Department of Neurology & Stroke, University of Tübingen, Tübingen, Germany.
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
J Physiol. 2023 May;601(10):1981-1998. doi: 10.1113/JP283986. Epub 2023 Apr 4.
The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) elegantly probes the excitability and connectivity of the human brain. However, TMS-EEG signals inevitably also contain sensory-evoked responses caused by TMS-associated auditory and somatosensory inputs, constituting a substantial confounding factor. Here we applied our recently established optimized SHAM protocol (Gordon et al., Neuroimage 2021:118708) to disentangle TMS-EEG responses caused by TMS vs. sensory input. One unresolved question is whether these responses superimpose without relevant interaction, a requirement for their disaggregation by the optimized SHAM approach. We applied in 20 healthy subjects a pharmacological intervention using a single oral dose of 20 mg of diazepam, a positive modulator of GABAA receptors. Diazepam decreased the amplitudes of the P60 and P150 components specifically in the ACTIVE TMS and/or the ACTIVE TMS minus SHAM conditions but not in the SHAM condition, pointing to a response caused by TMS. In contrast, diazepam suppressed the amplitude of the N100 component indiscriminately in the ACTIVE TMS and SHAM conditions but not in the ACTIVE TMS minus SHAM condition, pointing to a response caused by sensory input. Moreover, diazepam suppressed the beta-band response observed in the motor cortex specifically after ACTIVE TMS and ACTIVE TMS minus SHAM. These findings demonstrate a lack of interaction of TMS-EEG responses caused by TMS vs. sensory input and validate optimized SHAM-controlled TMS-EEG as an appropriate approach to untangle these TMS-EEG responses. This knowledge will enable the proficient use of TMS-EEG to probe the physiology of the human cortex. KEY POINTS: Optimized SHAM disentangles TMS-EEG responses caused by TMS vs. sensory input. Diazepam differentially modulates TMS-EEG responses caused by TMS vs. sensory input. Diazepam modulation of P60 and P150 indicate TMS-EEG responses caused by TMS. Diazepam modulation of N100 indicate a TMS-EEG response caused by sensory input.
经颅磁刺激(TMS)与脑电图(EEG)的联合应用,优雅地探测了人类大脑的兴奋性和连通性。然而,TMS-EEG 信号不可避免地也包含由 TMS 相关听觉和体感输入引起的感觉诱发电位,这构成了一个重要的混杂因素。在这里,我们应用了我们最近建立的优化的假刺激(SHAM)方案(Gordon 等人,Neuroimage 2021:118708)来区分 TMS 引起的 TMS-EEG 反应与感觉输入引起的 TMS-EEG 反应。一个尚未解决的问题是这些反应是否没有相关的相互作用而叠加,这是通过优化的 SHAM 方法对其进行分解的要求。我们在 20 名健康受试者中应用了一种药理学干预,即单次口服 20 毫克地西泮,这是 GABA A 受体的正变构调节剂。地西泮特异性降低了 ACTIVE TMS 和/或 ACTIVE TMS-减 SHAM 条件下的 P60 和 P150 成分的幅度,但在 SHAM 条件下没有降低,这表明是由 TMS 引起的反应。相比之下,地西泮在 ACTIVE TMS 和 SHAM 条件下无差别地抑制了 N100 成分的幅度,但在 ACTIVE TMS-减 SHAM 条件下没有抑制,这表明是由感觉输入引起的反应。此外,地西泮特异性抑制了运动皮层中观察到的β波段反应,特别是在 ACTIVE TMS 和 ACTIVE TMS-减 SHAM 之后。这些发现表明,由 TMS 引起的 TMS-EEG 反应与感觉输入引起的 TMS-EEG 反应之间没有相互作用,并验证了优化的 SHAM 对照 TMS-EEG 是一种合适的方法,可以解开这些 TMS-EEG 反应。这一知识将使熟练使用 TMS-EEG 来探测人类皮层的生理学成为可能。关键点:优化的 SHAM 区分了由 TMS 引起的 TMS-EEG 反应与感觉输入引起的 TMS-EEG 反应。地西泮对由 TMS 引起的 TMS-EEG 反应与感觉输入引起的 TMS-EEG 反应有不同的调节作用。P60 和 P150 的地西泮调节表明 TMS-EEG 反应是由 TMS 引起的。N100 的地西泮调节表明 TMS-EEG 反应是由感觉输入引起的。