (49) 40 (27) 17 (44)

Right TMS -9 (11) 17 (39) 5 (39) 18 (60) 53 (17) -22 (32)

All taps:

Left TMS 5 (14) 119 (89) 6 (23) 76 (65) 58 (56) 36 (53)

Right TMS 2 (12) 122 (52) 26 (34) 78 (66) 77 (49) 37 (44)

In summary, during bimanual tapping, two types of response were observed after TMS.

In some trials there was one less contralateral tap than ipsilateral tap in the post-TMS

period, whereas in other trials, the number of taps was equal for the contralateral and

ipsilateral hands. In the former, the effects of TMS over left and right M1 were similar,

and resembled the results observed during unimanual tapping. The increase in ITI for

the contralateral hand shifted from the interval after stimulation when TMS was

delivered close to an expected tap (short TMS-tap interval) to the interval of stimulation

when TMS was delivered earlier (long TMS-tap interval). In the ipsilateral hand, ITI

difference scores remained around zero after TMS over left and right M1 in these trials.

The change in contralateral ITI was greater after TMS over left M1 than right M1 at the

short TMS-tap interval only, and there were no differences in ipsilateral ITI between left

and right sided stimulation. In contrast, in trials in which the contralateral and ipsilateral

hands performed an equal number of taps, there was a larger effect on the contralateral

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hand after TMS over left M1 than right M1. In these responses, after TMS over left M1,

the patterns of results for the contralateral hand were similar to those for the previous

type of response. There was an increase in ITI in the ipsilateral hand which lasted four

intervals. In contrast, after TMS over right M1 there was little change in ITI with either

hand, due to large inter-individual variability.

Comparing the ITI difference scores in the two response types reveals that in trials with

an equal number of ipsilateral and contralateral taps in the post-TMS period (Figure 5.8,

right panel), changes in ITI in the contralateral hand were smaller than in trials with an

unequal number of ipsilateral and contralateral taps (Figure 5.8, left panel) after both

left and right-sided stimulation and at all TMS-tap intervals.

5.3 Discussion

Few studies have examined the effects of single-pulse TMS on ongoing rhythmical hand

movements. This study disrupted unimanual and bimanual tapping by applying TMS

over left or right M1 at various times during the inter-tap-interval and examined

changes in the timing of taps with the ipsilateral and contralateral hands.

General effects of TMS on the contralateral hand

During unimanual and bimanual tapping, TMS over either hemisphere delayed the

response with the contralateral hand. The interval in which the delay occurred depended

on the timing of TMS relative to the next tap. For the short TMS-tap interval (when

TMS was delivered close to the expected time of a tap), the first tap after TMS was not

affected, but the next tap was delayed. As the TMS-tap interval increased, the first tap

after TMS became progressively more delayed. On face value, these results seem

contrary to previous research findings that show an increasing delay in voluntary

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movement the closer in time TMS is delivered to the expected movement. However,

closer inspection of the timing of TMS relative to the EMG activity (rather than relative

to the next expected tap) indicates the current results are consistent with previous

findings (although the interval between TMS application and EMG activity was not

calculated, inspection of individual traces showed a consistent pattern of results). For

the short TMS-tap interval, at the time of TMS application, both the extensor muscle

activity, associated with raising the finger for the upcoming tap, and the flexor muscle

activity were complete. Therefore the first tap after TMS was completed without

interruption and the duration of the interval of stimulation was not affected. The first

burst of EMG activity expected after the delivery of TMS was the extensor muscle

activity associated with raising the finger for the second tap after TMS. TMS delayed

the onset of this activity, resulting in a delay of the second tap after TMS. Similarly for

the medium TMS-tap interval, TMS delayed the activity of the extensor muscle

associated with raising the finger for the second tap after stimulation, and this tap was

delayed. Previous studies timed TMS delivery relative to bursts of EMG activity in the

agonist muscles used in the task, and also measured movement onset from EMG

activity. For the short and medium intervals, the results are comparable to previous

findings; the closer the TMS occurred to an upcoming EMG burst, the longer the delay

between expected onset and actual onset of EMG burst, and hence the longer the delay

in the tap associated with that burst (J. T. Chen et al., 2005; Day et al., 1989). For the

long TMS-tap interval, TMS was sometimes delivered during a burst of extensor

muscle activity, which resulted in a silent period in that muscle and a delay of the next

two taps.

The effect of TMS on the contralateral hand during unimanual and bimanual tapping

was short-lived, consistent with a brief interruption of M1 output, with a preserved

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pattern of agonist and antagonist EMG bursts on the return of EMG activity. These

results are consistent with those reported by Day et al. (1989) who found that TMS

delayed reaction time by delaying the onset of the agonist muscle activity, but without

changing the pattern of agonist and antagonist EMG bursts. The results of the current

study extend this finding to ongoing rhythmical movements. The delays after

stimulation at the long TMS-tap interval indicate that the effects of TMS can extend

beyond a single interval, which is consistent with recent evidence that the primary

motor cortex encodes not only the upcoming movement, but also future elements in a

sequence of movements (Lu & Ashe, 2005).

Contralateral and ipsilateral effects of TMS during unimanual tapping

The magnitude of the effect on the contralateral hand during unimanual tapping was

approximately equal after TMS over left and right M1, consistent with previous reports

of equivalent contralateral effects of left- and right-sided stimulation on unimanual RT

(Foltys et al., 2001). There were small ipsilateral effects after TMS over left M1 at the

short and medium TMS-tap intervals and after TMS over right M1 at the medium TMS-

tap interval; the effects were mostly shortened ITIs. Although a cortical explanation of

the ipsilateral effect cannot be excluded, the ipsilateral effect could be a result of

distraction, caused by the auditory click associated with TMS discharge. When a single

distractor tone is presented during metronome-paced tapping, the next tap in the

sequence is shifted in time in the direction of the “event onset shift”, that is, if the

distractor occurs before the metronome tone, the next tap occurs sooner than expected

(Repp, 2003`, 2006). These distractor effects are not limited to metronome-paced

tapping; the effect is similar if a distractor tone is delivered during self-paced tapping.

There was no systematic asymmetry in the effects of left- and right-sided stimulation on

the ipsilateral hand during unimanual tapping, consistent with a distractor effect.

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Contralateral and ipsilateral effects of TMS during bimanual tapping

In contrast, during bimanual tapping, a number of asymmetrical effects of left- and

right-sided stimulation were found. First, it should be noted that the delays in taps with

the contralateral hand collapsed across all trials was of a similar magnitude during

unimanual and bimanual tapping for each TMS-tap interval (these data are presented in

Tables 5.5 and 5.10 for unimanual and bimanual tapping, respectively). This indicates

that the mean effect of TMS on the contralateral hand during bimanual tapping was of a

similar magnitude to the effect during unimanual tapping. Furthermore, no obvious

differences between the effects of left- and right-TMS on contralateral taps were

obvious in the bimanual data presented this way. However, closer inspection of the data

revealed two types of response after TMS; in some trials fewer taps were performed by

the contralateral hand than by the ipsilateral hand while in other trials an equal number

of taps were performed by the two hands. There was no systematic effect of the timing

of TMS on the proportion of each response type produced. However, there was an

asymmetry in the proportion of each response type after left- and right-sided

stimulation. After TMS over left M1, responses were more likely to fall into the “equal

taps” type, whereas after TMS over right M1, responses were more likely to fall into the

“unequal taps” type. This may be related to an asymmetry in SP duration after TMS

over left and right M1; the “unequal taps” responses (more common after right-sided

stimulation) were associated with longer contralateral delays than the “equal taps”

responses and the silent period was longer after TMS over right M1 than after TMS

over left M1 (a longer SP in the non-dominant hand has been reported previously`;

Priori et al., 1999).

In response series with fewer contralateral than ipsilateral taps, the effects of TMS were

almost identical to the effects of TMS on unimanual tapping; the timing of the effect in

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the contralateral hand depended on the timing of TMS relative to the next tap, and there

was little effect on the response with the ipsilateral hand. However, for trials with equal

numbers of ipsilateral and contralateral taps, TMS over left M1 delayed the responses of

both the contralateral and ipsilateral hands, whereas TMS over right M1 caused a

variable delay in the response with the contralateral hand, and had little effect on the

ipsilateral hand. The ipsilateral effect after stimulation over left M1 was not a

shortening of ITIs, as observed during unimanual tapping, but a prolongation of ITIs

which lasted several cycles. The tendency to temporally couple the hands during

bimanual movements is strong (Kelso, Southard, & Goodman, 1979) and the increase in

ITIs with the ipsilateral hand after TMS over left M1 probably reflects an adjustment to

the rate of this hand in order to achieve resynchronisation of the hands after TMS. This

ipsilateral effect was not seen in trials with an unequal number of ipsilateral and

contralateral taps, and in these trials resynchronization of the two hands after TMS was

achieved rapidly; the delay in tapping with the contralateral hand approximated the

duration of one ITI, and the two hands became temporally re-coupled on the first

contralateral tap and the second ipsilateral tap after TMS. In contrast, in trials with an

equal number of ipsilateral and contralateral taps, the delay in the contralateral hand

after TMS over left M1 was smaller and the lag between the hands greater than in the

previous response type. In these trials, adjusting the rate of one or both hands was

required for the two hands to become resynchronized. The disruption to tapping with the

contralateral (dominant) hand in these trials was short-lived, whereas the disruption to

the ipsilateral (non-dominant) hand persisted over three or four ITIs. Thus, while the

pre-TMS tapping rate of the dominant hand was rapidly resumed after the initial

disruption caused by TMS, tapping of the non-dominant hand was altered to achieve

resynchronization. The ipsilateral effect seen after TMS over left M1, therefore, is likely

to be a secondary result of adjusting to the contralateral effect, rather than a direct

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cortical result of TMS. These results can be conceptualized as the dominant hand

producing a master rhythm, which the non-dominant hand adapts to, resulting in

resynchronisation of the hands over several cycles of tapping.

That it was the dominant hand which appeared to produce the master rhythm and the

nondominant hand which followed suggests a greater influence of dominant hemisphere

processing on the nondominant hemisphere than vice versa during bimanual

coordination. Behavioural evidence for this can be seen in the greater degree of spatial

assimilation observed in the non-dominant hand than in the dominant hand when aiming

movements are made with the two hands concurrently over different distances

(Sherwood, 1994). Also, during cyclical bimanual movements, the phase of the non-

dominant hand is more strongly influenced by the phase of the dominant hand than vice

versa (Carson, 1993). Furthermore, transitions between asymmetric and symmetric

patterns of bimanual circle drawing are mediated by a change in the trajectory of the

non-dominant hand (Byblow, Carson, & Goodman, 1994; Wuyts, Summers, Carson,

Byblow, & Semjen, 1996) and intentional switches from in-phase to anti-phase

bimanual wrist movements are mediated by alterations to the rate of the non-dominant

hand while the dominant hand maintains its stable rhythm (de Poel, Peper, & Beek,

2006). In a recent study, resynchronization of bimanual coordination following an

external perturbation was shown to be mediated by a change in the rate of movement in

the non-dominant limb (de Poel, Peper, & Beek, 2007). The interpretation of these

results from the view that the dominant hemisphere exerts a stronger influence over the

non-dominant hemisphere is also supported by neurophysiological studies of bimanual

coordination. An EEG coherence study showed that during bimanual movements

cortical drive was greater from the dominant to the non-dominant primary sensorimotor

cortex than in the reverse direction (Serrien, Cassidy, & Brown, 2003). Furthermore,

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TMS studies have shown greater inter-hemispheric inhibition of the nondominant

hemisphere by the dominant hemisphere than in the reverse direction (Netz, Ziemann, &

Homberg, 1995), suggesting that the dominant hemisphere is more efficient at inhibiting

unwanted influence from the non-dominant hemisphere than vice-versa.

During bimanual tapping, a further asymmetry was observed in the magnitude of the

contralateral effects after TMS over left and right M1. In responses with an unequal

number of taps with the ipsilateral and contralateral hands, the magnitude of the

contralateral effect was greater after TMS over left M1 than right M1 at the short TMS-

tap interval. For the responses with an equal number of taps with the ipsilateral and

contralateral hands, the magnitude of the contralateral effect was greater after TMS over

left M1 than after TMS over right M1 at short and medium TMS-tap intervals. This last

finding was due to large variability in individual contralateral responses after TMS over

right M1. A tentative explanation for these findings is that they result from a more

focussed drive from the dominant hemisphere and a more diffuse drive from the

nondominant hemisphere. It is conceivable that TMS applied during a period of focused

drive would result in consistently large responses, and TMS delivered during a period of

diffuse drive would result in more variable responses between trials or between

subjects. Although speculative, a recent study which showed more sharply defined

EMG bursts for dominant than nondominant hand movements, with temporally

segregation of bursts of reciprocal muscle activity in the dominant hand, and greater co-

contraction of antagonistic muscle pairs in the nondominant limb (Heuer, 2007) is

consistent with this hypothesis.

Two aspects of dominant motor control during bimanual coordination are suggested

from these results. Firstly, they suggest a privileged status of dominant hand movements

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during bimanual coordination. The smaller period of disruption to the dominant hand

than nondominant hand in some bimanual trials suggests that programming of

movements by the dominant hemisphere takes priority (the dominant hand provides a

master rhythm to which the nondominant hand adapts). This is consistent with the

natural roles taken by the hands during bimanual tasks; with the dominant hand

performing the fine manipulations (the foreground task) while the nondominant hand

plays a stabilizing and orienting role (the background task). In the current study, the

privileged role of the dominant hand during a task requiring equivalent movements of

the two hands suggests that this is a basic feature of bimanual motor control. Secondly,

the results are consistent with a more focused drive from the dominant hemisphere and a

more diffuse drive from the nondominant hemisphere. This may be an important factor

in the superiority of the dominant hemisphere in fine motor control as it might permit

more precise specification of spatiotemporal and force characteristics of movement.

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CHAPTER 6. DISRUPTION OF UNIMANUAL AND BIMANUAL CIRCLE

DRAWING WITH TMS

In the previous study, TMS over left and right M1 during a discrete response sequence,

unimanual tapping, caused large disruptions to tapping with the contralateral hand, but

had little effect on the ipsilateral hand. During bimanual tapping, two patterns of

responses were observed. In some trials the hand contralateral to the side of TMS

application was “stalled” by a period approximately equal to the duration of a tap. In

these trials, the two hands were quickly resynchronised (within a single tapping cycle)

and the results were essentially the same as those seen during unimanual tapping. In

other trials, tapping with the hand contralateral to TMS application was stalled for a

shorter duration, and in the post-TMS period, a period of adjustment was observed

during which the two hands became resynchronized. In these trials, two lateralized

effects of TMS were observed: the effect of TMS on the contralateral hand was greater

after TMS over left M1 than right M1, and prolonged changes in inter-tap interval were

observed in the nondominant hand regardless of the side of stimulation. The first of

these effects was speculated to be due to a sharper temporal tuning of dominant than

nondominant hemisphere processes, while the latter was likely due to a “master-slave”

effect (the dominant hand produced a master rhythm, which the nondominant hand

adopted, a process resulting in resynchronisation of the hands over several cycles of

tapping).

The following study extends these findings to a task which demanded a greater degree

of spatiotemporal coordination: unimanual and bimanual circle drawing. The use of the

circle-drawing task permitted the measurement of spatial as well as temporal aspects of

performance. The small-circle drawing task used in the study in Chapter 3 was chosen

for this study because it requires the use of distal effectors, and is therefore more

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comparable to the finger tapping task used in the previous study than the large circle

drawing task.

Continuous circle drawing requires more complex spatiotemporal coordination than the

repetitive tapping task used in the previous study. As discussed in the introduction to

this section (Chapter 4), there is evidence to suggest that the greater contribution of left

M1 than right M1 to bimanual control may be related to task complexity rather than a

feature of bimanual control per se (Koeneke, Lutz, Wustenberg, & Jäncke, 2004). In the

current study, TMS over left M1 is predicted to disrupt ipsilateral spatial performance as

well as contralateral spatial performance, whereas TMS over right M1 is predicted to

disrupt only contralateral accuracy of circle drawing. These effects are likely to be seen

during both unimanual and bimanual drawing given the greater spatiotemporal

complexity of this task.

In addition to the difference in the degree of spatiotemporal complexity of the two tasks,

they are likely to differ in the neural control of timing. Repetitive discrete movements

and continuous movements have been shown to have distinct temporal control

mechanisms (Spencer & Zelaznik, 2003; Zelaznik, Spencer, & Ivry, 2002). Repetitive

discrete tasks like tapping are punctuated by distinct events (i.e., the finger contacting a

hard surface) whereas in continuous tasks like circle drawing, there are no obvious

events demarcating separate cycles. Timing of repetitive discrete movements involves

an explicit aspect of the task (contact of the finger with the table during tapping) and is

thought to be under cerebellar control (patients with cerebellar lesions show deficits in

the timing of discontinuous tasks`; Spencer, Zelaznik, Diedrichsen, & Ivry, 2003). In

contrast, during continuous movements, timing is thought to be an emergent property of

the movement itself. Patients with cerebellar lesions do not show deficits in the timing

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of continuous movements, suggesting a different neural origin for the processes

governing the timing of this mode of coordination. After callosotomy temporal coupling

between the hands is disrupted for continuous bimanual movements indicating that the

coupling of the hands requires interhemispheric transfer of information, and suggesting

a cortical involvement in the timing mechanism for continuous tasks (Kennerley,

Diedrichsen, Hazeltine, Semjen, & Ivry, 2002). Kennerley and colleagues proposed that

the coupling between the hands might result from the neural specification within the

cortex of movement direction or muscle activity, with similar specifications in each

hemisphere reinforcing each other via callosal interconnections. The implication of

these observations for the current study is that one might expect more extensive

temporal disruptions to both hands after TMS during bimanual continuous circle

drawing than were seen during bimanual repetitive tapping since a disruption to

movement specification within one hemisphere will disrupt between-hand coupling

which relies on interhemispheric transfer of information.

Two effects of TMS have the potential to disrupt ongoing motor behaviour: the

immediate excitatory effects culminating in an MEP, which results in an immediate

perturbation to ongoing movement, and the activation of long-lasting inhibitory

processes, which can be observed as the silent period in active muscle. However, it is

possible to activate the inhibitory circuits using low-intensity TMS without producing

an MEP in the target muscle (Wassermann et al., 1993). Indeed, Chen and colleagues

(2005) successfully used sub-threshold TMS to disrupt unimanual and bimanual

tapping, with both contralateral and ipsilateral effects during bimanual tapping, and only

contralateral effects during unimanual tapping. Three intensities of TMS were used in

the current study: supra-threshold, threshold, and sub-threshold intensities. At the lower

intensities used in this study, the effect of activating inhibitory processes within M1 on

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continuous motor behaviour was examined without the large initial disruption caused by

the production of an MEP. Cortical inhibitory circuits are thought to be critically

important in the precise modulation of force which is required during fine motor

coordination tasks, and have been shown to be asymmetrically activated in left and right

M1, implying a greater efficiency of inhibitory circuits in left than right M1 (Hammond

& Garvey, 2006). Given the more potent long-latency inhibitory circuits in the dominant

hemisphere, a lateralized effect of low intensity TMS on motor performance was

predicted, with larger effects expected after TMS over left M1 than after TMS over

right M1.

The effects of TMS on temporal and spatial aspects of performance during continuous

unimanual and bimanual circle drawing were examined. A differential effect of TMS

over left and right M1 on bimanual circle-drawing was predicted. Because of the

complex spatiotemporal requirements of the task, a greater contribution to the control of

bimanual drawing by left M1 is likely, therefore larger disruption to both hands is

expected after TMS over left M1 than after TMS over right M1 during bimanual

drawing. Additionally, because left M1 is implicated in ipsilateral control of the right

hand during sequential motor tasks, TMS over left but not right M1 is predicted to

disrupt ipsilateral performance during unimanual drawing. The effects of stimulation

over left M1 and right M1 on spatial accuracy, rate, spatial variability, and smoothness

of drawing were examined during unimanual and bimanual drawing.

6.1 Method

Participants

Ten right-handed subjects, 6 females and 4 males, with ages ranging from 22 to 42 years

(median age 28 years) participated. Handedness, measured as the Laterality Quotient

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(median 80). A brief screening questionnaire was administered to exclude individuals

who had previous or current neurological conditions, aneurism clips, pace makers,

cochlear implants, or who were taking drugs with psychoactive effects (Appendix A). If

participants responded in the affirmative on any item they were excluded from the study.

TMS

Magnetic stimuli generated by a Magstim 2002 stimulator were delivered through a

figure-of-eight coil (70-mm diameter). The manually held coil was aligned in the para-

sagittal plane with the handle posterior to the coil, and with the coil tangential to the

scalp. Scalp sites were identified on a snugly fitting cap with pre-marked sites at 1-cm

spacings.

Procedure

Electromyographic activity was recorded from the first dorsal interosseus (FDI) via

surface electrodes taped over the belly and tendon of the FDI. The EMG signal was

amplified (1000x), filtered (high-pass 100 Hz; low-pass 2 kHz), and digitized at a

frequency of 2 kHz for 500 ms following stimulation. The optimal site for eliciting an

MEP from FDI was determined by systematically delivering four stimuli over adjacent

scalp sites at an intensity sufficient to produce an MEP discernible above background

EMG in active muscle. The active threshold was then determined by stimulating at the

optimal site and progressively increasing the stimulus intensity from below to above

threshold. Threshold was defined as the minimum intensity at which three of four

successive stimulations elicited an MEP discernible above background EMG. During

determination of the optimal site and threshold, subjects maintained a slight contraction

of the FDI by holding a pen to emulate the level of FDI activation during circle-

drawing.

