Distinct Subdivisions of the Cingulo-Insular Region and Their Role in Modulating the Cardiac...

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.

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.

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 ms² [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).

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.