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bioRxiv · 10.64898/2026.09.14.751522

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

Huertas-Penen, S.·Fiene, M.·de Jong, B.·Hagen, J.·Heida, T.·van Wezel, R. J. A.·Schwab, B. C.
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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, pi/2, pi, 3pi/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 (DKL) 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 {beta}-peak FC frequency, where participants with {beta}-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 {beta}-peak connectivity frequency and the variability in the phase-lag associated with maximal FC change, our findings motivate further investigation of personalised neuromodulation protocols.

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Huertas-Penen, S., Fiene, M., de Jong, B., Hagen, J., Heida, T., van Wezel, R. J. A., Schwab, B. C.. 2026-09-21. Phase-lag-dependent modulation of interhemispheric β-band functional connectivity by dual-site tACS. https://doi.org/10.64898/2026.09.14.751522

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