Motor and Premotor Cortices in Subcortical Stroke

Abstract

Background Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. Objective We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. Methods In twenty participants at >6 months post-onset of a subcortical ischemic stroke and sixteen age and sex-matched healthy controls, the concentrations of N-acetylaspartate and myoinositol were quantified by proton magnetic resonance spectroscopy (1H-MRS). Regions of interest, identified by functional MRI, included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. Results N-acetylaspartate was lower in M1 (p=0.04) and SMA (p=0.004) and myo-inositol was higher in M1 (p=0.003) and PMd (p=0.03) in the injured (ipsilesional) hemisphere after stroke compared to the left hemisphere in controls. N-acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (p=0.04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (p=0.02, 0.01, 0.02 and 0.02 respectively). Conclusions Our preliminary results demonstrated that 1H-MRS is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke, and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

Positive Effect of Impairment-Oriented Training on N-Acetylaspartate Levels of Ipsilesional Motor Cortex in Subcortical Stroke: A Case Study

“…As expected, we found that our patient exhibited significantly lower elbow extension (15.2°) compared to a healthy control group (described previously [14]) who executed the same task (57.9 5.2°). Then, we focused the attention of the participant on this specific impairment decreased elbow extensionduring practice.…”

“…A similar decrease in NAA levels was found in the ischemic core in patients and the outcome predictions based upon the residual NAA in the infarct core have proved accurate [10,11]. More importantly, our recent 1H-MRS studies established a relationship between NAA levels in spared motor areas and behaviorally-relevant neurophysiological brain changes in chronic subcortical stroke [12-14]. Specifically, we found lower levels of NAA, putatively reflecting neuronal metabolic depression [15], in the paretic hand area representation in the ipsilesional motor and premotor areas.…”

“…The T1-weighted images were also segmented (SPM5, Welcome Department of Cognitive Neurology, London, UK). As previously shown [12-14], we overlaid the LCModel output on the segmented T1-weighted images (Matlab v7.1) to display NAA concentrations from LCModel and grey matter percentage from SPM in each voxel. Then, we selected three spectroscopic voxels corresponding to the hand representation in three core areas of motor-execution network [35]: primary motor cortex (M1), dorsal premotor cortex (dPM), and supplementary motor area (SMA) (http://neuro.imm.dtu.dk/services/jerne/ninf/voi.html).…”

“…Finally, the corrected NAA concentrations for all voxels were averaged to provide a mean NAA concentration per each area. Concentrations were expressed in millimoles (mM) per kilogram wet weight by converting the institutional unit in mM with a calibration factor obtained by matching the mean NAA concentration in our healthy control group (described previously [14]) to the mean concentration of NAA reported in healthy brain [41-43]. …”

“…Neuronal metabolic depression may also be due to diaschisis, the distant neurophysiological changes due to a direct inhibitory effect of injury [21-23]. Notably, lower levels of NAA in these areas were associated with larger extent of motor-related activation and poorer clinical outcomes [12-14]. In sum, these findings suggest that the neuronal state in spared motor areas is likely to impact the functional role of the ipsilesional hemisphere on movement and subsequently motor impairment.…”