Effects of Transcranial Magnetic Stimulation on Neurons in Behaving Primates

描述（由申请人提供）：经颅磁刺激（TMS）是一种用于刺激人脑的非侵入性方法。它极大地促进了我们对正常大脑功能的理解，并在精神和神经疾病的治疗中显示出希望。然而，TMS对神经元活动的确切作用仍然未知。我们将应用TMS的单脉冲，同时记录行为非人类灵长类动物的单个神经元。我们的TMS方法将与人类使用的方法相对应，并且很容易被任何灵长类动物神经生理学实验室采用。一组研究人员将设计定制的TMS线圈，将刺激的焦点引导到大脑皮层的精确位置，创新的电子设备，允许在TMS脉冲后1 ms内进行神经元记录，以及受控的视觉-视觉任务，允许行为和神经元状态的系统变化。我们将记录单个神经元和场电位在这两个网站的刺激，并在遥远的，但单突触连接的网站。我们工作的最终结果将是发现TMS如何在单个神经元和简单回路的水平上影响大脑。影响将包括改进的，生理指导的TMS协议，用于人类基础研究和治疗应用。 公共卫生相关性：在头部附近使用磁脉冲对人类大脑进行非侵入性刺激（“经颅磁刺激”或TMS）是研究视觉、认知和运动的有价值的工具，但TMS究竟如何影响大脑活动是一个悬而未决的问题。这项拟议中的工作将通过记录行为灵长类动物大脑中的单个神经元来回答这个问题。该项目是一项技术挑战，但其可行性已得到证实，其固有风险将由广泛的专家团队管理，其最终结果将是变革性的：关于TMS生理机制的数据将改善对人类大脑的基础研究，并帮助临床医生实现TMS作为有效治疗干预的承诺。

DESCRIPTION (provided by applicant): Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human brain. It has contributed greatly to our understanding of normal brain function and shows promise in therapies for psychiatric and neurological disorders. Exactly what TMS does to neuronal activity, however, remains unknown. We will apply single pulses of TMS while recording from single neurons in behaving non-human primates. Our TMS methods will correspond to those used in humans and will be easily adoptable by any primate neurophysiology laboratory. A team of researchers will design custom TMS coils to direct the focus of stimulation to precise locations of cerebral cortex, innovative electronics to permit neuronal recordings within 1 ms after TMS pulses, and controlled visual- oculomotor tasks to allow systematic variation of behavioral and thus neuronal state. We will record from single neurons and field potentials at both the site of stimulation and at distant but monosynaptically connected sites. The end result of our work will be to discover how TMS influences the brain at the level of single neurons and simple circuits. Implications will include improved, physiologically-guided TMS protocols for human basic research studies and therapeutic applications. PUBLIC HEALTH RELEVANCE: Non-invasive stimulation of the human brain using magnetic pulses near the head ("transcranial magnetic stimulation" or TMS) is a valuable tool for studying vision, cognition, and movement, but exactly how TMS affects brain activity is an open question. The proposed work will answer this question by recording from single neurons in the brains of behaving primates during TMS. The project is a technical challenge but its feasibility has been confirmed, its inherent risks will be managed by a team of wide-ranging experts, and its end result will be transformative: data on the physiological mechanisms of TMS will improve basic research on the human brain and help clinicians fulfill the promise of TMS as an effective therapeutic intervention.