Origins of the Auditory Brainstem Response in Mice Using Source Localization of Topographic Multichannel EEG

The auditory brainstem response (ABR) is a critical tool for assessing auditory brainstem function in biomedical mouse models. Remarkably, despite its importance, the origins of ABR waves specific to mice remain poorly identified. Here, we used EEG source reconstruction to reevaluate the mouse-specific ABR origins. We recorded the topography of ABRs using high-density EEG from the skull of adult mice of either sex combined with parallel multielectrode recordings in the auditory cortex. Individual ABR waves showed a series of distinct spatial topographies across the skull. Wave I' was strongly lateralized, supporting its auditory nerve origin. Waves II/III were also lateralized but had a more frontal distribution, supporting an origin in the cochlear nucleus and olivary complex. A distinct shift in wave IV topography showed focused activity directly above the inferior colliculus (IC). Source localization with beamforming supported the origin of wave IV and V in the IC. In addition, the slow IC wave, P₀, temporally overlapped with responses in the auditory cortex. We identify ABR wave IV as a marker of IC activity, separating earlier brainstem contributions (cochlear nucleus, olivary complex) from later thalamic and cortical components. This finding improves the anatomical specificity of the mouse ABR as a noninvasive marker in biomedical mouse models.