Objective: The link between brain function and cardiovascular dynamics is an important issue yet to be elucidated completely. The insula is a neocortical brain area that is thought to have a cardiac chronotropic regulatory function, but its role in cardiac contractility is unknown. We aimed to analyze the variability in heart rate and cardiac contractility after functional activation of different insular regions through direct electrical stimulation (E-stim) in humans.

Methods: This was an observational, prospective study, including patients admitted for stereo-electroencephalographic recording because of refractory epilepsy, in whom the insular cortex was implanted. Patients with anatomical or electrophysiological insular abnormalities and those in whom E-stim produced subjective symptoms were excluded. Variations in heart rate (HR), stroke volume (SV), and cardiac output (CO) were analyzed during insular E-stim and compared with control E-stim of non-eloquent brain regions and sham stimulations.

Results: Ten patients were included, 5 implanted in the right insula (52 E-stim) and 5 in the left (37 E-stim). Demographic and clinical characteristics of both groups were similar. E-stim of both right and left insulas induced a significant decrease of the CO and HR, and an increase of the SV. E-stim of control electrodes and sham stimulations were not associated with variations in cardiac function. Blood pressure and respiratory rate remained unaltered.

Interpretation: Our results suggest a direct chronotropic and inotropic cardiac depressor function of the right and left insulas. The evidence of an insular direct cardiac regulatory function might open a path in the prevention or treatment of heart failure, arrhythmias, and sudden unexpected death in epilepsy. ANN NEUROL 2021;89:1172-1180.