Abstract DP150: Hand recovery substrates depend on the stroke phases

Introduction: There is a growing population of stroke survivors who exhibit lifelong physical disability. Hand impairment is a major contributor to this. New strategies boosting the benefits of conventional rehabilitation are needed. One way is to develop mechanism-targeted approaches, but our current knowledge of neural mechanisms of motor recovery derives largely from animal stroke models. We studied longitudinal trajectories of MR Spectroscopy-detected biomarkers of several neural mechanisms proposed for hand recovery in survivors of a single subcortical stroke. Hypothesis: We hypothesized that neural targets relevant to hand recovery in the subacute phase may not be relevant in the chronic phase of disease. Methods: Stroke survivors in the subacute (n=21, 23.9[20.4] (mean[SD]) days post-onset, 66.2[9.9] years old, 14% female, Fugl-Meyer, 40.8[23.1] hand impairment; data analysis is underway) and chronic (n=21, 42.4[38.2] months, 58.5[10.8] years old, 16% female, Fugl-Meyer, 41.5[17.1]) phases of disease and 26 matched healthy controls were included. MEGA-sLASER was used to detect the biomarkers related to neuronal metabolic depression (N-acetylaspartate-NAA), glial changes ( myo -Inositol-mI), neuroinflammation (choline-Cho), and excitation-inhibition (E-I) imbalance (glutamate-glutamine complex-Glx and GABA). These measures were performed bilaterally in radiologically normal-appearing motor and premotor cortices. Results: Compared to controls, the subacute group showed neuronal metabolic depression (lower NAA) and increased neuroinflammation (higher Cho) and inhibition (higher GABA/lower Glx) across all cortices, along with increased glial activity/number (higher mI) in the cortices of the injured hemisphere (ipsilesional) ( p<0.01 for all). These alterations resolved in the chronic phase, but ipsilesional NAA ( p<0.05 ). Ipsilesional NAA and E-I biomarker levels correlated with the hand impairment in both groups ( p<0.05 for all). Conclusions: We have shown that cortical E-I balance, neuroinflammation, and glial response to a subcortical stroke changed remarkably over time; ipsilesional neural metabolic depression persisted years to decades after stroke, possibly reflecting neurodegenerative processes. These changes were functionally relevant for hand impairment. Such understanding may inform targeted rehabilitation strategies to enhance hand recovery, e.g., neurostimulation targeting increased inhibition is more beneficial if delivered early after stroke.