Stroke Clinical Trial
Official title:
Investigating the Neurobiologic Basis for Loss of Cortical 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).
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