Seewoo Bhedita J, Etherington Sarah J, Feindel Kirk W, Rodger Jennifer
Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia.
Centre for Microscopy, Characterization and Analysis, Research Infrastructure Centers, The University of Western Australia, Perth, WA, Australia.
Front Neurosci. 2018 Mar 23;12:180. doi: 10.3389/fnins.2018.00180. eCollection 2018.
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique, which has brain network-level effects in healthy individuals and is also used to treat many neurological and psychiatric conditions in which brain connectivity is believed to be abnormal. Despite the fact that rTMS is being used in a clinical setting and animal studies are increasingly identifying potential cellular and molecular mechanisms, little is known about how these mechanisms relate to clinical changes. This knowledge gap is amplified by non-overlapping approaches used in preclinical and clinical rTMS studies: preclinical studies are mostly invasive, using cellular and molecular approaches, while clinical studies are non-invasive, including functional magnetic resonance imaging (fMRI), TMS electroencephalography (EEG), positron emission tomography (PET), and behavioral measures. A non-invasive method is therefore needed in rodents to link our understanding of cellular and molecular changes to functional connectivity changes that are clinically relevant. fMRI is the technique of choice for examining both short and long term functional connectivity changes in large-scale networks and is becoming increasingly popular in animal research because of its high translatability, but, to date, there have been no reports of animal rTMS studies using this technique. This review summarizes the main studies combining different rTMS protocols with fMRI in humans, in both healthy and patient populations, providing a foundation for the design of equivalent studies in animals. We discuss the challenges of combining these two methods in animals and highlight considerations important for acquiring clinically-relevant information from combined rTMS/fMRI studies in animals. We believe that combining rTMS and fMRI in animal models will generate new knowledge in the following ways: functional connectivity changes can be explored in greater detail through complementary invasive procedures, clarifying mechanism and improving the therapeutic application of rTMS, as well as improving interpretation of fMRI data. And, in a more general context, a robust comparative approach will refine the use of animal models of specific neuropsychiatric conditions.
重复经颅磁刺激（rTMS）是一种非侵入性神经调节技术，它在健康个体中具有脑网络水平的效应，也被用于治疗许多被认为存在脑连接异常的神经和精神疾病。尽管rTMS已应用于临床环境，并且动物研究越来越多地确定了潜在的细胞和分子机制，但对于这些机制如何与临床变化相关却知之甚少。临床前和临床rTMS研究中使用的不重叠方法进一步加剧了这一知识差距：临床前研究大多是侵入性的，采用细胞和分子方法，而临床研究是非侵入性的，包括功能磁共振成像（fMRI）、TMS脑电图（EEG）、正电子发射断层扫描（PET）和行为测量。因此，需要一种在啮齿动物中使用的非侵入性方法，将我们对细胞和分子变化的理解与临床相关的功能连接变化联系起来。fMRI是检查大规模网络中短期和长期功能连接变化的首选技术，由于其高可转化性，在动物研究中越来越受欢迎，但迄今为止，尚无使用该技术进行动物rTMS研究的报道。本综述总结了在健康人群和患者人群中，将不同rTMS方案与fMRI相结合的主要研究，为设计动物等效研究提供了基础。我们讨论了在动物中结合这两种方法的挑战，并强调了从动物rTMS/fMRI联合研究中获取临床相关信息的重要考虑因素。我们认为，在动物模型中结合rTMS和fMRI将通过以下方式产生新知识：通过互补的侵入性程序可以更详细地探索功能连接变化，阐明机制并改善rTMS的治疗应用，以及改善对fMRI数据的解释。而且，在更一般的背景下，一种强大的比较方法将完善特定神经精神疾病动物模型的使用。
