Transcranial alternating current stimulation induces long-term augmentation of neural connectivity and sustained anxiety reduction

ABSTRACT Although transcranial alternating current stimulation (tACS) has demonstrated short-term effects in modulating neural oscillations, potential clinical efficacy of tACS for treating “oscillopathies” (disorders associated with aberrant neural oscillations) hinges on its ability to generate long-term neural plasticity, which can translate into lasting behavioral changes. Administering alpha-frequency tACS over 4 consecutive days, we evaluated short- and long-term (> 24 hours) effects of α-tACS on local alpha power and oscillatory connectivity, along with behavioral outcomes in anxious arousal and affective sensory perception. The α-tACS (vs. sham stimulation) group exhibited increases in posterior alpha power immediately and 30 minutes post-stimulation but not 24 hours post-stimulation, suggesting transient effects on local neuronal synchrony. Strikingly, long-range alpha-frequency Granger causal connectivity (posterior→frontal) increased not only immediately and 30 minutes but also 24 hours post-stimulation, paralleled by sustained reductions in anxious arousal and aversion to auditory stimuli. Therefore, tACS is capable of eliciting long-term plasticity in long-range oscillatory connectivity with direct, lasting behavioral consequences, while leaving endogenous local oscillations unaltered. This temporal disparity in local and network effects favors the view of large-scale network strengthening by tACS, calling for research attention to the circuit and network impacts of tACS. Critically, with the growing recognition of large-scale network dysfunctions as a transdiagnostic pathophysiology of psychiatric disorders, this connectivity plasticity advocates for the clinical application of tACS with its unique advantage in tackling network pathologies.