Neurobiological Principles Applied to the Rehabilitation of Stroke Patients

Previous studies have shown, that when patients learn a new motor movement, it may cause a
change in the way the nerves act in the area of the brain that controls movement. This change
is called use-dependent plasticity. The ability of that part of the brain, called the motor
cortex (M1), to reorganize 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 this proposed study, investigators will further examine influences
of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of
stroke subjects using a combination of non-invasive cortical stimulation, medication, and
exercise techniques. In Aim 1, investigators will test the effect of drugs that interact
specifically with different neurotransmitter systems on use-dependent plasticity in intact M1
of healthy humans. In Aim 2, investigators will identify the parameters for non-invasive
transcranial magnetic stimulation (TMS) of M1 that are most effective to enhance
use-dependent plasticity in intact healthy human M1. In Aim 3, investigators will test the
drugs and rTMS protocols that were demonstrated to be most effective to enhance use-
dependent plasticity in the Specific Aim 1 and 2 and apply them to participants who have
experienced a stroke. Results from this study will help to inform future research about the
efficacy of plasticity enhancing methods in injured M1 of stroke patients.

Aims 1 and 2

Inclusion Criteria:

- Normal neurological examination

- Ability to meet criteria of inclusion experiment

- Ability to give informed consent.

Exclusion Criteria:

- History or neurological or psychiatric disease

- Abnormal MRI of brain

- Abnormal neuropsychological testing

- Intake of CNS active drugs

- History of seizure disorder

- History of migraine headaches

- History of anaphylaxis or allergic reactions

- Contraindication to TMS

Aim 3:

Inclusion Criteria:

- Cerebral ischemic infarction more than 6 months prior to entering the study

- Single lesion as defined by MRI of the brain affecting the primary motor output system
of the hand at a cortical (M1) level or subcortical level, or unilateral, and
supratentorial in absence of history of a previous symptomatic stroke within 3 months
of the current stroke

- Dense paresis of the hand for more than three days after cerebral infarction (MRC of <
4- of wrist- and finger extension/flexion movements)

- Good functional 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

- Ability to meet criteria of inclusion experiment

- Ability to give informed consent

- Ability of TMS to elicit a measurable MEP of > 100 μV and an increase in MEP amplitude
with increasing stimulus intensity (up to 100% of MSO) of at least 20% over MEP
amplitude at MT

Exclusion Criteria:

- History or neurological or psychiatric disease, including bipolar disorder

- Intake of CNS active drugs

- History of seizure disorder

- History of migraine headaches

- History of anaphylaxis or allergic reactions

- Contraindication to TMS