High density probes reveal medullary seizure and rapid medullary shutdown in a model of fatal apnea in seizure.

Objective: Sudden unexpected death in epilepsy (SUDEP) is suggested to be a cardiorespiratory collapse that occurs shortly after a seizure. Prior work in rats suggests that reflexive apneas (produced by stimulation of trigeminal or vagal peripheral sensory targets) is highly fatal during seizure but well tolerated otherwise. These reflexes share network connectivity in the medulla, particularly the caudal solitary nucleus (NTS) and ventral respiratory column (VRC), and possibly other intermediate structures. We sought to observe the electrographic activity in these regions. Methods: We use urethane anesthetized long evans rats. We utilized either 125 Results: Seizure activity confounds many established methods of analyzing high-density single unit data such as provided by Neuropixels probes, and so our analyses focus on averaging responses over larger anatomical regions (120 Conclusions: These data support the theory that central apnea events in seizure are relatively safe as we observed they produce little change in the medullary tract network, while stimuli-induced-reflexive-apneas are dangerous because they produce profound quieting across respiratory centers. Our data suggest that seizure spreads to this medullary tract at approximately the same rate and intensity as forebrain, as previously described in this model. These data are supportive of SUDEP mechanisms involving brainstem inhibition as a primary cause, such as spreading depolarization waves. These findings likely extend beyond nasal irrigation to any sensory reflexive apnea caused by airway irritation of any kind, and may bear relevance to similar deaths seen in infants.