Modulation of large-scale cortical coupling by transcranial alternating current stimulation

Background: Long-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value. Objective: First, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space. Methods: Participants were stimulated bifocally with high-definition tACS in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields. EEG aftereffects were analyzed systematically in sensor and source space. Results: While total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipito-parietal areas. Conclusion: The relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects are not expected to differ between the stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.