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, modulation of neural activity by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the phase-specificity of tACS effects in humans is still critically debated. OBJECTIVE Here, we investigated the phase-specificity of tACS on visually evoked steady state responses (SSRs) in 24 healthy human participants. METHODS We used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. A neural network model served to validate the plausibility of experimental findings. RESULTS We observed a modulation of SSR amplitudes dependent on the phase shift between flicker and tACS. The tACS effect size was negatively correlated with the strength of flicker-evoked activity. Supported by simulations, data suggest that strong network synchronization limits further neuromodulation by tACS. 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 SSR phase delays in the tACS target region. CONCLUSIONS Overall, our data provide electrophysiological evidence for phase-specific modulations of rhythmic brain activity by tACS in humans. As the optimal timing of tACS application was dependent on cortical SSR phase delays, our data suggest that tACS effects were not mediated by retinal co-stimulation. These findings highlight the potential of tACS for controlled, phase-specific modulations of neural activity.

中文翻译：

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通过经颅交流电刺激对有节奏的大脑活动进行相位特异性操纵

背景振荡相位已被提议作为定义神经活动时空结构的关键参数。为了增强我们对脑节律的理解并改善病理条件下的临床结果，通过经颅交流电刺激 (tACS) 调节神经活动成为一种有前途的方法。然而，tACS 效应在人类中的阶段特异性仍然存在争议。目的 在这里，我们研究了 tACS 对 24 名健康人类参与者的视觉诱发稳态反应 (SSR) 的相位特异性。方法我们使用间歇性电刺激方案并评估了 tACS 对 tACS 后立即间隔内 SSR 振幅的影响。神经网络模型用于验证实验结果的合理性。结果 我们观察到 SSR 振幅的调制取决于闪烁和 tACS 之间的相移。tACS 效应大小与闪烁诱发活动的强度呈负相关。在模拟的支持下，数据表明强大的网络同步限制了 tACS 的进一步神经调节。相位特定效应的神经来源位于闪烁夹带区域内的顶枕叶皮层。重要的是，闪烁和与最强 SSR 相关的 tACS 之间的最佳相移与 tACS 目标区域中的 SSR 相位延迟相关。结论总体而言，我们的数据为人类 tACS 对节律性大脑活动的相位特异性调节提供了电生理学证据。由于 tACS 应用的最佳时机取决于皮质 SSR 相位延迟，我们的数据表明 tACS 效应不是由视网膜共刺激介导的。这些发现突出了 tACS 在神经活动的受控、特定阶段调制方面的潜力。