The Insular Cortex Dynamically Maps Changes in Cardiorespiratory Interoception

Palpitations and dyspnea are fundamental to the human experience of panic anxiety, but it remains unclear how the brain dynamically represents changes in these interoceptive sensations. We used isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline, to induce sensations of palpitation and dyspnea in healthy individuals (n=23) during arterial spin labeling functional magnetic resonance imaging (fMRI). We hypothesized that the right mid-insular cortex, a central recipient of viscerosensory input, would preferentially respond during the peak period of cardiorespiratory stimulation. Bolus infusions of saline and isoproterenol (1 or 2 μg) were administered in a blinded manner while participants continuously rated the intensity of their cardiorespiratory sensation using a dial. Isoproterenol elicited dose-dependent increases in cardiorespiratory sensation, with all participants reporting palpitations and dyspnea at the 2 μg dose. Consistent with our hypothesis, the right mid-insula was maximally responsive during the peak period of sympathetic arousal, heart rate increase, and cardiorespiratory sensation. Furthermore, a shift in insula activity occurred during the recovery period, after the heart rate had largely returned to baseline levels, with an expansion of activation into anterior and posterior sectors of the right insula, as well as bilateral regions of the mid-insula. These results confirm the right mid-insula is a key node in the interoceptive network, and inform computational models proposing specific processing roles for insula subregions during homeostatic inference. The combination of isoproterenol and fMRI offers a powerful approach for evaluating insula function, and could be a useful probe for examining interoceptive dysfunction in psychiatric disorders.