Introduction
Human imaging studies have revealed that early after subcortical stroke, restoration of paretic arm function is associated with a greater involvement of radiologically normal-appearing (or spared) motor (primary motor cortex or M1) and premotor (dorsal premotor cortex or PMd, supplementary motor area or SMA) areas in both injured (ipsilesional) and uninjured (contralesional) hemispheres.1-3 Later, successful recovery occurs in stroke survivors who exhibit relatively normal patterns of ipsilesional activation and less contralesional motor activation, whereas patients, who often show bilateral cortical activation, typically have less complete recovery.4-6 These results should be viewed in the context of the anatomic structures and pathways of these areas. Although M1 motor pathways are critical, the premotor areas also contribute to motor control and might be recruited during motor recovery after stroke. The parallel nature of the direct (corticospinal) pathways from premotor areas and M1 emphasizes that PMd and SMA are, in some respects, at a similar level of hierarchical organization as M1,7 although these projections to spinal cord motor neurons are less numerous and less efficient than those from M1.8-10 Another possibility is the indirect (corticoreticulospinal) projections to cervical propriospinal premotoneurons, which have divergent projections to muscle groups operating at multiple joints.11,12 Finally, corticocortical connections between these areas might also play an important role in poststroke recovery.7,13-15 Thus, understanding the neural events associated with the functional changes in these areas could provide critical insight into successful treatments of patient’s impairment.
Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive means to measure concentrations of certain metabolites associated with a specific cell type16 after stroke.17 Most clinical stroke studies report lower levels of N-acetylaspartate (NAA, putative marker of neuronal integrity) in spared ipsilesional M1 and PMd.18-21 In some instances, the NAA levels were related to clinical severity. In a series of studies of stroke survivors, we also found higher myo-inositol (mI, putative marker of glial cells) in ipsilesional and contralesional M1.21 However, none of these studies addressed the changes in key metabolites related to neuronal and glial compartments, that is, NAA and mI, in motor and premotor areas in stroke.
The first aim of the current study was to quantify NAA and mI concentrations in ipsilesional and contralesional motor and premotor areas in chronic subcortical stroke. Since neuronal integrity might be compromised in these remote areas,21,22 we expected NAA to be lower, especially in the ipsilesional areas. Given the role of glia in plastic brain changes,23-25 we also expected mI to be higher. The second aim was to explore correlations between metabolite concentrations and arm motor impairment. Since the premotor projections are significantly stronger on the proximal muscles than distal muscles compared with M18,9, we predicted that metabolite measures in ipsilesional PMd and SMA would be correlated with proximal (shoulder/elbow) motor impairment whereas those in M1 would be correlated with both proximal and distal (hand) impairments. Since both direct and indirect pathways from the contralesional M1 project to axial and proximal muscles rather than hand muscles,26,27 relationships between contralesional M1 metabolites and proximal impairment were also expected.
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