Abstracts

This is a Late Breaking abstract

Rationale: Recent research on sudden unexpected death in epilepsy (SUDEP) has revealed several examples of respiratory instability in both acute and chronic models, such as reduced sigh-apnea coupling [1]. In our previous works we explored the abnormally high mortality rate following ictal activation of the diving reflex [2], and the brainstem activity in de novo deaths in the kainate model [3].  In this work we sought to combine the two procedures, and investigate brainstem activity during normal, nonfatal ictal, and fatal ictal diving reflexes.

Methods: Long Evans rats are anesthetized with urethane and seizures are induced with systemic kainic acid. We recorded several physiological measures, including brainstem activity from a respiratory neuron in the ventral respiratory group and respiratory movement via video from 6 animals. We initiate a diving reflex with ~ 1mL of ice water delivered over 20 seconds to the nares via a cannula. We insert brainstem electrodes (50 or 125 µm) based on our published coordinates [3], and proceed along our track until we encounter a neuron or small unit which burst fires with the gasps which follow a diving reflex.

Results: Nonseizing animals display nearly perfect 1:1 coupling between neuron bursts and reflex gasps. During seizure we see gasp-burst decoupling. During the ictal reflex stimulus, we observe neuron bursts which do not initiate gasps. Once the stimulus is over, we observe gasps which do not recruit the neuron(s) of interest. During the fatal reflex we observe bursts which do not initiate gasps, and the total number of bursts and gasps is significantly reduced. Figure 1A shows bursts and gasps for a preictal stimulus, with good coupling. Figure 1B shows strong gasp-burst decoupling both during and after a nonfatal ictal reflex. Figure 1C shows burst-gasp decoupling in a fatal reflex. Red bars indicate regions of decoupling.

Conclusions: Gasps are strongly linked with autoresuscitation and survival from respiratory crisis. Our data suggest the brainstem gasping success is reduced, as our neuron of interest sometimes fire without initiating a gasp. Further, even if a gasp is successful, it is weaker than preictal gasps and does not recruit as many neurons, as the neuron of interest is not always recruited in ictal gasps. These data imply less network coordination during seizure. These results are significant as they suggest human ictal respiratory deaths, such as SUDEP, may occur due to the weakening of network coordination and recruitment in response to an apneic stimulus.
_x000D_ References:_x000D_ 1. Dhaibar et al. Neurobiology of Disease, 2019._x000D_ 2. Biggs et al. Epilepsia, 2021._x000D_ 3. Jefferys et al. Epilepsia, 2019.

Funding: NIH NS119390