Functional dissociation within insular cortex: The effect of pre-stimulus anxiety on pain

Brain activity resulting from changes in pain intensity may not only reflect changes in stimulus intensity but also in emotional distress. The anterior and mid-posterior insula have been associated with anticipatory anxiety and sensory-discrimination, respectively. We hypothesized that the two sub-divisions would exhibit different post-stimulus responses to increased pain intensity after removing the confounding effect of anticipatory anxiety. Using functional magnetic resonance imaging, activity was found in the anterior and mid-posterior insula in response to both low- and high-intensity painful stimuli delivered at the same level of anticipatory anxiety. Anterior insula activity covaried with anxiety ratings. When the pain intensity increased and the level of anticipatory anxiety was matched, increased activity was found in the mid-posterior insula but not in the anterior insula. The increase in activity covaried with increased pain intensity. These findings support the notion that encoding in the anterior insula primarily depends on the pre-stimulus context, i.e., anticipatory anxiety rather than the perceived pain intensity, and encoding in the mid-posterior insula is related to pain intensity changes.

► Anterior and mid-posterior insula respond to different aspects of pain processing.
► Mid-posterior insula responded to pain intensity changes when anxiety levels were matched.
► Anterior insula activation covaried with anticipatory anxiety ratings.
► Posterior insula activity covaried with pain intensity ratings.