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Task. Participants traced the contours of two small circles (15-mm diameter, centres 120

mm apart) on a digitizing tablet (WACOM Intuos 2 Graphics Tablet, Model No. XD-

1212-U) continuously for 10 seconds, at a comfortable and individually determined

pace. Circles were drawn in the clockwise direction with the left hand and in the

counterclockwise direction with the right hand for biomechanical equivalence. Drawing

was performed with the forearm resting on the surface of the graphics tablet, which was

the position adopted naturally by participants using their right hand. Subjects were

instructed to adopt this position with the left hand to eliminate the tendency to use the

whole arm during left-hand drawing, thus limiting proximal movements and promoting

distal movements, and ensuring task equivalence across the hands. EMG activity in both

FDI muscles, X and Y coordinates of pen positions, and pen force on the digitizing

tablet were sampled at 100 Hz with a laptop computer. Each trial began when force was

detected from one or both pens on the graphics tablet, indicating that the subject had

begun drawing.

TMS was applied over the left or right hemisphere during each trial. TMS was triggered

when at least five seconds had elapsed since the start of drawing, and when the pen

passed through the horizontal midline (± 2 mm) of the shape being drawn, to the right of

the vertical midline for the left hand and to the left of the vertical midline for the right

hand (Figure 6.1). The data from the initial two seconds of each trial were used to

determine the horizontal and vertical midlines of the shape being drawn.

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Figure 6.1. TMS was triggered when the pen position was within the grey boxed area (A or B for left and right, respectively). TMS was triggered relative to the position of the hand contralateral to the side of TMS delivery and the limits were determined from the initial 2 seconds of data acquired in each trial. Stimulation occurred when at least 5 seconds had elapsed in the trial, and when the pen was to the right or left of the vertical midline for the left and right hands respectively, and ± 2mm of the horizontal midline. Arrows indicate the direction of movement. Each participant completed three tasks: unimanual left, unimanual right, and bimanual

circle-drawing. TMS was delivered at three intensities (10% of stimulator output below

active motor threshold, active motor threshold, and 10% of stimulator output above

active motor threshold) and to both left and right M1 in a single testing session. Trials

were arranged in three blocks of 24 (one block at each of the three TMS intensities).

Each block consisted of two runs of 12 trials, one block for each side of TMS

stimulation. Each run consisted of four trials each of unimanual left, unimanual right,

and bimanual circle-drawing.

Data analysis

For each trial, EMG activity, time, and X and Y coordinates of the pen on the digitizing

tablet were stored for later analysis. The DC components of the X and Y waveforms

were removed and the data were dual band-pass filtered with the low cut-off frequency

determined as half the average peak frequency from the power spectra of X and Y

waveforms and the high cut-off determined using the method described by Winter

(2005). The purpose of the dual filtering process (filtering once in the forward and once

Left Right

15 mm A B

120 mm

112

in the reverse direction) was to correct the phase shift otherwise introduced by a single

filtering process. The linear excursion of the pen was calculated from consecutive X, Y

coordinate pairs. The data were separated into cycles, which were defined by every

second zero crossing in the Y dimension, with TMS occurring half-way through a cycle.

Period (time to complete one cycle) and circularity (defined below) were calculated for

each cycle in the pre- and post-TMS period. Circularity was calculated as described in

Chapter 3.

Differences between the hands and across tasks were expected in circularity and period

of circle drawing. To enable comparison of changes in circularity and period of circle

drawing after TMS across hands and tasks, each measure was normalized to baseline

(pre-TMS) values. The distribution of circularity scores is bounded by 0 and 1, therefore

it is appropriate to calculate the arcsine of these values to normalize the distribution.

However, statistical analyses of transformed scores produced similar results to ‘raw’

circularity scores, therefore non-transformed circularity results were used. Circularity

ratio was calculated for each cycle after TMS as the circularity during that cycle divided

by baseline circularity. Period difference scores were calculated for each cycle after

TMS as the period during that cycle minus the mean period in the 2.5 s prior to TMS.

Statistical analyses. Mean circularity and period scores prior to TMS were analysed

using two-way repeated measures ANOVAs with Hand (left and right) and Task

(unimanual and bimanual) as within-subject factors. The effects of TMS on circularity

and period were analysed for each hand after stimulation of left and right M1 in each

task (unimanual and bimanual). Separate one-way repeated-measures ANOVAs with

Cycle (5 cycles post-TMS) as the within-subject variable were conducted on circularity

ratio and period difference score for each hand and each side of TMS stimulation. Trend

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analyses were performed to identify any systematic relationships between the

behavioural measures and the movement cycle after TMS. Two-way repeated-measures

ANOVAs were performed with Side of TMS and Cycle after TMS as within-subject

variables for ipsilateral and contralateral hands separately to examine the effects of side

of stimulation on circularity and period. An alpha-level of 0.05 was used for all

statistical tests, and partial eta squared (η2) values are presented as estimates of effect

size.

6.2 Results

Baseline (pre-TMS) performance

Circularity. Table 6.1 shows mean circularity for the left and right hands in unimanual

and bimanual tasks prior to TMS. There was a significant effect of Hand (F(1,9) = 50.47,

p<.001, partial η2 = 0.85); shapes drawn with the left hand were less circular than

shapes drawn with the right hand during both unimanual and bimanual tasks.

Circularity during unimanual drawing did not differ significantly from circularity during

bimanual drawing. However, the left hand was less accurate during bimanual than

unimanual drawing, and the effect size for Task was moderate (partial η2 = 0.27),

although there was no significant effect of Task (F(1,9) = 3.31, p=.10) and no significant

interaction between Task and Hand (F(1,9) = 2.49, p=.15, partial η2 = 0.22).

114

Table 6.1.

Mean circularity for each hand in unimanual and bimanual circle drawing. Standard deviations are in parentheses. (N=10).

Left Right Mean

Unimanual 0.91 (0.01) 0.97 (0.01) 0.94 (0.01)

Bimanual 0.88 (0.06) 0.97 (0.01) 0.92 (0.03)

Mean 0.89 (0.03) 0.97 (0.01) 0.93 (0.01)

Period. Table 6.2 shows mean period for the left and right hands in unimanual and

bimanual tasks prior to TMS. There was a significant effect of Hand (F(1,9) = 112.60,

p<.001, partial η2 =.93) and Task (F(1,9) = 6.06, p = .036, partial η2 = .40) and a

significant interaction between Hand and Task (F(1,9) = 93.80, p < .001, partial η2 = .91).

During the unimanual task, period was longer with the left hand than the right hand

whereas during the bimanual task the period of the two hands was equal. The period of

the left hand was shorter and the period of the right hand was longer in bimanual than

unimanual drawing.

Table 6.2.

Mean period of circle drawing (ms) for each hand during unimanual and bimanual tasks. Standard deviations are in parentheses. N=10.

Left Right Mean

Unimanual 557 (98) 472 (103) 519 (99)

Bimanual 539 (112) 539 (111) 539 (111)

Mean 553 (104) 505 (106) 529 (105)

TMS was delivered over left and right M1, during unimanual and bimanual drawing and

this procedure was repeated at three TMS intensities: suprathreshold, threshold, and

subthreshold intensities. The effects of stimulation on circularity and period were

115

examined for the ipsilateral and contralateral hands. Each section begins with an

overview of the findings, followed by a detailed analysis.

TMS at 10% above threshold

During unimanual circle drawing, TMS over left M1 decreased circularity with the

ipsilateral and contralateral hands to a similar extent whereas TMS over right M1

decreased circularity only in the contralateral hand. TMS over both left and right M1

caused a large increase in period in the contralateral hand in the cycle after TMS. The

effect of TMS on ipsilateral period was small compared to the effect on contralateral

period after TMS over both left and right M1.

During bimanual circle drawing, TMS over left M1 caused a decrease in circularity with

both the contralateral and ipsilateral hand. TMS over right M1 caused a large decrease

in circularity with the contralateral hand and a small but consistent decrease in

circularity with the ipsilateral hand. The effects of TMS on period of circle drawing

were similar after stimulation over left and right M1. In each case, both ipsilateral and

contralateral hands were affected. There was a delay in the effect on the ipsilateral hand,

and the effect on contralateral hand was greatest during the cycle following the cycle of

stimulation.

Unimanual performance: Circularity. Figure 6.2 shows the tracings from a

representative subject for each hand during unimanual circle drawing. Two cycles

before and four cycles after TMS over left M1 and right M1 are shown. Two features of

these tracings are worth noting. First, a large disruption to circle drawing with the

contralateral hand occurred after TMS over both left M1 and right M1; this disruption

was not evident in the cycle during which TMS was delivered, but during the following

116

cycle. Second, ipsilateral circle drawing was disrupted after TMS over left M1 but not

after TMS over right M1. This can also be seen in the group data presented in Figure

6.3, which shows mean circularity ratios after TMS over left M1 and right M1. After

TMS over left M1 there was no decrease in circularity during the cycle in which TMS

was applied for either hand and the greatest decrease occurred during the following

cycle for both hands. Circularity returned to pre-stimulus levels over the following three

cycles. Trends (linear, quadratic and cubic) for these data are presented in Table 6.3.

In contrast, TMS over right M1 caused a large decrease in circularity in the contralateral

hand but had no effect on circularity in the ipsilateral hand (Figure 6.3, right panel).

Although circularity decreased in the contralateral hand during the cycle in which TMS

was applied, the greatest decrease did not occur until the following cycle. Circularity in

the contralateral hand returned to baseline levels over the following two cycles.

117

HAND

LEFT M1 TMS

Ipsilateral Contralateral

RIGHT M1 TMS

HAND

Ipsilateral Contralateral CYCLE

TMS - 2

TMS - 1

1

2

3

4

Figure 6.2. Sample tracings during the unimanual task with the ipsilateral and contralateral hands after TMS over left and right M1 showing disruption to both ipsilateral and contralateral drawing after TMS over left M1 but only to contralateral drawing after TMS over right M1.

118

Table 6.3. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).

1 2 3 4 50

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5

C

Figure 6.3. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Results of two-way repeated-measures ANOVAs comparing the effects of TMS over

left and right M1 are presented in Table 6.4. Note that the structure of these analyses is

different to the structure of the data in Figure 6.3; Figure 6.3 presented contralateral and

ipsilateral data together for each side of stimulation to allow a comparison of interlimb

changes in circularity, whereas the analyses in Table 6.4 were performed to determine if


Contralateral hand Linear 2.39 .157 .21 10.26 .011 .53 Quadratic 5.24 .048 .37 0.02 .878 .00 Cubic 2.92 .122 .24 8.76 .016 .49

Ipsilateral Hand Linear 0.77 .402 .08 2.20 .172 .20 Quadratic 16.97 .003 .65 0.64 .444 .07 Cubic 4.85 .055 .35 3.24 .105 .26

Cycle

CIR

CU

LAR

ITY

RA

TIO


119

there was a lateralized effect of TMS on the contralateral hand and on the ipsilateral

hand. The decrement in circle drawing with the contralateral hand was more

pronounced after TMS over right M1 than after TMS over left M1, reflected in a

significant interaction between Side of TMS and Cycle in the contralateral data.

Ipsilateral circularity was disrupted after TMS over left but not right M1, reflected in a

significant interaction between Side of TMS and Cycle in the ipsilateral data.

Table 6.4 Two-way Repeated Measures ANOVA for Circularity Ratios in Contralateral and Ipsilateral Hands During Unimanual Drawing. Side of TMS (Left, Right) and Cycle (6 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10).


The delayed maximal effect of TMS on circle drawing can be seen in Figure 6.4 which

shows X- and Y-pen excursion in the contralateral hand after TMS over left and right

M1. The shapes drawn during each cycle are shown at the top of the figure. TMS was

timed to occur midway through cycle 1, as indicated by the solid vertical line. The

effect of TMS on X- and Y-excursion began during cycle 1 and tended to be simple

over- or under-excursions in the X- and Y-planes. Later effects were more complex as

seen in both the X-Y- excursion plots and shapes drawn during cycle 2. The early

excitatory effect of TMS can be observed in the EMG activity; during cycle 1 a large

MEP is present. Peaks in the EMG trace can also be seen during cycle 2 which coincide

with the large disruptions in X- and Y-excursion. This participant was chosen because

her responses were particularly pronounced, making excursions in the X- and Y-planes


Side of TMS 1, 9 3.60 .090 .29 1, 9 3.74 .085 .29 Cycle 4, 36 6.87 <.001 .43 4, 36 4.52 .005 .33 Side TMS x Cycle 4, 36 3.86 .010 .30 4, 36 4.29 .006 .32

120

more obvious, however, in all cases, the largest responses were observed in the second

cycle.

Figure 6.5 shows X- and Y-pen excursion in a typical trial in the ipsilateral hand after

TMS over left and right M1. The effect of TMS over left M1 was evident as simple

under-excursions in both X- and Y-planes during cycle 2. There was no apparent effect

on X- and Y- pen excursion in the ipsilateral hand after TMS over right M1.

-10

X-e

xcur

sion

(m

m)

Y-e

xcur

sion

(m

m)

10

10

-10

Time (s) 10 4 Time (s) 10 4

1 2 3 1 2 3 Cycle: Cycle:

-1

1

EM

G a

mpl

itude

(m

V)

Figure 6.4. An example of X- and Y-pen excursions with the contralateral hand and EMG activity in the FDI during unimanual circle drawing after TMS over left and right M1. Dashed horizontal lines indicate mean excursion prior to TMS, solid vertical lines indicate time of TMS delivery, and dashed vertical lines indicate the endpoints of each cycle. The three small figures above each set of plots show shapes drawn in cycles 1 to 3 (arrow indicates drawing direction, dot indicates TMS timing).


121

X-e

xcur

sion

(m

m)

Y-e

xcur

sion

(m

m)

Time (s) 10 4

-10

10

-10

10

Time (s) 104

1 2 3 Cycle: 1 2 3 Cycle:

Figure 6.5. An example of X- and Y-pen excursions with the ipsilateral hand during unimanual circle drawing after TMS over left and right M1. Dashed horizontal lines indicate mean excursion prior to TMS, solid vertical lines indicate time of TMS delivery, and dashed vertical lines indicate the segregation of data into discrete cycles for analysis (note TMS was delivered midway through cycle 1). The three small figures above each set of plots show the shapes drawn during cycles 1 to 3.

Unimanual Performance: Period. Mean period difference scores (change from mean

period in the 2.5 s before TMS) after TMS over left and right M1 are shown in Figure

6.6. TMS over left M1 caused a large increase in contralateral period and a small

delayed increase in ipsilateral period. There was a small increase in period in the

contralateral hand in the cycle in which TMS was applied and a much greater increase

during the following cycle after which period returned to baseline levels. In contrast,

ipsilateral period did not change from baseline until two cycles after TMS delivery and

remained elevated for the following two cycles. Trends (linear, quadratic and cubic) for

these data are presented in Table 6.5.

Similarly, TMS over right M1 caused a large increase in contralateral period and a small

increase in ipsilateral period (Figure 6.6, right panel). The increase in contralateral


122

period was greatest during the cycle following the one in which TMS was delivered and

it gradually returned to baseline over the following three cycles. There was a small

increase in period in the ipsilateral hand during the cycle of TMS delivery, followed by

a decrease in circularity and a secondary small increase in period in later cycles.

Table 6.5. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores with Cycle (6 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).




Figure 6.6. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Cycle

PE

RIO

D D

IFF

ER

EN

CE

(m

s)


1 2 3 4 5-20

20

60

100

140

1 2 3 4 5

123

The results of two-way repeated-measures ANOVAs are presented in Table 6.6 (note

the structure of the ANOVA is different to the structure of data in Figure 6.6). There

was no significant difference between the effects of left and right TMS on the changes

in period in the contralateral hand. The changes in period in the ipsilateral hand after

TMS over left and right M1 followed a different evolution over time, and this was

reflected in a significant Side of TMS x Cycle interaction.

Table 6.6 Two-way Repeated Measures ANOVA for Period Difference Scores in Contralateral and Ipsilateral Hands During Unimanual Drawing. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .


Bimanual performance: Circularity. Figure 6.7 shows the tracings from a representative

subject for each hand during bimanual circle drawing. Two cycles before and four

cycles after TMS over left and right M1 are shown. TMS over both left and right

M1disrupted performance with the contralateral hand. Drawing with the ipsilateral hand

was disrupted more after TMS over left M1 than after TMS over right M1.


Side of TMS 1, 9 0.30 .597 .03 1, 9 0.26 .622 .03 Cycle 4, 36 12.19 <.001 .58 4, 36 2.44 .065 .21 Side TMS x Cycle 4, 36 0.64 .636 .07 4, 36 2.82 .039 .24

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HAND

LEFT M1 TMS

Ipsilateral

RIGHT M1 TMS

HAND Ipsilateral Contralateral Contralateral

HAND CYCLE

TMS - 2

TMS - 1

1

2

3

4

Figure 6.7. Sample tracings during the bimanual task with the ipsilateral and contralateral hands after TMS over left and right M1 showing disruption to contralateral circle-drawing in the cycle of TMS delivery and the following cycle and the greatest disruption to ipsilateral circle drawing in the cycle after TMS delivery over left M1.

Bimanual circularity is summarised in Figure 6.8. TMS over left M1 caused a decrease

in circularity with both the contralateral and the ipsilateral hand (left panel). After TMS

over left M1, the greatest decrease in circularity in the contralateral hand was during the

cycle of stimulation and circularity remained below baseline in the following cycle

before returning to pre-TMS values. Circularity with the ipsilateral hand decreased in

the cycle after TMS and remained low for the next three cycles. The data describing the

125

changes in circularity with the contralateral and ipsilateral hands after TMS over left

M1 had no significant linear, quadratic, or cubic trends (Table 6.7). Individual

participants’ responses with the contralateral and ipsilateral hands after TMS over left

M1 were variable, and are shown in the inset figures in Figure 6.8 (A and B,

respectively). Circularity decreased in the contralateral hand after TMS for most

participants; however one participant had a very large response. When this participant

was excluded from the analysis there was a significant linear trend (F(1,9) = 8.13, p =

.02, partial η2= .51). The responses in the ipsilateral hand were very variable, with no

consistent pattern, although circularity decreased for all participants.

TMS over right M1 caused a large decrease in circularity with the contralateral hand

and a small decrease in circularity with the ipsilateral hand (Figure 6.8, right panel). In

the contralateral hand, there was a large decrease in circularity during the cycle of TMS

delivery and an even larger decrease in the cycle after TMS, followed by a return to

baseline over the next three cycles. Ipsilateral circularity decreased slightly in the cycle

after TMS.

The results of two-way repeated-measures ANOVAs comparing the effects of TMS

over left and right M1 on circularity are presented in Table 6.8.The effect of TMS on

circularity in the contralateral hand during the bimanual task was greater after TMS

over right than left M1. The effects of TMS over left and right M1 on ipsilateral

circularity were not significantly different.

126

Table 6.7. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).


Contralateral hand Linear 3.25 .105 .26 37.08 <.001 .80 Quadratic 0.94 .358 .10 0.08 .784 .01 Cubic 3.62 .089 .29 3.26 .104 .27


Figure 6.8. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity. The inset graphs show individual data for the contralateral (A) and ipsilateral (B) hand after TMS over left M1 (the scale is the same as that in the large plots which resulted in truncation of two responses).

Cycle

CIR

CU

LAR

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RA

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A B

1 2 3 4 50

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5

C

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Table 6.8. Two-way Repeated Measures ANOVA for Circularity Ratios in Contralateral and Ipsilateral Hands. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .


Bimanual performance: Period. After TMS over left M1, both contralateral and

ipsilateral period increased from baseline (Figure 6.9, left panel). Contralateral period

increased during the cycle in which TMS was delivered then gradually returned to

baseline over the following four cycles. No significant trends described these data

(Table 6.9). The inset figure in the left panel of Figure 6.9 shows individual data for the

contralateral hand, showing two different patterns of response to TMS over left M1; for

six of 10 participants period increased and for the remainder period decreased. There

was no change in ipsilateral period during the cycle in which TMS was delivered, the

greatest increase occurring in the following cycle, after which period decreased to

baseline levels gradually over the following three cycles.


Side of TMS 1, 9 23.59 .001 .72 1, 9 3.10 .112 .26 Cycle 4, 36 11.69 <.001 .56 4, 36 0.89 .480 .09 Side TMS x Cycle 4, 36 8.61 <.001 .49 4, 36 0.81 .528 .08

128

Table 6.9. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).



Ipsilateral hand Linear 0.23 .644 .02 0.79 .397 .08 Quadratic 6.41 .032 .42 0.76 .405 .08 Cubic 0.84 .384 .08 3.59 .091 .28

Figure 6.9. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity. The inset figure represents individual responses in the contralateral hand after TMS over left M1 (period increased for 6 participants and decreased for 4).

