Transcranial alternating current stimulation affects the BOLD signal in a frequency and task-dependent manner.

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for manipulating ongoing brain oscillations. While previous studies demonstrated frequency-specific effects of tACS on diverse cognitive functions, its effect on neural activity remains poorly understood. Here we asked how tACS modulates regional fMRI blood oxygenation level dependent (BOLD) signal as a function of frequency, current strength, and task condition. TACS was applied over the posterior cortex of healthy human subjects while the BOLD signal was measured during rest or task conditions (visual perception, passive video viewing and motor task). TACS was applied in a blockwise manner at different frequencies (10, 16, 60 and 80 Hz). The strongest tACS effects on BOLD activity were observed with stimulation at alpha (10 Hz) and beta (16 Hz) frequency bands, while effects of tACS at the gamma range were rather modest. Specifically, we found that tACS at 16 Hz induced BOLD activity increase in fronto-parietal areas. Overall, tACS effects varied as a function of frequency and task, and were predominantly seen in regions that were not activated by the task. Also, the modulated regions were poorly predicted by current density modeling studies. Taken together, our results suggest that tACS does not necessarily exert its strongest effects in regions below the electrodes and that region specificity might be achieved with tACS due to varying susceptibility of brain regions to entrain to a given frequency.