Roadmapsbahc.org.sa/ISCIC_Sessions_2014/ISCIC_Workshops/3_Workshop edelle.pdf · Conforto et al. J...

1

Advanced rehabilitation strategies to optimize neurological recovery after SCI

Edelle C. Field-Fote, PhD, PT, FAPTAProfessor, Physical Therapy & Neurological Surgery

Principal Investigator, The Miami Project to Cure Paralysis

Roadmap: neuroplasticity and motor learning

1. What neural mechanisms underlie neuroplasticity ?

2. How does training influence neuroplasticity?

3. What is important about the type and amount of training?

Contemporary Concepts in Neuroplasticity

Old Views:• You are born with all the neurons you will

ever have• The nervous system is a hardwired

New Views:• New neurons are generated even in adults• There are new connections made between

neurons• The new connections rely on training and

practice

Neuroplasticity

• The capacity of the CNS to undergo changes in function and structure in response to use and motor learning

• May be favorable or unfavorable

2

Possible Mechanisms Underlying Neuroplasticity

• Altered Synaptic Efficacy– Increased/decreased excitability– Unmasking of Latent Connections

• New Connections– sprouting– synaptogenesis

• Neurogenesis

Rapid Mechanisms of Plasticity • Altered synaptic efficacy

– Changing the balance of excitatory and inhibitory connections

+

-

+

-

+ ++ ++

Rapid Mechanisms of Plasticity • Unmasking of latent connections

(silent synapses)

Telephone operators circa 1932

3





Changes in synaptic efficacy underlie changes in neural excitability and responsiveness

Kandel, Schwartz & Jessell, Principles of Neural Science, 2000

Changes in synaptic efficacy underlie ability to

Kandel, Schwartz & Jessell, Principles of Neural Science, 2000

retain effects of activation Slow Mechanisms of Plasticity

• Sprouting and synaptogenisis– Sprouting of new dendrites– Increased number of synapses

4

Neurogenesis in Humans

•Neurogenesis postnatally in:

•Hippocampus

•Subventricular Zone

•Olfactory Bulb

Running / exercise increase hippocampal neurogenesis in adult mice

van Praag, Kempermann G, and Gage. Nat Neurosci. 1999

After 12 days After 4 weeks

Walking associated with hippocampalneurogenesis in older adults

Erickson et al. PNAS. 2011

Stimulation Speaks the Language of the Nervous System

Field-Fote. Exerc Sport Sci Rev, 2004

5





Operational premise:

The goal of therapy is to:

engage specific neural circuits in order to…

enhance the activity of those circuitsin order to…

facilitate the related motor function

Requirements for Proficient Motor Performance

–Relevant movement experience–Repetition–Neuroplasticity

6

Chondroitinase + specific training improves reaching

García-Alías et al. Nat Neurosci. 2009;12:1145-51.

Reaching task performance


Ladder walking task impairs reaching skill acquisition BUT improves ladder walking


Pellet retrieval Ladder missteps

100’s – 1,000’s of reps/session over weeks to months

Chen XY… Wolpaw JR, et al. Neurosci Lett. 302: 85–88, 2001. Remple MS …and Kleim JA, et al. Behav Brain Res 123: 133–141, 2001.Nudo & Milliken. J Neurophysiol. 1996;75: 2144-2149.Chau C, Barbeau H, Rossignol S. J Neurophysiol 1998;79:392-409.de Leon RD, Hodgson JA, Roy RR, Edgerton VR. J Neurophysiol 1998;79:1329-40.

Dose Literature: animal models of practice dose

7

Dose Literature: rehab studies of practice dose

UE studies: 100+ reps/sessionLE studies: 1000+ steps/session

(many studies acknowledge importance of high repetitions but do not report the actual numbers)

Carey JR, Kimberley TJ, et al. Brain. 2002;125:773-788.Boyd L, Winstein C. J Neurol Phys Ther. 2006;30:46-59.Fine MS, Thoroughman KA. J Neurophysiol. 2006;96:710-720.

