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PreprintCC BY-NC-NDbioRxiv

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

  1. 1Biomedical Signal and Systems, Faculty of Electrical Engineering, Mathematics and Computer Science, University of Twente, Enschede, the Netherlands

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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BibTeX
@misc{huertaspenen2026phaselagdependent,
  title = {{Phase-lag-dependent modulation of interhemispheric β-band functional connectivity by dual-site tACS}},
  author = {S. Huertas-Penen and M. Fiene and B. de Jong and J. Hagen and T. Heida and R. J. A. van Wezel and B. C. Schwab},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.751522},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751522v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Phase-lag-dependent modulation of interhemispheric β-band functional connectivity by dual-site tACS
AU  - S. Huertas-Penen
AU  - M. Fiene
AU  - B. de Jong
AU  - J. Hagen
AU  - T. Heida
AU  - R. J. A. van Wezel
AU  - B. C. Schwab
PY  - 2026
DA  - 2026/09/14
PB  - bioRxiv
DO  - 10.64898/2026.09.14.751522
UR  - https://www.biorxiv.org/content/10.64898/2026.09.14.751522v1
AB  - 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.
ER  -