Cerebellar atrophy in Parkinson's disease and its implication for network connectivity

O'Callaghan, Claire, Hornberger, Michael ORCID: https://orcid.org/0000-0002-2214-3788, Balsters, Joshua H., Halliday, Glenda M., Lewis, Simon J.G. and Shine, James M. (2016) Cerebellar atrophy in Parkinson's disease and its implication for network connectivity. Brain, 139 (3). pp. 845-855. ISSN 0006-8950

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Abstract

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.

Item Type: Article
Additional Information: Funding Information: C.O. is supported by a National Health and Medical Research Council Neil Hamilton Fairley Fellowship. M.H. is supported by the Australian Research Council (DP110104202), and by Alzheimer's Research UK and the Newton Trust. S.J.G.L. is supported by a National Health and Medical Research Council Practitioner Fellowship (1003007). G.M.H. is supported by a National Health and Medical Research Council Senior Principal Research Fellowship (1079679). J.M.S. is supported by a National Health and Medical Research Council CJ Martin Fellowship.
Uncontrolled Keywords: cerebellum,parkinson's disease,resting state functional connectivity,subthalamic nucleus,voxel-based morphometry,clinical neurology ,/dk/atira/pure/subjectarea/asjc/2700/2728
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 18:30
Last Modified: 19 Jul 2022 00:26
URI: https://ueaeprints.uea.ac.uk/id/eprint/86564
DOI: 10.1093/brain/awv399

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