MEDETOMIDINE RESHAPES BRAIN-WIDE HEMODYNAMIC DYNAMICS AND INDUCES CORTICO–SUBCORTICAL DECOUPLING IN MICE

Sedatives are known to widely impact cortical activity, yet their brain-wide impact is less widely understood. This is, in part, due to the technical challenges of directly comparing awake and sedated states during whole-brain imaging. To address this gap, we used functional ultrasound imaging to compare spontaneous and sensory-driven brain-wide hemodynamic activity in head-fixed mice during wakefulness and under sedation with medetomidine, a selective α2-adrenergic agonist commonly used in rodent neuroimaging. Consistent with sedation, medetomidine reduced body and facial motion and altered pupil dynamics relative to wakefulness. At the brain-wide level, medetomidine slowed cortical hemodynamic fluctuations, increasing low-frequency power and autocorrelation times compared to wakefulness; these effects were more pronounced in cortex than in subcortical structures. Moreover, functional connectivity between cortical and subcortical areas was reduced under medetomidine, whereas local cortical connectivity was relatively preserved. Finally, we observed that somatosensory stimuli under medetomidine evoked robust subcortical responses but little to no detectable cortical activity. Together, these findings suggest that medetomidine shifts cortical dynamics toward a regime of enhanced internal coherence and weakened coupling to extra-cortical structures, altering both spontaneous fluctuations and sensory propagation at the whole-brain scale. Thus, this work provides insights on the brain-wide effects of medetomidine, with implications for the interpretation of functional imaging data acquired under sedation.