Handgrip-Related Activation in the Primary Motor Cortex Relates to Underlying Neuronal Metabolism After Stroke.

BACKGROUND: Abnormal task-related activation in primary motor cortices (M1) has been consistently found in functional imaging studies of subcortical stroke. Whether the abnormal activations are associated with neuronal alterations in the same or homologous area is not known. OBJECTIVE: Our goal was to establish the relationships between M1 measures of motor-task-related activation and a neuronal marker, N-acetylaspartate (NAA), in patients with severe to mild hemiparesis. METHODS: A total of 18 survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and 16 age- and sex-matched right-handed healthy controls underwent functional MRI during a handgrip task (impaired hand in patients, dominant hand in controls) and proton magnetic resonance spectroscopy ((1)H-MRS) imaging. Spatial extent and magnitude of blood oxygen level-dependent response (or activation) and NAA levels were measured in each M1. Relationships between activation and NAA were determined. RESULTS: Compared with controls, patients had a greater extent of contralesional (ipsilateral to impaired hand, P < .001) activation and a higher magnitude of activation and lower NAA in both ipsilesional (P = .008 and P < .001, respectively) and contralesional (P < .0001, P < .05) M1. There were significant negative correlations between extent of activation and NAA in each M1 (P = .02) and a trend between contralesional activation and ipsilesional NAA (P = .08) in patients but not in controls. CONCLUSIONS: Our results suggest that after stroke greater neuronal recruitment could be a compensatory response to lower neuronal metabolism. Thus, dual-modality imaging may be a powerful tool for providing complementary probes of post-stroke brain reorganization.

Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment.

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 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging 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 = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .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 = .02, .01, .02, and .02, respectively). CONCLUSIONS: Our preliminary results demonstrated that proton magnetic resonance spectroscopy 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.

Neuronal-glial alterations in non-primary motor areas in chronic subcortical stroke.

Whether functional changes of the non-primary motor areas, e.g., dorsal premotor (PMd) and supplementary motor (SMA) areas, after stroke, reflect reorganization phenomena or recruitment of a pre-existing motor network remains to be clarified. We hypothesized that cellular changes in these areas would be consistent with their involvement in post-stroke reorganization. Specifically, we expected that neuronal and glial compartments would be altered in radiologically normal-appearing, i.e., spared, PMd and SMA in patients with arm paresis. Twenty survivors of a single ischemic subcortical stroke and 16 age-matched healthy controls were included. At more than six months after stroke, metabolites related to neuronal and glial compartments: N-acetylaspartate, myo-inositol, and glutamate/glutamine, were quantified by proton magnetic resonance spectroscopy in PMd and SMA in both injured (ipsilesional) and un-injured (contralesional) hemispheres. Correlations between metabolites were also calculated. Finally, relationships between metabolite concentrations and arm motor impairment (total and proximal Fugl-Meyer Upper Extremity, FMUE, scores) were analyzed. Compared to controls, stroke survivors showed significantly higher ipsilesional PMd myo-inositol and lower SMA N-acetylaspartate. Significantly lower metabolite correlations were found between ipsilesional and contralesional SMA. Ipsilesional N-acetylaspartate was significantly related to proximal FMUE scores. This study provides evidence of abnormalities in metabolites, specific to neuronal and glial compartments, across spared non-primary motor areas. Ipsilesional alterations were related to proximal arm motor impairment. Our results suggest the involvement of these areas in post-stroke reorganization.

Primary motor cortex in stroke: a functional MRI-guided proton MR spectroscopic study.

BACKGROUND AND PURPOSE: Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal-glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke. METHODS: Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate, myo-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5×5 mm(2)) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated. RESULTS: The stroke survivors showed lower N-acetylaspartate and higher myo-inositol across ipsilesional and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke. CONCLUSIONS: Our preliminary data demonstrated significant alterations of neuronal-glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke.