Memory dependent modulation of hippocampal theta power through frontoparietal phase synchronous brain stimulation

Targeting subcortical regions like the hippocampus with non-invasive brain stimulation is challenging due to predominantly cortical distribution of electric fields. Frontoparietal phase-synchronous transcranial alternating stimulation (tACS) offers a promising approach to modulate hippocampal functions, though its ability to induce modulation of oscillatory activity in deep subcortical targets remains to be shown. In this pilot study, we applied dual-site theta-tACS (in-phase between left frontoparietal regions) during a temporal order memory task. To quantify hippocampal activity and connectivity, we performed subcortical source analyses of electroencephalography (EEG) data using a hierarchical subspace pursuit algorithm. While memory did not differ between tACS and sham conditions, we observed tACS-induced increases in hippocampal theta power and its connectivity in individuals with superior memory performance. This study provides first-time evidence that phase-synchronized tACS over lateral frontoparietal areas influences hippocampal theta oscillatory activity, substantiating its potential to modulate hippocampal functions in health and disease.