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. 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.

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