TMS over right M1 caused an increase in both ipsilateral and contralateral period

(Figure 6.9, right panel). Contralateral period increased slightly in the cycle of TMS

delivery and was greatest during the following cycle, returning to baseline over the next

three cycles. There were no significant trends in the contralateral period data after TMS

Cycle

PE

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D D

IFF

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EN

CE

(m

s)


1 2 3 4 5-20

20

60

100

140

1 2 3 4 5

129

over right M1, although the linear trend approached significance (Table 6.9). Ipsilateral

period increased in the cycle after TMS delivery and returned to baseline over the

following three cycles. The function describing the changes in ipsilateral period had a

cubic component which approached significance.

The effects of stimulation over left and right M1 on period were similar, and there were

no significant effects of Side of TMS or significant interactions between Side of TMS

and Cycle in either the contralateral or the ipsilateral hand (Table 6.10).

Table 6.10. Two-way Repeated Measures ANOVA for Period Difference Scores in Contralateral and Ipsilateral Hands During Bimanual Drawing. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .


In summary, during unimanual circle-drawing, suprathreshold TMS over left M1

disrupted circularity with both the contralateral and ipsilateral hand, whereas TMS over

right M1 disrupted only the contralateral hand. The effect on contralateral circularity

was larger after TMS over right than left M1. The circularity results were similar during

bimanual and unimanual circle-drawing, except that during bimanual drawing the

ipsilateral hand was also affected by TMS over right M1. However, the changes in

ipsilateral circularity were larger after TMS over left than right M1. During unimanual

drawing, TMS over left and right M1 caused an increase in period in the contralateral

hand, and a small increase in the ipsilateral hand. During the unimanual task, the

changes in period after TMS over left and right M1 were equivalent. During bimanual


Side of TMS 1, 9 1.41 .265 .14 1, 9 0.84 .384 .08 Cycle 4, 36 3.74 .012 .29 4, 36 2.36 .072 .21 Side TMS x Cycle 4, 36 0.88 .485 .09 4, 36 0.57 .689 .06

130

drawing, period increased in the contralateral and ipsilateral hand to an equivalent

extent. There were no lateralized effects of TMS on changes in period.

TMS at threshold

The effects of TMS at threshold intensity on contralateral and ipsilateral performance

were attenuated compared to the effects at suprathreshold intensity. However, similar to

the effects at higher intensity, the effects on circularity with the contralateral hand was

greater after TMS over right than left M1 during unimanual drawing. During bimanual

drawing TMS caused a decrease in circularity with the ipsilateral but not the

contralateral hand, and TMS over right M1 caused a decrease in circularity with the

contralateral but not the ipsilateral hand. Period changes were seen in both hands after

TMS over left and right M1.

Unimanual performance: Circularity. There was little change in circularity after TMS

over left M1 in either the ipsilateral or the contralateral hand (Figure 6.10), although a

linear trend in the ipsilateral data approached significance (Table 6.11) and there was a

significant linear trend in the contralateral data. There was a significant decrease in

circularity in the contralateral hand after TMS over right M1.

Contralateral circularity was affected more after TMS over right M1 than left M1 (a

significant Side of TMS x Cycle interaction, F(4,36) = 3.29, p = .02, partial η2 = .27).

There was no significant difference in the effects of TMS over left and right M1 on

ipsilateral circularity.

131

Table 6.11 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).


Contralateral hand Linear 6.76 .029 .43 12.49 .006 .58 Quadratic 3.83 .082 .30 0.01 .914 <.01 Cubic 2.60 .141 .22 0.16 .696 .02

Ipsilateral Hand Linear 4.89 .055 .35 0.09 .768 .01 Quadratic <0.01 .950 <.01 3.28 .104 .27 Cubic 0.20 .664 .02 1.45 .259 .14

Figure 6.10. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Unimanual performance: Period. After TMS over left M1, period increased slightly in

the contralateral hand in the cycle after TMS, after which it returned to pre-TMS levels

(Figure 6.11, left panel). Linear and cubic trends approached significance (Table 6.12).

Period increased in the ipsilateral hand three cycles after TMS delivery and this increase

was maintained during the following cycle. After TMS over right M1, there was a small

Cycle

CIR

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RA

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1 2 3 4 50

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5

132

increase in period in the contralateral hand (Figure 6.11, right panel), although no

significant trends described this data. There was a small increase in period in the

ipsilateral hand.

Table 6.12

Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).



Ipsilateral Hand Linear 7.27 .025 .45 0.78 .401 .08 Quadratic 0.03 .875 <.01 0.06 .805 <.01 Cubic 3.46 .096 .28 12.51 .006 .58

Figure 6.11. Mean period difference scores with contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Cycle

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(m

s)


1 2 3 4 5-20

20

60

100

140

1 2 3 4 5

133

There was no significant differences between changes in period in the contralateral hand

after TMS over left M1 and right M1, but there was a significant interaction between

Side of TMS and Cycle for the ipsilateral data (F(4,36) = 2.80, p = .04, partial η2 = .24).

Bimanual performance: Circularity. TMS over left M1 had no effect on circularity in

the contralateral hand (Figure 6.12, left panel). There was a decrease in circularity in the

ipsilateral hand which began during the third cycle and continued for the following two

cycles. TMS over right M1 caused a decrease in circularity in the contralateral hand

during the cycle of TMS and the following cycle (Figure 6.12, right panel). There was

no effect of TMS over right M1 on circularity with the ipsilateral hand. Trends for these

data are presented in Table 6.13.

Contralateral circularity was affected more by TMS over right M1 than TMS over left

M1 (significant effect of Side of TMS, F(1,9) = 6.70, p = .03, partial η2 = .43). In

contrast, ipsilateral circularity was affected more by TMS over left M1 than TMS over

right M1 (significant Side of TMS x Cycle interaction, F(4,36) = 2.99, p = .03, partial η2

= .25).

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Table 6.13

Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).




Figure 6.12. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Bimanual performance: Period. TMS over left M1 caused a slight increase in ipsilateral

period (Figure 6.13), although this was not significant, and there was no change in

contralateral period. TMS over right M1 caused a slight increase in both ipsilateral and

contralateral period, although neither change was significant. Table 6.14 shows trends

Cycle

CIR

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ITY

RA

TIO


1 2 3 4 50

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5140

135

for these data. There was no difference between the effects of TMS over left and right

M1 on changes in period in either the contralateral or ipsilateral hand.

Table 6.14

Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).



Ipsilateral Hand Linear 1.06 .330 .11 0.11 .752 .01 Quadratic 0.04 .852 <.01 2.44 .153 .213 Cubic 1.27 .290 .12 0.55 .478 .06

Figure 6.13. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at motor threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Cycle


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(m

s)

1 2 3 4 5-20

20

60

100

140

1 2 3 4 5

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TMS at 10% below threshold

The effects of TMS at 10% below threshold on circularity and period were small and

followed a similar pattern to the effects of TMS at threshold. TMS over left M1 caused

a decrease in ipsilateral but not contralateral circularity during unimanual and bimanual

drawing, whereas TMS over right M1 caused a decrease in contralateral circularity. The

effects of TMS over left M1 were also greater in the ipsilateral hand and after TMS over

right M1 were greater in the contralateral hand.

Unimanual performance: Circularity. TMS over left M1 (Figure 6.14, left panel) caused

a small decrease in ipsilateral circularity ratio, but no change in contralateral circularity.

There was no significant change in circularity ratio after TMS over right M1 in either

the contralateral or ipsilateral hand (Figure 6.14, right panel). Table 6.15 shows the

trends for these data.

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Table 6.15

Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).




Figure 6.14. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Unimanual performance: Period. After TMS over left M1 (Figure 6.15, left panel),

there was a small increase in period in the ipsilateral hand, but no significant change in

contralateral period. After TMS over right M1, ipsilateral period was not affected, but

Cycle

CIR

CU

LAR

ITY

RA

TIO


1 2 3 4 50

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5

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contralateral period increased for 5 cycles after TMS (Figure 6.15, right panel). Trends

for these data are shown in Table 6.16.

Table 6.16 Trend analyses: Results of One-way Repeated-Measures ANOVAs for period Difference Scores During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).



Ipsilateral Hand Linear 5.82 .044 .38 1.98 .193 .18 Quadratic 0.55 .477 .06 >0.01 .990 <.01 Cubic 0.10 .753 .01 2.35 .159 .21

Figure 6.15. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during unimanual drawing after TMS over left and right M1 at sub-threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Cycle

PE

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(m

s) Left M1 TMS Right M1 TMS

1 2 3 4 5-20

20

60

100

140

1 2 3 4 5

139

The changes in contralateral period were larger after TMS over left than right M1

(significant effect of Side of TMS, F(1,9) = 11.16, p = .009, partial η2 = .55). In contrast,

the changes in ipsilateral period were larger after TMS over right M1, although this

difference was not significant.

Bimanual performance: Circularity. Circularity decreased in the ipsilateral hand after

TMS over left M1 in the cycle of TMS delivery and remained lower than baseline for

the next four cycles (Figure 6.16, left panel). There was no change in the contralateral

hand. There were no significant changes in circularity after TMS over right M1 for

either hand (Figure 6.16, right panel). Trends for these data are presented in Table 6.17.

There was no significant difference between the effects of TMS over left and right M1

on contralateral circularity, however, TMS over left M1 caused a greater reduction in

ipsilateral circularity than TMS over right M1 (significant effect of Side of TMS, F(1,9) =

11.18, p = .009, partial η2 = .55).

140

Table 6.17 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).


Contralateral hand Linear 0.40 .542 .04 0.82 .390 .08 Quadratic >0.01 .952 >.01 0.30 .600 .03 Cubic 0.69 .427 .07 3.84 .082 .30


Figure 6.16. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

Bimanual performance: Period. There were small increases in period in both the

ipsilateral and contralateral hand after TMS over left M1, beginning in the cycle after

TMS delivery (Figure 6.7, left panel), although there were no significant trends for

either hand. No significant change occurred in ipsilateral or contralateral period after

CIR

CU

LAR

ITY

RA

TIO


Cycle 1 2 3 4 5

0

0.7

0.8

0.9

1.0

1.1

1 2 3 4 5

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TMS over right M1 (Figure 6.17, right panel). Trends for these data are presented in

Table 6.18.

Table 6.18 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).



Ipsilateral Hand Linear 0.17 .693 .02 0.02 .904 <.01 Quadratic 4.39 .066 .33 0.13 .724 .01 Cubic 0.05 .833 .01 0.21 .660 .02

Figure 6.17. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.

There was no significant difference between the effects of TMS over left and right M1

on changes in period in either the contralateral or ipsilateral hand.

PE

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(m

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Cycle 1 2 3 4 5-20

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6.3 Discussion

The main findings of this study were: suprathreshold TMS over primary motor cortex

during continuous circle drawing caused enduring decreases in circularity and increases

in period. The greatest effects on both circularity and period were delayed relative to the

time of TMS application. Left hemispheric stimulation decreased circularity with both

the contralateral hand and the ipsilateral hand whereas right hemispheric stimulation

decreased circularity only with the contralateral hand. This lateralized effect of TMS on

circularity was not limited to the bimanual case, but was also apparent during unimanual

drawing. In contrast, period of circle drawing was affected equally by stimulation over

left and right M1. During unimanual drawing, stimulation over both left and right M1

increased period with both hands and the increase was larger in the contralateral hand

than in the ipsilateral hand. During bimanual drawing, period of drawing with the

contralateral hand and the ipsilateral hand were affected to a similar extent by TMS over

both left and right M1. Stimulation using lower TMS intensities caused smaller

decreases in circularity and increases in period than suprathreshold TMS. The changes

in circularity and period after TMS at the lower intensities were most evident in the

ipsilateral hand after TMS over left M1, and the contralateral hand after TMS over right

M1.

At lower TMS intensities, left sided stimulation was predicted to have a greater effect

than right sided stimulation, due to the greater potency of inhibitory circuits in the

dominant M1 than nondominant M1 (Hammond, Faulkner, Byrnes, Mastaglia, &

Thickbroom, 2004). However, these predictions were not born out by the results of

threshold and sub-threshold stimulation in this study. Firstly, as expected, changes in

circularity and period after TMS at threshold and sub-threshold intensities were of a

smaller magnitude than after suprathreshold TMS. There were small changes in

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circularity at both threshold and sub-threshold intensities, which were more obvious

during bimanual than unimanual drawing. However, contrary to the predicted lateralized

effect, the largest decreases in circularity occurred in the ipsilateral hand after TMS over

left M1, and in the contralateral hand after TMS over right M1. The period data showed

a similar trend; the changes in period during unimanual drawing after threshold or sub-

threshold TMS were greater in the ipsilateral hand after TMS over left M1, and the

contralateral hand after TMS over right M1. During bimanual drawing, the changes in

period with the ipsilateral and contralateral hand were of a similar magnitude, and there

was little difference between the effects of left and right sided stimulation (similar to the

effect of supra-threshold stimulation on changes in period). Although many of the

changes in circularity and period after TMS at threshold and sub-threshold intensities

failed to reach significance, the general impression was that when performance

decrements were observed, it was the performance with the nondominant hand that was

most affected, regardless of the hemisphere being stimulated.

It seems unlikely that physiological processes in M1, such as the activation of

intracortical inhibitory circuits, could account for the contralateral effects after TMS

over right M1 and the ipsilateral effects after TMS over left M1, as the activation of

these circuits would be expected to have a greater effect on the contralateral hand than

the ipsilateral hand regardless of side of stimulation. A more plausible explanation is

that the nondominant hand was less resistant to interference by the startling effect of the

TMS acoustic stimulus than the dominant hand. Startle effects have been noted for low

intensity acoustic stimuli (Blumenthal, 1988). At first blush, it is difficult to see how an

autonomic response to the click associated with discharge of the TMS pulse could

account for the lateralized motor effects observed in the present study (the nondominant

hand was affected more than the dominant hand by both left and right-sided

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stimulation). Yet the changes in circularity and period after TMS at the lower intensities

do imply that control of the nondominant hand was the more sensitive to disruption than

control of the dominant hand. What might be the basis of this observation?

Asymmetries in the direction of attention could account for the effects during bimanual

coordination. There is evidence that the dominant hand is the main focus of attention

during bimanual coordination (Peters, 1981), which is consistent with the role taken by

each hand during naturally occurring bimanual tasks (the dominant hand usually

performs the task requiring directed attention, while the nondominant hand performs a

stabilizing role, and receives only indirect attention). However, this is unlikely to

account for the effects during unimanual drawing. There is evidence that participants

are able to prepare themselves for and resist the disruptive effects of TMS (Bonnard,

Camus, de Graaf, & Pailhous, 2003). In the current study no trials were delivered

without TMS, and knowing that a TMS pulse would occur around the middle of a trial

might have changed the behaviour of the participants; the current results might reflect a

greater ability to prepare for a disruption to the dominant hand. However, a more

parsimonious explanation which could account for the effects of low intensity stimuli

during both unimanual and bimanual coordination relates to a mechanical asymmetry

between drawing with the dominant and nondominant hand. In Chapter 3 it was noted

that more pressure was applied during circle drawing with the dominant than the

nondominant hand, which might result from a difference in confidence between drawing

with the dominant and nondominant hand (LaRoque & Obrzut, 2006). Greater force

applied with the dominant than nondominant hand, would have provided greater

friction, and may have afforded more stability to the dominant hand, rendering it less

susceptible than the nondominant hand to perturbation.

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The effects of suprathreshold TMS are likely to represent those effects seen after lower

intensity stimulation (due to mechanical stability differences between the hands), plus

any physiological effects of stimulation at a higher intensity. The effects after

suprathreshold stimulation were much larger than the effects seen after lower intensity

TMS pulses. In addition, qualitative differences between the effects after suprathreshold

stimulation and lower-intensity stimulation suggest that the magnitude of the difference

between these effects must represent physiological effects. Several features of these

qualitative differences deserve elaboration.

Firstly, the effect of suprathreshold TMS over left M1 on circularity was not immediate,

but emerged during the cycle after TMS. The effect of TMS over right M1 on circularity

emerged during the cycle of TMS but was greatest in the cycle after TMS. In both cases

the effects endured for several cycles after TMS. There was evidence in the X- and Y-

excursion data of small changes during the cycle of TMS, followed by greater changes

in the cycle after TMS. The small disruption to drawing during the cycle of TMS was

probably caused by a combination of immediate excitatory effects of TMS on M1

(resulting in a muscle twitch) and more sustained inhibitory effects of TMS on M1.

However, the greatest disruption to circle drawing occurred in the cycle after TMS, by

which time both the immediate excitatory and the more sustained inhibitory effects of

TMS would have resolved. This delayed effect on performance may have resulted, at

least in part, from the return of EMG activity after the silent period, which is consistent

with the timing of large secondary disruption to circle drawing evident in the tracings,

circularity index, and X- and Y-excursion data during the cycle after TMS.

Secondly, the effects of TMS on circularity were lasting; a return to stable, pre-TMS

levels of accuracy did not occur immediately, but developed over several cycles. By

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comparison, the time to return to stable simple rhythmic movements after mechanical

perturbation is relatively short; during a cyclical finger flexion-extension task

disruptions caused by a mechanical perturbation were overcome and a stable pattern of

movement re-established within a single cycle of movement (around 500 ms`; Kay,

Saltzman, & Kelso, 1991). This represents a much shorter adjustment period than that

observed in the present study. The enduring effect of TMS on circularity may reflect a

long period of post-TMS trajectory adjustments in order to return to a stable pattern of

drawing. Alternatively, the lasting effect on circularity may reflect an enduring effect of

TMS itself on M1 and motor output. Evidence from recent neurophysiological studies

implicates M1 in high-level aspects of motor control. Although traditionally labelled the

primary output stage of the motor cortex, a recent study in monkeys showed that for

complex sequences, neurons in M1 represent not only the movement being performed,

but also upcoming sequences of movements (Lu & Ashe, 2005). Furthermore, electrical

stimulation of M1 can produce complex, multijoint movements in the monkey that

resemble natural movements, suggesting that M1 encodes relatively high-level motor

plans (Graziano, Aflalo, & Cooke, 2005). The prolonged effect of TMS on circularity

may therefore reflect a disruption to the representation of upcoming movements,

although it is not possible to distinguish between the two alternative explanations in the

present study.

Suprathreshold TMS over left M1 caused approximately equal disruption to ipsilateral

and contralateral circularity whereas TMS over right M1 caused a large disruption to

contralateral circularity and very little disruption to ipsilateral circularity. Neuroimaging

data suggests that coupled bimanual movements are controlled predominantly by the

dominant hemisphere (Jäncke et al., 1998; Serrien, Cassidy, & Brown, 2003; Viviani,

Perani, Grassi, Bettinardi, & Fazio, 1998). However, in the present study, the effects of

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TMS on circularity were similar during unimanual and bimanual drawing; in both cases,

changes in ipsilateral circularity were greatest after TMS over left M1. This contrasts

with previous TMS studies which have shown no lateralized effect of TMS during

bimanual reaction time (Foltys et al., 2001) or during bimanual tapping (J. T. Chen et

al., 2005). It also contrasts with the previous study (Chapter 5) where lateralised effects

of TMS were only seen during bimanual finger-tapping. However, the task in the

current experiment required a more complex modulation of the activity of many hand

muscles for accurate circle drawing than the simple finger flexion-extension required in

the previous tasks. In this respect, the circle-drawing task can be thought of as a

sequencing task in that it requires the sequencing of many sub-movements to produce a

smooth circular movement. Neuroimaging and lesion studies have shown that left M1 is

dominant for complex sequences of hand movements (Rao et al., 1993; Salmelin, Forss,

Knuutila, & Hari, 1995; Verstynen, Diedrichsen, Albert, Aparicio, & Ivry, 2005; Wyke,

1971). Furthermore, as discussed in the introduction to this chapter, it has been

suggested that the greater activation of the dominant hemisphere during bimanual

compared to unimanual motor performance is not due to a difference in task (unimanual

versus bimanual) per se, but due to a difference in the complexity of the tasks (Koeneke,

Lutz, Wustenberg, & Jäncke, 2004). The greater effect after TMS over left M1 on

ipsilateral circularity in the current study, regardless of mode of drawing, provides

support for the dominance of the left hemisphere in the preparation of complex

sequential movements rather than a specific role in bimanual coordination.

In contrast to the effects of TMS on circularity, there was no difference between the

effects of left- and right-sided stimulation on period of circle drawing. During

unimanual drawing, TMS over both left and right M1 caused large increases in period

of circle drawing in the contralateral hand and small changes (mostly increases) in

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period of circle drawing in the ipsilateral hand. During bimanual drawing, TMS over

both left and right M1 caused increases in period of circle drawing with the ipsilateral

and contralateral hand. The increase in period in the contralateral hand preceded the

increase in period in the ipsilateral hand; there was a slight increase in period in the

cycle of TMS with the contralateral hand but not with the ipsilateral hand and a larger

increase in period in the cycle after TMS with both hands. The changes in period with

the two hands were of a similar magnitude and followed a similar time course during

bimanual drawing, suggesting that the hands became tightly temporally coupled soon

after the disruptive effects of TMS. Furthermore, after TMS over right M1, disruption to

the temporal control of both the ipsilateral and contralateral hands occurred without

major changes in ipsilateral circularity. In other words, the dominant hand maintained

spatial accuracy after TMS over right M1, but slowed to match the nondominant hand.

This observation contrasts with the finding in the previous study, which found that

during bimanual finger tapping, TMS increased the inter-response interval mainly with

the contralateral hand. These contrasting effects provide further support for the

hypothesis that different timing mechanisms are invoked during repetitive discrete

response tasks and continuous tasks (Spencer & Zelaznik, 2003; Zelaznik, Spencer, &

Ivry, 2002).

