Functional architecture of the human insula

The insular cortex has a central role in pain^1,2, interoception^3,4 and feelings^5,6, yet its functional architecture and causal electrophysiological relationships among its subregions remain poorly understood. Here we combine intracranial electrical stimulation and task-based electroencephalography recordings with connectivity mapping within a cytoarchitectonic atlas of the human insula^7-10 in 87 participants implanted with intracranial electrodes, and identify a quadripartite functional architecture comprising four distinct regions: (1) a dorsal-posterior region encoding somatotopically organized nociceptive/thermoceptive and somatosensory signals; (2) a ventral-posterior region with access to somatic information across multiple body parts; (3) a mid-anterior region associated with visceral sensations and anxiety states; and (4) an anterior-polar region, largely silent to direct stimulation, yet showing robust activation during salience detection and change of action mode. Critically, this anterior region, with its strong connections with the prefrontal cortex, including the anterior cingulate cortex, exerts strong and direct influence over other insular regions, while receiving less-strong indirect inputs from them, revealing an electrophysiological pathway for cognitive modulation of pain and bodily perception. Together, these findings define a functional architecture of the human insula that links cytoarchitecture to directed and asymmetric electrophysiological interactions, with mechanistic implications for cognitive modulation of pain and interoceptive experience.