Bradycardia is induced by hyperactivity of the vagus nerve and nucleus ambiguus during seizures propagating into the brainstem.

OBJECTIVE

Seizure-induced bradycardia and asystole have been documented by video-EEG monitoring periods in patients with 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 propagating to the brainstem, passing through the parasympathetic nerve and disrupting cardiac control networks.

METHODS

We simultaneously recorded activity from the brain and vagus nerve as well as heart rate and respiration in 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. Seizures were induced by injecting 4-AP into the hippocampal CA3 region. Following the injection, all signals were recorded and stored for analysis to study the interactions among these regions during seizures.

RESULTS

Local 4-AP injection successfully induced intermittent seizures in the hippocampus and cortex, with some seizures propagating into the nucleus ambiguus. When seizures invaded the nucleus ambiguus, the heart rate dropped following the onset of the seizures and returned to baseline during the seizures. The heart rate variability also increased significantly during the seizures. Furthermore, vagus nerve activity increased significantly by 0.21 ± 0.08 μV following the seizures propagating to the brainstem.

SIGNIFICANCE

Our findings indicate increased activity in the nucleus ambiguus during seizures can induce bradycardia through the vagus nerve. These changes in cardiac function via the autonomic nervous system could contribute to the instability of the autonomic control system during seizures and potentially explain one of the possible mechanisms underlying sudden unexpected death in epilepsy (SUDEP).

PLAIN LANGUAGE SUMMARY

This study investigates how seizures affect heart function and may contribute to sudden unexpected death in epilepsy (SUDEP). We studied the brain, vagus nerve, and heart rate in anesthetized rats. Seizures were triggered in the hippocampus, and recordings showed that when seizures spread to the nucleus ambiguus in the brainstem region, the heart rate dropped and became more irregular. The vagus nerve, which helps regulate heart function, also became more active. These findings suggest that seizures can disrupt heart control by affecting the autonomic nervous system, which may help explain one of the possible mechanisms of how SUDEP occurs.