Weaker Cerebellocortical Connectivity Within Sensorimotor and Executive Networks in Schizophrenia Compared to Healthy Controls: Relationships with Processing Speed

Brain Connect. 2020 Nov;10(9):490-503. doi: 10.1089/brain.2020.0792. Epub 2020 Oct 28.

Abstract

Background: The cognitive dysmetria theory of schizophrenia proposes that communication between the cerebellum and cerebral cortex is disrupted by structural and functional abnormalities, resulting in psychotic symptoms and cognitive deficits. Methods: Using publicly available data, resting-state functional connectivity (rsFC) was calculated from 20 hemispheric cerebellar lobules as seed regions of interest to the rest of the brain. Group differences in rsFC between individuals with schizophrenia (SZ) and healthy controls (HCs) were computed, and relationships between rsFC and symptom severity and cognitive functioning were explored. Results: HCs demonstrated stronger connectivity than SZ between several cerebellar lobules and cortical regions, most robustly between motor-related cerebellar lobules (V and VIIIa/b) and temporal and parietal cortices. In addition, seven of nine lobules in which reduced cerebellocortical connectivity was observed showed diagnosis × processing speed interactions; HC showed a positive relationship between connectivity and processing speed, whereas SZ did not show this relationship. Other cognitive domains and symptom severity did not show relationships with connectivity. Conclusions: These findings partially support the cognitive dysmetria theory, and suggest that disrupted cerebellocortical connectivity is associated with slowed processing speed in schizophrenia. Impact statement We show in this work that in chronic schizophrenia, there is weaker functional connectivity between previously unstudied inferior posterior cerebellar lobules and cortical association areas. These findings align and extend previous work showing abnormal connectivity of anterior cerebellar lobules. Further, we present a novel finding that these connectivity deficits are differentially associated with processing speed in the schizophrenia versus healthy control groups. Findings provide further evidence for cerebellocortical dysconnectivity and processing speed deficits as biomarkers of schizophrenia, which may have implications for downstream effects on higher order cognitive functions, in line with the cognitive dysmetria theory.

Keywords: cerebellum; fMRI; functional connectivity; processing speed; psychosis; schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebellum / diagnostic imaging
  • Cerebellum / physiology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / physiopathology
  • Executive Function / physiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / physiopathology*
  • Severity of Illness Index
  • Young Adult