Perfect Timing: Effects of Auditory Stimulation on Alpha Oscillations During Wakefulness and the Transition to Sleep are Phase-dependent in Humans

Alpha oscillations play a vital role in managing the brains resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators, is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (CLAS) as an EEG-based method to augment and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across three independent studies, we demonstrate that CLAS alters alpha power, frequency, and connectivity in a phase, amplitude and topography-dependent manner. Using a single-pulse-CLAS evoked potentials approach we show that the effects of auditory stimuli on alpha oscillations and resulting evoked potentials can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that CLAS modulates sleep onset dynamics in an alpha phase-dependent manner.