Transcranial magnetic stimulation (TMS) is used to make inferences about relationships between brain areas and their functions because, in contrast to neuroimaging tools, it modulates neuronal activity. The central aim of this article is to critically evaluate to what extent it is possible to draw causal inferences from repetitive TMS (rTMS) data. To that end, we describe the logical limitations of inferences based on rTMS experiments. The presented analysis suggests that rTMS alone does not provide the sort of premises that are sufficient to warrant strong inferences about the direct causal properties of targeted brain structures. Overcoming these limitations demands a close look at the designs of rTMS studies, especially the methodological and theoretical conditions which are necessary for the functional decomposition of the relations between brain areas and cognitive functions. The main points of this article are that TMS-based inferences are limited in that stimulation-related causal effects are not equivalent to structure-related causal effects due to TMS side effects, the electric field distribution, and the sensitivity of neuroimaging and behavioral methods in detecting structure-related effects and disentangling them from confounds. Moreover, the postulated causal effects can be based on indirect (network) effects. A few suggestions on how to manage some of these limitations are presented. We discuss the benefits of combining rTMS with neuroimaging in experimental reasoning and we address the restrictions and requirements of rTMS control conditions. The use of neuroimaging and control conditions allows stronger inferences to be gained, but the strength of the inferences that can be drawn depends on the individual experiment’s designs. Moreover, in some cases, TMS might not be an appropriate method of answering causality-related questions or the hypotheses have to account for the limitations of this technique. We hope this summary and formalization of the reasoning behind rTMS research can be of use not only for scientists and clinicians who intend to interpret rTMS results causally but also for philosophers interested in causal inferences based on brain stimulation research.

中文翻译：

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重复经颅磁刺激研究中的因果推论：挑战与展望

经颅磁刺激 (TMS) 用于推断大脑区域及其功能之间的关系，因为与神经成像工具相比，它调节神经元活动。本文的中心目标是批判性地评估从重复的 TMS (rTMS) 数据中得出因果推断的可能程度。为此，我们描述了基于 rTMS 实验的推理的逻辑局限性。所呈现的分析表明，单独的 rTMS 并不能提供足以保证对目标大脑结构的直接因果属性进行强有力推断的前提。克服这些限制需要仔细研究 rTMS 研究的设计，尤其是脑区与认知功能关系的功能分解所必需的方法论和理论条件。本文的主要观点是，基于 TMS 的推论受到限制，因为 TMS 副作用、电场分布以及神经影像学和行为方法的敏感性，刺激相关的因果效应不等同于结构相关的因果效应。检测与结构相关的效应并将它们从混淆中解脱出来。此外，假设的因果效应可以基于间接（网络）效应。提出了一些关于如何管理其中一些限制的建议。我们讨论了在实验推理中将 rTMS 与神经成像相结合的好处，并解决了 rTMS 控制条件的限制和要求。使用神经影像和控制条件可以获得更强的推论，但可以得出的推论的强度取决于个别实验的设计。此外，在某些情况下，TMS 可能不是回答因果关系问题的合适方法，或者假设必须考虑到这种技术的局限性。我们希望对 rTMS 研究背后的推理进行总结和形式化，不仅对打算以因果关系解释 rTMS 结果的科学家和临床医生有用，而且对对基于脑刺激研究的因果推断感兴趣的哲学家也有用。使用神经影像和控制条件可以获得更强的推论，但可以得出的推论的强度取决于个别实验的设计。此外，在某些情况下，TMS 可能不是回答因果关系问题的合适方法，或者假设必须考虑到这种技术的局限性。我们希望对 rTMS 研究背后的推理进行总结和形式化，不仅对打算以因果关系解释 rTMS 结果的科学家和临床医生有用，而且对对基于脑刺激研究的因果推断感兴趣的哲学家也有用。使用神经影像和控制条件可以获得更强的推论，但可以得出的推论的强度取决于个别实验的设计。此外，在某些情况下，TMS 可能不是回答因果关系问题的合适方法，或者假设必须考虑到这种技术的局限性。我们希望对 rTMS 研究背后的推理进行总结和形式化，不仅对打算以因果关系解释 rTMS 结果的科学家和临床医生有用，而且对对基于脑刺激研究的因果推断感兴趣的哲学家也有用。TMS 可能不是回答因果关系问题的合适方法，或者假设必须考虑到这种技术的局限性。我们希望对 rTMS 研究背后的推理进行总结和形式化，不仅对打算以因果关系解释 rTMS 结果的科学家和临床医生有用，而且对对基于脑刺激研究的因果推断感兴趣的哲学家也有用。TMS 可能不是回答因果关系问题的合适方法，或者假设必须考虑到这种技术的局限性。我们希望对 rTMS 研究背后的推理进行总结和形式化，不仅对打算以因果关系解释 rTMS 结果的科学家和临床医生有用，而且对对基于脑刺激研究的因果推断感兴趣的哲学家也有用。