In summary, the effects of subthreshold and threshold TMS were likely due to the

nondominant hand being less resistant to interference by the startling effect of the TMS

acoustic stimulus than the dominant hand due to mechanical differences in drawing with

the two hands. The effects of suprathreshold TMS were qualitatively and quantitatively

different from those evoked by lower intensity stimulation. Left hemispheric stimulation

decreased circularity with both the contralateral and the ipsilateral hand whereas right

hemispheric stimulation decreased circularity only with the contralateral hand. The

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lateralized effect of TMS on circularity was not limited to the bimanual case, but was

also apparent during unimanual drawing. These results contrast with the findings of the

previous study in which lateralized effects of TMS were seen only during bimanual

finger tapping. This suggests a role for the left hemisphere in control of complex

sequential organization of movement by both hands, and is consistent with lesions

studies which show left hemisphere lesions result in sequencing deficits with both

hands, whereas right hemisphere lesions result in sequencing deficits with the

contralateral hand only (Haaland & Harrington, 1994).

151

CHAPTER 7. UNIMANUAL AND BIMANUAL PERFORMANCE AFTER

UNILATERAL STROKE

Deficits in motor control following a stroke are common; between 70 and 85 percent of

stroke survivors are estimated to suffer from acute hemiparesis (Dobkin, 2004). While

some functional recovery occurs following a stroke, between 55 and 70 percent of

patients experience lasting impairments in upper limb functioning three to six months

post-stroke (Kwakkel, Kollen, van der Grond, & Prevo, 2003; Lai, Studenski, Duncan,

& Perera, 2002). Furthermore, even patients who have good recovery of strength on the

affected side often have enduring deficits in fine motor control (Heald, Bates, Cartlidge,

French, & Miller, 1993; Kunesch, Binkofski, Steinmetz, & Freund, 1995). In a group of

patients with lesions of the primary motor cortex, strength in the arm contralateral to the

lesion recovered considerably six weeks after the infarct, and four of seven patients had

no residual weakness at this stage (Kunesch, Binkofski, Steinmetz, & Freund, 1995).

Hand function also improved in these patients, but no patient gained a score indicating

‘no disturbance’ on a test of hand function (assessing, among other things, hand-writing,

buttoning, and tying shoelaces). Heald and colleagues (1993) found that manual motor

control (measured by performance on a peg moving task) remained outside the normal

range in a group of stroke patients, despite recovery of hand strength one year after a

stroke. Considering the importance of the use of our hands in our everyday lives,

recovery of upper limb function is a primary concern for stroke patients.

One approach to improving upper limb function that has been gaining support is

bilateral training. A recent review argued that bilateral arm training is a necessary

adjunct to unilateral training in regaining meaningful arm function (McCombe Waller &

Whitall, 2008); given that many of our daily activities require bimanual coordination,

152

for good functional recovery it makes sense to re-train bimanual movements. There has

been a recent surge in the use of “constraint induced movement therapy” which has the

potential to produce large improvements in functional outcomes by restraining the use

of the unaffected limb of stroke patients in order to encourage use of the affected limb

(Taub, Uswatte, & Pidikiti, 1999). This protocol has been shown to have substantial and

lasting effects 2 years after the intervention (Taub et al., 2006). A recent study

compared constraint induced movement therapy and bilateral training in a group of

patients with mild to moderate deficits after hemiparetic stroke and found that the

greatest improvements for functional outcomes were seen in the constraint group;

however, some benefits to upper function were only observed in the group who received

bilateral training (Lin, Chang, Wu, & Chen, 2009). This finding suggests that

incorporating cooperative bimanual behaviour within the rehabilitation regime may be

as important as constraining the unaffected limb. Additionally, training only on

unimanual tasks may not maximize recovery of bimanual functioning because such

training does not include an important aspect of bimanual behavior: the between-hand

coordinative aspect of bimanual coordination.

In normal bimanual movement, there is a strong tendency toward temporal synchrony

between the hands (e.g.`, Franz, Zelaznik, & McCabe, 1991; Semjen, Summers, &

Cattaert, 1995). Furthermore, when two different movements are produced

concurrently, an integration of features of the motor response of one limb into the motor

response of the other limb is seen, a phenomenon termed ‘assimilation’ (e.g.`, Franz,

1997; Marteniuk, MacKenzie, & Baba, 1984). These effects have traditionally been

viewed as constraints on bimanual movement (i.e., each hand is constrained by what the

other hand is doing); however, in the context of motor control after a stroke, the

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coupling of movements of the two hands may result in the facilitation of the

performance of the affected limb.

Several studies have investigated the effects of bilateral training on functional

improvements after stroke. Passive movement of the affected limb using a bilateral

training protocol has been shown to improve functional outcome for the affected limb in

some but not all patients (J. W. Stinear & Byblow, 2004). Whitall and colleagues (2000)

found that bilateral arm training led to improvement on functional tests of everyday

functioning, strength, and range of motion with the paretic arm in chronic hemiparetic

stroke patients however there was no comparison group included in the study against

which the relative effectiveness of bilateral training could be assessed. Using a similar

protocol, Luft and colleagues (2004) compared bilateral arm training with rhythmic

auditory cueing standard training exercises (matched for dose) on impaired limb

function. After training three times a week for six weeks there was no difference in

functional outcome between the groups as a whole. However, some participants

receiving bilateral training had significant increases in brain activation (measured with

functional magnetic resonance imaging), and these participants had greater

improvements in functioning than the control group. Mudie and Matyas (2000) also

reported greater improvements in the paretic limb in tests of functional unimanual

performance (e.g., simulated drinking) after bilateral than after unilateral whole-arm

training. Similarly, Summers et al. (2007) found that six sessions of bilateral training

led to a decrease in movement time with the impaired limb on the trained task (placing a

wooden dowel on a shelf) and an increase in functional ability with the impaired limb,

whereas six sessions of unilateral training was not associated with movement time or

functional improvements.

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The beneficial effects of bilateral training in all of these studies were examined for

unimanual movements of the affected limb. Given the importance of bimanual

coordination in everyday functioning, another important outcome of rehabilitation

strategies after stroke is an improvement in the functioning of the two limbs together.

Few studies have assessed the effects of bilateral training on bilateral performance. Two

studies found that bilateral training and unilateral training (of the affected limb)

improved bilateral performance to a similar extent (Desrosiers, Bourbonnais, Corriveau,

Gosselin, & Bravo, 2005; Platz, Bock, & Prass, 2001). Each of these studies included

only mild or moderately affected patients and the study by Desrosiers and colleagues

used unilateral or bilateral training in addition to usual care (some components of which

were bilateral activities), which limits the interpretations of the findings. A study

comparing unilateral and bilateral whole-arm training for patients with severe

impairments and another in patients with moderate deficits found no beneficial effect of

bilateral training, suggesting that this approach may not be beneficial in more severely

affected patients (Mudie & Matyas, 2001; Tijs & Matyas, 2006).

Several studies have investigated inter-limb coordination dynamics after unilateral

stroke. Movements with the impaired limb tend to be slower than movements with the

unimpaired limb, and there is a tendency for the arms to become temporally coupled

during bimanual movements (as observed in unimpaired individuals). This is often

achieved by a slowing of the unimpaired arm rather than facilitation of performance

with the impaired arm (Garry, van Steenis, & Summers, 2005; Kilbreath, Crosbie,

Canning, & Lee, 2006; Rice & Newell, 2001; Steenbergen, Hulstijn, de Vries, &

Berger, 1996). However, other studies have shown facilitation of performance with the

impaired limb when coupled with the unimpaired limb compared to unilateral

movements of the impaired limb alone. Faster movements with the impaired limb have

155

been shown during rapid bimanual aiming than unimanual aiming (Harris-Love,

McCombe Waller, & Whitall, 2005; Rose & Winstein, 2005) and Cunningham and

colleagues showed a trend towards smoother trajectories of elbow extensions during

bilateral movements than during unilateral movements (Cunningham, Phillips Stoykov,

& Walter, 2002). Furthermore, in-phase bimanual circle drawing facilitated

performance with the paretic arm in children with spastic hemiparesis compared to

unimanual performance (Volman, Wijnroks, & Vermeer, 2002) although a similar study

in stroke patients showed no facilitation of the paretic arm (Lewis & Byblow, 2004).

The inconsistencies in the studies of bilateral coordination dynamics may be in part due

to the differences in the complexities of tasks used. Stroke patients have obvious

difficulties with complex bimanual coordination; when participants attempted to

oscillate one limb at twice the frequency of the other limb’s movements, right-

hemispheric stroke patients were largely unsuccessful, reverting to a 1:1 in-phase

coordination pattern between the limbs (Rice & Newell, 2004). Taken together these

findings suggest that the tendency of the motor system to couple the actions of the two

hands may facilitate performance on the impaired side after stroke. Indeed, a recent

meta-analysis indicated that bilateral training, either alone, or combined with sensory

feedback, is an effective training protocol for functional arm recovery after stroke

(Stewart, Cauraugh, & Summers, 2006). However, it remains to be determined what

types of bimanual actions facilitate performance with the impaired limb and which tasks

have therapeutic potential for which patients.

The current study provided a preliminary examination of bimanual coordination in

participants who had suffered a unilateral stroke using the two tasks for which normal

results were presented in Chapters 2 and 3. Bimanual tapping and circle-drawing

performance was compared to unimanual performance in the impaired and unimpaired

156

limb in patients with mild, moderate, and severe upper-limb deficits. The findings from

the previous two chapters that support left hemispheric control of bimanual movement,

suggest that patients with left hemisphere lesions will demonstrate greater impairment

in bimanual coordination than patients with right hemisphere lesions. Furthermore, a

recent study showed greater interlimb coupling in patients with right hemisphere lesions

than in patients with left hemisphere lesions (Lewis & Perreault, 2007). It is predicted

that patients with right hemisphere lesions will show a greater facilitation of

performance with the affected limb during bimanual coordination than patients with left

hemisphere lesions.

7.1 Method

Participants

Participants were 12 individuals who had suffered a unilateral cerebral vascular accident

(age range 49 to 60). Four patients had mild, 4 had moderate, and 4 had severe upper

limb motor deficits. Individuals in the mild group had subjective motor deficits on

dexterous tasks such as writing, but all were able to use the affected limb in everyday

tasks, individuals in the moderate group were more obviously affected, but still had

some independent ability with the affected limb, and individuals in the severe group had

very limited ability to control the affected limb (although a prerequisite for participation

was having enough motor ability to grasp a pen with the affected limb). Individual

characteristics (age, sex, time since stroke, and side of stroke) are presented in table 7.1.

All participants were right handed (self reported writing hand) pre-stroke, except P7.

Patients were recruited from the occupational therapy department of a major teaching

hospital and from an inpatient rehabilitation unit, the occupational therapist responsible

for the rehabilitation of each patient judged each patient to be either mildly, moderately,

157

or severely motor impaired. All participants were capable of comprehending task

instructions, although no formal assessment of cognitive ability was performed, and all

gave informed written consent to participate.

Table 7.1

Characteristics of the patient groups.

Participant Sex Age Lesion side (hemisphere)

Months since stroke

Mild P1 M 59 Right 84 P2 M 60 Left 2 P3 F 49 Left 5 P4 F 58 Left 120

Moderate P5 M 53 Right 3 P6 F 54 Right 24 P7 M 57 Right 1.5 P8 M 61 Left 2

Severe P9 F 63 Right 2 P10 F 54 Right 1 P11 M 69 Left 1.5 P12 M 50 Left 1.5

Procedure

Each participant was tested in a single session. All participants completed the tapping

task. Participants with a mild or moderate deficit completed both small and large circle

drawing tasks; participants with a severe deficit completed only the large circle drawing

task. One participant (P6) refused circle-drawing with her affected arm, and one

participant (P9) was unable to attempt bimanual circle-drawing.

Tapping. Participants sat comfortably with their elbows flexed at approximately 90

degrees and both hands resting on a desk surface (palm down). Participants were

instructed to tap at a fast steady pace for ten seconds with their left hand alone, with

158

their right hand alone, or with both hands together, by extending and flexing their index

finger(s) around the metacarpal-phalangeal joint, keeping their hand and other fingers

flat on the table. Finger movement was measured with a miniature accelerometer

mounted in a resin block, attached to the index finger of each hand. Output from the

accelerometers was sampled from the audio input of a computer.

Inter-tap intervals (ITIs) were determined as the time between successive contacts in

ms. Coefficients of variation (CV) of the ITIs were calculated as a measure of tapping

variability as the standard deviation of ITIs on each trial divided by mean trial ITI

(expressed as a percentage).

Circle drawing. Participants traced the contours of circles (either 15-mm or 70-mm

diameter), centres 120 mm apart, on a digitizing tablet (WACOM Intuos 2 Graphics

Tablet, Model No. XD-1212-U) continuously for 10 seconds, at a comfortable and

individually determined pace. Some participants could not complete a sufficient number

of cycles for analysis with the affected limb in the 10 seconds; for these participants, the

duration of tracing was extended to 20 seconds. Circles were drawn in the clockwise

direction with the left hand and in the counter-clockwise direction with the right hand to

maintain biomechanical equivalence. For the small circle targets, drawing was

performed with the forearm resting on the surface of the graphics tablet, which was the

position adopted naturally by participants using their right hand. Subjects were

instructed to adopt this position with the left hand to eliminate the tendency to use the

whole arm during left-hand drawing, thus limiting proximal movements and promoting

distal movements, and ensuring task equivalence across the hands. For the large circle

targets, participants were free to adopt a comfortable drawing position. Each trial began

when force was detected from one pen (for unimanual drawing) or both pens (for

159

bimanual drawing) on the graphics tablet, indicating that the subject had begun drawing.

Circularity was used to assess accuracy of drawing. Circularity was calculated as

described in Chapter 3

RMS jerk was calculated as a measure of drawing smoothness. Jerk was calculated as

the third derivative of linear distance with respect to time.

Task order. Each participant completed the tapping task followed by the circle-drawing

task. Two trials of each task were completed. Task order was selected to progress from

easiest to most difficult: within each task, participants completed unimanual trials with

their unaffected limb first, followed by unimanual trials with their affected limb,

followed by bimanual trials. For participants who completed both small- and large-

circle drawing tasks, large circles were drawn first then small circles.

Control data. A preliminary analysis of the control data revealed no significant

differences between the results for participants aged over 50 and the whole group,

therefore the means from Chapter 2 (tapping data) and Chapter 3 (circle-drawing data)

are presented for comparison with the stroke patients’ data.

7.2 Results

Participants were classified into mild, moderate, and severe groups. However, forming

averages of each measure within groups was uninformative due to the large between-

subject variability in performance. Therefore individual results are presented.

160

Unimanual and bimanual tapping

Mean inter-tap interval (ITI) is shown in Figure 7.1 for each participant (affected limb is

indicated at top of each panel) and controls. The mild group of participants tapped at

around the same rate as control participants (tapping by P1 was slightly slower than

controls with both hands). Unimanual tapping was slower with the affected hand for all

participants except P4 who tapped faster with her right (affected) hand than her left

(unaffected) hand. There was little difference between tapping rates in the unimanual

and bimanual modes for any participant in this group.

In the moderate group (Figure 7.1, middle panel), tapping was slower with the affected

than the unaffected hand during unimanual tapping for all participants. This difference

was maintained during bimanual tapping for the three participants with left-hand

impairment (P5, P6, and P7), but not for the participant with right-hand impairment

(P8). Nevertheless, tapping with the affected hand was faster during bimanual than

unimanual tapping for three participants (P5, P6, P8), whereas for P7, tapping with the

affected hand was slower during bimanual than unimanual tapping.

There was little difference between unimanual and bimanual tapping rates on the

unaffected side for two participants (P6 and P8), and two tapped sightly slower with the

unaffected hand during bimanual than unimanual tapping (P5 and P7). None of the

participants in the moderate group showed the usual coupling of the hands during

bimanual tapping.

In the severe group (Figure 7.1, bottom panel), tapping was slower with the affected

than the unaffected hand during unimanual and bimanual tapping for all participants.

Furthermore, the affected hand was slower during bimanual than unimanual tapping for

161

all participants. The unaffected hand was also slower during bimanual than unimanual

tapping for all participants except P10. A comparison of the moderate and severe group

data suggests that although both were slower than the mild group, there was little

difference in tapping rates between the moderate and severe groups. However,

observations of the performance of patients in the severe group revealed a general

inability to perform the individuated movements of the index finger required to perform

the task as instructed; instead these participants adopted a strategy of tapping with the

whole hand or arm. Comparisons between the hands for this group should also be

interpreted cautiously; despite the fact that all participants tapped slower with the

affected than the unaffected side, it is likely that the differences between the hands are

underrated since they tapped in the instructed manner with the unaffected hand during

both unimanual and bimanual tapping. Nevertheless, tapping rates of the two hands

became more alike during bimanual tapping for two of the participants (P9 and P11),

and these two participants came close to achieving coupled tapping of the two hands.

There was no obvious pattern in the rates of tapping to support the hypothesis that

bimanual performance would be more impaired in patients with left hemisphere lesions

than in patients with right hemisphere lesions, and no indication in this group of patients

that bimanual facilitation of performance was greater for those with right hemisphere

lesions than those with left hemisphere lesions.

162

Figure 7.1. Mean inter-tap interval (ITI) during unimanual (Uni) and bimanual (Bi) tapping with the left ( ) and right ( ) hands for patients with mild, moderate, and severe deficits and mean control values. The affected limb is indicated at the top of each panel. Errors of control values are ±1 standard error of the mean.

ITI (

ms)

LEFT RIGHT

P1 P2 P3 P4

ITI (

ms)

0

200

400

600

800

1000

1200

0

200

400

600

800

1000

1200

0

200

400

600

800

1000

1200

ITI (

ms)

P5 P6 P7 P8

P9 P10 P11 P12

Uni Bi Uni Bi Uni Bi Uni Bi



Controls

Uni Bi

RIGHT LEFT

RIGHT LEFT

Mildly affected

Moderately affected

Severely affected

Controls

Uni Bi

Controls

Uni Bi

163

Figure 7.2 shows variability of tapping (CV of ITI) for all participants and controls. For

the mild group (top panel), tapping was more variable with the affected hand than with

the unaffected hand for all participants except P4 in the unimanual mode. Bimanual

tapping was more variable than unimanual tapping with the affected hand for all

participants in this group.

In the moderate group (Figure 7.2, middle panel), tapping was more variable with the

affected hand than with the unaffected hand for all participants except P5 (for P5 the

variability of the hands was equivalent during unimanual tapping). Of the three

participants in this group who tapped faster with the affected hand during bimanual than

unimanual tapping (P5, P6, and P8), one tapped with markedly less variability on the

affected side during bimanual than unimanual tapping (P8), one tapped with slightly

less variability (P6), and one with more variability (P5) on the affected side during

bimanual than unimanual tapping. The participant who tapped slower with the affected

hand during bimanual than unimanual tapping (P7) was also more variable on the

affected side during bimanual than unimanual tapping.

In the severe group, tapping was more variable with the affected hand than the

unaffected hand during unimanual tapping for all participants except P10 (for whom

variability of the two hands was equivalent during unimanual tapping). All participants

were more variable during bimanual than unimanual tapping with the affected hand

except P11. Despite the greater variability with the affected hand for three of the

participants during bimanual than unimanual tapping, the unaffected hand was less

variable during bimanual than unimanual tapping for three of the participants.

There was no obvious pattern in the results to differentiate the performance of patients

with left and right sided lesions.

164

Figure 7.2. Coefficient of variation of inter-tap interval during unimanual (Uni) and bimanual (Bi) tapping with the left ( ) and right ( ) hands for Patients with mild, moderate, and severe deficits and mean control values. The affected limb is indicated at the top of each panel. Errors of control values are ±1 standard error of the mean.

CV

of I

TI

LEFT RIGHT

P1 P2 P3 P4

CV

of I

TI

CV

of I

TI

P5 P6 P7 P8

P9 P10 P11 P12




RIGHT LEFT

RIGHT LEFT

0

20

40

60

80

100

120

140

160

0

20

40

60

80

100

120

140

160

0

20

40

60

80

100

120

140

160

Controls

Uni Bi

Mildly affected

Moderately affected

Severely affected

Controls

Uni Bi

Controls

Uni Bi

165

In summary, unimanual and bimanual tapping was slower and more variable with the

affected than with the unaffected hand for most participants. There was no indication of

a difference between the performance of the patients with left hemisphere lesions and

the performance of the patients with right hemisphere lesions. In the mild group,

performance on the tapping task did not appear to differ to performance by controls, and

no benefit of bimanual tapping was observed on the affected side for these participants.

In the moderately affected group, the hands did not become perfectly coupled during

bimanual tapping (tapping with the affected hand was slower than with the unaffected

hand, bimanually, for all participants), however, the difference in tapping rates between

the hands was reduced for three participants; for these participants there was evidence

of facilitation of tapping with the affected hand (tapping rate increased) during bimanual

tapping, with little or no change on the unaffected side. For all participants in the

severely affected group, tapping was slower on the affected side during the bimanual

than unimanual task, indicating little evidence of a benefit of pairing the affected with

the unaffected limb on tapping rate, although for two participants the tapping rates of

the hands became more alike during bimanual compared to unimanual tapping, and

there was less variability of tapping on the affected side during bimanual than

unimanual tapping for one of these participants.

