# Functional Architecture of the Human Insula Revealed by Causal Intracranial Mapping

## TL;DR

This study reveals the functional structure of the human insula and how its regions interact to process pain, emotion, and bodily sensations.

## Contribution

The paper introduces a causal electrophysiological mapping of the human insula, identifying a quadripartite architecture and its role in cognitive modulation of bodily perception.

## Key findings

- The human insula has four distinct functional regions with specific roles in nociception, somatosensation, visceral sensations, and salience detection.
- The anterior-polar region strongly influences other insular regions and is linked to cognitive modulation of pain and bodily perception.
- This region shows robust activation during salience detection and has strong connections with the prefrontal cortex.

## Abstract

The insular cortex plays a central role in pain, emotion, and cognition, yet its functional architecture and causal electrophysiological relationships among its subregions remain poorly understood. Here, we integrated intracranial electrical stimulation and task-based electroencephalography recordings with connectivity mapping within a cytoarchitectonic atlas of the human insula in 87 neurosurgical participants, identifying a quadripartite functional architecture comprising functionally distinct regions: (i) dorsal-posterior region encoding somatotopically organized nociceptive/thermoceptive and somatosensory signals; (ii) ventral-posterior region integrating somatic information across multiple body parts; (iii) mid-anterior region associated with visceral sensations and anxiety states; and (iv) 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 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.