Abstracts

Rationale: Approximately two-thirds of patients with ictal bradycardia or asystole have temporal lobe epilepsy. This cardiac dysfunction during or after seizures may contribute to sudden unexpected death in epilepsy (SUDEP). Abnormal neurocardiac function during seizures could potentially be caused by seizures in the brainstem that disrupt cardiac control networks. Although it is known that seizures can invade the brainstem from the forebrain, the response of these circuits to invading seizures is not well understood. The nucleus ambiguus contains preganglionic parasympathetic neurons that innervate postganglionic parasympathetic neurons in the heart. Therefore, seizure activity in the nucleus ambiguus could induce bradycardia via the vagus nerve. This study aims to investigate the relationship between the central nervous system, parasympathetic nervous system, and cardiac function during a seizure attack.

Methods: We simultaneously recorded activity from the brain and vagus nerve as well as heart rate and respiration in six adult Sprague Dawley rats under urethane anesthesia. Neural activity in the brain was recorded using carbon nanotube yarn (CNTY) electrodes implanted in the hippocampal CA3 region, the motor cortex (M1), and the nucleus ambiguus in the brainstem. Additionally, two CNTY electrodes were implanted in the vagus nerve to monitor its activity. ECG electrodes and an accelerometer were also implanted to record heart rate and respiration. Following a 20-minute baseline recording, seizures were induced by injecting 4-AP into the hippocampal CA3 region. Following injection, all signals were recorded for two hours and stored for analysis to study the interactions among these regions during seizures.


Results: The 4-AP injection in the hippocampal CA3 region successfully induced seizures in the hippocampus and cortex, with some seizures propagating into the nucleus ambiguus. When seizures did invade the nucleus ambiguus, the heart rate decreased by 5~30 % in six rats. Furthermore, vagus nerve activity increased significantly following the onset of brainstem seizures (0.025±0.07 mV RMS, p< 0.05). No significant changes in vagus nerve activity were observed when seizures were confined to the hippocampus and cortex. One of the six rats died during the seizure-induced bradycardia.