Rational Optimization of tACS for Targeting Thalamo-Cortical Oscillations

针对丘脑皮质振荡的 tACS 的合理优化

基本信息

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
项目类别：
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

项目摘要

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：经颅交流电刺激 (tACS) 已被证明可以改变认知和行为。然而，健康人类参与者的皮质阿尔法振荡和相关的认知功能。目前尚不清楚 tACS 如何参与和调节丘脑皮质振荡作为弥合这一差距将有助于发展刺激剂量（频率、幅度和持续时间）。用于针对精神疾病中α振荡的病理变化的 tACS 范式，例如我们研究的长期目标是将抑郁症、精神分裂症和自闭症结合起来。建模、体外和体内动物实验以及人体研究，以开发和验证 tACS 该应用程序的目标是（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、幅度和的函数这项工作的基本原理是基于机制的 tACS 剂量优化将增加其持续时间。从而提供新的科学和基于综合治疗的机会。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 的调节这项工作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 方法没有考虑与皮质下的功能相互作用丘脑等结构决定了目标参与度，因此这项研究意义重大。它提供了如何优化 tACS 以瞄准 α 振荡的机制理解，这发挥了最终，这项工作将使理性成为可能。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。