Biology and Biophysics of the Cortical Response to Transcranial Magnetic Stimulation

皮质对经颅磁刺激反应的生物学和生物物理学

• 批准号: 10264793
• 负责人: Angel V Peterchev
• 金额: $ 69.86万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264793
• 关键词: Acute; Affect; Anatomy; Area; Axon; Basic Science; Behavioral; Biologic Development; Biological; Biology; Biophysics; Brain; Brain Diseases; Brain region; Clinical; Cognitive; Computer Models; Computer Simulation; Corticospinal Tracts; Coupled; Custom; Data; Electroencephalography; Electromyography; Electrophysiology (science); Elements; Experimental Models; Foundations; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Goals; Head; Human; Knowledge; Macaca mulatta; Measurement; Measures; Mediating; Mental Depression; Mental disorders; Methodology; Methods; Migraine; Minority; Modeling; Morphologic artifacts; Motor Cortex; Neurons; Obsessive-Compulsive Disorder; Outcome; Patients; Pattern; Pharmacology; Physiologic pulse; Physiological; Physiology; Prefrontal Cortex; Procedures; Process; Protocols documentation; Recurrence; Research Personnel; Resistance; Safety; Site; Spatial Distribution; Spinal; Spinal Cord; Stimulus; Synaptic plasticity; System; Therapeutic; Therapeutic Intervention; Time; Training; Transcranial magnetic stimulation; United States National Institutes of Health; biophysical model; design; electric field; experimental study; hippocampal pyramidal neuron; human subject; imaging modality; improved; inhibitory neuron; insight; magnetic field; multi-scale modeling; nervous system disorder; neural circuit; neural recruitment; neurophysiology; neuroregulation; nonhuman primate; novel; relating to nervous system; repetitive transcranial magnetic stimulation; response; simulation; therapeutic target

The use of transcranial magnetic stimulation (TMS) as a therapeutic intervention is FDA-cleared for treating depression, obsessive-compulsive disorder, and migraine, and shows promise for a host of other brain disorders. The appeal of TMS is its safety, non-invasiveness, and well-established capacity for modulating the activity of brain regions. In human subjects, that modulation is assessed only at the gross scale of behavioral, cognitive, or aggregate physiological effects (e.g. EMG, EEG, fMRI). The fine-scale responses and mechanisms of TMS, at the level of biophysical and biological effects on neurons and circuits, remain poorly understood. This knowledge gap hinders rational design of TMS protocols and leaves researchers and clinicians dependent on trial-and-error approaches and inferences from macroscopic data to improve the methodology. The lack of reductionistic insight is particularly detrimental when targeting non-motor areas such as prefrontal cortex where a readout of the immediate neural response is unavailable, for example due to the stimulus artifact in EEG. Our overall goal is to fill in this knowledge gap by studying the neural circuit mechanisms of TMS in the non-human primate brain. The approach integrates neurophysiological experiments featuring direct single-unit and local field potential recordings and multiscale computational simulations of neural circuits in both primary motor cortex and prefrontal cortex. Aim 1 is to establish the circuit mechanisms of acute responses to single and paired TMS pulses. Determining the pulse response of single neural elements and recurrent cortical circuits permits a detailed examination of the biophysics and biology of neural recruitment at a short time scale. A main goal of TMS therapy is to achieve controlled, lasting neuromodulation, however, so in Aim 2 we will extend the same neurophysiological and modeling approaches to the study of responses to repetitive TMS (rTMS). Here the goal of the neurophysiology will be to quantify the effects of rTMS pulse trains on long-lasting changes in neural activity and, accordingly, the neural simulations will incorporate synaptic plasticity. Critically, in both Aims we will conduct the experiments and modeling both in primary motor cortex, where spinal potential recordings and electromyography can supplement direct readout of neural effects in cortex, and prefrontal cortex, where only cortical-level recordings are suited to characterize neuromodulatory effects. The overall product will be an experiment- and model-driven mechanistic understanding of the effect of TMS on cortical circuits, enabling a transformational advance in the interpretation of the effects of TMS. Taken together, the results will promote a more biologically-grounded, rational approach to designing TMS protocols for neuromodulation.

使用经颅磁刺激（TMS）作为治疗干预措施进行FDA处理以治疗 抑郁症，强迫症和偏头痛，并显示出许多其他脑部疾病的希望。 TMS的吸引力在于其安全性，无创性和良好的调节能力 大脑区域。在人类受试者中，该调制仅在行为，认知，认知， 或骨料生理效应（例如EMG，EEG，fMRI）。 TMS的细尺度响应和机制 在生物物理和生物学对神经元和电路的影响水平上，人们的理解仍然很少。这 知识差距阻碍了TMS协议的合理设计，并使研究人员和临床医生依赖于 宏观数据的试验方法和推论以改善方法。缺乏 当针对非运动区域（例如前额叶皮层）时，还原性的见解尤其有害 例如，由于脑电图中的刺激伪像，无法进行直接神经反应的读数。我们的 总体目标是通过研究非人类TMS的神经回路机制来填补这一知识差距 灵长类动物的大脑。该方法集成了具有直接单单元和局部领域的神经生理实验 原发性运动皮层和神经回路的潜在记录和多尺度计算模拟 前额叶皮层。 AIM 1是建立对单个和配对TM的急性响应的电路机制 脉冲。确定单个神经元素和复发性皮质电路的脉冲响应允许A 详细检查神经招募的生物物理学和生物学，以短期范围。一个主要目标 TMS治疗是为了实现受控的持久神经调节，但是在AIM 2中，我们将延伸相同 神经生理学和建模方法研究了对重复TMS（RTMS）的反应。这里的目标 神经生理学将是量化RTMS脉冲火车对神经长期变化的影响 活动，因此，神经模拟将结合突触可塑性。至关重要的是，在这两个目标中，我们都会 在脊柱电势记录和 肌电图可以补充皮质和前额叶皮质中神经效应的直接读数，其中仅 皮质级记录适合表征神经调节作用。总体产品将是 实验和模型驱动的机械理解TMS对皮层电路的影响，使A 在解释TMS效应的过程中的变革进步。综上所述，结果将促进 为设计用于神经调节的TMS方案的更具生物学的，合理的方法。