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Computational modelling of EEG and fMRI paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia

Adams, RA; Pinotsis, D; Tsirlis, K; Unruh, L; Mahajan, A; Horas, AM; Convertino, L; ... Anticevic, A; + view all (2021) Computational modelling of EEG and fMRI paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia. Biological Psychiatry 10.1016/j.biopsych.2021.07.024. (In press). Green open access

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Abstract

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 Participants with schizophrenia diagnoses (PScz, n=108), their relatives (n=57), and controls (n=107) underwent three electroencephalography (EEG) 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. Results Classic group differences in EEG features between PScz and controls were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40 Hz power. Across all four 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 three paradigms. Conclusions First, characteristic EEG changes in PScz in three 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.

Type: Article
Title: Computational modelling of EEG and fMRI paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biopsych.2021.07.024
Publisher version: https://doi.org/10.1016/j.biopsych.2021.07.024
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10133217
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