Transcranial alternating current stimulation (tACS) is a promising tool for modulating brain oscillations. Combining tACS with functional magnetic resonance imaging (fMRI), we recently showed that tACS applied over the occipital cortex did not exert its strongest effect on regions below the electrodes, but mainly on more distant fronto-parietal regions. Theoretically, this effect could be explained by tACS-induced modulation of functional connectivity between directly stimulated areas and more distant but anatomically and functionally connected regions. In the present study, we aimed to characterize the effect of tACS on low frequency fMRI signal fluctuations. We employed simultaneous fMRI-tACS in 20 subjects during resting state (eyes open with central fixation for ~ 8 min). Subjects received tACS at different frequencies (10, 16, 40 Hz) and with different electrode montages (Cz-Oz, P5–P6) previously used in behavioral studies. Electric field simulations showed that tACS over Cz-Oz directly stimulates occipital cortex, while tACS over P5–P6 primarily targets parietal cortices. Group-level simulation-based functional connectivity maps for Cz-Oz and P5–P6 resembled the visual and fronto-parietal control resting-state networks, respectively. The effects of tACS were frequency and partly electrode montage dependent. In regions where frequency-dependent effects of tACS were observed, 10 and 40 Hz tACS generally induced opposite effects. Most tACS effects on functional connectivity were observed between, as opposed to within, resting-state networks. The left fronto-parietal control network showed the most extensive frequency-dependent modulation in functional connectivity, mainly with occipito-parietal regions, where 10 Hz tACS increased and 40 Hz tACS decreased correlation values. Taken together, our results show that tACS modulates local spontaneous low frequency fluctuations and their correlations with more distant regions, which should be taken into account when interpreting tACS effects on brain function.
Bibliographical noteFunding Information:
We thank Ilona Pfahlert and Britta Perl for technical assistance during functional imaging experiments, Severin Heumüller and Hendrik Eichenauer for computer support, and Carsten Schmidt-Samoa for advice on statistical analysis. This work was supported by the Hermann and Lilly Schilling Foundation (to M. W.) and the European Neuroscience Campus Network, an Erasmus Mundus Joint Doctoral Program (to M.W. and K.W.).
© 2016 Elsevier Inc.
- Brain stimulation
- Cross-frequency coupling
- Intrinsic functional connectivity
- Resting state