Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany; Center for Non-invasive Brain Stimulation Munich-Augsburg (CNBS(MA)), Germany.
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany; Center for Non-invasive Brain Stimulation Munich-Augsburg (CNBS(MA)), Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany.
Exp Neurol. 2021 Jul;341:113713. doi: 10.1016/j.expneurol.2021.113713. Epub 2021 Mar 31.
Current hypotheses on the therapeutic action of non-invasive brain stimulation (NIBS) in psychiatric disorders build on the abundant data from neuroimaging studies. This makes NIBS a very promising tool for developing personalized interventions within a precision medicine framework. NIBS methods fundamentally vary in their neurophysiological properties. They comprise repetitive transcranial magnetic stimulation (rTMS) and its variants (e.g. theta burst stimulation - TBS) as well as different types of transcranial electrical stimulation (tES), with the largest body of evidence for transcranial direct current stimulation (tDCS). In the last two decades, significant conceptual progress has been made in terms of NIBS targets, i.e. from single brain regions to neural circuits and to functional connectivity as well as their states, recently leading to brain state modulating closed-loop approaches. Regarding structural and functional brain anatomy, NIBS meets an individually unique constellation, which varies across normal and pathophysiological states. Thus, individual constitutions and signatures of disorders may be indistinguishable at a given time point, but can theoretically be parsed along course- and treatment-related trajectories. We address precision interventions on three levels: 1) the NIBS intervention, 2) the constitutional factors of a single patient, and 3) the phenotypes and pathophysiology of illness. With examples from research on depressive disorders, we propose solutions and discuss future perspectives, e.g. individual MRI-based electrical field strength as a proxy for NIBS dosage, and also symptoms, their clusters, or biotypes instead of disorder focused NIBS. In conclusion, we propose interleaved research on these three levels along a general track of reverse and forward translation including both clinically directed research in preclinical model systems, and biomarker guided controlled clinical trials. Besides driving the development of safe and efficacious interventions, this framework could also deepen our understanding of psychiatric disorders at their neurophysiological underpinnings.
目前，关于非侵入性脑刺激（NIBS）在精神疾病治疗作用的假设是基于丰富的神经影像学研究数据。这使得 NIBS 成为在精准医学框架内开发个性化干预措施的非常有前途的工具。NIBS 方法在神经生理学特性上存在根本差异。它们包括重复经颅磁刺激（rTMS）及其变体（如 theta 爆发刺激 - TBS）以及不同类型的经颅电刺激（tES），其中经颅直流电刺激（tDCS）的证据最多。在过去的二十年中，NIBS 目标方面取得了重大的概念进展，即从单个脑区到神经网络和功能连接，以及它们的状态，最近导致了基于脑状态的调制闭环方法。关于结构和功能脑解剖，NIBS 遇到了个体独特的组合，在正常和病理生理状态下都有所不同。因此，个体的构成和疾病特征可能在给定的时间点无法区分，但理论上可以沿着病程和治疗相关的轨迹进行解析。我们在三个层面上解决精准干预问题：1）NIBS 干预，2）单个患者的体质因素，3）疾病的表型和病理生理学。我们以抑郁症研究为例，提出了一些解决方案，并讨论了未来的前景，例如基于 MRI 的个体电场强度作为 NIBS 剂量的替代指标，以及症状、其聚类或生物型而不是针对疾病的 NIBS。总之，我们建议沿着包括临床前模型系统中的临床指导研究和生物标志物指导的对照临床试验在内的逆向和正向翻译的一般轨迹，在这三个层面上进行交叉研究。除了推动安全有效的干预措施的发展外，该框架还可以加深我们对精神疾病在神经生理学基础上的理解。
