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

摘要 经颅交流电刺激（tACS）是一种无创神经调节技术， 大脑振荡的频率特异性夹带。许多认知功能的基础是 振荡时间和模式，以及神经精神疾病的认知缺陷与 在这些模式的干扰。tACS有可能使节律活动同步， 认知缺陷然而，一个主要的挑战是，tACS对脑振荡的影响取决于 个体的当前大脑状态以及相对于正在进行的阶段的刺激的定时 振荡使用工作记忆范式，我们将通过调查状态来解决这一挑战- tACS输送到左背外侧前额叶皮层（DLPFC）对θ-γ的依赖性影响 交叉频率耦合（tgCFC）和θ额顶相位同步，两个EEG标记 对工作记忆功能至关重要具体来说，在目标1中，我们将检验tACS与θ- 在具有强tgCFC的关键任务时期期间间歇性输送的嵌套伽马波形将得到改善 空间作业中的跨频交互作用和额顶相位同步 记忆任务，相对于无任务时期和假手术期间以相同波形输送的tACS 刺激.在目标2中，我们将检验闭环伽马tACS与以下条件同步应用的假设： 持续的θ振荡将增强交叉频率的相互作用和额顶相位 相对于具有θ嵌套伽马波形的开环tACS的同步。我们还将确定 tACS诱导的任务表现变化与EEG标记物变化之间的关系 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- θ和γ节律之间的频率相互作用并增强相位同步 额叶和顶叶之间的区域，支持工作记忆功能。他们还将把 为测试任务锁定和闭环刺激的有效性的潜在临床试验奠定基础 临床人群的范例。

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.