Dose Literature: studies of real-world practice dose

1Lang CE et al. J Neurol Phys Ther. 2007;31:3-10.2Kimberley TJ et al J Rehabil Res Dev. 2010;47:851-62.

Upper Extremity (reps) Lower extremity (steps)

Mean reps 95%CI Mean steps 95%CI

Stroke1 32 20 - 44 357 296 – 418

Stroke2 41 28 - 53 185 137 – 234

TBI2 61 40 - 82 317 181 – 446

Understanding therapy dose

Important for identifying…

• Dose-response relationships• Minimum dose needed for detectable change

• Dose associated with optimal change

Sleep consolidation

Walker et al Leaning and Memory, 2003

8

Roadmap: functional recovery in the upper extremity

1. What neuroplastic changes occur in the brain after CNS injury.

2. What is the evidence that training and stimulation can promote adaptive neuroplasticity?

3. What functional changes are observed with combined training and stimulation?

Unfavorable Neuroplasticity Occurs after CNS Injury

Maladaptive plasticity of the motor cortex after stroke

Nudo et al. J Neurosci, 1996

What is the source motor impairment after SCI?

Damage to descending tracts

Detrimental spinal reorganizationDamage to ascending tractsDetrimental cortical reorganization

9

Curt et al. J Neurotrauma, 2002

Cortical plasticity in individuals with SCIThe cortex reorganizes

after SCI…

Green et al. Neurology, 1998

…does this contribute to functional deficits?





Nudo RJ. Mol Psychiatry, 1997

10

Cortical activity associated with loss and recovery of hand funcion after cSCI

resembles that after stroke

• ↑ activation of M1 and ↓activation of associated sensorimotor areas

(Jurkiewicks et al., 2007)

Non-disabled subject

Subject with cSCI

1 mo

3 mo

6 mo

12 mo

Mental practice improves function and promotes cortical plasticity

Pascual-Leone et al J Neurophysiol. 1995; 74:1037-45.

Protocol: Mental Practice

Pre TestPerformance & cortical excitability

Mental Practice2 hrs 5x/week

• Sit in front of piano• Visualize finger sequence• Imagine sound

Post TestPerformance & cortical excitability

Pascual-Leone et al J Neurophysiol. 74:1037-45, 1995

Correlation between increases in cortical excitability and motor performance

(Kim et al, 2006

11

Sensory input influences the motor cortex

Asanuma & Mackel Jpn J Physiol , 1989.

Cortical excitability is increased with sensory stimulation

Pre MEP Post MEP

Ridding et al, Exp Brain Res, 2000

Somatosensory stimulation enlarges cortical areas activated by movement

Wu et al. Neuroimage, 2005

Sensory stimulation increases pinch strength post stroke

Conforto et al. Ann Neurol. 2002.

12

Effects of sensory stimulation + training on function post stroke

Conforto et al. J Neurol, 2007.

(single session)

(single session)

Median nerve stim (supra thrshld)

Control stim (sub thrshld)

Sensory stim + training improves function in individuals with stroke

Conforto et al. J Neurol, 2007.

Cortical Plasticity Occurs with LE StimulationFES for footdrop modifies MEP of TA

Thompson &Stein. Exp Brain Res, 2004

TENS to hand muscle increases size of cortical hand map in ND subjects

Meesen et al. Human Brain Mapping, 2010

TENS to APB • 100 Hz• 250 µs pulse width• 21 days 1hr/day

N = 24, 12/group

13

TENS improves hand sensory function in individuals with MS

(but not ND individuals)

