State-dependent modulation of interactions of theta and gamma rhythms in working memory

摘要 经颅交流电刺激(TACS)是一种非侵入性的神经调节技术，它可以 用于特定频率的大脑振荡的夹带。许多认知功能都是由 神经精神障碍的振荡时间和模式以及认知缺陷与 在这些模式中的骚乱。Tacs有可能同步节律活动并缓解 认知缺陷。然而，一个主要的挑战是，TAC对大脑振荡的影响取决于 个体当前的大脑状态以及相对于正在进行的阶段的刺激时间 震荡。使用工作记忆范式，我们将通过研究状态- 左侧背外侧前额叶皮质递送Tacs对β-γ的依赖效应 交叉频率耦合(Tgcfc)和theta额顶相同步，两个脑电标记物 对工作记忆功能至关重要。具体地说，在目标1中，我们将检验以下假设：Tacs with theta- 在具有较强tgcfc的关键任务阶段间歇提供的嵌套伽马波形将得到改善 空间作业中的交叉频率相互作用和额顶相位同步 内存任务，相对于在无任务时期和假时期期间以相同波形传递的TAC 刺激。在目标2中，我们将检验这样一个假设，即闭环伽马Tacs与 持续的theta振荡将增强交叉频率的相互作用和额顶相 与具有theta嵌套伽马波形的开环Tacs相关的同步。我们还将确定 不同性别Tacs作业绩效改变与脑电标记物改变的关系 不同的刺激条件。这些研究将帮助我们确定可靠的策略来操纵交叉 Theta和Gamma节律之间的频率相互作用和增强相位同步 额叶和顶叶区域之间，这支持工作记忆功能。他们还将铺设 为潜在的临床试验奠定基础，这些试验可以测试任务锁定和闭环式刺激的效果 临床人群中的范例。

ABSTRACT Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation technique that allows for frequency-specific entrainment of brain oscillations. Many cognitive functions are underpinned by oscillatory timing and patterns, and cognitive deficits in neuropsychiatric disorders are associated with disturbances in those patterns. tACS has the potential to synchronize rhythmic activity and mitigate cognitive deficits. However, a major challenge is that the effects of tACS on brain oscillations depend on the current brain state of the individual and on the timing of stimulation relative to the phase of ongoing oscillations. Using a working memory paradigm, we will address this challenge by investigating the state- dependent effects of tACS delivered to the left dorsolateral prefrontal cortex (DLPFC) on theta-gamma cross frequency coupling (tgCFC) and theta fronto-parietal phase synchronization, two EEG markers critical to working memory function. Specifically, in Aim 1, we will test the hypothesis that tACS with theta- nested gamma waveform delivered intermittently during key task epochs with strong tgCFC will improve cross-frequency interactions and frontoparietal phase synchrony during performance of a spatial working memory task, relative to tACS delivered with the same waveform during task-free epochs and sham stimulation. In Aim 2, we will test the hypothesis that closed-loop gamma tACS applied in phase with ongoing theta oscillations will enhance cross-frequency interactions and fronto-parietal phase synchronization relative to open-loop tACS with theta-nested gamma waveform. We will also determine the relationship between tACS-induced change in task performance and change in EEG markers across different stimulation conditions. These studies will help us identify reliable strategies to manipulate cross- frequency interactions between theta and gamma rhythms and to enhance phase synchronization between frontal and parietal regions, which support working memory function. They will also lay the groundwork for potential clinical trials that can test the efficacy of task-locked and closed-loop stimulation paradigms in clinical populations.