Rational Optimization of tACS for Targeting Thalamo-Cortical Oscillations

针对丘脑皮质振荡的 tACS 的合理优化

• 批准号: 9514245
• 负责人: Flavio Frohlich
• 金额: $ 69.97万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9514245
• 关键词: Animal Experiments; Animals; Autistic Disorder; Behavior; Brain; Cognition; Complex; Computer Simulation; Data; Development; Disease; Dose; Electrodes; Electroencephalography; Electrophysiology (science); Ferrets; Fostering; Foundations; Frequencies; Goals; Health; Human; Impairment; Implant; In Vitro; Individual; Intervention; Lateral; Maps; Mental Depression; Mental disorders; Methods; Mission; Motivation; National Institute of Mental Health; Neurons; North Carolina; Outcome; Parietal Lobe; Participant; Pathologic; Patients; Physiological; Play; Preparation; Psychiatric therapeutic procedure; Public Health; Pulvinar structure; Research; Research Domain Criteria; Role; Schizophrenia; Shapes; Slice; Structure; Synapses; System; Testing; Thalamic structure; Therapeutic; Translating; United States National Institutes of Health; Universities; Work; autism spectrum disorder; base; clinical research site; cognitive function; density; design; frontal lobe; improved; in vivo; innovation; neurosurgery; next generation; novel; therapy development; tool; treatment strategy

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.

项目摘要 - 北卡罗来纳大学教堂山分校，弗罗利希 α 振荡是一种丘脑皮质节律（8-12 Hz），在以下方面发挥着重要的功能作用： 认知和行为。经颅交流电刺激 (tACS) 已被证明可以改变 健康人类参与者的皮质阿尔法振荡和相关认知功能。然而，它 目前尚不清楚 tACS 如何参与和调节丘脑皮质振荡作为 刺激剂量（频率、幅度和持续时间）。弥合这一差距将有助于发展 用于针对精神疾病中α振荡的病理变化的 tACS 范式，例如 抑郁症、精神分裂症和自闭症。我们研究的长期目标是将计算与 建模、体外和体内动物实验以及人体研究，以开发和验证 tACS 精神疾病治疗的范例。此应用程序的目标是 (1) 通过 tACS 作为一种方法，从机制上剖析和优化丘脑皮质网络动力学的调节 刺激参数的函数，以及 (2) 在健康对照中验证 tACS 的目标参与 参与者和患者。我们将测试 tACS 调节 α 振荡的中心假设 丘脑皮质系统作为刺激参数频率、幅度和的函数 期间。这项工作的基本原理是基于机制的 tACS 剂量优化将提高其 功效，从而提供新的科学和治疗机会。基于综合 初步数据显示，三个具体目标是：（1）了解 tACS 频率和作用 调节丘脑皮质 α 振荡的幅度，(2) 绘制和机械剖析 作为 tACS 持续时间的函数，持久效应，以及 (3) 验证 tACS 对 α 的调节 人类参与者的振荡。该作品在跨学科和转化设计方面具有创新性； 该研究通过整合体内和体外克服了个别方法的局限性 使用计算模型优化 tACS 以靶向丘脑皮质 α 的动物研究 振荡并在人类参与者中验证了这些发现。这是向前迈出的关键一步 今天的 tACS 方法没有考虑如何与皮质下功能相互作用 丘脑等结构决定了目标参与度。拟议的研究意义重大，因为 它提供了如何优化 tACS 以瞄准 α 振荡的机制理解，这发挥了 在生理和病理状态中发挥核心作用。最终，这项工作将使理性 下一代 tACS 研究中刺激剂量的选择，均用于研究 行为中的丘脑皮质振荡和用于治疗精神疾病。