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Neuroplasticity in Recovery After SCI:

optimizing recovery through

rehabilitation interventions

Edelle C. Field-Fote, PhD, PT, FAPTA

Professor, Physical Therapy & Neurological Surgery

Principal Investigator, The Miami Project to Cure Paralysis

INTERNATIONAL SPINAL CORD INJURY CONFERENCE:

TOWARD BETTER QUALITY OF LIFE

Roadmap:

1. What neural mechanisms underlie

neuroplasticity?

2. What happens in the brain following CNS

injury and can we reverse these changes?

3. How can we use this information to

promote upper extremity function?

4. What is the innate capacity of spinal circuits

and do they respond to training?

5. Is there an optimal approach to improving

walking function?

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

neural excitability influences responsiveness

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

Spinal

motoneuron

Modified from Asanuma & Mackel Jpn J Physiol, 1989.

Sensory input influences the

motor cortex

Roadmap:

1. What neural mechanisms underlie

neuroplasticity?

2. What happens in the brain following CNS

injury and can we reverse these changes?

3. How can we use this information to

promote upper extremity function?

4. What is the innate capacity of spinal circuits

and do they respond to training?

5. Is there an optimal approach to improving

walking function?

The cortex reorganizes

after SCI…

Green et al. Neurology, 1998

…does this contribute

to functional deficits?

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Cortical excitability is increased with

sensory stimulation

Pre MEP Post MEP

Ridding et al, Exp Brain Res, 2000

Roadmap:

1. What neural mechanisms underlie

neuroplasticity?

2. What happens in the brain following CNS

injury and can we reverse these changes?

3. How can we use this information to

promote upper extremity function?

4. What is the innate capacity of spinal circuits

and do they respond to training?

5. Is there an optimal approach to improving

walking function?

Hand function is highest priority

among those with tetraplegia

Anderson K. J Neurotrauma, 2004

Gross UE Movement

Pinch

Pinch with rotation Grip with rotation

Grip

Massed practice for task-specific

training effects

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

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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

over median nerve

(recording electrodes over

thenar eminence)

Ridding et al. Exp Brain Res, 2000 (ND)

Conforto et al. Ann Neurol, 2002 (Stroke)

Outcome Measures

10 measure: Jebsen-Taylor Hand Function Test

Electrophysiologic (MEPs):

• AMT thenar

• RMT biceps (to determine rTMS frequency)

• Recruitment Curve thenar (active contraction)

20 Measures

Functional measures

• Pinch Grip Strength

• 9-Hole Peg Test

What approach is best for improving

motor & sensory function?

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

Jebsen-Taylor Hand Function Test Monofilament Sensory Testing

% Change (pre-post)

Pre training Functional Test

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Post training Functional Test Change in hand function is associated

with change in excitability

Pre-training

Post-training

Sample thenar MEP at 88% MSO

Co

rtic

al M

ap

pin

g

Hoffman & Field-Fote. Phys Ther, 2007

Is direct cortical activation more beneficial

than indirect (somatosensory) activation ?

Available approaches to direct cortical stimulation

– Transcranial direct current stimulation (tDCS)

•Modulates neuronal excitability

•Studies in persons with stroke

– anodal vs cathodal

– Repetitive transcranial magnetic stimulation

•Activates neurons

•Studies in persons with stroke (high frequency)

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tDCS

Effects on cortical excitability

– Neuromodulator

– Anode=

EXCITATION

– Cathode=

INHIBITION

ANODE CATHODE

(Fregni & Pascual-Leone, 2007)

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)

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

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Conclusions

• Both direct and direct cortical

activation augments training effects

• Stimulation choices depend on:

– Device availability

– Clinic vs home use

Roadmap:

1. What neural mechanisms underlie

neuroplasticity?

2. What happens in the brain following CNS

injury and can we reverse these changes?

3. How can we use this information to

promote upper extremity function?

4. What is the innate capacity of spinal circuits

and do they respond to training?

5. Is there an optimal approach to improving

walking function?

The spinal cord can coordinate the limbs

following complete spinal cord transection

Field & Stein. J Neurophysiol. 1997; 78: 1394-1403 and 1404-1413

Infant Stepping Response

evidence of central pattern generators in humans

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Roadmap:

1. What neural mechanisms underlie

neuroplasticity?

2. What happens in the brain following CNS

injury and can we reverse these changes?

3. How can we use this information to

promote upper extremity function?

4. What is the innate capacity of spinal circuits

and do they respond to training?

5. Is there an optimal approach to improving

walking function?

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

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

N = 74 enrolled, 64

completed (across 4 groups)

Note: Robotic Orthosis

used in Passive Mode Only

Changes in Walking Speed

by Intervention Group

Sp

eed

(m

/s)

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

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

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Changes in Walking Distance

by Intervention Group

Sp

eed

(m

/s)

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

Whole-body vibration decreases

spasticity and improves

walking in persons with SCI

Excitability in response to

stretch can be quantified

The Pendulum

T

est

Hig

h spastic

ity Lo

w spastic

ity

WBV is associated with improved

gait speed and quality

Ness & Field-Fote. Gait & Posture, 2009

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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

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

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Motor-incomplete SCI: Involuntary Stepping

with Muscle Vibration

Field-Fote et al, Neurorehabil Neural Repair. 2012

Motor-complete SCI: Involuntary Stepping

with Muscle Vibration

Field-Fote et al, Neurorehabil Neural Repair. 2012

Conclusions & Considerations

1. Neural mechanisms underlying

neuroplasticity rely on changes in

excitability

2. Neural excitability is influenced by

practice and by stimulation

3. Combining training and stimulation may

represent an optimal approach to

promoting adaptive neuroplasticity

For the future:

Repair strategies are likely to be effective

only when combined with rehabilitation

strategies

The BAD News:

To Date No Intervention has been shown to be More Effective than Rehabilitation

for Improving Function

The GOOD News:

To Date No Intervention has been shown to be More Effective than Rehabilitation

for Improving Function

REPAIR

REHABILITATION

+

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● National Institutes of Health ● The Schumann Foundation

● The Buoniconti Fund ● National Institute for Disability &

● Craig H. Nielsen Foundation Rehabilitation Research

PRIMARY

SPONSORS 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

Early vs Late Effects on Cortical Excitability

Rationale:

unilateral arm use is associated

with inhibition of the inactive cortex

INHIBITION↓ EXCITATION↑

(Mc Combe & Waller, 2008)

ACTIVE

CORTEX

(UNI)

INACTIVE

CORTEX

(UNI)

BILATERAL BASELINE

but…

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bilateral arm use is associated with

bihemispheric excitation

(Mc Combe & Waller, 2008)

BILATERAL BASELINE ACTIVE

CORTEX

(UNI)

INACTIVE

CORTEX

(UNI)

EXCITATION↑ EXCITATION↑

Field &Stein. J Neurophys, 1997

The spinal cord controls limb coordination

of innate, rhythmic behaviors

Bimanual typing task interface

N = 28 ND participants

Safety Study: Bihemispheric

Anodal tDCS Results

Mean change in scores BE-tDCS: 19.4 (95% CI 12.82-25.99)

Mean change in scores sham: 12.5 (95% CI 7.6-17.3)

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Conclusions in ND subjects

• tDCS yields greater gains in manual

performance versus practice alone.

• No effects on short term memory