Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation

Stroke is a leading cause of morbidity in the United States but identification of treatment strategies to improve outcome is limited by the incomplete understanding of the mechanisms of recovery. Motor cortex (M1) reorganization plays a major-role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery.

In Specific Aim 1, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances functional M1 reorganization in lesioned M1 of stroke patients.

In Specific Aim 2, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances structural cortical reorganization in lesioned M1 of stroke patients and to explore whether these structural changes are related to the training induced functional cortical reorganization.

The overall goal of this project is to determine the effect of Hebbian- type stimulation on both, functional and structural brain reorganization, thereby obtaining indirect evidence for the neuronal substrate underlying training related improvement and maintenance of motor function in stroke patients. This knowledge may have a substantial positive impact on treatment for stroke patients that may significantly improve recovery and could move the field of neuro-rehabilitation forward.

Stroke is a leading cause of morbidity in the United States but identification of treatment strategies to improve outcome is limited by the incomplete understanding of the mechanisms of recovery. Motor cortex (M1) reorganization plays a major-role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. Non-invasive cortical stimulation can enhance the beneficial effects of motor training on performance and functional plasticity of motor cortex. Among the different approaches used in these studies, Hebbian-type M1 stimulation is particularly intriguing, as it seems to be more effective when compared to random M1 stimulation. There is emerging evidence that motor training or cortical stimulation related improvement of function are associated with increases in the grey matter of targeted brain areas. While there is therefore some evidence supporting structural reorganization in human M1 in response to motor learning and cortical stimulation, the mechanisms underlying these changes and their relationship to functional plasticity are not known. A better understanding of the sequences of events is critical to development of optimal therapeutic interventions to improve recovery following stroke.

In Specific Aim 1, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances functional M1 reorganization in lesioned M1 of stroke patients.

In Specific Aim 2, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances structural cortical reorganization in lesioned M1 of stroke patients and to explore whether these structural changes are related to the training induced functional cortical reorganization.

The overall goal of this project is to determine the effect of Hebbian- type stimulation on both, functional and structural brain reorganization, thereby obtaining indirect evidence for the neuronal substrate underlying training related improvement and maintenance of motor function in stroke patients. This knowledge may have a substantial positive impact on treatment for stroke patients that may significantly improve recovery and could move the field of neuro-rehabilitation forward.

Eligibility Criteria:
Inclusion Criteria:

* Age 18-85
* Single cerebral ischemic infarction \> 6 month affecting the primary motor output system of the hand at a cortical (M1) level as defined by MRI of the brain
* At the time of cerebral infarct a motor deficit of hand of MRC of \<4- of wrist and finger extension/flexion movement
* Good recovery of hand function as defined by MRC of 4 or 4+ of wrist- and finger extension/flexion movements
* Ability to perform wrist extension movements
* No other neurological disorder
* No intake of CNS active drugs
* Ability to give informed consent
* Ability to meet criteria of inclusion experiment
* No major cognitive impairment
* No contraindication to TMS or MRI