Unimanual and bimanual circle-drawing

Figures 7.3, 7.4, and 7.5 show unimanual and bimanual tracings of small and large

circles with the left and right hands from participants in the mild, moderate, and severe

groups, respectively. Small circles drawn with the right (affected) hand by the mildly

affected participant (Figure 7.3) were less circular than circles drawn with the left

(unaffected hand). Small circles drawn with both hands appeared to be segmented (i.e.,

composed of multiple submovements) during unimanual drawing. This was less obvious

166

on the affected side during bimanual drawing, reflected in a larger value for circularity

on the affected side during bimanual drawing compared to unimanual drawing.

Differences between the hands were less obvious for large circles during unimanual

drawing, and performance with both hands deteriorated during bimanual drawing.

Submovements were particularly obvious in circles drawn with the affected hand by the

participant in the moderate group (Figure 7.4). Drawing was disordered with the

affected (left) hand in the unimanual mode when tracing both small and large circles,

and improved in the bimanual mode (shapes were more circular, were composed of

fewer submovements, and drawn with fewer cycles of acceleration-deceleration during

bimanual than unimanual drawing). There was little difference between unimanual and

bimanual performance with the unaffected hand.

The severely affected participant (Figure 7.5) also showed segmented drawing with the

affected (right) hand in the unimanual mode. Drawing with the affected limb was very

difficult and laboured; each cycle took 5.9 seconds to complete. During bimanual

drawing, the participant could not produce circles with the affected limb, but accuracy

with the unaffected limb was maintained.

167

Figure 7.3. Example of responses by a participant in the mild group (P2) with left hemispheric lesion during unimanual and bimanual drawing of small (template diameter = 15 mm) and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.

Left hand

(unaffected)

Right hand

(affected)

Small Circles

Unimanual

Bimanual

Circ: 0.87 Per: 1.00

X: 12.4 Y: 18.7

Ac/Dec: 3.7

Circ: 0.79 Per: 1.38

X: 9.6 Y: 11.9

Ac/Dec: 4.6

Circ: 0.78 Per: 1.49

X: 14.5 Y: 20.4

Ac/Dec: 5.7

Circ: 0.87 Per: 1.52

X: 8.2 Y: 10.4

Ac/Dec: 5.6

Left hand

(affected)

Right hand

(affected)

Large Circles

Unimanual

Bimanual

Circ: 0.92 Per: 1.77

X: 58.9 Y: 73.2

Ac/Dec: 6.2

Circ: 0.94 Per: 2.29

X: 47.8 Y: 62.6

Ac/Dec: 8.0

Circ: 0.80 Per: 2.73

X: 44.7 Y: 78.4

Ac/Dec: 9.2

Circ: 0.80 Per: 2.61

X: 31.4 Y: 54.1

Ac/Dec: 7.5

20 mm

10 mm

168

Figure 7.4. Example of responses by a participant in the moderate group (P5) with right hemispheric lesion during unimanual and bimanual drawing of small (template diameter = 15 mm) and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.

Small Circles Left hand

(affected)

Right hand

(unaffected)

Circ: 0.77 Per: 1.06

X: 11.5 Y: 17.6

Ac/Dec: 3.1

Circ: 0.46 Per: 1.87

X: 13.3 Y: 17.0

Ac/Dec: 6.7

Unimanual Circ: 0.97 Per: 0.90 X: 13.8 Y: 14.3

Ac/Dec: 4.2

Circ: 0.95 Per: 1.09 X: 11.9 Y: 11.7

Ac/Dec: 4.2

Bimanual

10 mm

Circ: 0.98 Per: 1.12

X: 66.1 Y: 68.9

Ac/Dec: 3.7

Circ: 0.75 Per: 1.89

X: 65.0 Y: 63.6

Ac/Dec: 6.3

Bimanual

Unimanual

Large Circles

Left hand

(affected)

Right hand

(unaffected)

Circ: 0.93 Per: 2.03

X: 59.3 Y: 59.2

Ac/Dec: 10.8

Circ: 0.81 Per: 1.95

X: 56.0 Y: 63.1

Ac/Dec: 5.8 20 mm

169

Figure 7.5. Example of responses by a participant in the severe group (P12) with left hemispheric lesion during unimanual and bimanual drawing of large circles (template diameter = 70 mm). Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.

Figure 7.6 shows mean circularity for each participant and controls during unimanual

and bimanual circle drawing of small and large circles (the severe group did not draw

small circles). For the mild group, circularity during small circle drawing was not

markedly different from control data. The participant with a right sided lesion (P1) was

more accurate with the unaffected (right) than the affected (left) hand, but circularity

with the affected hand was not different from control data, and there was little change

with either hand during bimanual drawing. One participant with a left sided lesion (P2)

was more accurate with the unaffected (left) hand than the affected (right) hand during

unimanual drawing, and performance on the affected side improved in the bimanual

mode, although accuracy with the unaffected hand was worse when coupled with the

Left hand

(unaffected)

Right hand

(affected)

Large Circles

Unimanual

Bimanual

Circ: 0.96 Per: 2.4

X: 64.5 Y: 62.7

Ac/Dec: 6.9

Circ: 0.50 Per: 5.97

X: 72.0 Y: 53.8

Ac/Dec: 6.9

Circ: 0.94 Per: 3.3

X: 67.9 Y: 69.3

Ac/Dec: 5.4

Circ: 0.47 Per: 19.3

X: 15.4 Y: 19.7

Ac/Dec: N/A 20 mm

170

affected hand. The other two participants with right-sided lesions (P3 and P4)

performed better with the affected (right) hand during both unimanual and bimanual

drawing. Circles with the affected hand were more accurate during bimanual than

unimanual drawing for P3 and less accurate during bimanual than unimanual drawing

for P4. During large circle drawing for the mild group, there was very little difference in

circularity between the hands. Furthermore, the results were similar to the control data

for all participants except P2; for this participant circularity was less with both hands in

the bimanual than unimanual mode.

For the two participants in the moderate group with right-sided lesions (P5 and P7)

small circles were less circular when drawn with the affected (left) hand than with the

unaffected (right) hand during both unimanual and bimanual drawing. Circles with the

affected hand were more accurate during bimanual than unimanual drawing for P5, and

less accurate during bimanual than unimanual drawing for P7. The participant with a

right sided lesion performed better with the affected (right) hand than the unaffected

(left) hand, but performance with both hands was worse during bimanual than

unimanual drawing. Accuracy of large-circle drawing by the moderate group was

similar to small-circle drawing.

In the severe group, circularity of large circle drawing was greater on the unaffected

side than the affected side for all participants during unimanual and bimanual drawing.

Furthermore, circularity was less during bimanual drawing than unimanual drawing

with the affected hand for all participants (P9 could not complete bimanual drawing).

There was no evidence that patients with left hemisphere lesions performed worse than

patients with right hemisphere lesions during bimanual circle drawing.

Figure 7.6. Mean circularity during unimanual (Uni) and bimanual (Bi) small-circle (top row) and large-circle (bottom row) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean.

CIR

CU

LAR

ITY

C

IRC

ULA

RIT

Y

RIGHT LEFT


0.0

0.2

0.4

0.6

0.8

1.0

0.0

0.2

0.4

0.6

0.8

1.0


Uni Bi Uni Bi Uni Bi

Uni Bi Uni Bi Uni Bi Uni Uni Bi Uni Bi Uni Bi

Uni Bi

Uni Bi

RIGHT LEFT

LEFT RIGHT

Mild Moderate Controls

RIGHT LEFT RIGHT LEFT

P1 P2 P3 P4 P5 P7 P8 Controls

P1 P2 P3 P4 P5 P7 P8 Controls P9 P10 P11 P12

Severe Controls Mild Moderate

17

1

172

Figure 7.7 shows mean period of the left and right hands during unimanual and

bimanual drawing of small and large circles for each participant and mean control

values. In the mild group, during small-circle drawing, the pattern of results for all but

one participant (P2) was similar to the control results; period of drawing was longer

with the left hand than the right hand in unimanual drawing, and period of drawing with

the left and right hands were the same during bimanual drawing. P2 was slower with the

affected hand during unimanual drawing, but like the other participants, during

bimanual drawing the period of circle drawing with the two hands was equivalent.

Period of large-circle drawing followed a similar pattern.

In the moderate group, both of the participants with right-sided lesions were slower on

the affected (left) side than on the unaffected side during unimanual small circle

drawing. The participant with a left sided lesion (P8) was slower on the unaffected (left)

side than on the affected (right) side during unimanual drawing. Only one participant

(P5) showed the usual coupling of the hands during bimanual drawing and this

represented a decrease in period of drawing on the affected side, and an increase on the

unaffected side; for the other two, the difference between the hands was maintained (P8)

or increased (P7) during bimanual drawing. Period of large-circle drawing followed a

similar pattern, and two participants showed near-coupling of the hands during

bimanual drawing (P5 and P8).

In the severe group, drawing was slower on the affected side than the unaffected side for

all participants during unimanual drawing. Bimanual drawing was too disordered on the

affected side to calculate period for P11. Rate of drawing with the affected limb was

faster during bimanual than unimanual drawing for P10, and for this participant, the

period of each hand was almost equivalent during bimanual drawing. The affected hand

173

was slower during bimanual than unimanual drawing for P12. Period of drawing with

the unaffected limb was similar during unimanual and bimanual drawing for all

participants who attempted the bimanual task.

Rate of circle drawing did not vary with side of lesion and there was no evidence that

the patients with left hemisphere lesions were more impaired on the bimanual circle

drawing task than patients with right hemisphere lesions.

Figure 7.7. Mean period of circle drawing during unimanual (Uni) and bimanual (Bi) small-circle (top panel) and large-circle (bottom panel) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean. * Bimanual drawing by P11 was too disordered with the affected limb to calculate period.

PE

RIO

D (

s)

PE

RIO

D (

s)

RIGHT LEFT





Uni Bi

Uni Bi

RIGHT LEFT

LEFT RIGHT

0

1

2

3

4

5

6

0

1

2

3

4

5

6

Mild Moderate

Severe Controls

Controls

Mild Moderate

RIGHT LEFT RIGHT LEFT

* 0

1

2

3

4

5

6

7



P9 P10 P11 P12

17

4

175

Figure 7.8 shows RMS jerk (the third derivative of distance with respect to time) for


circles for each participant and mean control values. The RMS jerk provides a

measure of the smoothness of the trajectories produced during circle-drawing. RMS

jerk values for the mild group were small, and of a similar magnitude to control

values. RMS jerk was generally smaller with the right than the left hand for all

participants, regardless of side of lesion, and there were only marginal differences

between the values during unimanual and bimanual drawing, indicating equally

smooth trajectories during unimanual and bimanual drawing in this group.

RMS jerk values for all participants in the moderate group were substantially larger

than control values. Furthermore, the values were large for both hands indicating that

the trajectories of both hands were less smooth than those produced by control

participants. For small circles drawn unimanually, RMS jerk was greater on the

affected side than the unaffected side for two participants (P5 and P8). For P7, RMS

jerk was greater on the unaffected (right) side than the affected (left) side; this

participant was left handed, so this represents smoother drawing with the dominant

hand than the non-dominant hand. For all participants, on the affected side, RMS jerk

was approximately the same during unimanual and bimanual drawing. For unimanual

large circle drawing RMS jerk was greater on the affected side than on the unaffected

side for all participants. RMS jerk on the affected side was smaller during bimanual

than unimanual drawing for P5 and larger during bimanual than unimanual drawing

for P8 (RMS jerk could not be calculated for P7).

In the severe group, RMS jerk was larger with the affected hand than with the

unaffected hand. Only one participant (P10) produced sufficient cycles with the

Figure 7.8. RMS jerk during unimanual (Uni) and bimanual (Bi) small-circle (top panel) and large-circle (bottom panel) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean. * Too few cycles produced by P7 with affected limb during bimanual drawing and drawing by P11, and P12 with the affected limb was too disordered to calculate RMS jerk.

RM

S J

ER

K (

mm

.s-3

) R

MS

JE

RK

(m

m.s

-3)

RIGHT LEFT





Uni Bi

Mild Moderate

Severe

Uni Bi

RIGHT LEFT

LEFT RIGHT

Controls

Controls

RIGHT LEFT

Mild Moderate

LEFT RIGHT

0

5

10

15

20

25

30

35

0

5

10

15

20

25

30

35

*

x1000

x1000

* *


P1 P2 P3 P4 P5 P7 P8 Controls P9 P10 P11 P12

17

6

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affected limb during bimanual drawing for RMS jerk to be calculated; for P10, RMS

jerk was larger during bimanual than unimanual drawing on the affected side.

In summary, for most participants circle drawing was less accurate, slower, and less

smooth with the affected than the unaffected hand. There was no suggestion in the data

of a greater bimanual deficit in patients with left hemisphere lesions than in patients

with right hemisphere lesions. There was evidence that all participants in the mild group

temporally coupled the hands during bimanual drawing, and for two participants the

affected side benefited from being paired with the unaffected hand during bimanual task

(accuracy of small circle drawing improved). In the moderately affected group, there

was no evidence of temporal coupling of the hands during bimanual drawing, but

accuracy of circle drawing was greater for one participant in the bimanual than

unimanual mode. Circle-drawing in the severely affected group was severely impaired

during the unimanual task and pairing the affected limb with the unaffected limb

worsened their performance with the affected limb.

7.3 Discussion

No overall differences between the performance of patients with left hemisphere lesions

and the performance of patients with right hemisphere lesions were observed. The study

was limited by small sample size and a heterogeneous mixture of patients (subacute and

acute, left and right sided stroke, and degree of deficit), which limited the comparison

between patients with left hemisphere lesions to observational evaluation. Previous

research has shown interlimb coupling to be more similar to control patterns in patients

with right than left hemisphere lesions (Lewis & Perreault, 2007), however, this

178

observation was based on a comparison between in-phase and anti-phase bimanual

coordination tasks within the two groups of stroke patients. A closer examination of the

in-phase coordination tasks reveals that the performance of stroke patients with left-

hemisphere lesions was similar to performance by patients with right-hemisphere

lesions. Furthermore, the effects of long term bimanual intervention (as used in

rehabilitation programs) on functional outcomes may differ from the effects of short

term bimanual coordination; a recent study found that patients with left hemispheric

lesions showed greater functional improvements than patients with right hemisphere

lesions after a six-week bilateral arm training intervention (McCombe Waller &

Whitall, 2005), which is in direct contrast to the predictions based on dominant

hemispheric control of bilateral movement. Whether bilateral training is beneficial

might therefore depend on a number of factors, including whether the task is symmetric

or asymmetric, as well as the side of the lesion. These issues warrant empirical

evaluation in larger studies.

The results of the current study provide evidence that, irrespective of lesion side, in

some stroke patients with mild-to-moderate motor deficits, the affected hand benefits

when acting with the unaffected hand. In the severely affected group of patients the

affected hand did not benefit when acting with the unaffected hand. The finding of a

benefit for mild to moderate but not severe patients is consistent with other studies

which have shown a benefit of bilateral training in mild-to-moderately affected stroke

patients (Mudie & Matyas, 2000; Summers et al., 2007), but not severely affected stroke

patients (Mudie & Matyas, 2001).

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The tasks used in the current study differed in the degree of spatiotemporal complexity:

tapping required the repetitive reciprocal activation of flexors and extensors, whereas

circle-drawing required a more complex multi-joint coordination and the sequential

activation of different muscles in a precise sequence. With increasing severity of deficit

there appeared to be a decrease in the ability to precisely control the sequential

activation of muscles in time. The mild group had no deficit on the simpler task of

tapping, but some evidence of impaired control on the more spatiotemporally

demanding task of circle-drawing. The moderate and severe groups showed evidence of

impairment on both tapping and circle drawing. The obvious spatial submovements

present in the circles drawn with the affected limb by some participants in all severity

groups (Figures 7.3 to 7.5) suggests an inability to fractionate the activation of

sequential movements in time. This is similar to the observation that after a stroke to the

primary motor cortex or corticospinal tract, patients have a reduced ability to produce

fractionated movements of the fingers (C. E. Lang & Schieber, 2004), and the degree of

independence of finger movement was shown to correlate with hand function.

Submovements in the current study were more obvious during small circle drawing, but

were also present during large circle drawing for moderately and severely affected

patients, possibly reflecting a gradient in submovement presence related to severity of

impairment. An increase in the number of submovements has been demonstrated

previously in the velocity profile of aiming movements made by stroke patients (Rohrer

et al., 2002). Furthermore, a study on infants showed that submovements become fewer

and more blended during development (von Hofsten, 1991), a similar pattern to that

seen during recovery from stroke (Rohrer et al., 2002; Rohrer et al., 2004). In the

current study, at least for the mildly and moderately affected patients, the appearance of

submovements in the trajectories of circles was reduced during bimanual drawing

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compared to unimanual drawing. This is similar to the smoother drawing (fewer cycles

of acceleration-deceleration and smaller jerk, and appearance of fewer submovements)

seen during bimanual than unimanual drawing of small circles in normal participants in

Chapter 3. The explanation for the findings in Chapter 3 could equally apply to the

observation in the stroke patients: features of the movement trajectories of the

unaffected limb may have become integrated into the motor response of the affected

limb, resulting in smoother trajectories with the affected limb.

Interlimb coupling

In the current study, there was evidence in some participants in the mild group of

temporal coupling of the hands and a benefit of bimanual coupling on the performance

of the affected limb during the more spatiotemporally demanding task of circle-drawing.

Some patients in the moderately affected group showed evidence of temporal coupling

and a benefit of bimanual coupling during both tapping and circle-drawing. In contrast,

the severe group showed little evidence of coupling of the hands and evidence of a

worsening of performance on the affected side when the affected hand was paired with

the unaffected hand during both tapping and the more demanding circle-drawing task.

The results suggest that temporal coupling of the limbs is crucial for facilitation of the

affected limb during the bimanual tasks used in the current study. An implication of

these findings is that if brain damage that is extensive enough to disable temporal

coupling between the limbs, bimanual facilitation is also eliminated.

An inability to temporally couple the limbs after stroke might result from a number of

causes. The degree of impairment during unimanual movements after stroke is at least

partly related to the degree of motor unit recruitment possible (Gowland, deBruin,

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Basmajian, Plews, & Burcea, 1992), and integrity of the corticospinal system (Ward et

al., 2006). In contrast, normative data which shows that bilateral movements are

associated with increased interactions between the two sensorimotor cortices (Serrien,

Cassidy, & Brown, 2003), and data in “split brain” individuals who have impairments in

bimanual coupling during continuous bimanual movements (Kennerley, Diedrichsen,

Hazeltine, Semjen, & Ivry, 2002), suggests that bimanual coupling is probably mediated

via transcallosal connections. It is not possible to rule out damage to the corpus

callosum in the participants who could not couple the limbs in the current study.

However, it is likely that both spared transcallosal connections, and at least a partially

intact corticospinal system are necessary for functional coupling of the limbs.

Mechanisms of facilitation of performance with the impaired limb

The performance deficits with the affected limb reflect impaired neural control by the

damaged hemisphere contralateral to the affected hand, and the improvements in the

performance of the affected limb when it is paired with the unaffected limb are unlikely

to result from an improvement in the capacity of the affected hemisphere to control the

affected limb. Rather, the improvements in the performance of the hand contralateral to

the lesion are likely to result from the undamaged hemisphere playing a role in the

control of that limb during bimanual coordination.

Neuroimaging studies have shown that bimanual movements are associated with

increases in the activity of M1 in the affected hemisphere of stroke patients compared to

unimanual movements of the affected limb (Staines, McIlroy, Graham, & Black, 2001).

This increase in activity in M1 of the damaged hemisphere during bimanual movements

is likely to be the result of interhemispheric facilitation from the undamaged

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hemisphere. Consistent with this hypothesis is the finding that short-term bilateral

training in normal individuals increased intracortical facilitation (ICF) and reduced

short-latency intracortical inhibition (SICI) bilaterally (McCombe Waller, Forrester,

Villagra, & Whitall, 2008).

Longer-term changes in brain functioning associated with functional improvement after

bimanual training might involve a “rebalancing” of excitatory and inhibitory processes.

Several studies have shown asymmetries in intracortical inhibition and excitation

between the lesioned and non-lesioned hemispheres after stroke; reduced intracortical

inhibition has been demonstrated in the non-lesioned hemisphere compared to normal

levels of inhibition seen in controls (Butefisch, Netz, Wessling, Seitz, & Homberg,

2003; Liepert, Storch, Fritsch, & Weiller, 2000), and increased transcallosal inhibition

from the non-lesioned to the lesioned hemisphere has also been demonstrated (Murase,

Duque, Mazzocchio, & Cohen, 2004). The enhancement of intracortical facilitation and

reduction in intracortical inhibition bilaterally with bimanual movements could

contribute to a rebalancing of these processes, which might lead to functional

improvements in the impaired limb. An active-passive bilateral therapy (active

movement of the unaffected limb coupled with passive movement of the affected limb)

was shown to increase M1 excitability in the lesioned hemisphere and increase M1

inhibition in the non-lesioned hemisphere (C. M. Stinear, Barber, Coxon, Fleming, &

Byblow, 2008). Furthermore, there is evidence that recovery of motor function after a

stroke is correlated with a normalization of the excitatory-inhibitory asymmetries

between the hemispheres (Rossini, Calautti, Pauri, & Baron, 2003), and a reduced

representation of the affected limb in the non-lesioned hemisphere (Summers et al.,

2007).

