Brain-wide fMRI responses to auditory and visual stimuli in awake mice

The functions of individual senses are well studied, but the mechanisms of cross-sensory integration remain poorly understood. Although invasive studies in mice can elucidate cellular and circuit-level processes, it is unclear whether mice exhibit macroscale cross-sensory activity comparable to that reported in human imaging studies-an important criterion for the translational relevance of preclinical studies. To address this gap, we investigated responses to unimodal and bimodal auditory and visual stimulation in awake mice using a quiet zero echo time (zero-TE) functional magnetic resonance imaging (fMRI) approach. Both stimulation modalities evoked responses in cross-sensory primary pathways, high-order regions, non-primary thalamus, and cerebellum, indicating robust brain-wide responses to simple sensory stimulation. Bimodal stimulation elicited subadditive responses in regions responsive to both modalities, and primary cortices contained subregions with stronger cross-modal responses. Many of these patterns resembled those observed in humans and non-human primates, suggesting conserved principles across species and supporting the translational value of mechanistic and disease model-oriented studies of cross-sensory processing in mice. In contrast, ketamine-xylazine anesthesia caused widespread suppression of cross-modal and high-order activity during sensory processing, highlighting the importance of performing cross-sensory investigations in awake animals.