Song Yufei, Gordon Pedro C, Roy Olivier, Metsomaa Johanna, Belardinelli Paolo, Rostami Maryam, Ziemann Ulf
Department of Neurology & Stroke, University of Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
Department of Neurology & Stroke, University of Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Germany; CERVO Brain Research Centre, Quebec, Canada; Department of Psychiatry and Neurosciences, Université Laval, Quebec, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111167. doi: 10.1016/j.pnpbp.2024.111167. Epub 2024 Oct 9.
The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS-EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS-EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS-EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS-EEG physiology, providing insights for its application in physiological and clinical research.
经颅磁刺激与脑电图（TMS-EEG）相结合正逐渐成为一种研究健康和疾病状态下脑功能的重要工具。然而，TMS-EEG反应背后的详细神经机制，包括经颅磁刺激诱发的脑电电位（TEP）和经颅磁刺激诱导的脑电振荡（TIO），在很大程度上仍不清楚。将TMS-EEG与药物干预相结合为阐明特定受体介导的神经传递在这些反应中的作用提供了独特的机会。在此，我们通过使用随机、安慰剂对照的交叉设计，评估毒蕈碱型乙酰胆碱受体（mAChR）拮抗剂对24名健康参与者的TEP和TIO的影响，研究了mAChR介导的胆碱能神经传递在TMS-EEG反应中的作用。在单次口服东莨菪碱（一种非选择性mAChR拮抗剂）、比哌立登（一种M1型mAChR拮抗剂）或安慰剂之前和之后测量TEP和TIO，经颅磁刺激靶向左侧内侧前额叶皮质（mPFC）、角回（AG）和辅助运动区（SMA）。结果表明，mAChR介导的胆碱能神经传递以靶点特异性方式在TEP中发挥作用，但在TIO中不起作用。具体而言，当经颅磁刺激应用于SMA而非mPFC或AG时，东莨菪碱显著增加了刺激后约40至63毫秒之间局部TEP成分的幅度。比哌立登产生了类似但不太明显的效果。重要的是，这些mAChR拮抗剂对TEP的影响独立于对经颅磁刺激相关感觉刺激引起的感觉诱发脑电电位的影响。这些发现扩展了我们对TMS-EEG生理学的理解，为其在生理学和临床研究中的应用提供了见解。