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Rebalancing the levels of excitation and inhibition within and between the hemispheres

is unlikely to represent the complete story of recovery of motor function after stroke. As

noted above, reduced motor unit recruitment is associated with poor performance on

arm function tasks, implying that the increasing the drive to effectors must be achieved

for functional recovery. Increased excitability within the lesioned hemisphere is one

mechanism by which increased drive may be achieved. Recruitment of additional motor

areas is likely to represent another. In rats, after pharmacological inactivation of areas of

M1, a rapid unmasking of connections from adjacent cortical areas has been shown to

occur (Jacobs & Donoghue, 1991). Indeed, large extensions of cortical maps of the M1

hand area have been shown in patients with subcortical lesions and good recovery of

hemiplegia (Weiller, Ramsay, Wise, Friston, & Frackowiak, 1993). Furthermore, the

extent of cortical map shift has been shown to correlate with grip strength with larger

map area tending to be associated with better function of the affected limb

(Thickbroom, Byrnes, Archer, & Mastaglia, 2004), and an enlargement of cortical hand

area has been shown to correlate with functional improvement in a study assessing

longitudinal changes in brain organization after cortical stroke (Traversa, Cicinelli,

Bassi, Rossini, & Bernardi, 1997).

Conclusions

In a subset of stroke patients with mild-to-moderate deficits, performance of the

affected limb was enhanced during bimanual coordination. Temporal coupling between

the limbs might be crucial for this facilitation of performance. The findings of the

current study have implications for identifying which stroke patients are likely to

benefit from bilateral training. Although it would be premature to decide which

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participants would benefit from bilateral training from their performance on a few trials,

it is reasonable to assume that if temporal coupling of the limbs is essential for

facilitation of the affected limb, individuals who are unable to achieve such coupling

will not benefit from bilateral training. The inability of some participants in the current

study to couple the limbs may have been associated with residual weakness or spasticity

in the affected limb. A recent study using an active-passive bilateral training approach

showed that unilateral training preceded by active-passive bilateral training was more

effective than unilateral training alone in a group of stroke patients with upper limb

weakness (C. M. Stinear, Barber, Coxon, Fleming, & Byblow, 2008). Bilateral coupling

of the arms using this passive approach may prove beneficial for those participants with

deficits which are severe enough to limit active coupling. Identifying which patients

will benefit from bilateral training and under which conditions will be important for

maximising results from rehabilitation.

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GENERAL DISCUSSION

The first section of this thesis examined between-hand differences in the dynamics of

performance during unimanual and bimanual coordination. During tapping, the

dominant hand was faster (for rapid tapping but not slow tapping) and less temporally

variable (at both tapping rates) than the nondominant hand (Chapter 2). The ability to

tap faster with the dominant than nondominant hand has been largely attributed to a

faster transition between movement directions by the dominant hand than by the

nondominant hand (Peters, 1980). Furthermore, during fast rhythmical finger

oscillations, muscle activation patterns in the dominant hand are characterized by

sharply defined, non-overlapping contractions of flexor and extensor muscles, whereas

in the nondominant hand they are characterized by greater co-contractions of these

muscles, indicating a more precise control of their reciprocal activation with the

dominant hand than with the non-dominant hand (Heuer, 2007).

During circle drawing, the dominant hand was faster, more accurate, less temporally

and spatially variable, and produced smoother trajectories than the nondominant hand

(Chapter 3). These asymmetries were most obvious during small circle drawing which

required precise control of the fine hand muscles. In contrast to the tapping task, in

which better performance seems be related to the ability to specify non-overlapping

antagonist muscle activity and to sharply define the onset and offset of this activity, in

the circle drawing task, superior performance seems to require a greater ability to

“blend” the activity of sequential muscles (contrast the circular shapes drawn by the

dominant hand with the “triangular” shapes drawn by the nondominant hand).

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The substrate for these asymmetries in motor control is still largely speculative.

However, several lines of evidence suggest that greater interconnectivity in the

dominant than nondominant M1 might mediate the superiority of the dominant hand for

fine motor control. Within M1, γ-aminobutyric acid (GABA) mediated inhibitory

circuits appear to play a particularly important role in shaping dexterous movements. In

monkeys, if the relative activity of these circuits is disrupted (by applying either a

GABA agonist or antagonist), independent finger movement is abolished (Matsumura,

Sawaguchi, Oishi, Ueki, & Kubota, 1991). Matsumura et al. suggested that precise

levels of inhibitory activity in M1 are necessary for correct spatiotemporal control of

hand movements. In humans, greater neuropil volume in dominant than nondominant

M1 suggests more profuse intracortical connections in the dominant than nondominant

hemisphere (Amunts et al., 1996). Furthermore, evidence from our laboratory and

others’ indicates that both short latency inhibitory circuits (Civardi, Cavalli, Naldi,

Varrasi, & Cantello, 2000; Hammond, Faulkner, Byrnes, Mastaglia, & Thickbroom,

2004) and long latency inhibitory circuits (Hammond & Garvey, 2006) are more potent

in dominant M1 than in non-dominant M1 of right-handers. It has been argued that the

short-latency inhibitory circuits are important for producing independent muscle

contractions (Reynolds & Ashby, 1999; C. M. Stinear & Byblow, 2003), while the long-

latency inhibitory circuits, which produce a longer-lasting inhibition than the short-

latency circuits, might modulate features of sustained activity (Rosenkranz & Rothwell,

2003). Although the exact functional role of these circuits remains unclear, the greater

efficacy of the inhibitory circuits in the dominant than nondominant hemisphere points

to a role in the spatiotemporal shaping of motor output involved in dexterous

movements.

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During bimanual coordination the actions of the hands became synchronized. Rate

asymmetries that had been present during unimanual movements were abolished during

bimanual coordination. Two other asymmetries between the hands were also attenuated

during bimanual coordination. Firstly, temporal variability of the two hands became

more alike during bimanual coordination. This was only observed during the rapid

tapping task and the attenuation represented a benefit to the nondominant hand with no

apparent change in performance of the dominant hand. There was also an attenuation of

the asymmetry in smoothness of circle drawing (cycles of acceleration/deceleration)

during bimanual coordination. This was only seen during small-circle drawing, and as

for temporal variability, it represented an improvement in the performance of the

nondominant hand, with no apparent change in the performance of the dominant hand,

which suggests an integration of features of the movement trajectory of the dominant

limb into the trajectory of the nondominant limb. A second measure of trajectory

smoothness (RMS jerk) was smaller for both hands during bimanual than unimanual

small circle drawing (although the absolute asymmetry between the hands was the same

during unimanual and bimanual coordination). The apparent discrepancy between the

two measures of movement smoothness might be due to a faster rate of circling with the

dominant hand during unimanual than bimanual modes which could have contributed to

its smaller jerk when coupled with the nondominant hand (i.e. the smaller jerk is

secondary to a decreased rate of movement). The rate of drawing with the nondominant

hand did not change markedly from unimanual to bimanual drawing (if anything its rate

was slightly faster in the bimanual mode) so this cannot explain the smoother

trajectories with the nondominant hand during bimanual movements. Apart from the

RMS jerk measure, what is common to the attenuation of the asymmetries in temporal

variability and trajectory smoothness is that they were both the result of unidirectional

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effects; the performance of the nondominant hand improved during bimanual coupling,

with little change in performance with the dominant hand. If performance asymmetries

between the hands during unimanual movement represent differences between the

neural control of the dominant and nondominant hemispheres, then the improvements in

the performance of the nondominant hand when it is paired with the “superior”

dominant hand are unlikely to result from an improvement in the capacity of the

nondominant hemisphere to control the nondominant hand. A more plausible

explanation is that the dominant hemisphere plays a role in controlling the nondominant

hand during bimanual coordination. This explanation is consistent with the findings of

brain imaging and EEG studies, which show greater activation in left than right M1

during bimanual than unimanual coordination (Jäncke et al., 1998; Viviani, Perani,

Grassi, Bettinardi, & Fazio, 1998) and greater coherence from the dominant to the

nondominant sensorimotor cortex during bimanual movements, suggesting greater

cortical drive from the dominant than from the nondominant hemisphere during

bimanual movements (Serrien, Cassidy, & Brown, 2003).

Despite the attenuation of performance asymmetries during bimanual movement

discussed above, several asymmetries persisted: temporal variability of self-paced

tapping, temporal variability of circle drawing, spatial accuracy (circularity, X- and Y-

amplitudes) of circle drawing, spatial variability of circle drawing, and smoothness of

large circle drawing. There was no obvious distinction between those features of

movements for which the asymmetries between the hands were attenuated during

bimanual movement, and those which were not. For the discrete repetitive movements,

temporal variability improved for the nondominant hand during fast, but not self-paced

tapping. Furthermore, the asymmetry during fast tapping was diminished but not

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abolished during bimanual coupling. During self-paced tapping, the difference in

variability between the hands was small, so it is possible that the performance of the

nondominant hand could not benefit further from bimanual coupling. This might also

account for the finding that there was no attenuation of asymmetries in temporal

variability during circle drawing. The unimanual asymmetries between the hands across

most features of movements in the continuous task were greater during small than large

circle drawing. However, the magnitude of the asymmetry during unimanual

coordination does not predict the features of movement which become more alike

during bimanual coordination and the features which do not; for example, the

asymmetry in accuracy of unimanual small-circle drawing (circularity) was relatively

large and the magnitude of this asymmetry was maintained during bimanual drawing.

Neither a simple temporal-spatial, magnitude of unimanual asymmetry, nor discrete-

continuous distinction could therefore classify those features for which the asymmetry

was attenuated during bimanual movement and those which remained. Nevertheless,

exploring which conditions lead to an attenuation of between-hand asymmetries, and for

which features of movement, may lead to important insights into on the control

mechanisms underlying interlimb coordination.

The second section of the thesis examined the effects of disrupting motor control with

TMS over the left or right primary motor cortex (M1) on the ongoing coordination

patterns between the hands. TMS over left and right M1 during unimanual tapping

(Chapter 5) caused large disruptions to tapping with the contralateral hand, but had little

effect on the ipsilateral hand. During bimanual tapping, two patterns of responses were

observed. In some trials the hand contralateral to the side of TMS application was

“stalled” by a period approximately equal to the duration of a tap. In these trials, the two

190

hands were quickly resynchronised (within a single tapping cycle) and the results were

essentially the same as those seen during unimanual tapping. In other trials, tapping

with the hand contralateral to TMS application was stalled for a shorter duration, and in

the post-TMS period, a period of adjustment was observed during which the two hands

became resynchronized. In these trials, two lateralized effects of TMS were observed:

prolonged changes in inter-tap interval were observed in the left hand regardless of the

side of stimulation, and the effect of TMS on the contralateral hand was greater after

TMS over left M1 than right M1. The first of these lateralized effects (prolonged

changes in inter-tap interval were observed in the left hand regardless of the side of

stimulation) was attributed to a “master-slave” effect (the dominant hand produced a

master rhythm, which the non-dominant hand adopted, a process resulting in

resynchronisation of the hands over several cycles of tapping). The second of these

lateralized effects (a larger effect after TMS over left M1 than right M1) was because

TMS over left M1 caused consistently large disruptions to the contralateral hand,

whereas TMS over right M1 caused more variable individual responses. A tentative

explanation for these findings is that they result from a more (temporally) focused drive

from the dominant hemisphere and a more diffuse drive from the nondominant

hemisphere. It is possible that TMS applied during a period of focused drive would

result in consistently large responses, and TMS delivered during a period of diffuse

drive would result in more variable responses. A recent study which showed more

sharply defined EMG bursts for dominant than nondominant hand movements, with

temporal segregation of bursts of reciprocal muscle activity in the dominant hand and

greater co-contraction of antagonistic muscle pairs in the nondominant limb (Heuer,

2007) is consistent with this hypothesis. Similarly, the dominant hemisphere has a

greater acuity for processing temporal information than the nondominant hemisphere

191

(Hammond, 1981`, 1982; Nicholls & Whelan, 1998). This suggests that a greater acuity

of processing within the dominant than nondominant hemisphere might be more a

widespread feature of this hemisphere. Furthermore, the neural substrate for such an

asymmetry could be the more profuse horizontal connections and more effective short

latency intracortical inhibitory control in the dominant than nondominant hemisphere,

discussed above. More profuse interconnections between motor representations within

the dominant than nondominant hemisphere would support a finer spatiotemporal acuity

of motor output from this hemisphere.

In Chapter 6, subthreshold, threshold, and suprathreshold TMS were delivered over

primary motor cortex during continuous circle drawing. The effects of subthreshold and

threshold TMS were qualitatively different from those evoked by suprathreshold TMS.

At the lower intensities, the effects were almost exclusively observed on the left hand,

regardless of side of stimulation. It seems unlikely that physiological processes in M1

could account for the contralateral effects after TMS over right M1 and ipsilateral

effects after TMS over left M1. Rather, the effect of TMS on the left hand at the lower

intensities was likely due to the left hand being less resistant to interference by the

startling effect of the TMS acoustic stimulus than the right hand; less pressure was

applied during circle drawing with the left hand than with the right hand, which may

have afforded less stability to the left hand, rendering it more susceptible than the right

hand to perturbation.

Suprathreshold TMS caused large enduring decreases in circularity and increases in

period. The greatest effects on both circularity and period were delayed relative to the

time of TMS application. Left hemispheric stimulation decreased circularity with both

192

the left hand and the right hand whereas right hemispheric stimulation decreased

circularity only with the left hand. These effects were much larger than the effects seen

after lower intensity TMS pulses, suggesting physiological processes rather than

mechanical stability differences between the hands. The lateralized effect of TMS on

circularity was not limited to the bimanual case, but was also apparent during

unimanual drawing. This suggests a role for the left hemisphere in control of complex

sequential organization of movement by both hands, and is consistent with lesions

studies which show left hemisphere lesions result in sequencing deficits with both

hands, whereas right hemisphere lesions result in sequencing deficits with the

contralateral hand only (Haaland & Harrington, 1994).

Although distinct effects were observed when TMS was delivered during the repetitive

discrete tapping task and during the continuous circle drawing task, these different

effects do not necessarily reflect the event-timing and emergent timing distinction

between the tasks (Ivry & Richardson, 2002). Studies which have provided evidence for

such a distinction have either exploited individual differences in timing variability (e.g.,

correlations between timing variability on two tasks; Zelaznik, Spencer, & Ivry, 2002),

compared timing variability as a function of interval across two tasks (Ivry & Hazeltine,

1995), or examined timing in different tasks after brain injury or surgery (Kennerley,

Diedrichsen, Hazeltine, Semjen, & Ivry, 2002; Spencer, Zelaznik, Diedrichsen, & Ivry,

2003; Tuller & Kelso, 1989). The studies in this thesis were not designed to provide

evidence for or against the distinction between event and emergent timing; different

individuals participated in the two different tasks, so correlations between temporal

variabilities across tasks could not be calculated; neither were the studies designed to

calculate variability as a function of temporal interval.

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The final study assessed bimanual motor control after unilateral stroke. In these

participants, unimanual and bimanual tapping was slower and more variable with the

affected than with the unaffected hand for most participants. Likewise, circle drawing

was less accurate, slower, and less smooth with the affected than the unaffected limb.

Furthermore, circle drawing with the affected side was characterized by obvious non-

blended sub-movements in the trajectories, much like the sub-movements seen in small

circles drawn by control participants with the non-dominant limb. The presence of sub-

movements suggests a degrading of the ability to successfully blend movement

components within the damaged hemisphere. Others have shown that submovements

become more blended in infants during development (von Hofsten, 1991) and in stroke

patients during recovery (Rohrer et al., 2002; Rohrer et al., 2004). For several

participants with mild to moderate deficits in the current study the sub-movements were

more blended during bimanual drawing than during unimanual drawing. This may

reflect an integration of features of the movement trajectory of the unaffected limb into

the trajectory of the affected limb, resulting in spatially smoother trajectories with the

affected limb. Furthermore, there was evidence of coupling of the limbs during

bimanual coordination for some participants in the mild and moderate group, and some

of these participants also showed evidence of facilitation of performance with the

affected limb when combined with the unaffected limb. This is similar to the previous

point that in control participants, performance with the nondominant hand improved

during bimanual movement. The performance deficits with the affected limb reflect

impaired neural control by the damaged hemisphere contralateral to the affected hand,

and the improvements in the performance of the affected limb when it is paired with the

unaffected limb are unlikely to result from an improvement in the capacity of the

affected hemisphere to control the affected limb. Rather, the improvements in the

194

performance of the hand contralateral to the lesion are likely to result from the

undamaged hemisphere playing a role in the control of that limb during bimanual

coordination. This is analogous to the mechanism proposed for the improvements in

nondominant limb performance, with the dominant limb playing a roe in the control of

the nondominant limb during bimanual movement.

That the participants whose affected-limb performance improved during bimanual

movement were limited to those who showed evidence of temporal coupling between

the limbs suggests that temporal coupling is crucial for the facilitation of the affected

limb during bimanual coordination. One implication of these findings is that if brain

damage is extensive enough to disable temporal coupling between the limbs, bimanual

facilitation is also eliminated. The findings also have therapeutic implications in

identifying which stroke patients are likely to benefit from bilateral training. The

inability of some participants in the current study to couple the limbs may have been

associated with residual weakness in the affected limb and an alternative approach to

rehabilitation would need to be considered for this group. One approach which makes

the benefits of bilateral training available for such individuals is an active-passive

training approach, which has been shown to be more effective than unilateral training in

a group of stroke patients with upper limb weakness (C. M. Stinear, Barber, Coxon,

Fleming, & Byblow, 2008). The observation that temporal coupling is essential for

facilitation of the affected limb needs to be verified empirically in order to identify

which patients will benefit from different bilateral rehabilitation regimes.

195

REFERENCES

Amassian, V. E., Cracco, R. Q., Maccabee, P. J., Bigland-Ritchie, B., & Cracco, J. B. (1991).

Matching focal and non-focal magnetic coil stimulation to properties of human

nervous system: mapping motor unit fields in motor cortex contrasted with altering

sequential digit movements by premotor-SMA stimulation. Electroencephalography &

Clinical Neurophysiology Supplement, 43, 3-28.

Amunts, K., Schlaug, G., Schleicher, A., Steinmetz, H., Dabringhaus, A., Roland, P. E., et al.

(1996). Asymmetry in the human motor cortex and handedness. Neuroimage, 4(3),

216-222.

Aranyi, Z., & Rosler, K. M. (2002). Effort-induced mirror movements. A study of transcallosal

inhibition in humans. Experimental Brain Research., 145(1), 76-82.

Barker, A. T., Jalinous, R., & Freeston, I. L. (1985). Non-invasive magnetic stimulation of human

motor cortex. Lancet., 1(8437), 1106-1107.

Ben-Shaul, Y., Drori, R., Asher, I., Stark, E., Nadasdy, Z., & Abeles, M. (2004). Neuronal activity

in motor cortical areas reflects the sequential context of movement. Journal of

Neurophysiology, 91(4), 1748-1762.

Bennett, K. M., & Lemon, R. N. (1996). Corticomotoneuronal contribution to the fractionation

of muscle activity during precision grip in the monkey. Journal of Neurophysiology,

75(5), 1826-1842.

Blumenthal, T. D. (1988). The startle response to acoustic stimuli near startle threshold: effects

of stimulus rise and fall time, duration, and intensity. Psychophysiology, 25(5), 607-

611.

Bohning, D. E., Shastri, A., Wassermann, E. M., Ziemann, U., Lorberbaum, J. P., Nahas, Z., et al.

(2000). BOLD-f MRI response to single-pulse transcranial magnetic stimulation (TMS).

Journal of Magnetic Resonance Imaging, 11(6), 569-574.

Bonnard, M., Camus, M., de Graaf, J., & Pailhous, J. (2003). Direct Evidence for a Binding

between Cognitive and Motor Functions in Humans: A TMS Study. Journal of Cognitive

Neuroscience, 15(8), 1207-1216.

Boyce, R. R., & Clark, W. A. V. (1964). The Concept of Shape in Geography. Geographical

Review, 54(4), 561-572.

Brinkman, C. (1984). Supplementary motor area of the monkey's cerebral cortex: short- and

long-term deficits after unilateral ablation and the effects of subsequent callosal

section. J. Neurosci., 4(4), 918-929.

Brinkman, J., & Kuypers, H. G. (1972). Splitbrain monkeys: cerebral control of ipsilateral and

contralateral arm, hand, and finger movements. Science, 176(34), 536-539.

Buchanan, J. J., & Ryu, Y. U. (2005). The interaction of tactile information and movement

amplitude in a multijoint bimanual circle-tracing task: Phase transitions and loss of

stability. The Quarterly Journal of Experimental Psychology Section A: Human

Experimental Psychology, 58(5), 769 - 787.

196

Burle, B., Bonnet, M., Vidal, F., Possamai, C. A., & Hasbroucq, T. (2002). A transcranial magnetic

stimulation study of information processing in the motor cortex: relationship between

the silent period and the reaction time delay. Psychophysiology, 39(2), 207-217.

Butefisch, C. M., Netz, J., Wessling, M., Seitz, R. J., & Homberg, V. (2003). Remote changes in

cortical excitability after stroke. Brain., 126(Pt 2), 470-481.

Byblow, W. D., Carson, R. G., & Goodman, D. (1994). Expressions of asymmetries and

anchoring in bimanual coordination. Human Movement Science, 13(1), 3-28.