Cuyers et al. Neurorehabil Neural Repair, 2010

Protocol: Massed Practice + Somatosensory Stimulation

Pre TestPerformance, strength, cortical excitability

Massed Practice + Stim• 2 hrs 5x/week for 3 weeks• 5 categories of tasks

(everyday activities)~ concurrent with ~

• SS to median nerve, 500ms trains, 10Hz

Post TestPerformance, strength, cortical excitability

Beekhuizen & Field-Fote. Arch Phys Med Rehabil, 89: 602-608, 2008





Hand function is highest priority among those with tetraplegia

Anderson K. J Neurotrauma, 2004

14

Gross UE Movement

Pinch

Pinch with rotation Grip with rotation

Grip

Massed practice for task-specific training effects


Massed practice categories and sample tasks


Task Modification for Success / Challenge

Somatosensory Stimulation Parameters• 2 hrs/day • median nerve stimulation (at wrist) • Either:

– in conjunction with MP training (MP +SS)– or alone (SS)

• Parameters: trains of stimulation– 10 Hz (500ms on / 500 ms off) – 1 msec pulse duration – Submotor threshold intensity

• (no visible thumb contraction)

• Goal: – Preferentially activate large proprioceptive

and cutaneous sensory fibers

stimulating electrode placement over the median nerve

recording electrodes over thenar eminence

Ridding et al. Exp Brain Res, 2000 (ND) Conforto et al. Ann Neurol, 2002 (Stroke)

15

Protocol: Massed Practice + Somatosensory Stimulation

Pre TestPerformance, strength, cortical excitability

Massed Practice + Stim• 2 hrs 5x/week for 3 weeks• 5 categories of tasks

(everyday activities)• SS to median nerve 500ms trains, 10Hz

Post TestPerformance, strength, cortical excitability


Functional hand use

Beekhuizen &Field-Fote . Arch Phys Med Rehabil, 2008

Jebsen -Taylor Hand Function test

Strength


Sensory Function


16

Pre training Functional Test Post training Functional Test

• Unimanual Training

• Bimanual Training

Bimanual Training

Hoffman & Field-Fote. J Neurol Phys Ther , 34:193-201, 2010

Bimanual activity engages more cortical areas than unimanual activity

De Weerd et al., 2003

Bi Asym

Bi Sym

Uni (Left)

17

Rationale: unilateral arm use is associated

with inhibition of the inactive cortex

INHIBITION↓EXCITATION↑

(Mc Combe & Waller, 2008)

ACTIVECORTEX

(UNI)

INACTIVECORTEX

(UNI)

BILATERALBASELINE

but…

bilateral arm use is associated with bihemispheric excitation

(Mc Combe & Waller, 2008)

BILATERALBASELINE ACTIVECORTEX

(UNI)

INACTIVECORTEX

(UNI)

EXCITATION↑ EXCITATION↑

Unimanual hand function outcomes


bimanual hand function outcomes


18

TMS cortical mapping to assess cortical plasticity Cortically Evoked Potentials after SCI

11 2233 11 2233

2

1

0

-1

-2

VA

DC

1

2

10

5

0

-5

-10

VA

DC

7

8

Keyboard9

-0.02 -0.01 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07s

MEP at 60%MSO in ND individual

11 2211 22

2

1

0

-1

-2

V

AD

C 0

1

10.0

7.5

5.0

2.5

0.0

-2.5

-5.0

V

AD

C 7

8

-0.04 -0.03 -0.02 -0.01 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10

MEP at 90% MSO in individual witincomplete cervical SCI

Sample Thenar MEP at 88% MSOPre-training

Post-training

The cortex reorganizes after SCI…

Green et al. Neurology, 1998

…does this contribute to functional deficits?

19

Subject with incomplete C5 injury

Green JB et al. Neurology,1999.

