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Objective: Sudden unexpected death in epilepsy (SUDEP) is linked to respiratory and autonomic failure with post-ictal periods of prolonged hypercapnia indicative of impaired central chemoreception. Yet how interictal hypercapnic cardioventilatory responses vary by seizure phenotype is unclear. We aimed to determine whether central chemoreception and autonomic regulation differ across epilepsy phenotypes during a standardized CO2 challenge. We hypothesized that rats with chronic generalized tonic–clonic seizures would show impaired hypercapnic cardioventilatory and autonomic responses compared with rats with generalized absence seizures and healthy controls.
Methods: We measured breathing frequency (fB), heart rate (HR), and heart rate variability (HRV) before, during, and after a 1h 10% CO2 exposure in three groups of male rats: kainic acid (KA; tonic–clonic), genetic absence epilepsy rat from Strasbourg (GAERS; absence), and Wistar controls.
Results: Controls showed increased fB and decreased HR during hypercapnia. KA rats exhibited blunted fB and HR responses; GAERS displayed preserved fBelevation with faster post-challenge normalization and intermediate HR changes. Coupling of fB and HR collapsed during CO2 in both epilepsy groups and re-emerged in recovery. In KA rats, Stage 3–4 seizure burden positively correlated with HR during hypercapnia. HRV reactivity to hypercapnia was robust in controls, attenuated in GAERS, and largely absent in KA, whereas interictal baseline HRV did not differ among the groups.
Significance: These data support seizure-type–specific disruption of chemoreflex–autonomic integration. Extending clinical hypercapnic ventilatory response (HCVR) testing, a hypercapnic cardioventilatory response (HCCVR), that is, a combined fB, HR, and HRV readout, may help to refine SUDEP risk stratification beyond seizure frequency and type.

Transcutaneous vagus nerve stimulation (tVNS) targets the auricular branch of the vagus nerve and can modulate brainstem arousal systems, including the locus coeruleus–noradrenaline (LC-NE) pathway. Blue-enriched light also affects LC activity and can enhance alertness and cognition. However, no study has tested whether combining tVNS with blue light could further boost noradrenergic activity in humans. We therefore measured pupil responses, a well-established marker of LC-NE function, to assess how light and tVNS interact. We conducted a randomized, within-subject block design with twenty-five healthy adults (13 men, 12 women, aged 18–34) who received short (3.4 s) bursts of tVNS or sham stimulation (cymba conchae vs. earlobe). Pupil size was recorded under four light conditions: high intensity-blue, low intensity-blue, orange, and dim. TVNS increased pupil diameter relative to sham across all light conditions. Pupil dilation was largest and most sustained under low-blue light compared with dim or high-blue conditions. These results indicate that moderate tonic LC activation (e.g., low-blue light) enhances phasic responses to stimulation (e.g., tVNS), consistent with an inverted U-shaped relationship between tonic and phasic LC activity. Overall, our findings provide causal evidence that light, particularly low intensity-blue, modulates the effects of tVNS in humans, and combining both increases noradrenergic activity, as highlighted by increased pupil dilation, suggesting a simple way to enhance vagal-based therapies.

The aim of this study was to evaluate the feasibility of low-density (LD) interictal (IIC) and ictal (IC) electrical source imaging (ESI), and to assess their individual and combined diagnostic accuracy and predictive value in a cohort of children with drug-resistant epilepsy (DRE) who underwent resective surgery before the age of 7. Retrospective analysis was conducted on de-identified EEG and MRI data, which were (semi)-automatically processed, blinded to clinical information, to compute both IIC and IC-ESI. The concordance of ESI localizations with the resection cavity at sublobar level, and the association with surgical outcome were assessed. Thirty-two children were included. IIC- and IC-ESI showed an accuracy of 66 ​% (CI 95 ​% 47–81 ​%) and 72 ​% (CI 95 ​% 53–86 ​%) and a diagnostic odds ratio (DOR) of 3.0 (CI 95 ​% 0,66–13,69; p ​= ​0,15) and 5.0 (CI 95 ​% 0,91–27,47; p ​= ​0,06), respectively. The combined approach increased diagnostic performance, achieving an overall accuracy of 75 ​% and a DOR of 11.4 (CI 95 ​% 1.08–120,35; p ​= ​0,042). In multivariate logistic regression analysis, the combined IIC/IC ESI result emerged as the strongest predictor of postsurgical seizure freedom (OR: 222,28; p ​= ​0,0262; AUC: 0.87). These findings demonstrate that combined (semi)-automated LD-IIC and IC-ESI is feasible and can accurately localize the epileptogenic zone and predict postsurgical seizure freedom in children under 7 years of age. ESI may support earlier surgical referral, reduce the time from epilepsy onset to surgery, and ultimately improve long-term outcomes.

One-third of epileptic patients are resistant to conventional treatments. Vagus nerve stimulation is a promising therapy, especially when applied early during seizure onset. This study explores vagus nerve activity (VNA) during seizures in Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model and explores how VNA changes with epilepsy duration. Eleven rats (4, 6, and 10 months old, n=4, 4, 3 respectively) were continuously recorded with electroencephalography, VNA recordings, and video for 24h. Ictal VNA root mean square (RMS) values preceded by NREM sleep extracted from 11 rats were studied in a total of 620 seizures.Overall, VNA RMS increased during seizures, with a median rise of 60%. However, this modulation decreased with age, despite stable seizure severity. Significant differences in VNA activity and inter-quartile range were observed between age groups.These results support seizure severity-dependent changes in ictal VNA modulation and point toward the potential of VNA as a biomarker for seizure detection and autonomic dysfunction.