title: Cerebellar atrophy in Parkinson's disease and its implication for network connectivity.
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.
authors.affiliation: 1 Brain and Mind Research Institute, University of Sydney, Sydney, Australia 2 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK mac.shine@sydney.edu.au.
authors.forename: Claire
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: 3 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornberger
authors.affiliation: 4 Department of Health Sciences and Technology, Neural Control of Movement Laboratory, ETH Zurich, Switzerland.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Balsters
authors.affiliation: 5 Neuroscience Research Australia, Sydney, Australia 6 Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: 1 Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Simon J G
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: 1 Brain and Mind Research Institute, University of Sydney, Sydney, Australia 5 Neuroscience Research Australia, Sydney, Australia 7 School of Psychology, Stanford University, Palo Alto, CA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Shine
mesh_terms: D000368:Aged; D001284:Atrophy / Q000150:complications / Q000175:diagnosis; D002531:Cerebellum / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D010300:Parkinson Disease / Q000150:complications* / Q000175:diagnosis*
keywords: Parkinson’s disease; cerebellum; resting state functional connectivity; subthalamic nucleus; voxel-based morphometry