Transcranial magnetic stimulation (TMS) based methods are emerging as a unique approach to evaluate in real-time brain electrical activity in healthy and pathological conditions. By applying TMS pulses in two different bran areas within a short temporal frame of few milliseconds, it is possible to investigate their physiological interactions. These paradigms, collectively termed dual-site TMS, have been inspired by Professor John Rothwell’s work, based on the idea that applying a conditioning stimulus over a cortical area may activate putative pathways projecting onto a second target area, thus providing a unique opportunity to test the causal effects between interconnected brain areas. This review highlights the most important features of dual-coil TMS protocols, mainly pioneered in Professor John Rothwell's lab. In the first part, I reviewed development of dual-site TMS protocols leading to the discovery of a distributed system of short-latency interactions within the human parieto-frontal network, likely mediated by direct anatomical pathways. In the second part, the physiological role of these dual-site TMS evoked pathways is considered, describing how these functional interactions are not fixed but vary depending on the brain activation, the condition and on the precise time window in which they are explored. Then, I reviewed recent advances showing that the repeated coupling of interconnected neuronal populations, by means of dual-coil TMS, is able to induce spike-time-dependent plasticity and to determine selective potentiation of physiological connectivity between two human brain regions. Finally, the therapeutic implications of these novel discoveries are discussed, pointing to multi-site TMS as a novel tool to identify early features of synaptic dysfunctions, to monitor disease progression and potentially to provide novel therapeutic approaches by reshaping plasticity in different neurological and psychiatric conditions.

基于经颅磁刺激 (TMS) 的方法正在成为一种独特的方法来评估健康和病理条件下的实时脑电活动。通过在几毫秒的短时间框架内在两个不同的麸皮区域应用 TMS 脉冲，可以研究它们的生理相互作用。这些范式统称为双位点 TMS，受到 John Rothwell 教授工作的启发，基于以下想法：在皮层区域施加条件刺激可能会激活投射到第二个目标区域的推定通路，从而提供独特的测试机会相互关联的大脑区域之间的因果关系。这篇综述重点介绍了双线圈 TMS 协议的最重要特征，主要由 John Rothwell 教授的实验室率先提出。在第一部分，我回顾了双站点 TMS 协议的发展，导致在人类顶额网络中发现了一个短延迟交互的分布式系统，可能由直接解剖路径介导。在第二部分，考虑了这些双位点 TMS 诱发通路的生理作用，描述了这些功能相互作用如何不是固定的，而是根据大脑激活、条件和探索它们的精确时间窗口而变化的。然后，我回顾了最近的进展，表明通过双线圈 TMS 重复耦合相互连接的神经元群，能够诱导尖峰时间依赖性可塑性，并确定两个人脑区域之间生理连接的选择性增强。最后，讨论了这些新发现的治疗意义，