Plasticity of the Motor Map Accompanying Recovery of Function Following SCI

Cor

tical

Map

ping

Hoffman & Field-Fote. Phys Ther, 2007

Cortical stimulation as an intervention

Biophysics of TMS

20

rTMS in SCI and ND

• High frequency (excitatory) rTMS– Direct cortical activation – Elicits motor response

(Pascual-Leone, 1994; Beradelli et al, 1998; Butefish et al, 2004; Kim et al, 2006; Tallelli & Rothwell, 2006)

Results: functional outcomes

Dashed line indicates threshold for moderate effect size

Is direct cortical activation more beneficial than indirect (somatosensory) activation ?

Transcranial direct current stimulation (tDCS)• Electrodes applied to the scalp• Simple unidirectional direct current• 1 mA current• Session time: 20 min• Mild adverse effects (itching), non-invasive, painless

Transcranial direct current stimulation (tDCS)

ANODAL CATHODAL

(Fregni & Pascual-Leone, 2007)

Lesioned hemisphere Non-Lesioned hemisphere

Polarizing currents applied to cortex modulate neuronal excitability

– Anodal = lowers threshold– Cathodal = raises threshold

Appears effective for hemiparesis

– Increase excitability of lesioned ctx

– Decrease excitability of non-lesioned ctx

21

Uni-hemispheric tDCS in stroke

Boggio et al. Rest Neurol Neurosci, 2007

Bi-hemispheric (anodal/cathodal) more effective than uni-hemispheric (ND subjects)

Vines et al. BMC Neurosci, 2008

Protocol: Transcranial Direct Current Stimulation

Pre TestFunctional hand performance

tDCS• Electrodes applied to the scalp• M1 & contra forehead (anodal ~OR~ cathodal)~OR~ M1 & ipsi forehead (anodal + cathodal)• 1 mA current• 20 min session duration• Mild adverse effects (itching)

Post TestFunctional hand performance

Boggio et al. Rest Neurol Neurosci, 2007

tDCS

• Cervical Spinal Cord Injury- Bilateral upper extremity impairment- What about bilateral excitatory

stimulation?

22

Experimental Setup• Bilateral anodal

corticomotor tDCS (1 mA, 20 min) or sham

• Outcome Measures: BT and STM tasks

Bimanual finger-sequencing scores

Rios-Gomes & Field-Fote. In review, 2013

*

Evidence suggests that stimulation can potentiate effects of motor practice…

Is there an advantage in choosing one modality over another?

VERSUS VERSUS

tDCS Vibration TENS

Methods/Research Design

MOTOR TRAINING

30 MIN BREAK

TESTING

TESTING

TESTING

SESSION

OR OR

OUTCOME MEASURES Active MEP Threshold Pinch Grip Strength Visuomotor Tracking Task 9-hole peg test

ONE SESSION PER WEEK3 SESSIONS TOTAL

23

Hand function in persons with tetraplegia -effects of direct vs indirect cortical activation

0

0.5

1

1.5

2

2.5

tDCS TENS VIB

9HPT (pegs)

Pinch force (kg)

Conclusions• Even in chronic CNS injury there is potential for improvement of hand function.

• Both stimulation & training affect neural structures that underlie movement – effects may be additive.

• There are changes in cortical neurophysiologic measures associated with functional change.

• Clinically available devices can be employed to increase cortical excitability

Roadmap:functional recovery in the lower extremity

1. What are the innate capabilities of the spinal cord?

2. How do spinal reflex circuits change after CNS injury?

3. Can we influence spinal circuits – do we want to?

4. How can stimulation augment training for improved walking?

The “smart” spinal cord

“The spinal cord functions as part of the brain and not its servant”

-- Reggie Edgerton

24

Stretch Reflex H-reflex: the electrical analogue of the stretch reflex

Spinal circuits generate innate rhythmic behaviors

Hultborn. J Rehabil Med, 2003.

