Advances in genetics may enable a deeper understanding of disease mechanisms and promote a shift to more personalised medicine in the epilepsies. At present, understanding of consequences of genetic variants mainly relies on preclinical functional work; tools for acquiring similar data from the living human brain are needed. Transcranial magnetic stimulation (TMS), in particular paired‐pulse TMS protocols which depend on the function of cortical GABAergic interneuron networks, has the potential to become such a tool. For this report, we identified and reviewed 23 publications on TMS studies of cortical excitability and inhibition in 15 different genes or conditions relevant to epilepsy. Reduced short‐interval intracortical inhibition (SICI) and reduced cortical silent period (CSP) duration were the most commonly reported findings, suggesting abnormal GABAA‐ (SICI) or GABABergic (CSP) signalling. For several conditions, these findings are plausible based on established evidence of involvement of the GABAergic system; for some others, they may inform future research around such mechanisms. Challenges of TMS include lack of complete understanding of the neural underpinnings of the measures used: hypotheses and analyses should be based on existing clinical and preclinical data. Further pitfalls include gathering sufficient numbers of participants, and the effect of confounding factors, especially medications. TMS‐EEG is a unique perturbational technique to study the intrinsic properties of the cortex with excellent temporal resolution; while it has the potential to provide further information of use in interpreting effects of genetic variants, currently the links between measures and neurophysiology are less established. Despite these challenges, TMS is a tool with potential for elucidating the system‐level in vivo functional consequences of genetic variants in people carrying genetic changes of interest, providing unique insights.

中文翻译：

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经颅磁刺激作为了解癫痫相关遗传状况的工具

遗传学的进步可能使人们能够更深入地了解疾病机制，并促进癫痫治疗向更加个性化的药物转变。目前，对遗传变异后果的理解主要依赖于临床前功能工作；需要从活的人脑中获取类似数据的工具。经颅磁刺激 (TMS)，特别是依赖于皮质 GABA 能中间神经元网络功能的双脉冲 TMS 协议，有可能成为这样的工具。在本报告中，我们确定并回顾了 23 篇关于 TMS 研究的出版物，这些研究涉及 15 种与癫痫相关的不同基因或病症的皮质兴奋性和抑制。减少的短间隔皮质内抑制（SICI）和减少的皮质静默期（CSP）持续时间是最常见的报告发现，提示 GABAA- (SICI) 或 GABABergic (CSP) 信号传导异常。对于几种情况，基于 GABAergic 系统参与的既定证据，这些发现是合理的；对于其他一些人来说，它们可能会为围绕此类机制的未来研究提供信息。TMS 的挑战包括对所用测量的神经基础缺乏完整的理解：假设和分析应基于现有的临床和临床前数据。进一步的陷阱包括收集足够数量的参与者，以及混杂因素的影响，尤其是药物。TMS-EEG 是一种独特的微扰技术，用于研究皮质的内在特性，具有出色的时间分辨率；虽然它有可能提供用于解释遗传变异影响的更多信息，目前，措施与神经生理学之间的联系尚不明确。尽管存在这些挑战，但 TMS 是一种工具，有可能阐明携带感兴趣的遗传变化的人体内遗传变异的系统级体内功能后果，提供独特的见解。