Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia.
J Neurosci Methods. 2021 Aug 1;360:109261. doi: 10.1016/j.jneumeth.2021.109261. Epub 2021 Jun 17.
BACKGROUND: Repetitive transcranial magnetic stimulation is a promising noninvasive therapeutic tool for a variety of brain-related disorders. However, most therapeutic protocols target the anterior regions, leaving many other areas unexplored. There is a substantial therapeutic potential for stimulating various brain regions, which can be optimized in animal models. NEW METHOD: We illustrate a method that can be utilized reliably to stimulate the anterior or posterior brain in freely moving rodents. A coil support device is surgically attached onto the skull, which is used for consistent coil placement over the course of up to several weeks of stimulation sessions. RESULTS: Our methods provide reliable stimulation in animals without the need for restraint or sedation. We see little aversive effects of support placement and stimulation. Computational models provide evidence that moving the coil support location can be utilized to target major stimulation sites in humans and mice. SUMMARY OF FINDINGS WITH THIS METHOD: Animal models are key to optimizing brain stimulation parameters, but research relies on restraint or sedation for consistency in coil placement. The method described here provides a unique means for reliable targeted stimulation in freely moving animals. Research utilizing this method has uncovered changes in biochemical and animal behavioral measurements as a function of brain stimulation. CONCLUSIONS: The majority of research on magnetic stimulation focuses on anterior regions. Given the substantial network connectivity throughout the brain, it is critical to develop a reliable method for stimulating different regions. The method described here can be utilized to better inform clinical trials about optimal treatment localization, stimulation intensity and number of treatment sessions, and provides a motivation for exploring posterior brain regions for both mice and humans.
背景:重复经颅磁刺激是一种很有前途的、针对各种与大脑相关疾病的非侵入性治疗工具。然而,大多数治疗方案都针对前脑区域,而许多其他区域仍未得到探索。刺激各种大脑区域具有很大的治疗潜力,而这可以在动物模型中得到优化。
新方法:我们展示了一种可用于在自由活动的啮齿动物中可靠地刺激前脑或后脑的方法。一个线圈支撑装置被手术固定在头骨上,在长达数周的刺激过程中,该装置可用于一致地放置线圈。
结果:我们的方法为动物提供了可靠的刺激,而无需约束或镇静。我们发现支撑物放置和刺激的负面效应很小。计算模型提供的证据表明,可以利用移动线圈支撑位置来针对人类和小鼠的主要刺激部位。
这种方法的发现:动物模型是优化脑刺激参数的关键,但研究依赖于约束或镇静来保持线圈放置的一致性。这里描述的方法为在自由活动的动物中进行可靠的靶向刺激提供了一种独特的手段。利用这种方法的研究揭示了脑刺激作为生化和动物行为测量的函数的变化。
结论:大多数关于磁刺激的研究都集中在前脑区域。鉴于大脑中存在大量的网络连接,开发一种可靠的方法来刺激不同的区域至关重要。这里描述的方法可用于更好地为临床试验提供关于最佳治疗定位、刺激强度和治疗次数的信息,并为探索小鼠和人类的后脑区域提供动力。
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