Cerebello-Thalamo-Cortical Dysconnectivity in Schizophrenia Spectrum Disorders: A Resting-State Functional Magnetic Resonance Imaging Meta-Analysis.

Abstract

Background: Cerebello-thalamo-cortical (CTC) network dysfunctions are well documented in schizophrenia spectrum disorders (SSDs) 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 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the recommendations of the Cochrane Handbook. A systematic search was conducted in 3 databases in September 2023. Included articles used seed-based resting-state functional magnetic resonance imaging in patients with SSDs, patients with first-episode psychosis, participants at clinical high risk for psychosis, and healthy control participants. 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 Organization for Human Brain Mapping recommendations.

Results: In SSDs thalamic hypoconnectivity was found in the prefrontal cortex, limbic lobe, thalamus, and cerebellum, whereas hyperconnectivity was observed in the somatomotor and visual association areas (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 CTC dysconnectivity in SSDs, suggesting that 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.