Closed-loop phase-locked EEG-tACS enables adaptive control of cortical beta synchrony and motor control

Neural oscillations dynamically coordinate communication across distributed brain networks, and their pathological synchronization is a common feature of neurological and psychiatric disease. In Parkinsons disease, excessive beta-band synchronization within cortico-basal ganglia-thalamo-cortical loops is closely linked to motor impairment, highlighting the need for neuromodulation strategies that can selectively and adaptively reshape this brain synchrony online. Transcranial alternating current stimulation (tACS) offers a non-invasive approach to modify endogenous oscillatory activity, yet it is typically delivered in an open-loop manner, limiting control over the timing, direction, and functional network consequences of oscillatory modulation. Here, we developed an online adaptive EEG-guided closed-loop system that continuously tracked the instantaneous phase of ongoing cortical oscillations and delivered stimulation either aligned (in-phase) or 180 degrees opposed (anti-phase) to the endogenous beta rhythm. Thirty-eight right-handed healthy participants performed a stop-signal task while receiving adaptive closed-loop 4 x 1 HD-tACS over pre-supplementary motor cortex (preSMA) targeting beta-band activity (15-30 Hz) implicated in motor inhibition, under in-phase, anti-phase, or sham stimulation. Anti-phase tACS produced a robust suppression of beta synchrony relative to both in-phase and sham stimulation, consistent with destructive interference of the endogenous rhythm. Behaviorally, anti-phase tACS reduced inhibition performance by impairing the stopping process, whereas in-phase stimulation reduced peak force rate during go trials and decreased variability of the go response, consistent with increased inhibitory tone and stabilization of ongoing motor states. These results provide converging behavioral and neurophysiological evidence for destructive interference of anti-phase tACS and establish a mechanistic framework for phase-specific closed-loop neuromodulation, paving the way to implement a non-invasive therapeutic strategy aimed at desynchronizing pathological beta in neurological conditions such as Parkinsons disease.