Debo Dong1, Dezhong Yao1,2, Yulin Wang3,4, Seok-Jun Hong5,6, Sarah Genon7,8, Fei Xin1, Kyesam Jung7,8, Hui He1,9, Xuebin Chang1, Mingjun Duan9, Boris C Bernhardt10, Daniel S Margulies11, Jorge Sepulcre12,13, Simon B Eickhoff7,8, Cheng Luo1,14. 1. The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, School of Life Science and Technology, University of Electronic Science and Technology of China, China. 2. Research Unit of NeuroInformation, Chinese Academy of Medical Sciences, 2019RU035, Chengdu, China. 3. Faculty of Psychological and Educational Sciences, Department of Experimental and Applied Psychology, Vrije Universiteit Brussel, Belgium. 4. Faculty of Psychology and Educational Sciences, Department of Data Analysis, Ghent University, Belgium. 5. Center for the Developing Brain, Child Mind Institute, NY, USA. 6. Department of Biomedical Engineering, Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, South Korea. 7. Institute for Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 8. Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany. 9. Department of Psychiatry, The Fourth People's Hospital of Chengdu, Chengdu, China. 10. Multimodal Imaging and Connectome Analysis Lab, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. 11. Centre National de la Recherche Scientifique (CNRS) UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France. 12. Department of Radiology, Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 13. Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 14. Department of Neurology, Brain Disorders and Brain Function Key Laboratory, First Affiliated Hospital of Hainan Medical University, Haikou, China.
Abstract
BACKGROUND: Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. METHODS: We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). RESULTS: We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). CONCLUSIONS: The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.
BACKGROUND:Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. METHODS: We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). RESULTS: We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). CONCLUSIONS: The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.