Imaging Laterality in Chronic Stroke Patients

One factor that may contribute to elevated activity in the contralesional PMC is increased
cortical excitatory tone within the contralesional hemisphere (Aim 1).

While approximately 80% of the descending corticospinal neurons that control the right hand
originate in the left PMC, 20% originate in the right PMC. Elevated activity in the right PMC
of left-sided stroke patients may reflect compensatory activity of these descending fibers.
Neural activity in the PMC reflects the balance of local excitatory (glutamatergic) and
inhibitory (GABAergic) processing. It can be measured in two manners: 1)
electrophysiologically, using single hemisphere paired pulse transcranial magnetic
stimulation (TMS), and 2) neurochemically, using magnetic resonance spectroscopy (MRS).

Another factor that may contribute to elevated activity in the contralesional PMC is a loss
of transcallosal inhibition between the hemispheres (Aim 2). During right hand movement, the
left PMC of healthy individuals actively inhibits the right PMC via inhibitory projections
through the corpus callosum. In left MCA stroke patients, elevated activity in the
contralesional (right) PMC when moving the right hand may reflect a loss of typical
inhibition from the left PMC. The integrity of inter-hemispheric information transfer can be
measured in two manners: 1) using bi-hemispheric paired-pulse TMS, and 2) using a multimodal
brain stimulation/brain imaging approach, interleaved TMS/MRI.

Through interleaved TMS/MRI, the investigators can selectively stimulate the ipsilesional PMC
and quantify the amount of TMS-induced activity in the contralesional PMC. These two
explanations will be tested through a cross-sectional investigation of neural function in
left MCA stroke patients with mild-moderate right upper extremity impairment and controls
matched for age and cardiovascular risk factors. To assess the clinical relevance of these
factors on motor dysfunction, the investigators will perform a detailed kinematic assessment
of movement efficiency, smoothness and compensation (Aim 3).

Inclusion Criteria For Both Groups:

- 21-80 years old of any race and ethnicity

- At least 2 cardiovascular risk factors (smoking, high blood pressure, high
cholesterol, diabetes, overweight, age (>55 for men, >65 for women), family history of
stroke).

Inclusion Criteria For Stroke Patients:

- Left middle cerebral artery ischemic stroke with at least 6 month chronicity

- Right upper extremity weakness with a Rasch-modified Fugl-Meyer upper extremity score
of 20 to 50

- Ability to voluntarily flex the affected elbow and shoulder from 10-75% of the normal
range

- Ability to make a fist and relax the affected hand (note: this motion will be required
in the functional MRI task)

Exclusion Criteria For Both Groups:

- Primary intracerebral hematoma or subarachnoid hemorrhage

- Bi-hemispheric ischemic strokes

- History of prior right-sided stroke or old infarct demonstrated on the CT or MRI or
documented in medical records

- Other concomitant neurological disorders affecting upper extremity motor function

- Documented history of dementia before or after stroke

- Presence of any MRI, TMS, or transcranial direct current stimulation risk factors such
as an electrically, magnetically or mechanically activated metal or nonmetal implant
including cardiac pacemaker, intracerebral vascular clips or any other electrically
sensitive support system

- Pregnancy as the effect of MRI on the fetus is unknown, females of child bearing age
must undergo a pregnancy test to confirm eligibility

- History of seizure disorder or post-stroke seizure

- Preexisting scalp lesion or wound or bone defect or hemicraniectomy

- Left-hand dominance (before the stroke in the stroke patients) as the typical pattern
of laterality is not as strong in left-handed healthy individuals

- Current nicotine dependence (Note: nicotine use is not an exclusionary criteria as
there is no known association between acute use and BOLD signal changes in
non-dependent smokers)