Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia
Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia
Abstract Diminished synaptic gain – the sensitivity of postsynaptic responses to neural inputs – may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms. Participants with schizophrenia (Scz, n=108), their relatives (n=57), and controls (n=107) underwent three electroencephalography paradigms – resting, mismatch negativity, and 40 Hz auditory steady-state response – and resting functional magnetic resonance imaging. Dynamic causal modelling was used to quantify synaptic connectivity in cortical microcircuits. Across all four paradigms, characteristic Scz data features were best explained by models with greater self-inhibition (decreased synaptic gain), in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in Scz, in three paradigms. Thus, psychotic symptoms of Scz may result from a downregulation of inhibitory interneurons that may compensate for diminished postsynaptic gain in pyramidal cells.
Pinotsis Dimitris、Convertino Laura、Kochunov Peter、Repovs Grega、Murray John D、Friston Karl J、Horas Ana Montero、Anticevic Alan、Adams Rick A、Summerfelt Ann、Mahajan Aashna、Sampath Hemalatha、Unruh Leonhardt、Du Xiaoming Michael、Hong L Elliot、Tsirlis Konstantinos、Ji Jie Lisa
Centre for Mathematical Neuroscience and Psychology and Department of Psychology, City University of London||The Picower Institute for Learning & Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of TechnologyInstitute of Cognitive Neuroscience, University College London, 17 Queen SquareDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of MedicineDepartment of Psychology, University of LjubljanaDepartment of Psychiatry, Yale University School of MedicineThe Wellcome Centre for Human Neuroimaging, University College LondonCentre for Medical Image Computing and AI, University College LondonDepartment of Psychiatry, Yale University School of MedicineCentre for Medical Image Computing and AI, University College London||Max Planck-UCL Centre for Computational Psychiatry and Ageing Research||Department of Psychiatry, Yale University School of Medicine||Institute of Cognitive Neuroscience, University College London, 17 Queen SquareDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of MedicineCentre for Medical Image Computing and AI, University College LondonDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of MedicineInstitute of Cognitive Neuroscience, University College London, 17 Queen SquareDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of MedicineDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of MedicineCentre for Medical Image Computing and AI, University College LondonDepartment of Psychiatry, Yale University School of Medicine
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
Pinotsis Dimitris,Convertino Laura,Kochunov Peter,Repovs Grega,Murray John D,Friston Karl J,Horas Ana Montero,Anticevic Alan,Adams Rick A,Summerfelt Ann,Mahajan Aashna,Sampath Hemalatha,Unruh Leonhardt,Du Xiaoming Michael,Hong L Elliot,Tsirlis Konstantinos,Ji Jie Lisa.Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia[EB/OL].(2025-03-28)[2025-05-22].https://www.medrxiv.org/content/10.1101/2021.01.07.21249389.点此复制
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