All ETDs from UAB

Advisory Committee Chair

Edward Taub

Advisory Committee Members

David C Knight

Gitendra Uswatte

Victor W Mark

Adrienne C Lahti

Kristina M Visscher

Document Type

Dissertation

Date of Award

2019

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Constraint-Induced Movement Therapy (CIMT) is a rehabilitation treatment that produces large motor function improvements in patients with chronic stroke. One of the hypothesized mechanisms by which CIMT achieves its therapeutic effect is the large functional and structural plastic changes that it produces in the brain. The goal of the present project was to determine the neural underpinnings of cortical reorganization produced by CIMT in chronic stroke using proton magnetic resonance spectroscopy (1H-MRS). Before applying the proposed 1H-MRS techniques (i.e., single voxel spectroscopy/SVS and whole brain magnetic resonance spectroscopic imaging/WB-MRSI) to evaluate longitudinal changes in brain metabolites after CIMT, it is an important first step to assess the reproducibility and variability of these techniques. The reproducibility of SVS and WB-MRSI was assessed in both healthy participants and patients with chronic stroke. Participants were scanned using both techniques on three occasions one week apart. The test-retest reliability of the quantification of each candidate metabolite for each technique was measured using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The candidate metabolites included: N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI). These two methodological studies provided reference information for selecting an optimum spectroscopic technique for assessing the neurometabolic changes produced by CIMT in chronic stroke. Finally, motor improvements and brain neurometabolites changes were measured in patients that received CIMT, in order to determine the structural changes that may contribute to the therapeutic effect of CIMT. Similar reliable quantification of the candidate metabolites was observed using SVS and WB-MRSI in the healthy subjects, but not in patients with chronic stroke (better reproducibility using SVS than WB-MRSI). The degree of variability in the metabolite concentration ratios varied with the ROI selected and the quantification method. Significant in-laboratory and real-world motor improvements were observed after CIMT in chronic stroke. In addition, increased cell metabolism (indicated by increased Cho) and upregulated glial involvement (indicated by increased mI) was found within bilateral motor areas after CIMT. These findings suggest increased glial processes may be a potential mechanisms mechanism that underlying underlies the treatment efficacy of CIMT.

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