MECHANISMS OF DEEP BRAIN STIMULATION.

人类大脑内的电刺激现在是治疗某些类型的运动障碍的公认方法。然而，脑深部刺激(DBS)的作用机制仍不十分清楚。目前的两种假说是，DBS通过从该区域的抑制性神经元或终末PR终末释放GABA，或通过引起周围神经元的去极化阻断，来产生对电极附近神经元的抑制。我们的建议旨在获得有关星展银行可能机制的新信息。新开发的双微电极记录系统将用于功能性立体定向手术，在帕金森病患者的丘脑底核(STN)和苍白球(GP)植入DBS电极。两个电极中的一个将用于微刺激，或在某些情况下用于宏观刺激，并评估这种刺激对在250微米或更远距离记录的神经元放电的影响。此外，还将评估STN内高频注射利多卡因和蝇草酚对震颤、僵硬和运动迟缓的影响。使用这些方法的初步研究表明，在GP中的刺激非常有效地抑制了大多数神经元的放电，这种方式强烈地表明GABA的释放。然而，对STN和运动丘脑的初步研究表明，可能涉及其他或额外的机制(S)。这些集中在STN的研究结果将为DBS的机制提供新的见解，并可能导致电极设计、电极放置和最佳刺激参数的改进，从而提高该技术的治疗效果。

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.