Pharmaco-TMS-EEG: Establishing a novel tool for measuring excitability in human cerebral cortex

Pharmaco-TMS-EEG：建立一种测量人类大脑皮层兴奋性的新工具

• 批准号: 318343452
• 负责人: Professor Dr. Ulf Ziemann
• 金额: --
• 依托单位: Abteilung Neurologie mit Schwerpunkt neurovaskuläre Erkrankungen und Neuroonkologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/318343452?language=en
• 关键词: Pharmaco; TMS; EEG; Establishing; novel

Pharmaco-TMS-EMG, i.e. the combination of neuropharmacology with transcranial magnetic stimulation (TMS) of motor cortex and recording of motor evoked potentials with electromyography (EMG) from a hand muscle has provided important insight to use TMS-EMG for differentiated non-invasive assessment of excitation and inhibition in motor cortex [Ziemann et al. 2015, Clin Neurophysiol 126:1847-68]. On this basis, TMS-EMG is being employed worldwide to detect abnormal excitability in neurological and psychiatric diseases. However, applications and gain of knowledge of TMS-EMG are significantly limited because recordings are made from a muscle (rather than from the brain) and assessment is restricted to motor cortex (no quantifiable responses with stimulation elsewhere). Recent advances in electroencephalography (EEG) amplifier technology allow now recordings of TMS-evoked responses directly from the brain. Therefore, TMS-EEG has a significant potential to overcome these limitations of currently practiced TMS-EMG technology. Focal TMS of primary motor cortex results reliably in TMS-evoked EEG potentials with reproducible latency and topology (e.g., P25, N45, P70, N100, and P180). However, the physiological mechanisms of these potentials are largely unknown. Therefore, observations of alterations of these potentials by experimental manipulation or in disease conditions remain, at present, at the descriptive level. We have started recently, to characterize these TMS-evoked EEG potentials by CNS active drugs. We could show for the first time that GABAAergic inhibition contributes to the N45 and GABABergic inhibition to the N100 [Premoli et al. 2014, J Neurosci 34:5603-12; Premoli et al. 2014, NeuroImage 103C:152-62]. To extend these data, and in analogy to a large body of previous work on pharmaco-TMS-EMG, we propose here a systematic pharmacological characterization of TMS-evoked EEG potentials. We will focus on CNS active drugs with specific modes of action in the glutamatergic and GABAergic system, and on blockers of voltage-gated ion channels. We expect from this research a novel, direct and therefore highly informative tool to assess excitability of the human cerebral cortex. This tool could, as soon as pharmaco-physiologically characterized, play an important role in the diagnostic assessment of abnormal brain excitability in neurological and psychiatric diseases.

Pharmaco-TMS-EMG，即神经药理学与运动皮层的经颅磁刺激（TMS）和用来自手部肌肉的肌电图（EMG）记录运动诱发电位的组合，为使用TMS-EMG对运动皮层的兴奋和抑制进行差异化非侵入性评估提供了重要见解[Ziemann et al. 2015，Clin Neurophysiol 126：1847-68]。在此基础上，TMS-EMG在世界范围内被用于检测神经和精神疾病的异常兴奋性。然而，TMS-EMG的应用和知识的获得受到显著限制，因为记录是从肌肉（而不是从大脑）进行的，并且评估仅限于运动皮层（在其他地方没有可量化的刺激反应）。脑电图（EEG）放大器技术的最新进展现在允许直接从大脑记录TMS诱发的反应。因此，TMS-EEG具有克服目前实践的TMS-EMG技术的这些局限性的显著潜力。初级运动皮层的局灶性TMS可靠地产生具有可再现的潜伏期和拓扑结构的TMS诱发的EEG电位（例如，P25、N45、P70、N100和P180）。然而，这些潜力的生理机制在很大程度上是未知的。因此，通过实验操作或在疾病条件下观察到这些电位的改变，目前仍处于描述性水平。我们最近已经开始用中枢神经系统活性药物来表征这些TMS诱发的EEG电位。我们可以首次证明GABA能抑制有助于N45和GABA能抑制N100 [Premoli et al. 2014，J Neurosci 34：5603-12; Premoli et al. 2014，NeuroImage 103 C：152-62]。为了扩展这些数据，并在类比的药物TMS-EMG的大量以前的工作，我们在这里提出了一个系统的药理学表征TMS诱发的EEG电位。我们将重点介绍在多巴胺能和γ-氨基丁酸能系统中具有特定作用模式的中枢神经系统活性药物，以及电压门控离子通道阻滞剂。我们期望从这项研究中获得一种新颖、直接、信息量大的工具来评估人类大脑皮层的兴奋性。一旦药物生理学表征，该工具可以在神经和精神疾病中异常脑兴奋性的诊断评估中发挥重要作用。