MECHANISMS OF DEEP BRAIN STIMULATION.

深部脑刺激机制。

• 批准号: 6490983
• 负责人: JONATHAN O DOSTROVSKY
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-22 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6490983
• 关键词: Parkinson's disease; abnormal involuntary movement; brain electrical activity; clinical research; electrostimulus; human subject; human therapy evaluation; lenticular nucleus; lidocaine; microelectrodes; muscimol; nervous system disorder therapy; neuropharmacology; neurosurgery; substantia nigra; thalamic nuclei; tremor

Electrical stimulation within the human brain is now an accepted method for the treatment of some types of movement disorders. However the mechanism of action of deep brain stimulation (DBS) is still not well understood. Two current hypotheses are that DBS produces inhibition of the neurons in the vicinity of the electrode by releasing GABA from inhibitory neurons or terminals pr terminals in the region or by causing a depolarization block of the surrounding neurons. Our proposal aims to obtain new information on the possible mechanisms of DBS. A newly developed dual microelectrode recording system will be employed during functional stereotactic surgery for implantation of DBS electrodes in the subthalamic nucleus (STN) and globus pallidus (GP) of Parkinson's disease patients. One of the two electrodes will be used for micro- or in some cases macro-stimulation and the effects of such stimulation assessed on the firing of neurons recorded at distances of 250 mum or more. Additionally, effects of high frequency and of lidocaine and muscimol microinjections into STN will be assessed on tremor, rigidity and bradykinesia. Preliminary studies using these methods have shown that stimulation in the GP very effectively inhibits the firing of most neurons in a manner that strongly suggests release of GABA. However, pilot studies in STN and motor thalamus, suggest that other or additional mechanism(s) might be involved. The findings of these studies focused on STN should provide new insights into the mechanisms underlying DBS and may lead to improvements in electrode design, electrode placement and optimal stimulation parameters thus leading to improvements in the therapeutic efficacy on this technique.

在人脑中进行电刺激现在是治疗某些类型的运动障碍的公认方法。然而，脑深部电刺激（DBS）的作用机制仍不清楚。目前有两种假说认为，DBS通过从该区域的抑制性神经元或终末或终末释放GABA或通过引起周围神经元的去极化阻滞来抑制电极附近的神经元。我们的建议旨在获得有关DBS可能机制的新信息。一种新开发的双微电极记录系统将在帕金森病患者的丘脑底核（DBS）和苍白球（GP）中植入DBS电极的功能性立体定向手术中使用。两个电极中的一个将用于微刺激或在某些情况下的宏刺激，并且评估这种刺激对在250 μ m或更远的距离处记录的神经元放电的影响。此外，还将评估高频和利多卡因和蝇蕈醇微量注射入小脑对震颤、强直和运动迟缓的影响。使用这些方法的初步研究表明，GP中的刺激非常有效地抑制了大多数神经元的放电，其方式强烈表明GABA的释放。然而，对丘脑和运动丘脑的初步研究表明，可能涉及其他或额外的机制。这些研究的结果集中在脑电刺激，应提供新的见解DBS的机制，并可能导致电极设计，电极放置和最佳刺激参数的改进，从而导致这种技术的治疗效果的改善。