The Wiping Reflex of the Spinal Frog: Target-Specific Movement Trajectory. From Fukson OI, Berkinblit MB, Feldman AG. The spinal frog takes into account the scheme of its body during the wiping reflex. Science 209: 1261- 1263, 1980

Spinal Cord Performs Sensory – Motor Transformation

25

Field &Stein. J Neurophys, 1997

The spinal cord controls limb coordinationof innate, rhythmic behaviors Scratching in the spinal turtle

Intra- and interlimb coordination following complete spinal cord transection

Spinal stepping response in human infant

26

Involuntary stepping after SCI as evidence of human locomotor CPG

Similar case in: Calancie et al. Brain, 1994

Principles of motor control generalize across species






Disrupted reflex modulation

27

Modulation of spinal circuitry is essential for normal movement

Lundbye-Jensen & Nielsen. J Physiol , 2008.

Excitability in response to stretch can be quantified

The

Pend

ulum

Tes

t

Hig

h sp

astic

ity

L

ow

spa

stic

ity

Motor Disorder Probable Origin

Spasticity Increased responsiveness to stretch, ETC.

Clonus Loss/reduction of post-activation depression

Co-contraction Loss/reduction of reciprocal inhibition

Flexor spasms Increased responsiveness to FRA input

Spastic gait pattern Decreased phase-dependent modulation

Disrupted reflex modulation is associated with disordered motor output Immobilization of ND subjects induces

reflex changes similar to CNS injury

Lundbye-Jensen & Nielsen , J Physiol 2008

28

Spasticity during walking is correlated with severity of SCI

Fung & Barbeau J Neurophysiol, 1994

non-disabled mildly impaired moderately impaired severely impaired

Foot contact

Toe off






Spinal reflexes respond to training

Wolpaw et al, Brain Res, 1983

Stimulation improves reciprocal inhibition in those with spasticity

Crone et al. Brain, 1994

● ND subjects (n =74)

o subjects with spasticity (n=39)

subjects with spasticity who used CPN stim (n=4)

29

CPN stimulation improves phase-dependent reflex modulation

Fung & Barbeau. J Neurophysiol,1994; 72: 2090-2104

■ static□ walking

Central pattern generators respond to trainingCPG plasticity

Hodgson et al Med Sci Sports Exerc, 1994

Should we train to ↓ reflexes or to ↑ voluntary control?

N =12

3 baseline sessions

12 training sessions(3/wk x 4 wks)

Manella, Roach, Field-Fote. J Neurophys. In press, 2013

Sample SOL ↓ Outcome


30

OutcomesEMG, clinical, walking, reflexes







Approaches to locomotor training in individuals with chronic CNS injury

• Treadmill-based training with BWS• manual assisted• FES assisted• robotic assisted

• Overground training

Treadmill vs skilled overground training in chronic SCI

Musselman et al. Phys Ther, 2009

Crossover design case series: BWSTT followed by OG or BWSTT2 – 3x/week for 12 weeks

Conclusion: speed gains with skill-based OG training were greater than with BWSTT

N = 4 (8 per group)

31

Locomotor training improves walking in those with chronic incomplete SCI….

But what is the best approach

to improving walking function?

Protocol: Locomotor Training

Pre TestWalking speed & distance, reflexes, balance, etc

Randomization to 1 of 4 groups•1 hr/day •5 days/wk•12 week training

Post TestWalking speed & distance, reflexes, balance, etc

Field-Fote & Roach. Phys Ther, 91:48-60, 2011

TS

OG LR

Locomotor training improves walking in SCI – is there a “best” approach?

• Treadmill training with manual assistance (TM)

• Treadmill training with CPN stimulation assist (TS)

• Overground training with CPN stimulation assist (Walkaide II stimulator; OG)

• Treadmill training with robotic assistance (Lokomat robotic orthosis; LR)

TM


N = 74 enrolled, 64 completed (across 4 groups)

Lokomat using passive mechanical guidance only

32

Changes in Walking Speed by Intervention Group

Sp

eed

(m

/s)

Walking speed in ND individuals is 1.2 m/s (2.7mph)


Proportion of subjects who increased walking speed by more than .05 m/sec

Field-Fote & Roach. Phys Ther, 2011

Changes in Walking Distance by Intervention Group

Sp

ee

d (

m/s

)


Proportion of subjects who increased walk distance by more than 2 meters


33

Proportion of subjects who improved in distance and/or speed

Pro

po

rtio

n

What is the influence of training speed?

