Dataset Information

Disintegration of Sensorimotor Brain Networks in Schizophrenia.

ABSTRACT:

Background

Schizophrenia is a severe mental disorder associated with derogated function across various domains, including perception, language, motor, emotional, and social behavior. Due to its complex symptomatology, schizophrenia is often regarded a disorder of cognitive processes. Yet due to the frequent involvement of sensory and perceptual symptoms, it has been hypothesized that functional disintegration between sensory and cognitive processes mediates the heterogeneous and comprehensive schizophrenia symptomatology.

Methods

Here, using resting-state functional magnetic resonance imaging in 71 patients and 196 healthy controls, we characterized the standard deviation in BOLD (blood-oxygen-level-dependent) signal amplitude and the functional connectivity across a range of functional brain networks. We investigated connectivity on the edge and node level using network modeling based on independent component analysis and utilized the brain network features in cross-validated classification procedures.

Results

Both amplitude and connectivity were significantly altered in patients, largely involving sensory networks. Reduced standard deviation in amplitude was observed in a range of visual, sensorimotor, and auditory nodes in patients. The strongest differences in connectivity implicated within-sensorimotor and sensorimotor-thalamic connections. Furthermore, sensory nodes displayed widespread alterations in the connectivity with higher-order nodes. We demonstrated robustness of effects across subjects by significantly classifying diagnostic group on the individual level based on cross-validated multivariate connectivity features.

Conclusion

Taken together, the findings support the hypothesis of disintegrated sensory and cognitive processes in schizophrenia, and the foci of effects emphasize that targeting the sensory and perceptual domains may be key to enhance our understanding of schizophrenia pathophysiology.

SUBMITTER: Kaufmann T

PROVIDER: S-EPMC4601711 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Project description: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.