Department of Medical Neurobiology (Physiology), The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical Association School of Medicine and Hadassah University Hospital, Jerusalem 91120, Israel.
Neuron. 2011 Oct 20;72(2):370-84. doi: 10.1016/j.neuron.2011.08.023.
Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. Application of pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Furthermore, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. Thus, closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.
持续高频深部脑刺激（DBS）是一种广泛应用于治疗晚期帕金森病（PD）的疗法。然而，DBS 效果的机制仍然是个谜，也是正在进行的争论的主题。在这里，我们提出并测试了一种用于 PD 的闭环刺激策略，该策略应用于 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 灵长类动物模型。苍白球闭环刺激的应用导致基底神经节（BG）放电率和模式的变化分离，为 PD 病理生理学提供了深入的了解。此外，皮质苍白球闭环刺激对运动不能和皮质和苍白球放电模式的影响明显大于标准开环 DBS 和匹配的对照刺激范式。因此，闭环 DBS 范式通过调节病理性振荡活动而不是 BG-皮质网络的放电率，可能为晚期 PD 的管理提供更有效的方法。这种策略有可能对其他可以识别病理性神经元放电模式的脑部疾病有效。
