Imaging Laterality in Chronic Stroke Patients
Imaging Laterality in Chronic Stroke Patients
In healthy individuals, unimanual movement (with either the left or right hand) is associated
 with activity in a network of predominantly contralateral brain regions, including the
 primary motor cortex (PMC). This laterality is often compromised following a middle cerebral
 artery (MCA) stroke. Neuroimaging studies of these patients have shown that unimanual
 movements with the effected hand are associated with elevated Blood Oxygen-Level Dependent
 (BOLD) signal in both the lesioned and the nonlesioned primary motor cortices. Elevated
 activity in the contralesional PMC is well-established in chronic stroke patients and is
 associated with poor motor rehabilitation outcomes. Yet the neurobiologic basis for this
 aberrant neural activity is equivocal. The overarching goal of this project is to determine
 the neurobiologic basis for elevated activity in the contralesional primary motor cortex.
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)