BRAIN PLASTICITY AFTER SPINAL CORD INJURY

CORTICAL REORGANIZATION AFTER CHRONIC SCI

Mar Cortes

Non-invasive Brain Stimulation and Human Motor Control Lab

Burke Medical Research Institute

Cornell University

New York

SCI PHASES AND KEY PATHOLOGICAL EVENTS

Rowland et al, Neurosurg Focus, 2008

• Prevention of injury• Reduction of secondary damage• Replacement of lost cells • Strategies to enhance regeneration• The development of new circuitry/ rehabiliation of remaining

circuitry

STRATEGIES FOR SPINAL CORD REPAIRMultiple systems affected - multivariety of approaches

•Neurophysiology – to understand the underlying mechanisims of dysfunction

•Neuromodulation - to enhance cortical/spinal cord excitability

•Training therapies - to enhance/repair motor function

MEP at 110% RMT

0.1mV

200ms

0.1 mV

20ms

EMG at maximum voluntary contraction (MVC)

Healthy Subject SCI Patient

Edwards et al, in preparation

BRAIN NETWORKS INVOLVED IN MOTOR CONTROL REMAIN RESPONSIVE IN CHRONIC PARALYSIS

Motor Power1/55/5

) (

α

) (

α

Magstim

EMG Instrument

Stimulating coil

Magstim

EMG Instrument

MagstimMagstim

EMG Instrument

EMG Instrument

Stimulating coil

Transcranial Magnetic Stimulation: Mapping

vertex

Right hemisphereLeft hemisphere

max

REORGANIZATION AND PRESERVATION OF MOTOR CONTROL OF THE BRAIN IN SCI

Kotilo et al, J Neurotrauma (2011)

CORTICOMOTOR REPRESENTATION OF FOREARM MUSCLES FOLLOWING CERVICAL SCI

AIM: Investigate changes in cortical map reorganization of forearm muscles with lack of voluntary activation but corticospinal response in chronic SCI non-invasively

Preservation of corticospinal responses of impared muscles Changes in somatotopic localization Differences in map area and volume compared with healthies

SIGNIFICANCE: Therapeutic strategies aiming for restoring spinal cord function even with chronic sci can build on a preserved competent brain control

CORTICAL REORGANIZATION AFTER CHRONIC SCI

PATIENT #

GENDER AGELEVEL

OF INJURY

ASIATYPE

TIME SINCE INJURY

MUSCLE SIDEMOTOR POWER

1 F 29 C4 B 2.3 FCR L 1

2 M 31 C5 B 7.5 FCR L 1

3 M 44 C4 C 1.8 ECR R 1

4 F 55 C5 A 2.1 FCR R 1

5 M 54 C6 A 2.2 FCR R 1

6 M 70 C1 D 3 ECR R 1

7 F 24 C4 B 5.8 ECR L 1

8 M 17 C4 B 4 ECR R 1

9 M 50 C6 A 29 FCR L 0

10 M 50 C1 C 3 ECR L 1

Presence of MEP > 100uV in forearm muscle, with normal latency range. Motor Power of forearm muscle 0-1/5. Chronic SCI (>1year after injury). Cervical injury. Tetraplegic. Traumatic/non-traumatic. Complete/Incomplete

CORTICAL REORGANIZATION AFTER CHRONIC SCI:OPTIMAL SITE LOCATION OF FOREARM MUSCLES

Cz

Right hemisphere

Left hemisphere

Healthy subjects (n=18)

Chronic tetraplegic SCI (n=10) Cortes et al, in prep

CORTICAL REORGANIZATION AFTER CHRONIC SCI:

MEDIAL SHIFT OF THE OPTIMAL SITE IN SCI SUBJECTS

Cz

Right hemisphere

Left hemisphere

Healthy subjects

Chronic tetraplegic SCI

EMG BIOFEEDBACK MUSCLE SPECIFIC TRAINING RESTORES NEUROPHYSIOLOGICAL VALUES IN CHRONIC SCI

Healthy subjectSCI pre training SCI post training

CONCLUSIONS

TMS GUIDED REHABILITATION

Muscles that are profoundly affected after SCI, can be identified by TMS

GREATER POTENTIAL FOR RECOVERY

Muscles with corticospinal response to TMS, despite being clinically silent, may have biological substrate for functional enhancement, even in chronic phase

CORTICAL REORGANIZATION AFTER CHRONIC SCI

- Changes in cortical organization occurs after SCI

- Clinically silent muscles in tetraplegic patients have a medial shift cortical representation, in the direction of the deafferented lower limb

- The understanding of the cortical reorganization after chronic SCI may have implications for function recovery, by using therapeutic strategies that specifically target that brain area (brain stimulation protocols…)

Neuromodulation to enhance spinal excitability

100μV

20ms

TMS80%RMT Only

PNS Only

Combined TMS80%RMT+PNS

TMS

TMS PNS

PNS

20ms

Electrical Stimulator

MagneticStimulator

Peripheral stimulation of somatosensory afferents conditioned by TMS, increases spinal excitability, traduced in a larger H-reflex

amplitude

Cortes et al, Clin Neurophys, 2011

90 paired stimuli

PNSPNSTMSTMS

20ms

0.1 Hz

9000 10

40

30

20

50

890

sec

PRE POSTINTERVENTION(15 min)H-Reflex RC H-Reflex RC

Neuromodulation paradigm to modulate spinal excitability:

Spinal Associative Stimulation protocol

Repetitive paired stimulation can induce changes in excitability at the spinal cord level that are sustained after the intervention period

H-reflex amplitude progressively increased over the paired pulse intervention period

Left shift of the H reflex RC after the intervention period, with a lower threshold

H-reflex recruitment curve

CONCLUSIONS

Non-invasive Brain Stimulation can be used as a neuromodulatory tool to target spinal cord and induce changes and enhance excitability at that level

SAS may be useful to strength residual pathways after incomplete injuries.

SCI plastic changes outlast intervention period => therapeutic window to apply behavioral training in order to enhance motor recovery

FUTURE CONSIDERATIONS TO ENHANCE MOTOR RECOVERY AFTER SCI

COMBINED THERAPIES

BEHAVIORALTRAINING

NEUROMODULATION TECHNIQUES

PHARMACOLOGY

CELLTRANSPLANTAION

NEUROPHYSIOLY GUIDED REHAB

ACKNOWLEDGEMENTS

Dylan J EdwardsRaj RatanBruce VolpeAvrielle Rykman

Alvaro Pascual-Leone

Gary Thickbroom

Josep Valls-Sole

Thank you

Pre – training Post - training

Chronic SCI motor performance after Upper limb Robotic Training