20.500.12556/RUL-135017 Computational modeling of electroencephalography and functional magnetic resonance imaging paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia 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. computational modeling electroencephalography EEG functional magnetic resonance imaging fMRI mismatch negativity psychosis resting state schizophrenia auditory steady-state dynamic causal model računsko modeliranje elektroencefalografija EEG funkcijsko magnetnoresonančno slikanje fMRI negativnost neujemanja psihoza mirovno stanje shizofrenija avditorno stabilno stanje dinamično kavzalno modeliranje true false false Angleški jezik Slovenski jezik Neznano 2022-02-17 11:48:33 2022-02-17 11:48:36 2022-09-14 04:11:12 0000-00-00 00:00:00 2022 0 0 Str. 202-215 iss. 2 Vol. 91 2022 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 159.91:616.895.8 0006-3223 10.1016/j.biopsych.2021.07.024 97496067 https://www.biologicalpsychiatryjournal.com/article/S0006-3223(21)01499-2/fulltext 1 ec11adaa-8fde-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153835 RAZ_Adams_Rick_2022.pdf RAZ_Adams_Rick_2022.pdf 1 A866CE3F63FA9AD8301DD79B02039588 922aa31c14140688b912b178845940ffe03666f0df8a75fb35ae5e56d04d1065 55419a66-8fe1-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153838 Filozofska fakulteta 0 0 0