neuroplasticity and rehabilitation strategies robert k. shin m.d. va ms center of excellence...

Neuroplasticity and Rehabilitation Neuroplasticity and Rehabilitation StrategiesStrategies

Robert K. Shin M.D.Robert K. Shin M.D.VA MS Center of ExcellenceVA MS Center of Excellence

Assistant ProfessorAssistant ProfessorDepartments of Neurology and OphthalmologyDepartments of Neurology and Ophthalmology

University of Maryland School of MedicineUniversity of Maryland School of Medicine

Neuroplasticity?Neuroplasticity?

The ability of cortex to reorganize in response to The ability of cortex to reorganize in response to injuryinjury

QuestionQuestion

Is the brain compensating for damage from MS in Is the brain compensating for damage from MS in order to maintain normal function?order to maintain normal function?

Functional MRIFunctional MRI

BOLD contrast analysisBOLD contrast analysis

– OxyhemoglobinOxyhemoglobin

– DeoxyhemoglobinDeoxyhemoglobin

Alternating periods of task vs. restAlternating periods of task vs. rest

Activated regions determined statisticallyActivated regions determined statistically

Reddy et al. Neurology 2000;54:236-244

A dynamic cortical response?A dynamic cortical response?

Initially increased activation of contralateral Initially increased activation of contralateral sensorimotor cortexsensorimotor cortex

Ipsilateral activation seen initially as wellIpsilateral activation seen initially as well

Activation gradually reduced as patient recoveredActivation gradually reduced as patient recovered

Clinically isolated syndromeClinically isolated syndrome

16 consecutive patients with a CIS suggestive of 16 consecutive patients with a CIS suggestive of multiple sclerosismultiple sclerosis

15 age- and sex-matched controls15 age- and sex-matched controls

Functional MRI during finger flexionFunctional MRI during finger flexion

Rocca et al. NeuroImage 2003;18:847-855Rocca et al. NeuroImage 2003;18:847-855

Rocca et al. NeuroImage 2003;18:847-855Rocca et al. NeuroImage 2003;18:847-855

A response to cortical pathology?A response to cortical pathology?

Decreased NAA found in clinically stable Decreased NAA found in clinically stable CIS patientsCIS patients

Increase in activation of somatomotor cortex Increase in activation of somatomotor cortex correlated with worsening brain damagecorrelated with worsening brain damage

Another puzzleAnother puzzle

Optic neuritis causes vision loss and prolonged Optic neuritis causes vision loss and prolonged VEPsVEPs

Vision in optic neuritis almost always recoversVision in optic neuritis almost always recovers

VEPs frequently remain abnormalVEPs frequently remain abnormal

QuestionQuestion

Is the brain somehow compensating for impaired Is the brain somehow compensating for impaired optic nerve function?optic nerve function?

Recovery from optic neuritsRecovery from optic neurits

7 patients who had recovered from optic neuritis7 patients who had recovered from optic neuritis

7 controls7 controls

Functional MRI during photic stimulationFunctional MRI during photic stimulation

Werring, et al. JNNP 2000;68:441-449Werring, et al. JNNP 2000;68:441-449

Werring, et al. JNNP 2000;68:441-449Werring, et al. JNNP 2000;68:441-449

Functional reorganization?Functional reorganization?

Only occipital activation seen in controlsOnly occipital activation seen in controls

Additional extra-occipital areas were activated in Additional extra-occipital areas were activated in patients who had recovered from optic neuritispatients who had recovered from optic neuritis

Attention and memoryAttention and memory

22 patients with RR-MS22 patients with RR-MS 22 age-matched controls22 age-matched controls

Functional MRI studyFunctional MRI study– Paced Auditory Serial Addition Test (PASAT)Paced Auditory Serial Addition Test (PASAT)– Recall taskRecall task

Mainero, et al. NeuroImage 2004;21:858-867Mainero, et al. NeuroImage 2004;21:858-867

Mainero, et al. NeuroImage 2004;21:858-867Mainero, et al. NeuroImage 2004;21:858-867

PASAT

Mainero, et al. NeuroImage 2004;21:858-867Mainero, et al. NeuroImage 2004;21:858-867

Recall

Mainero, et al. NeuroImage 2004;21:858-867Mainero, et al. NeuroImage 2004;21:858-867

T2 LL

An adaptive mechanism?An adaptive mechanism?

Altered activation during cognitive tasks in MS Altered activation during cognitive tasks in MS patientspatients

Activation increases as T2 lesion load increases Activation increases as T2 lesion load increases

But activation is greater in patients with better But activation is greater in patients with better functionfunction

ConclusionsConclusions

Functional MRI activity is altered in MS Functional MRI activity is altered in MS patientspatients

These changes appear to be an adaptive These changes appear to be an adaptive response to brain damageresponse to brain damage

Implications for rehabilitation?Implications for rehabilitation?

Can functional MRI be used to prognosticate?Can functional MRI be used to prognosticate?

Can “cortical plasticity” be enhanced?Can “cortical plasticity” be enhanced?– Proprioceptive stimulationProprioceptive stimulation

– Forced useForced use

– Neurotrophic factorsNeurotrophic factors

– Increased neurotransmitter releaseIncreased neurotransmitter release