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. 2021 Aug 21;47(5):1421-1430.
doi: 10.1093/schbul/sbab038.

Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals

Sheeba Arnold Anteraper  1   2 , Xavier Guell  3 , Guusje Collin  4   5   6 , Zhenghan Qi  7 , Jingwen Ren  1 , Atira Nair  1 , Larry J Seidman  4 , Matcheri S Keshavan  4 , Tianhong Zhang  8 , Yingying Tang  8 , Huijun Li  9 , Robert W McCarley  10 , Margaret A Niznikiewicz  10 , Martha E Shenton  6   11   12 , William S Stone  4 , Jijun Wang  8 , Susan Whitfield-Gabrieli  1   5
Affiliations

Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals

Sheeba Arnold Anteraper et al. Schizophr Bull. .

Abstract

Objective: The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia.

Methods: We used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis.

Results: RsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated.

Conclusions: We show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.

Keywords: cerebellum; psychosis; resting-state functional connectivity; schizophrenia.

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Figures

Fig. 1.
Fig. 1.
Structural location and functional territories of the dentate nuclei as reported in Guell et al. Red = default-mode network functional territory. Blue = salience-motor functional territory. Green = visual functional territory. Color figure is available in the web version.
Fig. 2.
Fig. 2.
Top panel: RsFc results for CHR+ vs CHR− contrast at a voxel-level height threshold of p < 0.005 (2-sided) and cluster size FDR corrected threshold of P < .05. A, B, and C correspond to DMN, salience-motor, and visual functional territories of DN. Bottom panel: Bar plots for each of the significant clusters in the healthy control, CHR+, and CHR− groups. Notably, for each of these group contrasts, CHR− participants were not significantly different compared to healthy controls. Color figure is available in the web version.
See this image and copyright information in PMC

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