Work

Phase-lag-dependent modulation of interhemispheric β -band functional connectivity by dual-site tACS

Year: 2026

Type: preprint

Abstract: Dual-site transcranial alternating current stimulation (ds-tACS) is a promising tool for causally manipulating interhemispheric communication; nevertheless, how different stimulation phase-lags selectively modulate functional connectivity (FC) remains unclear. We recruited 29 healthy participants and included 23 in the final analyses. Participants received 20 Hz ds-tACS over the bilateral primary motor cortices (M1s) using four phase-lags (0, π/ 2, π , 3 π/ 2) and sham stimulation, combined with recording of high-density EEG before and after stimulation. We quantified the interhemispheric FC using the debiased weighted phase-lag index. No significant differences were found in the average FC changes between overall active stimulation and sham. However, the phase-lag associated with maximum absolute FC changes varied substantially across participants. Accordingly, the assessment of phase-lag-dependency of FC using the Kullback-Leibler distance ( D KL ) revealed a significant phase-lag-dependent modulation of FC that was transient (limited to the first 5 s after stimulation), restricted to frequencies around the stimulation frequency (18-22 Hz), and occurred without corresponding phase-lag-dependent modulation of the spectral power. In an exploratory analysis, the modulation magnitude showed a quadratic relationship with the individual β– peak FC frequency, where participants with β -peak frequencies farther from the 20 Hz stimulation frequency exhibited stronger effects. These findings indicate that ds-tACS can induce time- and frequency-specific modulation of interhemispheric FC across phase-lags. Given the observed association with individual β– peak connectivity frequency and the variability in the phase-lag associated with maximal FC change, our findings motivate further investigation of personalised neuromodulation protocols. Highlights Modulation of interhemispheric β -band functional connectivity across four phase-lags (0, π/ 2, π, 3 π/ 2). Effects are limited to the immediate post-stimulation window (5 s) and specific to the frequency range around the stimulation frequency (18-22 Hz). High interindividual variability in phase-lags of maximal effect emphasises the need for personalised phase optimisation. Abstract Figure

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.09.14.751522