Hussain Sara J, Freedberg Michael V
The University of Texas at Austin.
J Cogn Neurosci. 2025 May 1;37(5):1009-1022. doi: 10.1162/jocn_a_02288.
Repetitive TMS (rTMS) is a powerful neuroscientific tool with the potential to noninvasively identify brain-behavior relationships in humans. Early work suggested that certain rTMS protocols (e.g., continuous theta-burst stimulation, intermittent theta-burst stimulation, high-frequency rTMS, low-frequency rTMS) predictably alter the probability that cortical neurons will fire action potentials (i.e., change cortical excitability). However, despite significant methodological, conceptual, and technical advances in rTMS research over the past few decades, overgeneralization of early rTMS findings has led to a stubbornly persistent assumption that rTMS protocols by their nature induce behavioral and/or physiological inhibition or facilitation, even when they are applied to nonmotor cortical sites or under untested circumstances. In this Perspectives article, we offer a "public service announcement" that summarizes the origins of this problematic assumption, highlighting limitations of seminal studies that inspired them and results of contemporary studies that violate them. Next, we discuss problems associated with holding this assumption, including making brain-behavior inferences without confirming the locality and directionality of neurophysiological changes. Finally, we provide recommendations for researchers to eliminate this misguided assumption when designing and interpreting their own work, emphasizing results of recent studies showing that the effects of rTMS on neurophysiological metrics and their associated behaviors can be caused by mechanisms other than binary changes in excitability of the stimulated brain region or network. Collectively, we contend that no rTMS protocol is by its nature either excitatory or inhibitory, and that researchers must use caution with these terms when forming experimental hypotheses and testing brain-behavior relationships.
重复经颅磁刺激（rTMS）是一种强大的神经科学工具，有潜力在不侵入人体的情况下识别大脑与行为之间的关系。早期研究表明，某些rTMS方案（如连续theta爆发刺激、间歇性theta爆发刺激、高频rTMS、低频rTMS）可预测地改变皮质神经元产生动作电位的概率（即改变皮质兴奋性）。然而，尽管在过去几十年里rTMS研究在方法、概念和技术上取得了重大进展，但早期rTMS研究结果的过度概括导致了一个顽固持续的假设，即rTMS方案本质上会诱导行为和/或生理抑制或促进，即使将其应用于非运动皮质部位或在未经测试的情况下也是如此。在这篇观点文章中，我们发布一则“公共服务声明”，总结这一有问题假设的起源，强调启发这些假设的开创性研究的局限性以及违反这些假设的当代研究结果。接下来，我们讨论持有这一假设所带来的问题，包括在未确认神经生理变化的局部性和方向性的情况下进行大脑与行为的推断。最后，我们为研究人员在设计和解释自己的工作时消除这一错误假设提供建议，强调近期研究结果表明，rTMS对神经生理指标及其相关行为的影响可能由刺激脑区或网络兴奋性的二元变化以外的机制引起。我们共同认为，没有任何rTMS方案本质上是兴奋性或抑制性的，研究人员在形成实验假设和测试大脑与行为关系时必须谨慎使用这些术语。
