Objective:

We used electrical stimulation of the insular cortex in non-epileptic patients to delineate how different insular subregions influence cardiac rhythm. 

Background:

The location and function of cortico-cardiac regulation by the insular cortex remain unclear in humans. 

Design/Methods:

ECG were obtained from 4 subjects (3 females, 67.7 ± 15.8 years) enrolled in a chronic pain DBS trial. Longitudinal insular depth electrodes (10 contacts, 5mm spacing) were implanted bilaterally. Bi-polar stimulations (50Hz, bi-phasic, 250µs PD, 2-8mA) were delivered in 10-30s trains. Insular sub-regions were defined by side ((L)eft/(R)ight, i.e. L/R) and by the central sulcus ((A)nterior/(P)osterior). The mean ± one standard deviation of the pre-stimulation (~30s) R-R intervals (RRI) was used to identify RRI responses. RMSSD was calculated to measure heart rate variability (HRV). 

Results:

Ninety-eight stimulations were delivered to the LA (23), RA (23), LP (32), and RP (20) insular subregions. Stimulus-evoked sensory symptoms were observed in all subjects, confined to the posterior insula. Forty-eight of these stimulations evoked RRI responses, evenly split between increased and decreased RRI. Overall, increased and decreased RRI were associated with the anterior-posterior axis of the insula cortex (χ²(1) = 4.148, p = 0.042). A greater proportion of decreased RRI was found in the posterior insula compared to the anterior insula (two-proportion Z test, 17/21 vs. 7/27, p = 0.00016). The RP insular subregion tended to elicit more decreased than increased RRI compared to chance (8/10, one-proportion Z test, p = 0.058). Furthermore, no significant changes in HRV were found across all four insular subregions (Wilcoxon rank sum test, p > 0.05). 

Conclusions:

Preliminary results suggest a role for the insular cortex in cardiac rhythm. Stimulation of the right posterior insula likely increases heart rate, expanding our understanding of human insular cortex. More subjects are needed to further validate findings in the current study.