Better living through understanding the insula: Why subregions can make all the difference

Author: Samuel W Centanni1, Amy C Janes2, David L Haggerty3, Brady Atwood3, Frederic W Hopf4
1 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address:
2 Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
3 Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
4 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
Conference/Journal: Neuropharmacology
Date published: 2021 Aug 27
Other: Special Notes: doi: 10.1016/j.neuropharm.2021.108765. , Word Count: 251

Insula function is considered critical for many motivated behaviors, with proposed functions ranging from attention, behavioral control, emotional regulation, goal-directed and aversion-resistant responding. Further, the insula is implicated in many neuropsychiatric conditions including substance abuse. More recently, multiple insula subregions have been distinguished based on anatomy, connectivity, and functional contributions. Generally, posterior insula is thought to encode more somatosensory inputs, which integrate with limbic/emotional information in middle insula, that in turn integrate with cognitive processes in anterior insula. Together, these regions provide rapid interoceptive information about the current or predicted situation, facilitating autonomic recruitment and quick, flexible action. Here, we seek to create a robust foundation from which to understand potential subregion differences, and provide direction for future studies. We address subregion differences across humans and rodents, so that the latter's mechanistic interventions can best mesh with clinical relevance of human conditions. We first consider the insula's suggested roles in humans, then compare subregional studies, and finally describe rodent work. One primary goal is to encourage precision in describing insula subregions, since imprecision (e.g. including both posterior and anterior studies when describing insula work) does a disservice to a larger understanding of insula contributions. Additionally, we note that specific task details can greatly impact recruitment of various subregions, requiring care and nuance in design and interpretation of studies. Nonetheless, the central ethological importance of the insula makes continued research to uncover mechanistic, mood, and behavioral contributions of paramount importance and interest.

Keywords: Motivation; Subregion; insula.

PMID: 34461066 DOI: 10.1016/j.neuropharm.2021.108765