Sutton Alexander C, O'Connor Katherine A, Pilitsis Julie G, Shin Damian S
Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.
Division of Neurosurgery, Albany Medical Center, 47 New Scotland Ave, Albany, NY, 12208, USA.
Brain Struct Funct. 2015 Nov;220(6):3595-609. doi: 10.1007/s00429-014-0876-8. Epub 2014 Aug 15.
Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN-DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55% during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and 28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45% during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus.
深部脑刺激（DBS）对精心挑选的帕金森病患者的运动症状管理有效。最近的研究表明，基底神经节（BG）中的DBS可改变传统基底神经节 - 丘脑 - 皮质（BG - TH - CX）环路之外的神经回路。例如，功能成像显示，丘脑底核（STN）进行DBS时，小脑活动会发生改变。然而，这些成像研究几乎没有揭示细胞特异性小脑活动如何响应STN刺激，以及这些变化是否有助于其疗效。在本研究中，我们评估STN - DBS是否通过激发小脑活动来有效管理帕金森病的运动症状。我们通过对偏侧帕金森病大鼠应用STN - DBS，并同时记录STN、脑干和小脑的神经元活动来实现这一点。我们发现，在DBS期间，STN神经元的放电活动降低了55%（P = 0.038），这与脚桥被盖核和浦肯野神经元的活动分别降低29%（P < 0.001）和28%（P = 0.003）相吻合。相反，在DBS期间，小脑深部核团的放电活动增加了45%（P < 0.001），这可能是由于浦肯野细胞传入活动减少所致。然后，我们在亚治疗电流下应用STN - DBS并同时刺激小脑深部核团，发现前肢运动不能的改善与单独使用治疗性STN - DBS相似。这表明STN - DBS可激发小脑活动以改善帕金森病的运动症状。我们的研究首次描述了帕金森病中的STN - DBS如何在体内利用电生理学改变小脑活动，并揭示了刺激小脑以增强丘脑底核深部脑刺激效果的潜力。
