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

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.

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.

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.

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.

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.