Role of seizure activity within the parafascicular nucleus in cessation of respiratory rhythm and potentially SUDEP

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with uncontrolled epilepsy, yet the mechanisms underlying SUDEP are unknown. Recent data suggests that as seizures propagate in the brain, they can cause respiratory and/or cardiac arrest, leading to death (e.g. SUDEP). Although the precise mechanisms are unknown, seizure‐induced respiratory arrest (S‐IRA) is the most likely cause of SUDEP. The neural pathways propagating seizure (SZR) activity from areas in the brain where seizures initiate (cortex, hippocampus and thalamus) to autonomic respiratory centers in the brainstem, resulting in respiratory failure and SUDEP are unknown. To identify SZR propagation pathways, I am using a new mouse brainslice preparation that includes cortex, hippocampus and thalamus as well as autonomic medullary areas controlling breathing. Preliminary electrophysiological data suggest that seizure‐like activity resulting in repeated activation of the parafascicular nucleus (PFn) of the thalamus, disrupts and then stops rhythmic respiratory activity generated by the medullary respiratory neural network, the pre‐Bötzinger Complex (preBötC). I am testing my hypothesis that SZR propagation from the cortex to the PFn can interrupt respiratory activity, which may underlie or significantly contribute to respiratory arrest and/or SUDEP. The centromedial/parafascicular (CMn/PFn) thalamic nuclear complex is a deep brain stimulation target for control of epilepsy. However, little is known about the role the PFn may play in seizure propagation, control of breathing and/or SUDEP. The data support the hypothesis that the PFn may play a role in SUDEP, as it: 1) initiates and/or propagates SZRs; 2) innervates respiratory rhythm networks in the medulla, including the preBötC; and, 3) its activation inhibits breathing.