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

Adams, Rick (avtor), Repovš, Grega (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: computational modeling, electroencephalography EEG, functional magnetic resonance imaging fMRI, mismatch negativity, psychosis, resting state, schizophrenia, auditory steady-state, dynamic causal model
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FF - Filozofska fakulteta
• Leto izida: 2022
• Št. strani: Str. 202-215
• Številčenje: Vol. 91, iss. 2
• PID: 20.500.12556/RUL-135017
• UDK: 159.91:616.895.8
• ISSN pri članku: 0006-3223
• DOI: 10.1016/j.biopsych.2021.07.024
• COBISS.SI-ID: 97496067
• Datum objave v RUL: 17.02.2022

Gradivo je del revije

• Naslov: Biological psychiatry
• Skrajšan naslov: Biol. psychiatry
• Založnik: Elsevier
• ISSN: 0006-3223
• COBISS.SI-ID: 9486553

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 09.08.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: računsko modeliranje, elektroencefalografija EEG, funkcijsko magnetnoresonančno slikanje fMRI, negativnost neujemanja, psihoza, mirovno stanje, shizofrenija, avditorno stabilno stanje, dinamično kavzalno modeliranje

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J7-8275
• Naslov: Stabilni in dinamični vzorci EEG in fMR funkcijske konektivnosti ter njihove povezave z individualnimi razlikami

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0338
• Naslov: Fiziološki mehanizmi nevroloških motenj in bolezni