Effect of Theta Transcranial Alternating Current Stimulation and Phase-Locked Transcranial Pulsed Current Stimulation on Learning and Cognitive Control

Non-invasive brain stimulation (NIBS) is emerging as a robust treatment alternative for major depressive disorder, with a potential for achieving higher remission rates by providing targeted stimulation to underlying brain networks, such as the salience network (SN). Growing evidence suggests that these therapeutic effects are dependent on the frequency and phase synchrony between SN oscillations and stimulation as well as the task-specific state of the SN during stimulation. However, the development of phase-synchronized non-invasive stimulation has proved challenging until recently. Here, we use a phase-locked pulsed brain stimulation approach to study the effects of two NIBS methods: transcranial alternating current stimulation (tACS) versus phase-locked transcranial pulsed current stimulation (tPCS), on the SN during an SN activating task. 20 healthy volunteers participated in the study. Each volunteer partook in four sessions, receiving one stimulation type at random (theta-tACS, peak tPCS, trough tPCS or sham) while undergoing a learning game, followed by an unstimulated test based on learned material. Each session lasted approximately 1.5 h, with an interval of at least 2 days to allow for washout and to avoid cross-over effects. Our results showed no statistically significant effect of stimulation on the event related potential (ERP) recordings, resting electroencephalogram (EEG), and the performance of the volunteers. While stimulation effects were not apparent in this study, the nominal performance of the phase-locking algorithm offers a technical foundation for further research in determining effective stimulation paradigms and conditions. Specifically, future work should investigate stronger stimulation and true task-specific stimulation of SN nodes responsible for the task as well as their recording. If refined, NIBS could offer an effective, homebased treatment option.