Computational modeling of electroencephalography and functional magnetic resonance imaging paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia

Adams, Rick (author), Repovš, Grega (author)

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 selfinhibition (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.

• Language: English
• Keywords: computational modeling, electroencephalography EEG, functional magnetic resonance imaging fMRI, mismatch negativity, psychosis, resting state, schizophrenia, auditory steady-state, dynamic causal model
• Typology: 1.01 - Original Scientific Article
• Organization: FF - Faculty of Arts
• Year: 2022
• Number of pages: Str. 202-215
• Numbering: Vol. 91, iss. 2
• PID: 20.500.12556/RUL-135017
• UDC: 159.91:616.895.8
• ISSN on article: 0006-3223
• DOI: 10.1016/j.biopsych.2021.07.024
• COBISS.SI-ID: 97496067
• Publication date in RUL: 17.02.2022

Record is a part of a journal

• Title: Biological psychiatry
• Shortened title: Biol. psychiatry
• Publisher: Elsevier
• ISSN: 0006-3223
• COBISS.SI-ID: 9486553

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 09.08.2021

Secondary language

• Language: Slovenian
• Keywords: računsko modeliranje, elektroencefalografija EEG, funkcijsko magnetnoresonančno slikanje fMRI, negativnost neujemanja, psihoza, mirovno stanje, shizofrenija, avditorno stabilno stanje, dinamično kavzalno modeliranje

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J7-8275
• Name: Stabilni in dinamični vzorci EEG in fMR funkcijske konektivnosti ter njihove povezave z individualnimi razlikami

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0338
• Name: Fiziološki mehanizmi nevroloških motenj in bolezni