The negative chronotropic control of the insula: An SEEG-based investigation

The insula is implicated in heart rate modulation within brain-cardiac interactions, yet direct electrophysiological evidence remains limited. This study investigates dynamic insula-cardiac coupling during ictal heart rate fluctuations to elucidate the insula's role in chronotropic regulation. Patients with drug-resistant epilepsy exhibiting both insular stereoelectroencephalography coverage and ictal heart rate changes underwent simultaneous intracranial electroencephalography and electrocardiography monitoring during seizures. Phase transfer entropy (PTE) was used to analyze directed information flow between the seizure onset zone (SOZ) and the insula. PTE dynamics between the insula and the heart, along with heart rate changes, were tracked to determine insular involvement in heart rate regulation. Thirteen patients (24 seizures) were included, with 11 patients (20 seizures) showing tachycardia and 2 patients (4 seizures) showing bradycardia. SOZ-to-insula PTE increased in 22 of 24 seizures. Insula-to-heart PTE inversely correlated with heart rate: during tachycardia (20 seizures), PTE was decreased in 17 cases; during bradycardia (4 seizures), PTE increased in all cases. These changes occurred exclusively in the 0.01-1 Hz band. Temporal analysis revealed that changes in heart rate did not coincide with changes in PTE. The insula may impose frequency-specific inhibitory control over heart rate. The insula may function as a coordinator rather than an initiator of heart rate modulation.