Imaging Laterality in Chronic Stroke Patients

Early Phase 1

Completed

• Conditions: Stroke; Motor Cortex; Lesion
• Interventions: Diagnostic Test: Rasch modified version of the Fugl-Meyer Motor assessment; Diagnostic Test: Anatomical image acquisition; Diagnostic Test: Functional MRI task and acquisition

• Registration Number: NCT03584425
• Lead Sponsor: Medical University of South Carolina

Brief Summary

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.

Detailed Description

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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-12-15
• Study First Submitted: 2018-06-15
• Study First Submitted QC: 2018-06-28
• Study First Posted: 2018-07-12
• Primary Completion: 2019-05-30
• Study Completion: 2019-05-30
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-22
• Last Update Posted: 2019-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Controls	Rasch modified version of the Fugl-Meyer Motor assessment	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition
Healthy Controls	Functional MRI task and acquisition	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition
Healthy Controls	Anatomical image acquisition	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition
Stroke Participants	Functional MRI task and acquisition	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition
Stroke Participants	Rasch modified version of the Fugl-Meyer Motor assessment	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition
Stroke Participants	Anatomical image acquisition	Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition

Primary Outcome Measures

Name	Time	Method
Compare the ratio of gluatamte and gaba concentrations within the contralesional primary motor cortex	Through study completion, an average of two weeks	Using spectroscopy investigators will determine if the ratio of glutamate/GABA is higher in stroke patients than controls. Furthermore, in healthy controls prepulse inhibition will be positively correlated with the concentration of GABA, and prepulse facilitation will be positively correlated with the concentration of glutamate. Although we expect this relationship to be true in both the controls and the stroke patients, variation from this pattern in the stroke patients would suggest that there is another factor beyond simple within-hemisphere measurements that is affecting the contralesional cortex activity.

Secondary Outcome Measures

Name	Time	Method
Quantify the relationship between neural activity and motor performance using the Rasch modified version of the Fugl-Meyer motor assessment battery to acquire three aspects of motor performance for all individuals in both groups.	Through study completion, an average of two weeks	Impairment on bimanual tasks will be related to the outcome measures of previous Aims. That is, individuals with less transcallosal inhibition will perform worse on the bimanual task (less efficiency and smoothness) than individuals with transcallosal inhibition closer to healthy controls. This is based on pilot data from Dr. Woodbury of the Quantitative Behavioral Assessment and Rehabilitation Core that suggests during bimanual tasks the kinetics of the impaired arm remain the same but the previously unimpaired limb performs worse. This suggests that loss of inhibition 'infects' the arm movement typically controlled by the contralesional hemisphere.

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States