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Alterations in Cognition-Related Cerebello-Cerebral Networks in Multiple System Atrophy

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Abstract

We aimed to elucidate the effect of cerebellar degeneration in relation to cognition in multiple system atrophy (MSA). Thirty-two patients diagnosed with probable MSA and 32 age- and gender-matched healthy controls (HCs) were enrolled. We conducted voxel-based morphometry (VBM) for anatomical images and independent component analysis (ICA), dual-regression analysis, and seed-based analysis for functional images with voxel-wise gray matter correction. In the MSA group, a widespread cerebellar volume loss was observed. ICA and dual-regression analysis showed lower functional connectivity (FC) in the left executive control and salience networks in regions located in the cerebellum. Seed-based analysis using the identified cerebellar regions as seeds showed extensive disruptions in cerebello-cerebral networks. Global cognitive scores correlated with the FC values between the right lobules VI/crus I and the medial prefrontal/anterior cingulate cortices and between the same region and the amygdala/parahippocampal gyrus. Our study indicates that cerebellar degeneration in MSA causes segregation of cerebellar-cerebral networks. Furthermore, the cognitive deficits in MSA may be driven by decreased cerebello-prefrontal and cerebello-amygdaloid functional connections.

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Funding

This study was partially supported by a Grant- in-Aid from the Research Committee of Central Nervous System Degenerative Diseases by the Ministry of Health, Labour, and Welfare, Integrated Research on Neuropsychiatric Disorders project carried out Strategic Research Program for Brain Sciences (SRPBS), a Grant-in-Aid for Scientific Research on Innovative Areas (Brain Protein Aging and Dementia Control 26117002) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and Integrated Research on neuropsychiatric disorders carried out under the SRPBS, Scientific Research on Innovative Areas (Comprehensive Brain Science Network), and Integrated Research on Depression, Dementia and Development Disorders by SRPBS from Japan Agency for Medical Research and Development.

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  1. Kazuya Kawabata and Kazuhiro Hara contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kazuya Kawabata, Kazuhiro Hara, Aya Ogura, Michihito Masuda, Takamasa Yokoi, Toshiyasu Kato, Mizuki Ito & Masahisa Katsuno

  2. Brain and Mind Research Center, Nagoya University, Nagoya, Japan

    Hirohisa Watanabe, Epifanio Bagarinao, Reiko Ohdake & Gen Sobue

  3. Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Gen Sobue

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  1. Kazuya Kawabata
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  2. Kazuhiro Hara
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  12. Gen Sobue
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Correspondence to Hirohisa Watanabe or Gen Sobue.

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This study conformed to the Ethical Guidelines for Medical and Health Research Involving Human Subjects endorsed by the Japanese government and was approved by the Ethics Committee of Nagoya University Graduate School of Medicine.

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Kawabata, K., Hara, K., Watanabe, H. et al. Alterations in Cognition-Related Cerebello-Cerebral Networks in Multiple System Atrophy. Cerebellum 18, 770–780 (2019). https://doi.org/10.1007/s12311-019-01031-7

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