How the insula speaks to the heart: Cardiac responses to insular stimulation in humans

Abstract

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency, LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases.

Keywords: RR intervals; autonomic nervous system; bradycardia; heart; insula; tachycardia.

Figure 1

Autonomic cardiac reactivity to insular stimulations. Time course of (a) RR intervals (RRI), (b) low frequency power (LF), (c) high frequency power (HF), and (d) LF/HF ratio variations (mean and standard deviation), before (10 heartbeats) and after (15 heartbeats) electrical stimulations in the insular cortex according to the type of evoked cardiac response (bradycardia, tachycardia, and no cardiac response). Data were normalized in percentage, relative to the basal period values. Both tachycardia and bradycardia were evoked by insular electrical stimulations, whichever the side of stimulations. Parasympathetic reactivity was underpinned by changes in HF during bradycardia, whereas sympathetic reactivity by changes in LF/HF during tachycardia. For RRI, statistical analysis was applied to the mean of five heartbeats pre‐ and post‐stimulus, and for parameters of RRI variability on the mean of 10 heartbeats pre‐ and post‐stimulus*p < 0.05 from baseline. #p < 0.05 from the other two evoked cardiac responses. Vertical dotted lines symbolize stimulation onset [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Spatial distribution of evoked cardiac responses according to (a) their Talairach coordinates; (b) the barycenters and standard deviations of their Talairach coordinates (y and z axes). Despite an overlap in the location of the different type of cardiac responses, the location of stimulation sites evoking tachycardia were more posterior than those evoking bradycardia or no cardiac response (y‐axis, p = 0.013). Due to interindividual variability of insula anatomy, some contacts are located outside this virtual line, although located in the insula individually, for each patient. Some stimulation sites could not be illustrated by circles, either because their coordinates were identical in several patients or because they were located at different contact depths along the x‐axis of the same electrode. For illustration, a sagittal insular mean image averaged from 24 subjects was superimposed onto the spatial distribution of stimulation site stereotactic coordinates. PC‐AC: posterior commissure‐anterior commissure horizontal plane; VAC: vertical anterior commissure coronal plane. *p < 0.05

Figure 3

Spatial distribution of evoked cardiac responses according to the stimulation side, in right (a) and left insula (b). The barycenters and standard deviations of their Talairach coordinates (y and z axes) in right (c) and left. (d) Insula show that although left and right stimulations induced as much tachycardia as bradycardia, the implication of different insular subregions depended on the side stimulated: Tachycardia was preferentially evoked by stimulating insula in its right ventral posterior part, and in its left dorsal posteromedian part, whereas bradycardia was mainly induced by stimulations in the right dorsal insula and in the left ventral insula. PC‐AC: posterior commissure‐anterior commissure horizontal plane; VAC: vertical anterior commissure coronal plane [Color figure can be viewed at http://wileyonlinelibrary.com]