Distinct Subdivisions of the Cingulo-Insular Region and Their Role in Modulating the Cardiac Sympathetic-Parasympathetic Balance

BACKGROUND: The cingulo-insular region is crucial for modulating cardiac activity. However, the distinct roles of its anatomic subdivisions in modulating sympathetic-parasympathetic balance remain poorly defined. We aimed to explore the distinct contributions of subdivisions within the cingulo-insular region to modulating cardio-autonomic balance. METHODS: In this prospective observational study, patients with drug-resistant epilepsy undergoing stereo-electroencephalography with electrical cortical stimulation of the cingulo-insular region were enrolled. Stereo-electroencephalography and ECG signals were synchronously recorded during electrical cortical stimulation of the cingulo-insular region. Heart rate variability and R-R interval analyses were conducted to assess cardiac sympathetic-parasympathetic balance. The correlation coefficient between heart rate variability and the strength of phase-amplitude coupling in stereo-electroencephalography was calculated before and after stimulation. RESULTS: Data from 33 patients (70 electrode contacts, 287 trials) were analyzed. Stimulation of the anterior cingulate gyrus enhanced parasympathetic activity, correlated with increased local phase-amplitude coupling strength. The left anterior cingulate gyrus stimulation increased pNN50 (median difference, −5.00% [95% CI, −17.99 to −0.16]; P =0.044); right anterior cingulate gyrus stimulation increased the SD of all normal-to-normal intervals (median difference, −14.22 ms [95% CI, −26.68 to −1.63]; P =0.019) and SD2 (median difference, −19.49 ms [95% CI, −33.26 to −3.22]; P =0.013). Meanwhile, stimulation of the posterior insula significantly reduced the parasympathetic component of heart rate variability and short-term R-R interval. The left posterior insula decreased the SD1/SD2 ratio (median difference, 0.08 [95% CI, 0.03–0.15]; P =0.005); right posterior insula decreased power in the high-frequency range (median difference, 25.30 ms 2 [95% CI, 3.98–49.35]; P =0.013) and the approximate entropy (median difference, 0.15 [95% CI, 0.04–0.29]; P =0.004). CONCLUSIONS: Within the cingulo-insular region, the anterior cingulate gyrus is associated with a relative cardio-parasympathetic dominance, while the posterior insula is linked to a relative cardio-sympathetic dominance. These findings provide a deeper understanding of the neural modulation of cardio-autonomic balance, and may have implications for the prevention and treatment of cardio-autonomic dysfunction in neurological disorders.