title: Transcranial alternating current stimulation modulates spontaneous low frequency fluctuations as measured with fMRI.
abstract: 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 ~8min). Subjects received tACS at different frequencies (10, 16, 40Hz) 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 40Hz 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 10Hz tACS increased and 40Hz 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.
authors.affiliation: Department of Cognitive Neurology, University Medical Center, Georg-August University Goettingen, Robert-Koch-Str. 40, Goettingen 37075, Germany; German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, Goettingen 37077, Germany. Electronic address: yurany.cabral-calderin@med.uni-goettingen.de.
authors.forename: Yuranny
authors.initials: Y
authors.lastname: Cabral-Calderin
authors.affiliation: Department of Cognitive Neurology, University Medical Center, Georg-August University Goettingen, Robert-Koch-Str. 40, Goettingen 37075, Germany.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Williams
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Center for the Developing Brain, Child Mind Institute, New York, NY 10022, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Opitz
authors.affiliation: Department of Cognitive Neurology, University Medical Center, Georg-August University Goettingen, Robert-Koch-Str. 40, Goettingen 37075, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dechent
authors.affiliation: Department of Cognitive Neurology, University Medical Center, Georg-August University Goettingen, Robert-Koch-Str. 40, Goettingen 37075, Germany; German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, Goettingen 37077, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wilke
mesh_terms: D000328:Adult; D001683:Biological Clocks / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D058256:Brain Waves / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009778:Occipital Lobe / Q000502:physiology*; D010296:Parietal Lobe / Q000502:physiology*; D065908:Transcranial Direct Current Stimulation / Q000379:methods*
keywords: Brain stimulation; Cross-frequency coupling; Entrainment; Intrinsic functional connectivity; Oscillations; Resting state; fALFF/ALFF; fMRI; tACS