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

Abstract

Oscillatory phase has been proposed as key parameter defining the spatiotemporal structure of neural activity. Phase alignment of oscillations by transcranial alternating current stimulation (tACS) may offer a unique opportunity to enhance our understanding of brain rhythms and to alter brain function. However, the precise mechanism and effectiveness of tACS are still critically debated. Here, we investigated the phase-specificity of tACS effects on visually evoked steady state responses (SSR) measured by electroencephalography (EEG). Using an intermittent electrical stimulation protocol, we assessed the influence of tACS on SSR amplitude as a function of phase shift between rhythmic sensory and electrical stimulation in the interval immediately following tACS. Visual flicker was delivered at six different phase angles relative to the tACS cycle. Participants were presented with flicker and high-definition tACS over the occipital cortex at 10 Hz in two sessions using active or sham stimulation. We observed that the phase shift between flicker and tACS modulates evoked SSR amplitudes. The amplitude change over phase shift conditions was significant for both general and sinusoidal modulation measures. Neural sources of phase-specific effects were localized in the parietooccipital cortex within flicker-aligned regions. Importantly, tACS effects were stronger in subjects with lower phase locking between EEG and flicker. Overall, our data provide evidence for phase alignment of brain activity by tACS, since the change in SSR amplitude can only result from phase-specific interactions with the applied electric fields. This finding corroborates the physiological efficacy of tACS and highlights its potential for controlled modulation of brain signals. Keywordstranscranial alternating current stimulation (tACS), EEG, phase, alpha oscillations, visual flicker Significance StatementThe lacking proof of phase-specific effects of transcranial alternating current stimulation (tACS) on neural activity in humans still restricts its potential to advance knowledge on the functional significance of brain oscillations. We show that the phase shift between concurrent 10 Hz tACS and precisely controlled oscillatory activity via visual flicker modulated the amplitude of evoked neural oscillations. Interindividual differences in tACS effect size were dependent on the current brain state. Our findings provide electrophysiological evidence for the capability of tACS to phase-align intrinsic neural activity. These mechanistic insights emphasize the value of tACS to advance research on the causal role of brain rhythms and offer important implications for the treatment of disturbed oscillatory patterns and cortical connectivity in brain disorders.

Theta Phase-dependent Modulation of Perception by Concurrent Transcranial Alternating Current Stimulation and Periodic Visual Stimulation

“…Our findings are unlikely to be due to a general tACS effect on motor performance as the phase of tACS relative to the visual stimulus would not be expected to affect performance in such case. Further, electrophysiological evidence for the efficiency of tACS applied over the occipital cortex in phase-specific modulation of SSVEPs has recently been reported, although in the alpha frequency range (Fiene et al, 2019). More broadly, our findings support the literature suggesting sensory perception is modulated by the phase of oscillations in the sensory cortices (e.g.…”

“…Our Study contributes to the recently developing literature on concurrent use of tACS and periodic visual stimulation as a promising research technique in neuroscience (Ruhnau et al, 2016: Chai et al, 2018 and the importance of phase synchrony between them (Fiene et al, 2019) and demonstrate a behavioural effect for the first time. This will be of interest to researchers using electrical brain stimulation and sensory stimulation techniques.…”

Sustained neural rhythms reveal endogenous oscillations supporting speech perception

“…Individualizing brain stimulation protocols has therefore been proposed as a crucial step to advance the theoretical and practical application of this line of research (25)(26)(27). A recent study (59) reported that the phase relation between tACS and visual flicker modulates the magnitude of EEG responses to the flicker when tACS is turned off. Moreover, the individual "best" phase relation between tACS and flicker (leading to strongest EEG responses) was correlated with the individual phase relation between EEG and flicker.…”

Cognitive Fatigue in Multiple Sclerosis: An Objective Approach to Diagnosis and Treatment by Transcranial Electrical Stimulation

“…tACS involves the application of rapidly alternating electrical currents to the scalp and is assumed to cause periodic shifts in membrane potential and an entrainment (i.e., temporal phase alignment), of neural activity to the externally applied current [128,129]. Although the direct assessment of neural tACS effects in humans is still complicated by electrical artifacts in concurrent neural recordings, findings on behavioral effects during stimulation and analyses of electrophysiological stimulation aftereffects provide good evidence for the efficacy of tACS to modulate oscillatory activity in a phase- and frequency-dependent manner [130,131,132]. Lasting power and connectivity changes at the stimulation frequency have been interpreted as spike-timing-dependent plasticity effects as a consequence of synchronized activity during stimulation [131,133].…”