Immediate Modulation of the Blood Oxygenation Level-Dependent Signals by Dual-Site Transcranial Alternating Current Stimulation Propagates Across the Whole Brain

Transcranial alternating current stimulation (tACS) is assumed to target specific brain regions and modulate their activity. Recent discussions of tACS propose that, entraining the phase of brain activity to the stimulation current, stimulation effects extend globally across the whole brain based on phase differences. However, immediate online spatiotemporal propagation of resting-state blood oxygenation level-dependent (BOLD) signals within the brain due to multi-region stimulation remains unclear. The objectives of the present study were three-fold: 1) to elucidate the immediate online effect of tACS on BOLD signal, 2) to examine the extent of the influence on the brain when applying tACS, and 3) to explore whether variations in the phase difference between two brain regions result in differential effects on the stimulated areas and the whole brain. Through two experiments involving high-definition tACS with simultaneous measurements using a functional magnetic resonance imaging (fMRI), we revealed that the immediate online stimulation effects not only altered BOLD signals in the stimulated regions but also propagated across the whole brain in specific spatiotemporal patterns (functional networks). Stimulation effects were observed specifically in regions rich in neural fibres, including the grey and white matter, with no effect in regions containing cerebrospinal fluid. The timing of the signal value peaks depended on the stimulated region and functional networks, with a notable trend observed. Thus, tACS with a specific phase difference in two anatomically connected brain regions can immediately modulate online neural dynamics at both local and global scales. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/610912v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@124d6e1org.highwire.dtl.DTLVardef@1976b16org.highwire.dtl.DTLVardef@1f78294org.highwire.dtl.DTLVardef@9df1b7_HPS_FORMAT_FIGEXP M_FIG C_FIG