Reliability of Repetitive TMS-induced Modulation of Cortical Excitability

TMS 诱导的皮质兴奋性重复调节的可靠性

• 批准号: 10112309
• 负责人: Mouhsin Shafi
• 金额: $ 53.68万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112309
• 关键词: Address; Adult; Basic Science; Behavior; Behavioral; Benchmarking; Brain; Brain region; Clinical; Clinical Research; Cognition; Computer Models; Data; Development; Devices; Diagnostic; Disease; Dose; Electroencephalography; Electromyography; Ensure; Evoked Potentials; Fingers; Foundations; Functional disorder; Future; Genetic; Genotype; Grant; Hand; Head; Human; Individual; Individual Differences; Knowledge; Laboratories; Left; Magnetic Resonance Imaging; Measures; Menstrual cycle; Mental Depression; Mental disorders; Methods; Modeling; Motor; Motor Cortex; Motor Evoked Potentials; Neuropsychology; Neurosciences; Neurosciences Research; Outcome Measure; Participant; Performance; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Protocols documentation; Randomized; Reporting; Reproducibility; Research Personnel; Resistance; Rest; Sample Size; Secure; Series; Short-Term Memory; Site; Sleep; Source; Structure; Techniques; Testing; Therapeutic; Time; Translational Research; United States Food and Drug Administration; Woman; age group; behavior measurement; behavioral outcome; behavioral phenotyping; cohort; design; experimental study; genetic testing; insight; inter-individual variation; magnetic resonance imaging/electroencephalography; middle age; nervous system disorder; neuroimaging; neurophysiology; neuropsychiatric disorder; neuroregulation; noninvasive brain stimulation; nutrition; repetitive transcranial magnetic stimulation; repository; research study; response; young adult

ABSTRACT Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive brain stimulation technique capable of modulating activity in the targeted brain region and its connected brain circuits beyond the duration of the stimulation itself. rTMS is utilized in neuroscience research to investigate brain function during human cognition and behavior, and to understand brain pathophysiology in neuropsychiatric diseases. Clinically, rTMS protocols have diagnostic and therapeutic utility across a wide spectrum of disease states, and four rTMS devices are cleared by the Food and Drug Administration (FDA) for treatment of medication-resistant depression. However, the variability of the neuromodulatory effects of rTMS and its sources are ill-defined. This knowledge gap represents a fundamental limitation for both, the interpretation of rTMS results and the design of studies. For example, it is challenging to calculate or assess the sample size for a study, and one cannot optimize rTMS parameters for an individual without knowing whether individual differences in rTMS response are reproducible. In addition, one cannot assume that rTMS protocols tested in motor cortex will produce similar neuromodulatory effects when administered to other brain regions. In this proposal we will use MRI-guided rTMS in combination with EMG, EEG and behavioral measures to characterize the variability of rTMS effects in primary motor cortex (M1) and in dorsolateral prefrontal cortex (DLPFC). In a cohort of 60 subjects, we will evaluate the inter-subject and intra-subject test-retest reliability of the modulatory effects of the most widely used rTMS protocols applied to M1. We will compare the impact of different rTMS protocols on corticospinal excitability (measured via motor-evoked potentials), cortical excitability (measured via simultaneous TMS-EEG), and motor performance (using a sequential finger tapping task). Each subject will undergo a total of 10 TMS-EMG-EEG-behavior sessions, evaluating repeated sessions of excitatory and inhibitory protocols. In a separate cohort of 60 subjects, we will evaluate the transfer of rTMS effects across brain regions by applying 10 Hz rTMS and iTBS to both M1 and DLPFC. Each subject will undergo a total of 10 TMS-EEG-behavior sessions contrasting stimulation protocols across regions (M1 versus DLPFC). All subjects will undergo extensive baseline assessment, including detailed exam, neuropsychological measures, structural and resting-state functional-connectivity MRI, computational modeling, laboratory and genetic testing, and EEG to identify predictors of inter-subject variability in response to rTMS. All data will be placed in a secure repository and made publicly accessible to other investigators. This study will define the reproducibility of the neuromodulatory effects of rTMS, quantifying the intrinsic variability of the method within and across individuals, across levels of analysis (neurophysiologic and behavioral) and brain regions (M1 versus DLPFC). These results will serve as a foundation to guide the planning, development and interpretation of all future studies utilizing rTMS to modulate brain function.

抽象的 重复经颅磁刺激（rTMS）是一种无创脑刺激技术，能够 在持续时间之外调节目标大脑区域及其连接的大脑回路的活动 刺激本身。 rTMS 在神经科学研究中用于研究人类认知过程中的大脑功能 和行为，并了解神经精神疾病的大脑病理生理学。临床上，rTMS 方案 具有跨多种疾病状态的诊断和治疗效用，四种 rTMS 设备 经美国食品和药物管理局 (FDA) 批准用于治疗药物抵抗性抑郁症。 然而，rTMS 神经调节作用的变异性及其来源尚不清楚。这些知识 差距代表了 rTMS 结果解释和研究设计的根本限制。 例如，计算或评估一项研究的样本量具有挑战性，并且无法优化 在不知道 rTMS 反应的个体差异是否存在的情况下，个体的 rTMS 参数 可重现。此外，我们不能假设在运动皮层中测试的 rTMS 协议会产生类似的结果。 当给予其他大脑区域时产生神经调节作用。 在本提案中，我们将使用 MRI 引导的 rTMS 结合肌电图、脑电图和行为测量来 表征初级运动皮层 (M1) 和背外侧前额叶皮层 rTMS 效应的变异性 （DLPFC）。在 60 名受试者的队列中，我们将评估受试者间和受试者内重测的可靠性 最广泛使用的 rTMS 协议应用于 M1 的调节效果。我们将比较影响 关于皮质脊髓兴奋性（通过运动诱发电位测量）、皮质的不同 rTMS 协议 兴奋性（通过同步 TMS-EEG 测量）和运动性能（使用连续的手指敲击 任务）。每个受试者将接受总共 10 次 TMS-EMG-EEG 行为课程，并重复评估 兴奋性和抑制性方案的会议。在一个由 60 名受试者组成的单独队列中，我们将评估转移 通过将 10 Hz rTMS 和 iTBS 应用于 M1 和 DLPFC，研究 rTMS 对整个大脑区域的影响。各科目 将进行总共 10 次 TMS-EEG 行为会话，对比各区域的刺激方案（M1 与 DLPFC 相比）。所有科目都将接受广泛的基线评估，包括详细的检查， 神经心理学测量、结构和静息态功能连接 MRI、计算 建模、实验室和基因测试以及脑电图来识别受试者间反应差异的预测因素 至 rTMS。所有数据将被放置在一个安全的存储库中，并可供其他调查人员公开访问。 这项研究将定义 rTMS 神经调节作用的可重复性，量化内在的 该方法在个体内部和个体之间、跨分析水平（神经生理学和 行为）和大脑区域（M1 与 DLPFC）。这些结果将作为指导的基础 规划、开发和解释所有未来利用 rTMS 调节大脑功能的研究。