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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