Exploring delta/alpha and theta/alpha ratios as longitudinal treatment-response biomarkers in post-stroke rehabilitation

Introduction Post-stroke motor recovery relies on rebalancing of network connectivity, yet objective biomarkers for longitudinal monitoring remain limited. The delta/alpha ratio (DAR) is an established quantitative electroencephalography (qEEG) index of pathological slow-wave activity associated with stroke outcomes; the theta/alpha ratio (TAR) is a related but less-established measure. In this exploratory analysis, we investigated whether these biomarkers can serve as longitudinal treatment-response markers during neurorehabilitation, using electromagnetic network targeting field (ENTF) stimulation. Patients and methods We conducted a longitudinal analysis of 21 subacute ischemic stroke patients from a double-blind, sham-controlled randomized trial. Participants received either active ENTF stimulation or sham treatment over 15 sessions spanning 2 months. Resting-state EEG was recorded from 8 scalp electrodes. DAR and TAR were computed per session. Linear mixed-effects models (LMM) assessed session-by-treatment interactions. Secondary exploratory analyses examined coherence-based functional connectivity. Results LMM analysis revealed significant session-by-treatment interactions for both DAR (β = −0.29, p = 0.016) and TAR (β = −0.034, p < 0.001). The active group was associated with steeper biomarker declines in DAR and TAR than sham. Secondary connectivity analyses showed no robust effects. Discussion In this analysis, DAR and TAR showed treatment-associated longitudinal changes, and were associated with functional improvement trajectories, consistent with their behavior as candidate treatment-response markers. Conclusion These exploratory findings are consistent with DAR and TAR behaving as longitudinal treatment-response markers in post-stroke rehabilitation. The results are hypothesis-generating and require confirmation in a trial with pre-specified endpoints.