Adaptive Compensatory Neurophysiological Biomarkers of Motor Recovery Post-Stroke: Electroencephalography and Transcranial Magnetic Stimulation Insights from the DEFINE Cohort Study

Objective: This study aimed to explore longitudinal relationships between neurophysiological biomarkers and upper limb motor function recovery in stroke patients, focusing on electroencephalography (EEG) and transcranial magnetic stimulation (TMS) metrics. Methods: This longitudinal cohort study analyzed neurophysiological, clinical, and demographic data from 102 stroke patients enrolled in the DEFINE cohort. We investigated the associations between baseline and post-intervention changes in the EEG theta/alpha ratio (TAR) and TMS metrics with upper limb motor functionality, assessed using the outcomes of five tests: the Fugl-Meyer Assessment (FMA), Handgrip Strength Test (HST), Pinch Strength Test (PST), Finger Tapping Test (FTT), and Nine-Hole Peg Test (9HPT). Results: Our multivariate models identified that a higher baseline TAR in the lesioned hemisphere was consistently associated with poorer motor outcomes across all five assessments. Conversely, a higher improvement in the TAR was positively associated with improvements in FMA and 9HPT. Additionally, an increased TMS motor-evoked potential (MEP) amplitude in the non-lesioned hemisphere correlated with greater FMA-diff, while a lower TMS Short Intracortical Inhibition (SICI) in the non-lesioned hemisphere was linked to better PST improvements. These findings suggest the potential of the TAR and TMS metrics as biomarkers for predicting motor recovery in stroke patients. Conclusion: Our findings highlight the significance of the TAR in the lesioned hemisphere as a predictor of motor function recovery post-stroke and also a potential signature for compensatory oscillations. The observed relationships between the TAR and motor improvements, as well as the associations with TMS metrics, underscore the potential of these neurophysiological measures in guiding personalized rehabilitation strategies for stroke patients.