High-resolution functional MRI identified distinct global intrinsic functional networks of nociceptive posterior insula and S2 regions in squirrel monkey brain

ABSTRACT Numerous functional imaging and electrophysiological studies in humans and animals indicate that the two contiguous areas of secondary somatosensory cortex (S2) and posterior insula (pIns) are core regions in nociceptive processing and pain perception. In this study, we tested the hypothesis that the S2‐pIns connection serves as a hub for connecting distinct sensory and affective nociceptive processing networks in the squirrel monkey brain. At 9.4 T, we first mapped the brain regions that respond to nociceptive heat stimuli with high‐resolution fMRI, and then used seed‐based resting‐state fMRI (rsfMRI) analysis to delineate and refine the global intrinsic functional connectivity circuits of the proximal S2 and pIns regions. In each subject, nociceptive (47.5 °C) heat‐evoked fMRI activations were detected in many brain regions, including primary somatosensory (S1), S2, pIns, area 7b, anterior cingulate cortex (ACC), primary motor cortex, prefrontal cortex, supplementary motor area, thalamus, and caudate. Using the heat‐evoked fMRI activation foci in S2 and pIns as the seeds, voxel‐wise whole‐brain resting‐state functional connectivity (rsFC) analysis revealed strong functional connections between contralateral S2 and pIns, as well as their corresponding regions in the ipsilateral hemisphere. Spatial similarity and overlap analysis identified each region as part of two distinct intrinsic functional networks with 7% overlap: sensory S2‐S1‐area 7b and affective pIns‐ACC‐PCC networks. Moreover, a high degree of overlap was observed between the combined rsFC maps of nociceptive S2 and pIns regions and the nociceptive heat‐evoked activation map. In summary, our study provides evidence for the existence of two distinct intrinsic functional networks for S2 and pIns nociceptive regions, and these two networks are joined via the S2‐pIns connection. Brain regions that are involved in processing nociceptive inputs are also highly interconnected at rest. The presence of robust and distinct S1‐S2‐area 7b and pIns‐ACC‐PCC rsFC networks under anesthesia underscores their fundamental roles in processing nociceptive information. HIGHLIGHTSNociceptive heat evoked fMRI activations in multiple refined brain regions.Nociceptive S2 and pIns regions exhibited distinct global rsFC networks.S1‐S2‐area 7b and pIns‐ACC‐PCC rsFC networks joined via S2‐pIns connection.