Connectivity impairment of cerebellar and sensorimotor connector hubs in Parkinson's disease

Epifanio Bagarinao; Kazuya Kawabata; Hirohisa Watanabe; Kazuhiro Hara; Reiko Ohdake; Aya Ogura; Michihito Masuda; Toshiyasu Kato; Satoshi Maesawa; Masahisa Katsuno; Gen Sobue

doi:10.1093/braincomms/fcac214

Connectivity impairment of cerebellar and sensorimotor connector hubs in Parkinson's disease

Brain Commun. 2022 Aug 20;4(5):fcac214. doi: 10.1093/braincomms/fcac214. eCollection 2022.

Authors

Epifanio Bagarinao^{1

2}, Kazuya Kawabata^{2

3}, Hirohisa Watanabe^{2

3

4}, Kazuhiro Hara³, Reiko Ohdake⁴, Aya Ogura^{2

3}, Michihito Masuda³, Toshiyasu Kato³, Satoshi Maesawa^{2

5}, Masahisa Katsuno³, Gen Sobue^{2

6}

Affiliations

¹ Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 461-8673Japan.
² Brain & Mind Research Center, Nagoya University, Nagoya, Aichi, 466-8550Japan.
³ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550Japan.
⁴ Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192Japan.
⁵ Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550Japan.
⁶ Aichi Medical University, Nagakute, Aichi, 480-1195Japan.

Abstract

Cognitive and movement processes involved integration of several large-scale brain networks. Central to these integrative processes are connector hubs, brain regions characterized by strong connections with multiple networks. Growing evidence suggests that many neurodegenerative and psychiatric disorders are associated with connector hub dysfunctions. Using a network metric called functional connectivity overlap ratio, we investigated connector hub alterations in Parkinson's disease. Resting-state functional MRI data from 99 patients (male/female = 44/55) and 99 age- and sex-matched healthy controls (male/female = 39/60) participating in our cross-sectional study were used in the analysis. We have identified two sets of connector hubs, mainly located in the sensorimotor cortex and cerebellum, with significant connectivity alterations with multiple resting-state networks. Sensorimotor connector hubs have impaired connections primarily with primary processing (sensorimotor, visual), visuospatial, and basal ganglia networks, whereas cerebellar connector hubs have impaired connections with basal ganglia and executive control networks. These connectivity alterations correlated with patients' motor symptoms. Specifically, values of the functional connectivity overlap ratio of the cerebellar connector hubs were associated with tremor score, whereas that of the sensorimotor connector hubs with postural instability and gait disturbance score, suggesting potential association of each set of connector hubs with the disorder's two predominant forms, the akinesia/rigidity and resting tremor subtypes. In addition, values of the functional connectivity overlap ratio of the sensorimotor connector hubs were highly predictive in classifying patients from controls with an accuracy of 75.76%. These findings suggest that, together with the basal ganglia, cerebellar and sensorimotor connector hubs are significantly involved in Parkinson's disease with their connectivity dysfunction potentially driving the clinical manifestations typically observed in this disorder.

Keywords: Parkinson’s disease; cerebellum; connector hubs; resting-state networks; sensorimotor.