Byblow, W. D., Lewis, G. N., Stinear, J. W., Austin, N. J., & Lynch, M. (2000). The subdominant

hand increases in the efficacy of voluntary alterations in bimanual coordination.

Experimental Brain Research, 131(3), 366-374.

Carson, R. G. (1993). Manual asymmetries: Old problems and new directions. Human

Movement Science, 12(5), 479-506.

Carson, R. G., Riek, S., Mackey, D. C., Meichenbaum, D. P., Willms, K., Forner, M., et al. (2004).

Excitability changes in human forearm corticospinal projections and spinal reflex

pathways during rhythmic voluntary movement of the opposite limb. Journal of

Physiology, 560(Pt 3), 929-940.

Carson, R. G., Smethurst, C. J., Oytam, Y., & de Rugy, A. (2007). Postural Context Alters the

Stability of Bimanual Coordination by Modulating the Crossed Excitability of

Corticospinal Pathways. J Neurophysiol, 97(3), 2016-2023.

Carson, R. G., Thomas, J., Summers, J. J., Walters, M. R., & Semjen, A. (1997). The dynamics of

bimanual circle drawing. Quarterly Journal of Experimental Psychology A, 50(3), 664-

683.

Chen, J. T., Lin, Y. Y., Shan, D. E., Wu, Z. A., Hallett, M., & Liao, K. K. (2005). Effect of

transcranial magnetic stimulation on bimanual movements. Journal of


Chen, R., Gerloff, C., Hallett, M., & Cohen, L. G. (1997). Involvement of the ipsilateral motor

cortex in finger movements of different complexities. Annals of Neurology, 41(2), 247-

254.

Chen, R., Yaseen, Z., Cohen, L. G., & Hallett, M. (1998). Time course of corticospinal excitability

in reaction time and self-paced movements. Annals of Neurology., 44(3), 317-325.

Chiappa, K. H., Cros, D., Kiers, L., Triggs, W., Clouston, P., & Fang, J. (1995). Crossed inhibition

in the human motor system. Journal of Clinical Neurophysiology, 12(1), 82-96.

Civardi, C., Cavalli, A., Naldi, P., Varrasi, C., & Cantello, R. (2000). Hemispheric asymmetries of

cortico-cortical connections in human hand motor areas. Clinical Neurophysiology,

111(4), 624-629.

Collyer, C. E., Broadbent, H. A., & Church, R. M. (1994). Preferred rates of repetitive tapping

and categorical time production. Perception & Psychophysics, 55(4), 443-453.

Cunningham, C. L., Phillips Stoykov, M. E., & Walter, C. B. (2002). Bilateral facilitation of motor

control in chronic hemiplegia. Acta Psychologica, 110(2-3), 321-337.

197

Day, B. L., Rothwell, J. C., Thompson, P. D., Maertens de Noordhout, A., Nakashima, K.,

Shannon, K., et al. (1989). Delay in the execution of voluntary movement by electrical

or magnetic brain stimulation in intact man. Evidence for the storage of motor

programs in the brain. Brain, 112(Pt 3), 649-663.

de Poel, H. J., Peper, C. L., & Beek, P. J. (2006). Intentional switches between bimanual

coordination patterns are primarily effectuated by the nondominant hand. Motor

Control, 10(1), 7-23.

de Poel, H. J., Peper, C. L. E., & Beek, P. J. (2007). Handedness-related asymmetry in coupling

strength in bimanual coordination: furthering theory and evidence. Acta Psychologica,

124(2), 209-237.

Debaere, F., Swinnen, S. P., Beatse, E., Sunaert, S., Van Hecke, P., & Duysens, J. (2001). Brain

areas involved in interlimb coordination: a distributed network. Neuroimage, 14(5),

947-958.

Desrosiers, J., Bourbonnais, D., Corriveau, H., Gosselin, S., & Bravo, G. (2005). Effectiveness of

unilateral and symmetrical bilateral task training for arm during the subacute phase

after stroke: a randomized controlled trial. Clinical Rehabilitation, 19(6), 581-593.

Diedrichsen, J., Hazeltine, E., Nurss, W. K., & Ivry, R. B. (2003). The Role of the Corpus Callosum

in the Coupling of Bimanual Isometric Force Pulses. J Neurophysiol, 90(4), 2409-2418.

Dobkin, B. H. (2004). Strategies for stroke rehabilitation. The Lancet Neurology, 3(9), 528-536.

Donchin, O., Gribova, A., Steinberg, O., Bergman, H., & Vaadia, E. (1998). Primary motor cortex

is involved in bimanual coordination. Nature, 395(6699), 274-278.

Donoghue, J. P., Leibovic, S., & Sanes, J. N. (1992). Organization of the forelimb area in squirrel

monkey motor cortex: representation of digit, wrist, and elbow muscles. Experimental

Brain Research, 89(1), 1-19.

Drewing, K., & Aschersleben, G. (2003). Reduced timing variability during bimanual coupling: A

role for sensory information. The Quarterly Journal of Experimental Psychology A:

Human Experimental Psychology, 56A(2), 329-350.

Evarts, E. V. (1966). Pyramidal tract activity associated with a conditioned hand movement in

the monkey. Journal of Neurophysiology, 29(6), 1011-1027.

Flash, T., & Hogan, N. (1985). The coordination of arm movements: an experimentally

confirmed mathematical model. J. Neurosci., 5(7), 1688-1703.

Foltys, H., Sparing, R., Boroojerdi, B., Krings, T., Meister, I. G., Mottaghy, F. M., et al. (2001).

Motor control in simple bimanual movements: a transcranial magnetic stimulation and

reaction time study. Clinical Neurophysiology, 112(2), 265-274.

Franz, E. A. (1997). Spatial coupling in the coordination of complex actions. Quarterly Journal of

Experimental Psychology. A, Human Experimental Psychology, 50(3), 684-704.

Franz, E. A., Eliassen, J. C., Ivry, R. B., & Gazzaniga, M. S. (1996). Dissociation of spatial and

temporal coupling in the bimanual movements of callosotomy patients. Psychological

Science, 7(5), 306-310.

198

Franz, E. A., Rowse, A., & Ballantine, B. (2002). Does Handedness Determine Which Hand Leads

in a Bimanual Task? Journal of Motor Behavior, 34(4), 402.

Franz, E. A., Zelaznik, H. N., & McCabe, G. (1991). Spatial topological constraints in a bimanual

task. Acta Psychologica, 77(2), 137-151.

Fuhr, P., Agostino, R., & Hallett, M. (1991). Spinal motor neuron excitability during the silent

period after cortical stimulation. Electroencephalography & Clinical Neurophysiology,

81(4), 257-262.

Garry, M. I., van Steenis, R. E., & Summers, J. J. (2005). Interlimb coordination following stroke.

Human Movement Science, 24(5-6), 849-864.

Georgopoulos, A. P., Kalaska, J. F., & Massey, J. T. (1981). Spatial trajectories and reaction

times of aimed movements: effects of practice, uncertainty, and change in target

location. J Neurophysiol, 46(4), 725-743.

Glencross, D. J., Piek, J. P., & Barrett, N. C. (1995). The coordination of bimanual synchronous

and alternating tapping sequences. Journal of Motor Behavior, 27(1), 3-15.

Goble, D. J., & Brown, S. H. (2008). The biological and behavioral basis of upper limb

asymmetries in sensorimotor performance. Neuroscience & Biobehavioral Reviews,

32(3), 598-610.

Gowland, C., deBruin, H., Basmajian, J. V., Plews, N., & Burcea, I. (1992). Agonist and

antagonist activity during voluntary upper-limb movement in patients with stroke.

PHYS THER, 72(9), 624-633.

Graziano, M. S., Aflalo, T. N., & Cooke, D. F. (2005). Arm movements evoked by electrical

stimulation in the motor cortex of monkeys. Journal of Neurophysiology, 94(6), 4209-

4223.

Guiard, Y. (1987). Asymmetric division of labor in human skilled bimanual action: The

kinematic chain as a model. Journal of Motor Behavior, 19(4), 486-517.

Guilford, J. P. (1965). Fundamental statistics in psychology and education (4th ed.). New York:

McGraw-Hill Book Company.

Haaland, K. Y., Elsinger, C. L., Mayer, A. R., Durgerian, S., & Rao, S. M. (2004). Motor sequence

complexity and performing hand produce differential patterns of hemispheric

lateralization. Journal of Cognitive Neuroscience, 16(4), 621-636.

Haaland, K. Y., & Harrington, D. L. (1989). Hemispheric control of the initial and corrective

components of aiming movements. Neuropsychologia, 27(7), 961-969.

Haaland, K. Y., & Harrington, D. L. (1994). Limb-sequencing deficits after left but not right

hemisphere damage. Brain & Cognition, 24(1), 104-122.

Haaland, K. Y., Harrington, D. L., & Knight, R. T. (2000). Neural representations of skilled

movement. Brain, 123(Pt 11), 2306-2313.

Hammond, G. R. (1981). Finer temporal acuity for stimuli applied to the preferred hand.

Neuropsychologica, 19, 325-329.

199

Hammond, G. R. (1982). Hemispheric differences in temporal resolution. Brain and Cognition,

1, 95-118.

Hammond, G. R., Bolton, Y., Plant, Y., & Manning, J. (1988). Hand asymmetries in interresponse

intervals during rapid repetitive finger tapping. Journal of Motor Behavior, 20(1), 67-

71.

Hammond, G. R., Faulkner, D., Byrnes, M., Mastaglia, F., & Thickbroom, G. (2004). Transcranial

magnetic stimulation reveals asymmetrical efficacy of intracortical circuits in primary

motor cortex. Experimental Brain Research, 155(1), 19-23.

Hammond, G. R., & Garvey, C.-A. (2006). Asymmetries of long-latency intracortical inhibition in

motor cortex and handedness. Experimental Brain Research, 172(4), 449-453.

Harris-Love, M. L., McCombe Waller, S., & Whitall, J. (2005). Exploiting Interlimb Coupling to

Improve Paretic Arm Reaching Performance in People With Chronic Stroke. Archives of

Physical Medicine and Rehabilitation, 86(11), 2131-2137.

Hashimoto, T., Inaba, D., Matsumura, M., & Naito, E. (2004). Two different effects of

transcranial magnetic stimulation to the human motor cortex during the pre-

movement period. Neuroscience Research, 50(4), 427-436.

Heald, A., Bates, D., Cartlidge, N. E., French, J. M., & Miller, S. (1993). Longitudinal study of

central motor conduction time following stroke. 2. Central motor conduction

measured within 72 h after stroke as a predictor of functional outcome at 12 months.

Brain, 116(Pt 6), 1371-1385.

Heffner, R. S., & Masterton, R. B. (1983). The role of the corticospinal tract in the evolution of

human digital dexterity. Brain, Behavior & Evolution, 23(3-4), 165-183.

Helmuth, L. L., & Ivry, R. B. (1996). When two hands are better than one: Reduced timing

variability during bimanual movements. Journal of Experimental Psychology: Human

Perception & Performance, 22(2), 278-293.

Heuer, H. (2007). Control of the dominant and nondominant hand: exploitation and taming of

nonmuscular forces. Experimental Brain Research, 178(3), 363-373.

Hogan, N., & Flash, T. (1987). Moving gracefully: quantitative theories of motor coordination.

Trends in Neurosciences, 10(4), 170-174.

Hore, J., Watts, S., Tweed, D., & Miller, B. (1996). Overarm throws with the nondominant arm:

kinematics of accuracy. Journal of Neurophysiology, 76(6), 3693-3704.

Ilmoniemi, R. J., Virtanen, J., Ruohonen, J., Karhu, J., Aronen, H. J., Naatanen, R., et al. (1997).

Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity.

NeuroReport., 8(16), 3537-3540.

Inghilleri, M., Berardelli, A., Cruccu, G., & Manfredi, M. (1993). Silent period evoked by

transcranial stimulation of the human cortex and cervicomedullary junction. Journal of

Physiology, 466, 521-534.

200

Ivry, R. B., & Hazeltine, R. E. (1995). Perception and production of temporal intervals across a

range of durations: evidence for a common timing mechanism. Journal of Experimental

Psychology, Human Perception and Performance, 21(1), 3-18.

Ivry, R. B., & Richardson, T. C. (2002). Temporal Control and Coordination: The Multiple Timer

Model. Brain and Cognition, 48(1), 117-132.

Iwano, S., Nakamura, T., Kamioka, Y., & Ishigaki, T. (2005). Computer-aided diagnosis: A shape

classification of pulmonary nodules imaged by high-resolution CT. Computerized

Medical Imaging and Graphics, 29(7), 565-570.

Jacobs, K. M., & Donoghue, J. P. (1991). Reshaping the cortical motor map by unmasking latent

intracortical connections. Science, 251(4996), 944-947.

Jäncke, L., Peters, M., Himmelbach, M., Nösselt, T., Shah, J., & Steinmetz, H. (2000). fMRI study

of bimanual coordination. Neuropsychologia, 38(2), 164-174.

Jäncke, L., Peters, M., Schlaug, G., Posse, S., Steinmetz, H., & Muller-Gartner, H. (1998).

Differential magnetic resonance signal change in human sensorimotor cortex to finger

movements of different rate of the dominant and subdominant hand. Cognitive Brain

Research, 6(4), 279-284.

Kagerer, F. A., Summers, J. J., & Semjen, A. (2003). Instabilities during antiphase bimanual

movements: are ipsilateral pathways involved? Experimental Brain Research, 151(4),

489-500.

Kansaku, K., Muraki, S., Umeyama, S., Nishimori, Y., Kochiyama, T., Yamane, S., et al. (2005).

Cortical activity in multiple motor areas during sequential finger movements: an

application of independent component analysis. Neuroimage, 28(3), 669-681.

Kawashima, R., Yamada, K., Kinomura, S., Yamaguchi, T., Matsui, H., Yoshioka, S., et al. (1993).

Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in

humans related to ipsilateral and contralateral hand movement. Brain Research,

623(1), 33-40.

Kay, B. A., Saltzman, E. L., & Kelso, J. A. (1991). Steady-state and perturbed rhythmical

movements: a dynamical analysis. Journal of Experimental Psychology: Human

Perception & Performance, 17(1), 183-197.

Kazennikov, O., Hyland, B., Wicki, U., Perrig, S., Rouiller, E. M., & Wiesendanger, M. (1998).

Effects of lesions in the mesial frontal cortex on bimanual co-ordination in monkeys.

Neuroscience, 85(3), 703-716.

Kazennikov, O., Wicki, U., Corboz, M., Hyland, B., Palmeri, A., Rouiller, E. M., et al. (1994).

Temporal Structure of a Bimanual Goal-directed Movement Sequence in Monkeys.

European Journal of Neuroscience, 6(2), 203-210.

Kelso, J. A. (1984). Phase transitions and critical behavior in human bimanual coordination. Am

J Physiol Regul Integr Comp Physiol, 246(6), R1000-1004.

Kelso, J. A., Southard, D. L., & Goodman, D. (1979). On the coordination of two-handed

movements. Journal of Experimental Psychology: Human Perception & Performance,

5(2), 229-238.

201

Kennerley, S. W., Diedrichsen, J., Hazeltine, E., Semjen, A., & Ivry, R. B. (2002). Callosotomy

patients exhibit temporal uncoupling during continuous bimanual movements. Nature

Neuroscience., 5(4), 376-381.

Kermadi, I., Liu, Y., Tempini, A., Calciati, E., & Rouiller, E. M. (1998). Neuronal activity in the

primate supplementary motor area and the primary motor cortex in relation to spatio-

temporal bimanual coordination. Somatosensory & Motor Research, 15(4), 287-308.

Kilbreath, S. L., Crosbie, J., Canning, C. G., & Lee, M. J. (2006). Inter-limb coordination in

bimanual reach-to-grasp following stroke. Disability & Rehabilitation, 28(23), 1435-

1443.

Kim, S. G., Ashe, J., Hendrich, K., Ellermann, J. M., Merkle, H., Ugurbil, K., et al. (1993).

Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and

handedness. Science, 261(5121), 615-617.

Koeneke, S., Lutz, K., Wustenberg, T., & Jäncke, L. (2004). Bimanual versus unimanual

coordination: what makes the difference? Neuroimage, 22(3), 1336-1350.

Kornatz, K. W., Christou, E. A., & Enoka, R. M. (2005). Practice reduces motor unit discharge

variability in a hand muscle and improves manual dexterity in old adults. J Appl Physiol,

98(6), 2072-2080.

Kunesch, E., Binkofski, F., Steinmetz, H., & Freund, H.-J. (1995). The pattern of motor deficits in

relation to the site of stroke lesions. European Neurology, 35(1), 20-26.

Kuypers, H. G. J. M. (1981). Anatomy of the descending pathways. In V. B. Brooks (Ed.),

Handbook of Physiology Section 1: The Nervous System (Vol. II Motor control, Part 1,

pp. 597-666). Bethesda, Maryland: American Physiological Society.

Kwakkel, G., Kollen, B. J., van der Grond, J., & Prevo, A. J. H. (2003). Probability of Regaining

Dexterity in the Flaccid Upper Limb: Impact of Severity of Paresis and Time Since Onset

in Acute Stroke. Stroke, 34(9), 2181-2186.

Lai, S.-M., Studenski, S., Duncan, P. W., & Perera, S. (2002). Persisting Consequences of Stroke

Measured by the Stroke Impact Scale. Stroke, 33(7), 1840-1844.

Lang, C. E., & Schieber, M. H. (2004). Reduced muscle selectivity during individuated finger

movements in humans after damage to the motor cortex or corticospinal tract. Journal

of Neurophysiology, 91(4), 1722-1733.

Lang, W., Obrig, H., Lindinger, G., Cheyne, D., & Deecke, L. (1990). Supplementary motor area

activation while tapping bimanually different rhythms in musicians. Experimental Brain

Research, 79(3), 504-514.

LaRoque, S. D., & Obrzut, J. E. (2006). Pencil Pressure and Anxiety in Drawings: A Techno-

Projective Approach. Journal of Psychoeducational Assessment, 24(4), 381-393.

Latash, M. L., Danion, F., & Bonnard, M. (2003). Effects of transcranial magnetic stimulation on

muscle activation patterns and joint kinematics within a two-joint motor synergy.


202

Lewis, G. N., & Byblow, W. D. (2004). Bimanual coordination dynamics in poststroke

hemiparesis. Journal of Motor Behavior, 36(2), 174-188.

Lewis, G. N., & Perreault, E. J. (2007). Side of lesion influences bilateral activation in chronic,

post-stroke hemiparesis. Clinical Neurophysiology, 118(9), 2050-2062.

Liepert, J., Classen, J., Cohen, L. G., & Hallett, M. (1998). Task-dependent changes of

intracortical inhibition. Experimental Brain Research, 118(3), 421-426.

Liepert, J., Storch, P., Fritsch, A., & Weiller, C. (2000). Motor cortex disinhibition in acute

stroke. Clinical Neurophysiology, 111(4), 671-676.

Lin, K.-c., Chang, Y.-f., Wu, C.-y., & Chen, Y.-a. (2009). Effects of Constraint-Induced Therapy

Versus Bilateral Arm Training on Motor Performance, Daily Functions, and Quality of

Life in Stroke Survivors. Neurorehabil Neural Repair, 23(5), 441-448.

Lu, X., & Ashe, J. (2005). Anticipatory activity in primary motor cortex codes memorized

movement sequences.[see comment]. Neuron, 45(6), 967-973.

Luft, A., McCombe Waller, S., Whitall, J., Forrester, L. W., Macko, R., Sorkin, J., et al. (2004).

Repetitive Bilateral Arm Training and Motor Cortex Activation in Chronic Stroke: A

Randomized Controlled Trial. JAMA October, 292(15), 1853-1861.

Mack, L., Gonzalez Rothi, L. J., & Heilman, K. M. (1993). Hemispheric specialization for

handwriting in right handers. Brain & Cognition, 21(1), 80-86.

Marteniuk, R. G., MacKenzie, C. L., & Baba, D. M. (1984). Bimanual movement control:

Information processing and interaction effects. Quarterly Journal of Experimental

Psychology. A, Human Experimental Psychology, 36A(2), 335-365.

Matsumura, M., Sawaguchi, T., Oishi, T., Ueki, K., & Kubota, K. (1991). Behavioral deficits

induced by local injection of bicuculline and muscimol into the primate motor and

premotor cortex. Journal of Neurophysiology, 65(6), 1542-1553.

Matsunaga, K., Uozumi, T., Tsuji, S., & Murai, Y. (1998). Age-dependent changes in

physiological threshold asymmetries for the motor evoked potential and silent period

following transcranial magnetic stimulation. Electroencephalography & Clinical


McCombe Waller, S., Forrester, L., Villagra, F., & Whitall, J. (2008). Intracortical inhibition and

facilitation with unilateral dominant, unilateral nondominant and bilateral movement

tasks in left- and right-handed adults. Journal of the Neurological Sciences, 269(1-2),

96-104.

McCombe Waller, S., Harris-Love, M., Liu, W., & Whitall, J. (2006). Temporal coordination of

the arms during bilateral simultaneous and sequential movements in patients with

chronic hemiparesis. Experimental Brain Research, 168(3), 450-454.

McCombe Waller, S., & Whitall, J. (2005). Hand dominance and side of stroke affect

rehabilitation in chronic stroke. Clinical Rehabilitation, 19(5), 544-551.

