Tobias Kaufmann1, Kristina C Skåtun2, Dag Alnæs3, Nhat Trung Doan2, Eugene P Duff4, Siren Tønnesen2, Evangelos Roussos4, Torill Ueland5, Sofie R Aminoff6, Trine V Lagerberg2, Ingrid Agartz7, Ingrid S Melle2, Stephen M Smith4, Ole A Andreassen2, Lars T Westlye5. 1. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; tobias.kaufmann@medisin.uio.no. 2. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 3. Department of Psychology, University of Oslo, Oslo, Norway; 4. FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 5. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; 6. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Specialized Inpatient Treatment, Division of Mental Health Services, Akershus University Hospital, Oslo, Norway; 7. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
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.
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.
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