Cortical consequences of comorbidity: distinct effects of hearing loss and the 22q11.2 deletion on temporal processing in the auditory cortex

Lu, C.; Linden, J. F.

doi:10.64898/2026.03.26.714426

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bioRxiv · 10.64898/2026.03.26.714426

Cortical consequences of comorbidity: distinct effects of hearing loss and the 22q11.2 deletion on temporal processing in the auditory cortex

Lu, C.·Linden, J. F.

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Abstract

BackgroundPeripheral hearing loss is associated with auditory hallucinations and increased risk for psychotic disorder, particularly in genetically vulnerable individuals. Moreover, both hearing loss and schizophrenia disrupt auditory temporal acuity, a sensitive measure of auditory brain function. Here, we used mouse models of hearing loss and schizophrenia to reveal how neural mechanisms of auditory cortical temporal acuity depend on sensory and genetic risk factors for psychosis. MethodsWe quantified auditory cortical temporal acuity in mice with or without hearing loss and with or without the 22q11.2 deletion -- one of the strongest known genetic risk factors for schizophrenia. Cortical single-unit and population activity were recorded in awake mice (N = 23) during presentations of loudness-adjusted gap-in-noise stimuli with varying durations of silent gap, which are commonly used to assess auditory temporal acuity in humans. ResultsBoth hearing loss and the 22q11.2 deletion disrupted auditory cortical temporal acuity, but through distinct mechanisms. Hearing loss broadly degraded temporal acuity at the level of single-unit responses and neural population activity. In contrast, the 22q11.2 deletion selectively impaired gap duration thresholds in regular-spiking (putative excitatory) but not fast-spiking (putative inhibitory) neurons. Mice with comorbid hearing loss and 22q11.2 deletion exhibited both abnormalities in auditory cortical temporal acuity. ConclusionsSensory and genetic risk factors for psychosis can disrupt auditory cortical temporal acuity via distinct mechanisms that remain partially dissociable even under comorbid conditions. These findings underscore the importance of accounting for hearing loss comorbidity when interpreting auditory cortical dysfunction in psychotic disorder.

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Lu, C., Linden, J. F.. 2026-03-26. Cortical consequences of comorbidity: distinct effects of hearing loss and the 22q11.2 deletion on temporal processing in the auditory cortex. https://doi.org/10.64898/2026.03.26.714426

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