Computational modelling of novelty detection in the mismatch negativity protocols and its impairments in schizophrenia

Eissa, A.; Kismul, J. F.; Pentz, A. B.; Elvsashagen, T.; Metzner, C.; Akkouh, I.; Djurovic, S.; Shadrin, A.; Linne, M.-L.; Einevoll, G.; Andreassen, O.; Mäki-Marttunen, T.

doi:10.1101/2025.09.30.679453

bioRxiv · 10.1101/2025.09.30.679453

Computational modelling of novelty detection in the mismatch negativity protocols and its impairments in schizophrenia

Eissa, A.·Kismul, J. F.·Pentz, A. B.·Elvsashagen, T.·Metzner, C.·Akkouh, I.·Djurovic, S.·Shadrin, A.·Linne, M.-L.·Einevoll, G.·Andreassen, O.·Mäki-Marttunen, T.

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Abstract

The human auditory system rapidly distinguishes between novel and familiar sounds, a process reflected in mismatch negativity (MMN), an EEG-based biomarker of auditory novelty detection. MMN is impaired in psychiatric conditions, most notably schizophrenia (SCZ), yet the neuronal mechanisms underlying this deficit remain unclear. Here, we combined computational modelling and genetic analyses to investigate how SCZ-associated cellular abnormalities affect auditory novelty detection. We developed an integrate-and-fire spiking network model capable of detecting four types of auditory novelty, including stimulus omission. Based on assumptions of short-term depressing synapses between the subpopulations of the network and the existence of neuronal inputs that are phase-locked to the rhythm of the recently experienced stimulus sequence, the model reliably reproduced MMN-like novelty detection and allowed systematic testing of SCZ-related cellular alterations. Simulations revealed that both reduced pyramidal cell excitability, linked to ion-channel dysfunction, and decreased spine density impaired novelty detection, with the latter producing stronger deficits. Our work provides a flexible spiking network model of auditory novelty detection that can link cellular-level abnormalities to measurable MMN deficits, improving their mechanistic interpretation and helping to explain the heterogeneity of SCZ.

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Eissa, A., Kismul, J. F., Pentz, A. B., Elvsashagen, T., Metzner, C., Akkouh, I., Djurovic, S., Shadrin, A., Linne, M.-L., Einevoll, G., Andreassen, O., Mäki-Marttunen, T.. 2025-10-01. Computational modelling of novelty detection in the mismatch negativity protocols and its impairments in schizophrenia. https://doi.org/10.1101/2025.09.30.679453

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