Rational Optimization of tACS for Targeting Thalamo-Cortical Oscillations

项目摘要-北卡罗来纳大学-查佩尔山，弗罗里希 α振荡是一种丘脑-皮层节律（8-12 Hz），在以下方面发挥重要的功能作用： 认知和行为。经颅交流电刺激（tACS）已被证明可以改变 健康人参与者的皮质α振荡和相关认知功能。但 目前还不清楚tACS如何参与和调节丘脑-皮层振荡作为一个功能， 刺激剂量（频率、振幅和持续时间）。弥合这一差距将有助于发展 tACS范例，用于针对精神疾病中α振荡的病理变化， 抑郁症精神分裂症和自闭症我们研究的长期目标是将联合收割机 建模、体外和体内动物实验以及人体研究，以开发和验证tACS 治疗精神疾病的范例。本申请的目的是（1） 机械地剖析和优化丘脑-皮层网络动态的调制，tACS作为一个 刺激参数的函数，以及（2）在健康对照中通过tACS验证靶接合 参与者和患者。我们将测试中心假设，即tACS调节α振荡， 作为刺激参数频率、振幅和 持续时间这项工作的基本原理是，基于机制的剂量优化tACS将增加其 从而提供新的科学和治疗机会。基于综合 初步数据，三个具体目标是：（1）了解tACS频率的作用， 振幅调制丘脑-皮质α振荡，（2）映射和机械解剖 作为tACS持续时间的函数的持久效应，以及（3）验证tACS对α的调节 人类参与者中的振荡。该作品在跨学科和翻译设计方面具有创新性; 该研究通过整合体内和体外研究，克服了单个方法的局限性 利用计算建模优化靶向丘脑-皮质α的tACS的动物研究 振荡，并在人类参与者中验证这些发现。这是一个关键的一步， 今天的tACS方法，没有考虑皮层下的功能性相互作用， 诸如丘脑的结构形成目标接合。这项研究意义重大，因为 它提供了如何优化tACS以瞄准α振荡的机制理解，α振荡起着 在生理和病理状态中的核心作用。最终，这项工作将使理性的 下一代tACS研究中刺激剂量的选择，既用于研究 行为中的丘脑-皮质振荡和用于治疗精神疾病。

PROJECT SUMMARY - UNIVERSITY OF NORTH CAROLINA-CHAPEL HILL, FROHLICH The alpha oscillation is a thalamo-cortical rhythm (8-12 Hz) that serves important functional roles in cognition and behavior. Transcranial alternating current stimulation (tACS) has been shown to alter cortical alpha oscillations and associated cognitive function in healthy human participants. However, it remains unclear how tACS engages and modulates thalamo-cortical oscillations as a function of stimulation dose (frequency, amplitude, and duration). Bridging this gap will enable the development of tACS paradigms for targeting pathological changes in alpha oscillations in psychiatric illnesses such as depression, schizophrenia, and autism. The long-term goal of our research is to combine computational modeling, in vitro and in vivo animal experiments, and human studies to develop and validate tACS paradigms for the treatment of psychiatric disorders. The objective of this application is to (1) mechanistically dissect and optimize the modulation of thalamo-cortical network dynamics by tACS as a function of stimulation parameters, and (2) validate the target engagement by tACS in healthy control participants and patients. We will test the central hypothesis that tACS modulates alpha oscillations in the thalamo-cortical system as a function of the stimulation parameters frequency, amplitude, and duration. The rationale of this work is that mechanism-based dose optimization of tACS will increase its efficacy and thus provide new scientific and therapeutic opportunities. Based on comprehensive preliminary data, the three specific aims are: (1) to understand the role of tACS frequency and amplitude in modulating thalamo-cortical alpha oscillations, (2) to map and mechanistically dissect the outlasting effects as a function of tACS duration, and (3) to validate tACS for the modulation of alpha oscillations in human participants. The work is innovative in its interdisciplinary and translational design; the proposed research overcomes the limitations of individual methods by integrating in vivo and in vitro animal studies with computational modelling to optimize tACS for targeting thalamo-cortical alpha oscillations and validates these findings in human participants. This is a critical step forward from today’s approach to tACS, which does not consider how functional interaction with subcortical structures such as the thalamus shapes target engagement. The proposed research is significant since it provides mechanistic understanding how to optimize tACS to target alpha oscillations, which play a central role in both physiological and pathological states. Ultimately, this work will enable the rational choice of stimulation dose in the next generation of tACS studies, both for studying the functional role of thalamo-cortical oscillations in behavior and for treating psychiatric disorders.