Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, United States of America.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, United States of America.
Sci Rep. 2017 Apr 28;7:46675. doi: 10.1038/srep46675.
There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.
在理解神经递质在正常和病理性大脑功能中的作用方面已经取得了重大进展。然而，旨在改善治疗干预的临床前试验并没有利用疾病进展和对药物、认知、行为和神经调节治疗的反应等动态大脑过程中的实时体内神经化学变化。这部分是由于缺乏灵活的研究工具，这些工具允许对大脑化学的动态变化进行体内测量。在这里，我们提出了一个研究平台，WINCS Harmoni，它可以同时测量多个解剖学靶点的体内神经化学活性，以研究正常和病理性大脑功能。此外，WINCS Harmoni 可以通过其同步刺激和神经化学感应功能，为神经化学水平的闭环控制提供实时神经化学反馈。我们在非人类灵长类动物、猪和啮齿动物的深部脑刺激 (DBS) 模型中展示了该平台的这些和其他关键特性。最终，像这里描述的这样的系统将改善我们对神经疾病和治疗干预背景下大脑生理学动态的理解，这可能导致开发精准医学和个性化治疗以实现最佳治疗效果。
