Cerebello-Thalamo-Cortical Dysconnectivity in Schizophrenia Spectrum Disorders: A Resting-State fMRI Meta-Analysis.

Abstract

Background: Cerebello-thalamo-cortical (CTC) network dysfunctions are well-documented in schizophrenia spectrum disorders (SSD) and preclinical states. However, small samples and methodological heterogeneity often limit individual neuroimaging studies. To overcome these challenges, we conducted a coordinate-based meta-analysis to characterize CTC alterations across illness stages and examine associations with symptom dimensions.

Methods: Our meta-analysis was preregistered and followed the PRISMA guideline and the recommendations of the Cochrane Handbook. A systematic search was conducted in three databases in September 2023. Included articles used seed-based resting-state fMRI in patients with schizophrenia-spectrum disorders, first-episode psychosis, clinical high-risk for psychosis, and healthy control groups. Seeds were defined in the thalamus and the cerebellum. Two coordinate-based meta-analytic methods, Activation Likelihood Estimation and Seed-based D Mapping were used. Risk of bias was evaluated per the OHBM recommendations.

Results: Thalamic hypoconnectivity in the prefrontal cortex, limbic lobe, thalamus and the cerebellum, and hyperconnectivity in the somato-motor and visual association areas was found in SSD (29 studies, 2768 patients). Dysconnectivity was linked to disease progression and symptoms. Cerebellar analysis indicated hypoconnectivity in the prefrontal cortex, cerebellum, and thalamus, with hyperconnectivity in the motor cortex, somatosensory cortex, and orbitofrontal cortex (19 studies, 1159 patients). Cerebellar clusters did not survive multiple comparison correction.

Conclusions: Our findings provide robust meta-analytic evidence of cerebello-thalamo-cortical dysconnectivity in SSD, suggesting this network captures a core neurobiological feature of psychotic disorders. Consistent patterns of altered CTC connectivity underscore the importance of future clinical investigations of this network as a potential target for therapeutic interventions.