1 Brain and Mind Research Institute, University of Sydney, Sydney, Australia 2 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
3 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Brain. 2016 Mar;139(Pt 3):845-55. doi: 10.1093/brain/awv399. Epub 2016 Jan 20.
Pathophysiological and atrophic changes in the cerebellum are documented in Parkinson's disease. Without compensatory activity, such abnormalities could potentially have more widespread effects on both motor and non-motor symptoms. We examined how atrophic change in the cerebellum impacts functional connectivity patterns within the cerebellum and between cerebellar-cortical networks in 42 patients with Parkinson's disease and 29 control subjects. Voxel-based morphometry confirmed grey matter loss across the motor and cognitive cerebellar territories in the patient cohort. The extent of cerebellar atrophy correlated with decreased resting-state connectivity between the cerebellum and large-scale cortical networks, including the sensorimotor, dorsal attention and default networks, but with increased connectivity between the cerebellum and frontoparietal networks. The severity of patients' motor impairment was predicted by a combination of cerebellar atrophy and decreased cerebellar-sensorimotor connectivity. These findings demonstrate that cerebellar atrophy is related to both increases and decreases in cerebellar-cortical connectivity in Parkinson's disease, identifying potential cerebellar driven functional changes associated with sensorimotor deficits. A post hoc analysis exploring the effect of atrophy in the subthalamic nucleus, a cerebellar input source, confirmed that a significant negative relationship between grey matter volume and intrinsic cerebellar connectivity seen in controls was absent in the patients. This suggests that the modulatory relationship of the subthalamic nucleus on intracerebellar connectivity is lost in Parkinson's disease, which may contribute to pathological activation within the cerebellum. The results confirm significant changes in cerebellar network activity in Parkinson's disease and reveal that such changes occur in association with atrophy of the cerebellum.
小脑的病理生理和萎缩变化在帕金森病中有记载。如果没有代偿性活动，这些异常可能对运动和非运动症状产生更广泛的影响。我们研究了小脑萎缩如何影响 42 名帕金森病患者和 29 名对照受试者小脑内和小脑皮质网络之间的功能连接模式。体素形态测量学证实，患者组的运动和认知小脑区域存在灰质丢失。小脑萎缩的程度与小脑与包括感觉运动、背侧注意和默认网络在内的大皮质网络之间的静息状态连接减少有关，但与小脑与额顶网络之间的连接增加有关。患者运动障碍的严重程度可由小脑萎缩和小脑-感觉运动连接减少的组合来预测。这些发现表明，小脑萎缩与帕金森病中小脑皮质连接的增加和减少有关，确定了与感觉运动缺陷相关的潜在小脑驱动的功能变化。一项事后分析探讨了小脑传入源丘脑底核萎缩的影响，结果证实对照组中观察到的灰质体积与内在小脑连接之间的显著负相关在患者中不存在。这表明，丘脑底核对小脑内连接的调节关系在帕金森病中丧失，这可能导致小脑内的病理性激活。研究结果证实了帕金森病中小脑网络活动的显著变化，并揭示了这些变化与小脑萎缩有关。
