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Abstract
Despite the association between brainstem lesions and coma, a mechanistic understanding
of coma pathogenesis and recovery
is lacking. We developed a coma model in the rat mimicking human brainstem coma, which
allowed multimodal analysis of a brainstem
tegmentum lesion’s effects on behavior, cortical electrophysiology, and global brain
functional connectivity. After coma
induction, we observed a transient period (~1h) of unresponsiveness accompanied by
cortical burst-suppression. Comatose rats then
gradually regained behavioral responsiveness concurrent with emergence of delta/theta-predominant
cortical rhythms in primary
somatosensory cortex. During the acute stage of coma recovery (~1 to 8h), longitudinal
resting-state functional MRI revealed an
increase in functional connectivity between subcortical arousal nuclei in the thalamus,
basal forebrain, and basal ganglia and
cortical regions implicated in awareness. This rat coma model provides an experimental
platform to systematically study
network-based mechanisms of coma pathogenesis and recovery, as well as to test targeted
therapies aimed at promoting recovery of
consciousness after coma.