McCombe Waller, S., & Whitall, J. (2008). Bilateral arm training: Why and who benefits?

NeuroRehabilitation, 23(1), 29-41.

203

Meyer, B. U., & Voss, M. (2000). Delay of the execution of rapid finger movement by magnetic

stimulation of the ipsilateral hand-associated motor cortex. Experimental Brain

Research, 134(4), 477-482.

Mudie, M. H., & Matyas, T. A. (2000). Can simultaneous bilateral movement involve the

undamaged hemisphere in reconstruction of neural networks damaged by stroke?

Disability & Rehabilitation, 22, 23-37.

Mudie, M. H., & Matyas, T. A. (2001). Responses of the Densely Hemiplegic Upper Extremity to

Bilateral Training. Neurorehabil Neural Repair, 15(2), 129-140.

Murase, N., Duque, J., Mazzocchio, R., & Cohen, L. G. (2004). Influence of interhemispheric

interactions on motor function in chronic stroke. Annals of Neurology, 55(3), 400-409.

Netz, J., Ziemann, U., & Homberg, V. (1995). Hemispheric asymmetry of transcallosal inhibition

in man. Experimental Brain Research, 104(3), 527-533.

Newell, K. M., & Van Emmerik, R. E. (1989). The acquisition of coordination: Preliminary

analysis of learning to write. Human Movement Science. Vol, 8(1), 17-32.

Nicholls, M. E. R., & Whelan, R. E. (1998). Hemispheric asymmetries for the temporal

resolution of brief tactile stimuli. Journal of Clinical & Experimental Neuropsychology,

20(4), 445-456.

Nickerson, R. S. (1970). The effect of preceding and following auditory stimuli on response

times to visual stimuli. Acta Psychologica, Amsterdam, 33, 5-20.

Oldfield, R. (1971). The assessment and analysis of handedness: The Edinburgh inventory.

Neuropsychologia, 9(1), 97-113.

Palmer, E., & Ashby, P. (1992). Corticospinal projections to upper limb motoneurones in

humans. Journal of Physiology, 448, 397-412.

Palmer, E., Cafarelli, E., & Ashby, P. (1994). The processing of human ballistic movements

explored by stimulation over the cortex. Journal of Physiology, 481(Pt 2), 509-520.

Pascual-Leone, A., Brasil-Neto, J. P., Valls-Solé, J., Cohen, L. G., & Hallett, M. (1992). Simple

reaction time to focal transcranial magnetic stimulation. Comparison with reaction

time to acoustic, visual and somatosensory stimuli. Brain, 115 Pt 1, 109-122.

Perrig, S., Kazennikov, O., & Wiesendanger, M. (1999). Time structure of a goal-directed

bimanual skill and its dependence on task constraints. Behavioural Brain Research,

103(1), 95-104.

Peters, M. (1976). Prolonged practice of a simple motor task by preferred and nonpreferred

hands. Perceptual & Motor Skills, 43(2), 447-450.

Peters, M. (1980). Why the preferred hand taps more quickly than the non-preferred hand:

Three experiments on handedness. Canadian Journal of Psychology, 34(1), 62-71.

Peters, M. (1981). Attentional asymmetries during concurrent bimanual performance.

Quarterly Journal of Experimental Psychology. A, Human Experimental Psychology, 1,

95-103.

204

Peters, M. (1985). Constraints in the performance of bimanual tasks and their expression in

unskilled and skilled subjects. The Quarterly Journal of Experimental Psychology

Section A, 37(2), 171-196.

Peters, M. (1989). The relationship between variability of intertap intervals and interval

duration. Psychological Research, 51(1), 38-42.

Peters, M., & Durding, B. (1979). Left-handers and right-handers compared on a motor task.

Journal of Motor Behavior, 11(2), 103-111.

Phillips, J. G., Gallucci, R. M., & Bradshaw, J. L. (1999). Functional asymmetries in the quality of

handwriting movements: a kinematic analysis. Neuropsychology, 13(2), 291-297.

Platz, T., Bock, S., & Prass, K. (2001). Reduced skilfulness of arm motor behaviour among motor

stroke patients with good clinical recovery: does it indicate reduced automaticity? Can

it be improved by unilateral or bilateral training? A kinematic motion analysis study.


Pollok, B. C. A., Muller, K., Aschersleben, G., Schnitzler, A., & Prinz, W. (2004). Bimanual

coordination: neuromagnetic and behavioral data. Neuroreport, 15(3), 449-452.

Priori, A., Oliviero, A., Donati, E., Callea, L., Bertolasi, L., & Rothwell, J. C. (1999). Human

handedness and asymmetry of the motor cortical silent period. Experimental Brain

Research, 128(3), 390-396.

Rao, S. M., Binder, J. R., Bandettini, P. A., Hammeke, T. A., Yetkin, F. Z., Jesmanowicz, A., et al.

(1993). Functional magnetic resonance imaging of complex human movements.

Neurology, 43(11), 2311-2318.

Repp, B. H. (2003). Phase attraction in sensorimotor synchronization with auditory sequences:

Effects of single and periodic distractors on synchronization accuracy. Journal of

Experimental Psychology: Human Perception and Performance, 29(2), 290-309.

Repp, B. H. (2006). Does an auditory distractor sequence affect self-paced tapping? Acta

Psychologica, 121(1), 81-107.

Reynolds, C., & Ashby, P. (1999). Inhibition in the human motor cortex is reduced just before a

voluntary contraction [see comments]. Neurology, 53(4), 730-735.

Rice, M. S., & Newell, K. M. (2001). Interlimb coupling and left hemiplegia because of right

cerebral vascular accident. Occupational Therapy Journal of Research, 21, 12-28.

Rice, M. S., & Newell, K. M. (2004). Upper-extremity interlimb coupling in persons with left

hemiplegia due to stroke. Archives of Physical Medicine and Rehabilitation, 85(4), 629-

634.

Rohrer, B., Fasoli, S., Krebs, H. I., Hughes, R., Volpe, B., Frontera, W. R., et al. (2002).

Movement Smoothness Changes during Stroke Recovery. J. Neurosci., 22(18), 8297-

8304.

Rohrer, B., Fasoli, S., Krebs, H. I., Volpe, B., Frontera, W. R., Stein, J., et al. (2004).

Submovements grow larger, fewer, and more blended during stroke recovery. Motor

Control, 8(4), 472-483.

205

Romaiguère, P., Possamai, C. A., & Hasbroucq, T. (1997). Motor cortex involvement during

choice reaction time: a transcranial magnetic stimulation study in man. Brain Research,

755(2), 181-192.

Rose, D. K., & Winstein, C. J. (2005). The co-ordination of bimanual rapid aiming movements

following stroke. Clinical Rehabilitation, 19(4), 452.

Rosenkranz, K., & Rothwell, J. C. (2003). Differential effect of muscle vibration on intracortical

inhibitory circuits in humans. The Journal of Physiology, 551(2), 649-660.

Rossini, P. M., Calautti, C., Pauri, F., & Baron, J. C. (2003). Post-stroke plastic reorganisation in

the adult brain. Lancet Neurology, 2, 493-502.

Rouiller, E. M., Babalian, A., Kazennikov, O., Moret, V., Yu, X. H., & Wiesendanger, M. (1994).

Transcallosal connections of the distal forelimb representations of the primary and

supplementary motor cortical areas in macaque monkeys. Experimental Brain

Research, 102(2), 227-243.

Ryu, Y. U., & Buchanan, J. J. (2004). Amplitude Scaling in a Bimanual Circle-Drawing Task:

Pattern Switching and End-Effector Variability. Journal of Motor Behavior, 36(3), 265-

279.

Sadato, N., Yonekura, Y., Waki, A., Yamada, H., & Ishii, Y. (1997). Role of the supplementary

motor area and the right premotor cortex in the coordination of bimanual finger

movements. Journal of Neuroscience, 17(24), 9667-9674.

Salmelin, R., Forss, N., Knuutila, J., & Hari, R. (1995). Bilateral activation of the human

somatomotor cortex by distal hand movements. Electroencephalography & Clinical


Sato, K. C., & Tanji, J. (1989). Digit-muscle responses evoked from multiple intracortical foci in

monkey precentral motor cortex. J Neurophysiol, 62(4), 959-970.

Sawaki, L., Okita, T., Fujiwara, M., & Mizuno, K. (1999). Specific and non-specific effects of

transcranial magnetic stimulation on simple and go/no-go reaction time. Experimental


Schluter, N. D., Rushworth, M. F., Passingham, R. E., & Mills, K. R. (1998). Temporary

interference in human lateral premotor cortex suggests dominance for the selection of

movements. A study using transcranial magnetic stimulation. Brain, 121(Pt 5), 785-

799.

Schmidt, S. L., Oliveira, R. M., Krahe, T. E., & Filgueiras, C. C. (2000). The effects of hand

preference and gender on finger tapping performance asymmetry by the use of an

infra-red light measurement device. Neuropsychologia, 38(5), 529-534.

Semjen, A., Summers, J. J., & Cattaert, D. (1995). Hand Coordination in Bimanual Circle

Drawing. Journal of Experimental Psychology: Human Perception and Performance,

21(5), 1139-1157.

Serrien, D. J., Cassidy, M. J., & Brown, P. (2003). The importance of the dominant hemisphere

in the organization of bimanual movements. Human Brain Mapping, 18(4), 296-305.

206

Sherwood, D. E. (1990). Practice and assimilation effects in a multilimb aiming task. Journal of

Motor Behavior, 22(2), 267-291.

Sherwood, D. E. (1994). Hand preference, practice order, and spatial assimilations in rapid

bimanual movement. Journal of Motor Behavior, 26(2), 123-134.

Singh, L. N., Higano, S., Takahashi, S., Kurihara, N., Furuta, S., Tamura, H., et al. (1998).

Comparison of ipsilateral activation between right and left handers: a functional MR

imaging study. Neuroreport, 9(8), 1861-1866.

Spencer, R. M. C., & Zelaznik, H. N. (2003). Weber (Slope) Analyses of Timing Variability in

Tapping and Drawing Tasks. Journal of Motor Behavior, 35(4), 371-381.

Spencer, R. M. C., Zelaznik, H. N., Diedrichsen, J., & Ivry, R. B. (2003). Disrupted Timing of

Discontinuous But Not Continuous Movements by Cerebellar Lesions. Science,

300(5624), 1437-1439.

Staines, W. R., McIlroy, W. E., Graham, S. J., & Black, S. E. (2001). Bilateral movement enhances

ipsilesional cortical activity in acute stroke: a pilot functional MRI study. Neurology,

56(3), 401-404.

Steenbergen, B., Hulstijn, W., de Vries, A., & Berger, M. (1996). Bimanual movement

coordination in spastic hemiparesis. Experimental Brain Research, 110(1), 91-98.

Stephan, K. M., Binkofski, F., Halsband, U., Dohle, C., Wunderlich, G., Schnitzler, A., et al.

(1999). The role of ventral medial wall motor areas in bimanual co-ordination. A

combined lesion and activation study. Brain, 122(Pt 2), 351-368.

Stephan, K. M., Binkofski, F., Posse, S., Seitz, R. J., & Freund, H. J. (1999). Cerebral midline

structures in bimanual coordination. Experimental Brain Research, 128(1-2), 243-249.

Stewart, K. C., Cauraugh, J. H., & Summers, J. J. (2006). Bilateral movement training and stroke

rehabilitation: A systematic review and meta-analysis. Journal of the Neurological

Sciences, 244(1-2), 89-95.

Steyvers, M., Etoh, S., Sauner, D., Levin, O., Siebner, H., Swinnen, S., et al. (2003). High-

frequency transcranial magnetic stimulation of the supplementary motor area reduces

bimanual coupling during anti-phase but not in-phase movements. Experimental Brain

Research, 151(3), 309-317.

Stinear, C. M., Barber, P. A., Coxon, J. P., Fleming, M. K., & Byblow, W. D. (2008). Priming the

motor system enhances the effects of upper limb therapy in chronic stroke. Brain,

131(5), 1381-1390.

Stinear, C. M., & Byblow, W. D. (2003). Role of intracortical inhibition in selective hand muscle

activation. Journal of Neurophysiology., 89(4), 2014-2020.

Stinear, J. W., & Byblow, W. D. (2004). Rhythmic bilateral movement training modulates

corticomotor excitability and enhances upper limb motoricity poststroke: a pilot study.

Journal of Clinical Neurophysiology, 21, 124-131.

207

Stucchi, N., & Viviani, P. (1993). Cerebral dominance and asynchrony between bimanual two-

dimensional movements. Journal of Experimental Psychology, Human Perception and

Performance, 19, 1200-1220.

Summers, J. J., Kagerer, F. A., Garry, M. I., Hiraga, C. Y., Loftus, A., & Cauraugh, J. H. (2007).

Bilateral and unilateral movement training on upper limb function in chronic stroke

patients: A TMS study. Journal of the Neurological Sciences, 252(1), 76-82.

Swinnen, S. P. (2002). Intermanual coordination: from behavioural principles to neural-

network interactions. Nature Reviews Neuroscience, 3(5), 350-361.

Swinnen, S. P., Jardin, K., & Meulenbroek, R. (1996). Between-limb asynchronies during

bimanual coordination: effects of manual dominance and attentional cueing.


Swinnen, S. P., & Wenderoth, N. (2004). Two hands, one brain: cognitive neuroscience of

bimanual skill. Trends in Cognitive Sciences, 8(1), 18-25.

Tanji, J., & Kurata, K. (1982). Comparison of movement-related activity in two cortical motor

areas of primates. Journal of Neurophysiology, 48(3), 633-653.

Taub, E., Uswatte, G., King, D. K., Morris, D., Crago, J. E., & Chatterjee, A. (2006). A Placebo-

Controlled Trial of Constraint-Induced Movement Therapy for Upper Extremity After

Stroke. Stroke, 37(4), 1045-1049.

Taub, E., Uswatte, G., & Pidikiti, R. (1999). Constraint-Induced Movement Therapy: a new

family of techniques with broad application to physical rehabilitation--a clinical review.

Journal of Rehabilitation Research & Development, 36(3), 237-251.

Taylor, J. L., Wagener, D. S., & Colebatch, J. G. (1995). Mapping of cortical sites where

transcranial magnetic stimulation results in delay of voluntary movement.

Electroencephalography & Clinical Neurophysiology: Electromyography & Motor

Control, 97(6), 341-348.

Teulings, H. L., Contreras-Vidal, J. L., Stelmach, G. E., & Adler, C. H. (1997). Parkinsonism

reduces coordination of fingers, wrist, and arm in fine motor control. Experimental

Neurology., 146(1), 159-170.

Thickbroom, G., Byrnes, M., Archer, S., & Mastaglia, F. (2004). Motor outcome after subcortical

stroke correlates with the degree of cortical reorganization. Clinical neurophysiology :

official journal of the International Federation of Clinical Neurophysiology, 115(9),

2144-2150.

Tijs, E., & Matyas, T. A. (2006). Bilateral Training Does Not Facilitate Performance of Copying

Tasks in Poststroke Hemiplegia. Neurorehabil Neural Repair, 20(4), 473-483.

Todor, J. I., & Kyprie, P. M. (1980). Hand differences in the rate and variability of rapid tapping.

Journal of Motor Behavior, 12(1), 57-62.

Toyokura, M., Muro, I., Komiya, T., & Obara, M. (1999). Relation of bimanual coordination to

activation in the sensorimotor cortex and supplementary motor area: Analysis using

functional magnetic resonance imaging. Brain Research Bulletin, 48(2), 211-217.

208

Traversa, R., Cicinelli, P., Bassi, A., Rossini, P. M., & Bernardi, G. (1997). Mapping of motor

cortical reorganization after stroke. A brain stimulation study with focal magnetic

pulses. Stroke, 28(1), 110-117.

Truman, G., & Hammond, G. R. (1990). Temporal regularity of tapping by the left and right

hands in timed and untimed finger tapping. Journal of Motor Behavior, 22(4), 521-535.

Tuller, B., & Kelso, J. A. (1989). Environmentally-specified patterns of movement coordination

in normal and split-brain subjects. Experimental Brain Research, 75(2), 306-316.

Ullen, F., Forssberg, H., & Ehrsson, H. H. (2003). Neural Networks for the Coordination of the

Hands in Time. J Neurophysiol, 89(2), 1126-1135.

Verstynen, T., Diedrichsen, J., Albert, N., Aparicio, P., & Ivry, R. B. (2005). Ipsilateral Motor

Cortex Activity During Unimanual Hand Movements Relates to Task Complexity.

Journal of Neurophysiology, 93(3), 1209-1222.

Verstynen, T., Konkle, T., & Ivry, R. B. (2006). Two Types of TMS-Induced Movement Variability

After Stimulation of the Primary Motor Cortex. J Neurophysiol, 96(3), 1018-1029.

Viviani, P., Perani, D., Grassi, F., Bettinardi, V., & Fazio, F. (1998). Hemispheric asymmetries and

bimanual asynchrony in left- and right-handers. Experimental Brain Research, 120(4),

531-536.

Volkmann, J., Schnitzler, A., Witte, O. W., & Freund, H. (1998). Handedness and asymmetry of

hand representation in human motor cortex. Journal of Neurophysiology, 79(4), 2149-

2154.

Volman, M. J. M., Wijnroks, A., & Vermeer, A. (2002). Bimanual circle drawing in children with

spastic hemiparesis: effect of coupling modes on the performance of the impaired and

unimpaired arms. Acta Psychologica, 110(2-3), 339-356.

von Hofsten, C. (1991). Structuring of early reaching movements: A longitudinal study. Journal

of Motor Behavior. Vol, 23(4), 280-292.

Walsh, V., & Rushworth, M. (1999). A primer of magnetic stimulation as a tool for

neuropsychology. Neuropsychologia, 37(2), 125-135.

Ward, N. S., Newton, J. M., Swayne, O. B. C., Lee, L., Thompson, A. J., Greenwood, R. J., et al.

(2006). Motor system activation after subcortical stroke depends on corticospinal

system integrity. Brain, 129(3), 809-819.

Wassermann, E. M., Pascual-Leone, A., Valls-Solé, J., Toro, C., Cohen, L. G., & Hallett, M.

(1993). Topography of the inhibitory and excitatory responses to transcranial magnetic

stimulation in a hand muscle. Electroencephalography & Clinical Neurophysiology:

Electromyography & Motor Control, 89(6), 424-433.

Weiller, C., Ramsay, S. C., Wise, R. J., Friston, K. J., & Frackowiak, R. S. (1993). Individual

patterns of functional reorganization in the human cerebral cortex after capsular

infarction. Annals of Neurology, 33(2), 181-189.

Weiss, P., & Jeannerod, M. (1998). Getting a Grasp on Coordination. News Physiol Sci, 13(2),

70-75.

209

Whitall, J., McCombe Waller, S., Silver, K., & Macko, R. F. M. D. (2000). Repetitive Bilateral Arm

Training With Rhythmic Auditory Cueing Improves Motor Function in Chronic

Hemiparetic Stroke. Stroke October, 31(10), 2390-2395.

Wilson, S. A., Lockwood, R. J., Thickbroom, G. W., & Mastaglia, F. L. (1993). The muscle silent

period following transcranial magnetic cortical stimulation. Journal of the Neurological

Sciences, 114(2), 216-222.

Wilson, S. A., Thickbroom, G. W., & Mastaglia, F. L. r. n. (1993). Topography of excitatory and

inhibitory muscle responses evoked by transcranial magnetic stimulation in the human

motor cortex. Neuroscience Letters, 154(1-2), 52-56.

Wing, A. M., & Kristofferson, A. B. (1973). Response delays and the timing of discrete motor

responses. Perception & Psychophysics, 14(1), 5-12.

Winter, D. A. (2005). Biomechanics and motor control of human movement (3rd ed.). Hoboken,

New Jersey: John Wiley & Sons.

Wuyts, I. J., Summers, J. J., Carson, R. G., Byblow, W. D., & Semjen, A. (1996). Attention as a

mediating variable in the dynamics of bimanual coordination. Human Movement

Science, 15(6), 877-897.

Wyke, M. (1971). The effects of brain lesions on the performance of bilateral arm movements.


Yamanishi, J.-i., Kawato, M., & Suzuki, R. (1980). Two coupled oscillators as a model for the

coordinated finger tapping by both hands. Biological Cybernetics, 37(4), 219-225.

Zelaznik, H. N., Spencer, R. M. C., & Ivry, R. B. (2002). Dissociation of Explicit and Implicit

Timing in Repetitive Tapping and Drawing Movements. Journal of Experimental

Psychology: Human Perception and Performance, 28(3), 575-588.

Zelaznik, H. N., Spencer, R. M. C., Ivry, R. B., Baria, A., Bloom, M., Dolansky, L., et al. (2005).

Timing variability in circle drawing and tapping: probing the relationship between

event and emergent timing. Journal of Motor Behavior, 37(5), 395-403.

Ziemann, U., Tergau, F., Netz, J., & Homberg, V. (1997). Delay in simple reaction time after

focal transcranial magnetic stimulation of the human brain occurs at the final motor

output stage. Brain Research, 744(1), 32-40.

Zoghi, M., Pearce, S. L., & Nordstrom, M. A. (2003). Differential modulation of intracortical

inhibition in human motor cortex during selective activation of an intrinsic hand

muscle. Journal of Physiology, 550(Pt 3), 933-946.

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APPENDIX A

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