Training Speed

0.000.100.200.300.400.500.600.700.800.90

TM TS OG LR

Groups

Me

an

Sp

ee

d (

m/s

)

Pre Test

Post Test

Field-Fote & Lindley J Neurol Phys Ther, 2005

Pre-Intervention 2-Minute Walk Test Post-Intervention 2-Minute Walk Test

34

Pendulum TestPendulum Test Change in ROM

0

10

20

30

4050

60

70

80

90

TM TS OG LR

Groups

Deg

rees

of M

otion

PRE

POST *

* sig increase in

ROM p = .044

Knee Angle at First Contraction

-5

0

5

10

15

20

25

30

TM TS OG LR

Groups

Per

cen

tage

Chan

ge

How might we use what we know about effects of sensory input to improve

locomotor function?

How might vibration influence the locomotor CPG?

Vibration elicits involuntary step-like movement in ND individuals

•Vibration elicits locomotor-like movements•Single muscle or contralateral leg•Cyclic behavior suggesting CPG origin

Gurfinkel et al. Eur J Neurosci, 10:1608-1612, 1998

35

Vibration elicits involuntary stepping in individuals with SCI

Vibration: 60 Hz, ~1 mm displacement

ND Individual: Involuntary Stepping with Muscle Vibration

Field-Fote et al, Neurorehabil Neural Repair. 2012

Motor-incomplete SCI: Involuntary Stepping with Muscle Vibration


Motor-complete SCI: Involuntary Stepping with Muscle Vibration


36

Whole-body Vibration (WBV)

• Literature supports:– decreased spasticity in

individuals with CP (Ahlborg ‘06)

– Increased walking speed in elders and individuals with PD

(Kawanabe ‘07, Ebersbach ‘08)

– Improved balance in individuals with stroke

(van Nes, ‘04 & ‘06)

FS

E (

deg

rees

)

Ness & Field-Fote. Restor Neurol Neurosci, 2009.

WBV is associated with decreased quadriceps spasticity

WBV influences on spasticity• cumulative multi-session effects• early within-session effects • late within-session effects

FS

E (

deg

rees

)

Intervention week

Ness & Field-Fote. Restor Neurol Neurosci, 2009

WBV is associated with improved gait speed and quality

Ness & Field-Fote. Gait & Posture, 2009

37

Improved walking following 12-session course of WBV

Protocol: Whole Body Vibration

Pre TestQuad spasticity, walking speed (10m)

WBV: • Static squat• 50 Hz• low amplitude • 4x45sec – 1min rest • 3 days/week x 4 wks

Post TestQuad spasticity, walking speed (10m)

Ness & Field-Fote. Gait & Posture, 2009 (Walking function)Ness & Field-Fote. Restor Neurol Neurosci, 2009 (Spasticity)

Journey’s End1. Neural mechanisms underlying

neuroplasticity rely on changes excitability

2. Excitability is influenced by practice and by stimulation

3. Neuroplastic cortical changes appear to reflect changes in function

4. Spinal reflex and pattern-generating circuits respond training in the same way as cortical circuits

5. Combining training and stimulation may represent an optimal approach to promoting adaptive neuroplasticity

Activating the nervous system

can make a difference today

Roadmapsbahc.org.sa/ISCIC_Sessions_2014/ISCIC_Workshops/3_Workshop edelle.pdf · Conforto et al. J...

Documents

Transcript of Roadmapsbahc.org.sa/ISCIC_Sessions_2014/ISCIC_Workshops/3_Workshop edelle.pdf · Conforto et al. J...