How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation

Large-scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual-site Transcranial Alternating Current Stimulation (ds-TACS) has been recently introduced as non-invasive technique to manipulate the temporal phase relationship of local oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation parameters such as focality and stimulation intensity should be matched to enable an unambiguous interpretation of the behavioral effects. Using electric field simulations based on a realistic head geometry, we tested how well this goal has been met in studies, which have employed ds-TACS up to now. Separating the induced electrical fields in their spatial and temporal components, we investigated how the chosen electrode montages determined the spatial field distribution and the generation of phase variations in the injected electric fields. Considering the basic physical mechanisms, we derived recommendations for an optimized stimulation montage. The latter allows for a principled design of in- and anti-phase ds-TACS conditions with matched spatial distributions of the electric field. This knowledge will help cognitive neuroscientists to design optimal ds-TACS configurations, which are suited to probe unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain.