Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients, Charleston, South Carolina, 2014-2016 (ICPSR 37313)

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Colleen Ann Hanlon, Medical University of South Carolina

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The primary goal of this project was to determine the neurobiologic basis for elevated activity in the contralesional primary motor cortex (PMC). 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. 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.

One factor that may contribute to elevated activity in the contralesional PMC is increased cortical excitatory tone within the contralesional hemisphere. 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: electrophysiologically, using single hemisphere paired pulse transcranial magnetic stimulation (TMS), and 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. 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: using bi-hemispheric paired-pulse TMS, and using a multimodal brain stimulation/brain imaging approach, interleaved TMS/MRI. Through interleaved TMS/MRI, researchers can selectively stimulate the ipsilesional PMC and quantify the amount of TMS-induced activity in the contralesional PMC.

These two explanations were 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 researchers performed a detailed kinematic assessment of movement efficiency, smoothness and compensation.

Hanlon, Colleen Ann. Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients, Charleston, South Carolina, 2014-2016. Inter-university Consortium for Political and Social Research [distributor], 2019-09-26.

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Medical University of South Carolina (P20 GM109040)

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Inter-university Consortium for Political and Social Research

2014 -- 2016
2014-11-18 -- 2016-10-11

The specific aims of this study are: to quantify the ratio of excitatory/inhibitory tone within the contralesional PMC, to quantify the level of information flow between the left and right PMC, and to quantify the relationship between neural activity and performance. The results of these aims will clarify the relative contribution of within and between hemisphere adaptations to cortical reorganization. These cross-sectional data will also be the foundation of a longitudinal R01 that will determine which patterns of laterality predict favorable treatment outcomes.

VISIT 1: Screening. The Screening Visit lasted approximately 2 hours. Individuals were pre-screened for eligibility on the phone by a clinical research assistant with experience working with stroke patients for research studies. Those who met initial inclusion criteria via phone screen visited the laboratory and were asked to provide written informed consent. Participants performed a comprehensive assessment of motor function utilizing the resources and staff of the Quantitative Behavioral Assessment and Rehabilitation (QBAR) Core. Specifically, all stroke patients completed the Rasch modified version of the Fugl-Meyer Motor assessment battery and a kinematic assessment of both unimanual and bimanual movements using a 45 sensor 3D optical imaging system. The three primary measures investigated in the kinematics analyses include: movement efficiency, movement smoothness, and motor compensation.

VISIT 2: Stimulation/Scanning/Written Assessments. Based on the results of Visit 1 assessments, participants that met the inclusion criteria were invited to participate in Visit 2. This visit lasted approximately 4 hours. In addition to a series of written psychological questionnaires, individuals received:

  • Anatomical Imaging (both T1 MPRAGE and diffusion tensor imaging (DTI)
  • Functional MRI (to document elevated blood-oxygenation-level-dependent (BOLD) signal in the contralesional cortex)
  • Magnetic resonance (MR) spectroscopy (to quantify Glu and GABA in the ipsi hemisphere)
  • Interleaved transcranial magnetic stimulation (TMS)/MRI (to determine the pattern of activity associated with stimulating)
  • Single hemisphere paired-pulse TMS (to test contralesional facilitation and inhibition)
  • Bi-hemispheric paired-pulse TMS (to test transcallosal inhibition and facilitation time)

The researchers recruited from the Registry for Stroke Recovery (RESTORE) which is a research tool sponsored by the National Institutes of Health (NIH) Center of Biomedical Research Excellence (COBRE) in Stroke Recovery with subjects consented for future contact to support stroke recovery research conducted at the Medical University of South Carolina (MUSC). RESTORE staff queried the registry for potential subjects and provided the Principal Investigator (PI) with the contact information of subjects who meet their criteria. The PI or research staff contacted subjects to further screen for potential enrollment.

Researchers used a cross-sectional cohort design of hemiparetic chronic stroke patients with right-sided upper extremity weakness subsequent to a left hemisphere cortical stroke, as well as a group of neurologically healthy, age-matched controls with similar cardiovascular risk factors. All subjects were recruited from the larger Charleston community using digital and print advertisements. The study required the participants to attend a Screening Visit and a Scanning/Stimulation visit.


Control group and stroke patients: Adults aged 21-80 with at least two cardiovascular risk factors (smoking, high blood pressure, high cholesterol, diabetes, overweight, age (over 55 for men, over 65 for women), family history of stroke).

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, and ability to make a fist and relax the affected hand.



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