Modulating Interaction of Motor Learning Networks in Rehabilitation of Stroke

Stroke is the leading cause of permanent disability in the United States. In the absence of
treatments to restore the lost tissue, clinical scientists have focused upon repetitive
forced used of the paretic limb to promote neural reorganization in preserved tissue and
reduce disability. However, forced use interventions are time intensive and the extent of
functional recovery is variable. One potential contributor to this variability is the
potential trade-off between compensatory cognitive motor control strategies and the extent of
procedural learning that can occur. Compensatory strategies adopted by patients may produce
quick short-term increases in performance but retard slower sustained improvements by
interfering with development of procedural learning. Consistent with this hypothesis, the
investigators' previous work documents an increased reliance upon dorsolateral prefrontal
cortex during performance of learned skills post-stoke. However, the investigators' previous
work also demonstrates that the effect of increased activity in dorsolateral prefrontal
cortex may limit reorganization in important areas involved in the consolidation of practice
thereby limiting functional recovery post-stroke.

Transcranial magnetic stimulation offers a unique opportunity to investigate the relationship
between dorsolateral prefrontal cortex activity and consolidation of motor
practice/rehabilitaion post-stroke. Here the investigators' objective is to determine whether
suppression of the contralesional dorsolateral prefrontal cortex, with continuous theta burst
transcranial magnetic brain stimulation (cTBS), a form of transcranial magnetic stimulation,
prior to motor practice enhances brain reorganization in critical areas and leads to greater
sustained improvements in motor ability over time.

The proposed work will enhance the understanding of motor learning post-stroke and provide
preliminary evidence for the benefits of dorsolateral prefrontal cTBS as an adjunct to
current rehabilitation interventions.

Inclusion Criteria:

1. Age between 50-75 years

2. movement-related deficit associated with first time middle cerebral artery stroke

3. greater than 6-months post-stroke

4. Fugl-Meyer score between 15 and 60

5. ability to elicit a motor evoked potential from the ipsilesional cortex

Exclusion Criteria:

1. a score <27 on the Mini-Mental Status Exam

2. a score of <123 on the Mattis Dementia Rating Scale

3. a score of <13 on the Frenchay Aphasia Screen

4. a history of seizure/epilepsy, head trauma, major psychiatric diagnosis,
neurodegenerative disorder or substance abuse

5. a history of congestive heart failure

6. systolic blood pressure above 120 mmHg and/or diastolic pressure above 80 mmHg

7. the taking of any GABAergic, NMDA-receptor antagonist or other drug known to influence
the neural receptors that facilitate neural plasticity

8. an infarct resulting from ischemic stroke of anterior or posterior cerebral artery OR
an infarct that encroaches within 2cm of the site of cTBS stimulation

9. absence of an MEP in response to single pulse transcranial magnetic stimulation over
ipsilesional M1 and 10) any other contraindication to TMS or MRI.