1. Neuroplasticity and Rehabilitation Strategies Robert K. Shin M.D. VA MS Center of Excellence Assistant Professor Departments of Neurology and Ophthalmology University of Maryland School of Medicine

2. Neuroplasticity? The ability of cortex to reorganize in response to injury The ability of cortex to reorganize in response to injury

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

4. Functional MRI BOLD contrast analysis BOLD contrast analysis –Oxyhemoglobin –Deoxyhemoglobin Alternating periods of task vs. rest Alternating periods of task vs. rest Activated regions determined statistically Activated regions determined statistically

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

7. A dynamic cortical response? Initially increased activation of contralateral sensorimotor cortex Initially increased activation of contralateral sensorimotor cortex Ipsilateral activation seen initially as well Ipsilateral activation seen initially as well Activation gradually reduced as patient recovered Activation gradually reduced as patient recovered

8. Clinically isolated syndrome 16 consecutive patients with a CIS suggestive of multiple sclerosis 16 consecutive patients with a CIS suggestive of multiple sclerosis 15 age- and sex-matched controls 15 age- and sex-matched controls Functional MRI during finger flexion Functional MRI during finger flexion Rocca et al. NeuroImage 2003;18:847-855

11. A response to cortical pathology? Decreased NAA found in clinically stable CIS patients Decreased NAA found in clinically stable CIS patients Increase in activation of somatomotor cortex correlated with worsening brain damage Increase in activation of somatomotor cortex correlated with worsening brain damage

12. Another puzzle Optic neuritis causes vision loss and prolonged VEPs Optic neuritis causes vision loss and prolonged VEPs Vision in optic neuritis almost always recovers Vision in optic neuritis almost always recovers VEPs frequently remain abnormal VEPs frequently remain abnormal

14. Question Is the brain somehow compensating for impaired optic nerve function? Is the brain somehow compensating for impaired optic nerve function?

15. Recovery from optic neurits 7 patients who had recovered from optic neuritis 7 patients who had recovered from optic neuritis 7 controls 7 controls Functional MRI during photic stimulation Functional MRI during photic stimulation Werring, et al. JNNP 2000;68:441-449

17. Functional reorganization? Only occipital activation seen in controls Only occipital activation seen in controls Additional extra-occipital areas were activated in patients who had recovered from optic neuritis Additional extra-occipital areas were activated in patients who had recovered from optic neuritis

18. Attention and memory 22 patients with RR-MS 22 patients with RR-MS 22 age-matched controls 22 age-matched controls Functional MRI study Functional MRI study –Paced Auditory Serial Addition Test (PASAT) –Recall task Mainero, et al. NeuroImage 2004;21:858-867

19. PASAT

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

21. Mainero, et al. NeuroImage 2004;21:858-867 T2 LL

22. An adaptive mechanism? Altered activation during cognitive tasks in MS patients Altered activation during cognitive tasks in MS patients Activation increases as T2 lesion load increases Activation increases as T2 lesion load increases But activation is greater in patients with better function But activation is greater in patients with better function

23. Conclusions Functional MRI activity is altered in MS patients Functional MRI activity is altered in MS patients These changes appear to be an adaptive response to brain damage These changes appear to be an adaptive response to brain damage

24. 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 stimulation –Forced use –Neurotrophic factors –Increased neurotransmitter release