biostudies-literatureUnknownFernandez Pujol CNCATS NIH HHSNINDS NIH HHSThe mismatch negativity, or MMN, is a ubiquitous evoked brain response elicited by any discriminable change of an otherwise regular stimulus sequence. Despite its potential clinical relevance - the MMN is known to be affected by brain state, lesions, and neurologic/psychiatric disorders - and a growing body of animal work, the underlying neurophysiology of the MMN is not well understood. This hinders translation of circuit-level animal findings and mitigates the utility of the MMN as a neurologic/psychiatric biomarker. Here, we used biophysical modeling to examine the neurophysiological basis of the MMN as measured in a canonical auditory oddball paradigm with frequency deviants (i.e., tones whose frequency was shifted slightly with respect to standard tones). The response to standards wasbioRxiv : the preprint server for biology2025.11.08.687373https://www.ebi.ac.uk/biostudies/studies/S-EPMC12637574biostudies-literatureNeurophysiology of mismatch negativity generation: a biophysical modeling study.PMC12637574U24 NS129945UL1 TR002736Dykstra ARBruce JFernandez Pujol CThorpe RVJones SRfalseNeurophysiology of mismatch negativity generation: a biophysical modeling study.The mismatch negativity, or MMN, is a ubiquitous evoked brain response elicited by any discriminable change of an otherwise regular stimulus sequence. Despite its potential clinical relevance - the MMN is known to be affected by brain state, lesions, and neurologic/psychiatric disorders - and a growing body of animal work, the underlying neurophysiology of the MMN is not well understood. This hinders translation of circuit-level animal findings and mitigates the utility of the MMN as a neurologic/psychiatric biomarker. Here, we used biophysical modeling to examine the neurophysiological basis of the MMN as measured in a canonical auditory oddball paradigm with frequency deviants (i.e., tones whose frequency was shifted slightly with respect to standard tones). The response to standards was2025-01-01T00:00:00Z2025 Nov2026-06-10T03:12:59.047Z2026-06-10T03:07:43.298ZS-EPMC126375744127921710.1101/2025.11.08.687373