This study will determine in stroke patients whether stimulation of the injured side of the
brain combined with stimulation of the weak hand can temporarily improve motor function of
the paralyzed hand. It will also examine whether stimulation of the healthy side of the
brain combined with stimulation of the weak hand can temporarily improve motor function in
the paralyzed hand.
Healthy adult volunteers and adults who have had a stroke more than 3 months before entering
the study may be eligible to participate. Candidates are screened with a physical and
neurological examination. Stroke patients also have magnetic resonance imaging (MRI), a test
that uses a strong magnetic field and radio waves to obtain images of the brain.
Participants perform several tasks (described below) in a practice session and then during
five more sessions on separate days. They perform the tasks before and after undergoing
transcranial direct current stimulation (tDCS) plus electrical stimulation (ES), and during
a procedure that involves sham stimulation. For tDCS, small rubber electrodes are soaked
with water and taped to the subject's head, one above the eye and the other on the back of
the head. The current passes between the two electrodes. For ES, two pairs of electrodes are
attached to the subject's wrist with a paste. A very short pulse of current is passed
between the electrodes, creating an electrical field that stimulates the brain. For the sham
stimulation, the electrodes are similarly placed, but there is no stimulation. The tasks
- Jebsen-Taylor test: Subjects write, lift small common objects like paper clips, and
perform activities like turning pages, stacking checkers or lifting large objects. They
do these tasks as fast as possible.
- Pinch force: Subjects press a wedged instrument between their thumb and index finger as
hard as they can. There are several trials every 10 seconds.
- Speed tapping: Subjects press a key on a keyboard as quickly as possible for 10
- Simple reaction time task: Subjects perform a quick wrist movement as quickly as
possible in response to a "go" signal presented on a computer monitor. Muscle activity
in the forearm is recorded using electrodes.
- Motor sequence learning/Learning a finger movement sequence: Subjects practice a finger
movement exercise on a keyboard by pressing keys that correspond to a number displayed
on a video screen.
- Visual analog scales: Subjects complete three questionnaires about their attention,
fatigue, and mood.
- Sensory monitoring: Subjects are blindfolded and asked to judge the difference in
various sensations, such as the feel of plastic domes with gratings, vibration, or a
plastic hair applied to their fingertip.
- Scoring MRC scale: The muscle strength of the subject's hands is measured.
- Fugl-Meyer scale: The subject's ability to move his or her limbs is measured.
- Mini-mental state examination: The subject's mental ability is measured briefly.
- Handedness questionnaire: The subject's dominant hand is determined.
Participants also undergo transcranial magnetic stimulation (TMS) and electromyography (EMG)
before, during and after these activities. For TMS, a wire coil is held on the scalp. A
brief electrical current is passed through the coil, creating a magnetic pulse that
stimulates the brain. The effect of TMS on the muscles is detected with small electrodes
taped to the skin of the arms or legs. EMG measures the electrical activity of the muscles.
For this test, small electrodes are taped to the skin over the muscle.
There is no universally accepted strategy to promote recovery of motor function after
chronic stroke, the main cause of long-term disability among adults. It is desirable to
develop strategies to improve motor function in stroke patients. Recently a study in stroke
patients demonstrated that transcranial direct current cortical stimulation (tDCS) in
association with motor training leads to improvements of performance and motor learning.
Similarly, somatosensory stimulation (peripheral nerve stimulation, PNS) of the paretic hand
in stroke patients results in improvement of performance and motor learning (Celnik,
The purpose of this protocol is to apply tDCS to the motor cortex of the affected hemisphere
(tDCS affected) in combination with PNS of the paretic hand of patients with chronic stroke,
to test the hypothesis that combined tDCS affected with PNS will lead to more prominent
improvement in motor performance of functional relevant tasks in the paretic hand relative
to either intervention alone.
Furthermore, recent studies have demonstrated that the unaffected hemisphere exerts
abnormally high inhibitory influence over the affected hemisphere. This abnormality might
adversely influence motor recovery. Therefore a further purpose of the study is to apply
tDCS to the unaffected hemisphere (tDCS unaffected) to test the hypothesis that down
regulation of activity in the intact hemisphere, in combination with PNS of the affected
hemisphere, will elicit more prominent improvement in functional relevant tasks than either
We plan to study patients with chronic strokes and healthy age, gender and hand dominance
To test the hypothesis each subject will participate in 13 sessions in a double blind
design. The order that patients and controls will receive the interventions will be
Primary outcome measure will be the total time to complete functional relevant tasks of the
hand, Jebsen-Tailor-Test (JTT). Secondary outcomes are tapping speed with one finger; simple
reaction times (SRT); pinch force; and number of correct keyboard piano sequences played in
30sec with the paretic hand. To better understand the mechanisms underlying the proposed
behavioral gains, we will use transcranial magnetic stimulation (TMS) to identify
corticomotor excitability changes.
- INCLUSION CRITERIA:
We will include patients with thromboembolic non-hemorrhagic hemispheric lesions at least
6 months after the stroke. We will choose patients who initially had a severe motor
paresis (below MRC grade 2), which subsequently recovered to the point that they have a
residual motor deficit but can perform the required tasks. Assessment of the initial
functional state will be taken either from patient report or medical records. As a control
group, we will include age- and gender matched healthy volunteers with matched
non-dominant/dominant hand (to the affected hand of the stroke patients).
Patients with more than one stroke in the medial cerebral artery territory.
Patients with bilateral motor impairment.
Patients with cerebellar or brainstem lesions.
Patients or healthy volunteers unable to perform the task (wrist or elbow flexion at least
MRC grade 2).
Patients or healthy volunteers with history of severe alcohol or drug abuse, psychiatric
illness like severe depression, poor motivational capacity, or severe language
disturbances, particularly of receptive nature or with serious cognitive deficits (defined
as equivalent to a mini-mental state exam score of 23 or less).
Patients or healthy volunteers with severe uncontrolled medical problems (e.g.
cardiovascular disease, severe rheumatoid arthritis, active joint deformity of arthritic
origin, active cancer or renal disease, any kind of end-stage pulmonary or cardiovascular
disease, or a deteriorated condition due to age, uncontrolled epilepsy or others).
Patients or healthy volunteers with increased intracranial pressure as evaluated by
Patients with unstable cardiac arrhythmia.
Patients or healthy volunteers with h/o hyperthyroidism or individuals receiving drugs
acting primarily on the central nervous system.
Patients or healthy volunteers with more than moderate to severe microangiopathy,
polyneuropathy, diabetes mellitus, or ischemic peripheral disease.
Patients or healthy volunteers with diseased or damaged skin over the face or scalp.
Patients or healthy volunteers who have professionally practiced playing a keyboard
musical instrument or trained as a typist.