Computational Modeling of Electroencephalography and Functional Magnetic Resonance Imaging Paradigms Indicates a Consistent Loss of Pyramidal Cell Synaptic Gain in Schizophrenia.

Autor: Adams RA; Centre for Medical Image Computing and Artificial Intelligence, University College London, London, United Kingdom; Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Max Planck-UCL Centre for Computational Psychiatry and Ageing Research, London, United Kingdom; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: rick.adams@ucl.ac.uk., Pinotsis D; Centre for Mathematical Neuroscience and Psychology and Department of Psychology, City University of London, London, United Kingdom; Picower Institute for Learning & Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts., Tsirlis K; Centre for Medical Image Computing and Artificial Intelligence, University College London, London, United Kingdom., Unruh L; Institute of Cognitive Neuroscience, University College London, London, United Kingdom., Mahajan A; Centre for Medical Image Computing and Artificial Intelligence, University College London, London, United Kingdom., Horas AM; Centre for Medical Image Computing and Artificial Intelligence, University College London, London, United Kingdom., Convertino L; Institute of Cognitive Neuroscience, University College London, London, United Kingdom., Summerfelt A; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland., Sampath H; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland., Du XM; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland., Kochunov P; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland., Ji JL; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut., Repovs G; Department of Psychology, University of Ljubljana, Ljubljana, Slovenia., Murray JD; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut., Friston KJ; Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom., Hong LE; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland., Anticevic A; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2022 Jan 15; Vol. 91 (2), pp. 202-215. Date of Electronic Publication: 2021 Aug 10.
DOI: 10.1016/j.biopsych.2021.07.024
Abstrakt: Background: 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.
Methods: People with schizophrenia diagnoses (PScz) (n = 108), their relatives (n = 57), and control subjects (n = 107) underwent 3 electroencephalography (EEG) paradigms-resting, mismatch negativity, and 40-Hz auditory steady-state response-and resting functional magnetic resonance imaging. Dynamic causal modeling was used to quantify synaptic connectivity in cortical microcircuits.
Results: Classic group differences in EEG features between PScz and control subjects were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40-Hz power. Across all 4 paradigms, characteristic PScz data features were all 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 PScz in 3 paradigms.
Conclusions: First, characteristic EEG changes in PScz in 3 classic paradigms are all attributable to the same underlying parameter change: greater self-inhibition in pyramidal cells. Second, psychotic symptoms in PScz relate to disinhibition in neural circuits. These findings are more commensurate with the hypothesis that in PScz, a primary loss of synaptic gain on pyramidal cells is then compensated by interneuron downregulation (rather than the converse). They further suggest that psychotic symptoms relate to this secondary downregulation.
(Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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