Functional connectivity of the human insular cortex during noxious and innocuous thermal stimulation

The insula plays a key role in brain processing of noxious and innocuous thermal stimuli. The anterior and the posterior portions of the insular cortex are involved in different ways in nociceptive and thermoceptive processing. Therefore, their stimulus-specific functional connectivity may also differ. Here we used functional magnetic resonance imaging (fMRI) to investigate the activity and functional connectivity of insular cortex subregions during noxious and innocuous thermal stimulation. In 11 healthy subjects, psychophysically controlled noxious and innocuous warm and cold stimuli were applied to the left forearm. To differentiate between the subregions of the insular cortex involved in pain processing and those involved in temperature processing, a 2×2 factorial fMRI analysis was performed. Pain processing insular areas (main effect of pain) were detected in bilateral aINS and contralateral pINS. Temperature processing insular areas (main effect of temperature) were also found in bilateral aINS and contralateral pINS. The individual signal time courses from the pain- and temperature processing insular activation clusters were used for calculation and comparison of stimulus-specific functional connectivity of aINS and pINS by means of a correlation analysis. As expected, both aINS and pINS were functionally connected to a large brain network - which predominantly includes areas involved in nociception and thermoception: primary (S1) and secondary (S2) somatosensory cortices, cingulate gyrus, prefrontal cortex (PFC) and parietal association cortices (PA). When statistically compared, during both noxious and innocuous stimulation, aINS was more strongly connected to PFC and to ACC than was pINS; pINS meanwhile was more strongly connected to S1 and to the primary motor cortex (M1). Interestingly, S2 was more strongly connected to aINS than to pINS during painful stimulation but not during innocuous thermal stimulation. We conclude that aINS is more strongly functionally connected to areas known for affective and cognitive processing, whereas pINS is more strongly connected with areas known for sensory-discriminative processing of noxious and somatosensory stimuli.