DECIPHERING AUTONOMIC DYSREGULATION IN EPILEPSY THROUGH VAGUS NERVE ACTIVITY

Previous findings from our laboratory showed that vagus nerve activity (VNA) during absence seizures in GAERS (Genetic Absence Epilepsy Rats from Strasbourg) rats varies with cumulative seizure burden, suggesting parasympathetic dysfunction. Respiratory disturbances such as apnea are a major concern in epilepsy and SUDEP, and hypercapnia represents a powerful tool to unmask abnormal autonomic reactivity. Vagal impairment or sympathetic overcompensation during respiratory stress may critically alter cardiorespiratory homeostasis. We therefore aimed to characterize VNA responses to hypercapnic challenge as an index of autonomic integrity, while also assessing vigilance-state modulation. Freely moving healthy rats (n = 9); 4.5 months GAERS (n = 7) and 11.5 months GAERS (n = 7) were implanted with epidural EEG electrodes and intraneural/control vagus nerve electrodes under sevoflurane anesthesia. After 24 h of continuous baseline recordings, animals underwent a 3-h protocol including baseline, 10% CO₂ exposure, and recovery. VNA was analyzed using compound action potential (CAP) detection based on local maxima thresholding, with neural-specific events isolated by excluding signals shared with control electrodes.
Hypercapnia significantly increased VNA in GAERS rats, whereas in NEC VNA remained unchanged during CO₂ exposure and showed a pronounced rebound during recovery, a response absent in epileptic animals, indicating altered autonomic responsiveness to respiratory stress. CAP density was higher during NREM sleep than during active wakefulness in healthy rats, consistent with circadian parasympathetic modulation.
Altered vagal responses to hypercapnic challenge reveal autonomic dysfunction in epilepsy, supporting vagus nerve activity as a promising biomarker for respiratory stress sensitivity and SUDEP-related mechanisms.