Phase-specific manipulation of neural oscillatory activity by transcranial alternating current stimulation

Background: Oscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, phase-specific modulation of oscillations by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the effectiveness of tACS in humans is still critically debated. Objective: Here, we investigated the phase-specificity of tACS effects on visually evoked steady state responses (SSRs) in 24 healthy human participants of either sex. Methods: To this end, we used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. Results: We observed that the phase shift between flicker and tACS modulates evoked SSR amplitudes. The tACS effect size was dependent on the strength of flicker-evoked oscillatory activity, with larger effects in participants showing weaker locking of neural responses to flicker phase. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with cortical SSR onset delays over the visual cortex. Conclusions: Overall, our data provide electrophysiological evidence for phase-specific modulations of oscillatory activity by tACS in humans. As the optimal timing of tACS application was dependent on neural conduction times as measured by SSR onset delays, data suggest that the interaction between tACS effect and SSR was cortical in nature. These findings corroborate the physiological efficacy of tACS and highlight its potential for controlled modulations of brain signals.