RT Journal Article SR Electronic T1 Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.08.11.553052 DO 10.1101/2023.08.11.553052 A1 Rosanally, Sana A1 Mazza, Frank A1 Yao, Heng Kang A1 Hay, Etay YR 2024 UL http://biorxiv.org/content/early/2024/04/10/2023.08.11.553052.abstract AB Reduced cortical inhibition by parvalbumin-expressing (PV) interneurons has been associated with impaired cortical processing in the prefrontal cortex (PFC) and altered EEG signals such as oddball mismatch negativity (MMN) in schizophrenia. However, establishing the link between reduced PV interneuron inhibition and reduced MMN experimentally in humans is currently not possible. To overcome these challenges, we used detailed computational models of human PFC microcircuits, and modeled schizophrenia microcircuits by integrating gene-expression data from schizophrenia patients indicating reduced PV interneuron inhibition output and NMDA input. We simulated spiking activity and EEG in microcircuits with different levels of reduced PV interneuron mechanisms and showed that a double effect of the reduction indicated by gene-expression led to a reduced MMN amplitude within the range seen in Schizophrenia patients, whereas a single effect resulted in a smaller decrease in MMN that matched the magnitude seen in patients at high-risk of schizophrenia. In addition, we showed that simulated resting EEG of schizophrenia microcircuits exhibited a right shift from alpha to beta frequencies. Our study thus links the level of reduced PV interneuron inhibition to distinct EEG biomarkers that can serve to better stratify different severities of schizophrenia and improve the early detection using non-invasive brain signals.Competing Interest StatementThe authors have declared no competing interest.