The Insula: An Underestimated Brain Area in Clinical Neuroscience, Psychiatry, and Neurology

Abstract

Supported by recent human neuroimaging studies, the insula is re-emerging as an important brain area not only in the physiological understanding of the brain, but also in pathological contexts in clinical research. In this opinion article, we briefly introduce the anatomical and histological features of the human insula. We then summarize the physiological functions of the insula and underscore its pathological roles in psychiatric and neurological disorders that have long been underestimated. We finally propose possible strategies through which the role of the insula may be further understood for both basic and clinical neuroscience.

Keywords: cognition; feeling; insula; motivation; neurological diseases; psychiatric diseases.

Figure 1. Anatomy of the human insula

The human insular cortex is bilaterally located deep within the lateral sulcus separating the temporal lobe from the parietal and frontal lobes. The insula is covered with folds of the adjacent frontal, parietal, and temporal opercula. The circumference of the insula is outlined by the circular sulcus, and the deep central sulcus of the insula separates the anterior and posterior parts. Three short insular gyri are found in the anterior insula (AI), whereas two long insular gyri lie in the posterior insula (PI). Cytoarchitecturally, the insula is roughly divided into anterior agranular and posterior granular sections with a transitional dysgranular mid-section.

Figure 2. Interoceptive information and its integration with emotional, cognitive, and motivational signals from an array of cortical and subcortical regions

Interoceptive information of constantly changing body states arrives in the posterior insula by ascending sensory inputs from dedicated spinal and brainstem pathways via specific thalamic relays. This information is projected rostrally onto the anterior insula, where it is integrated with emotional, cognitive, and motivational signals from an array of cortical and subcortical regions. As a result, the anterior insula supports unique subjective feeling states. The anterior insula regulates the introduction of subjective feelings into cognitive and motivational processes by virtue of its cortical location at the cross-roads of numerous pathways involved in higher cognition and motivation. AI: anterior insula; PI: posterior insula; THAL: thalamus; AMG: amygdala; VS: ventral striatum; VMPFC: ventromedial prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; dACC: dorsal anterior cingulate cortex.

Figure 3. Strategies for better understanding the causal roles of the insula in brain function

Computational and statistical efforts in human brain image processing and analysis, as well as recent advances in non-invasive brain stimulation techniques, may be useful in providing causal insights into the insula without major ethical constraints in human studies. Given the corresponding cytoarchitecture and connectivity, the homology between human and rodent insula has been identified. Taking advantage of mice may provide a great opportunity for better understanding casual roles of the insula as it allows for invasive brain manipulations that are ruled out by ethical constraints in human studies. Recent technological advances in preclinical studies using mice allow us to acquire a sophisticated understanding of neuronal circuit architecture and activity information in behaviorally relevant contexts. The anatomically and genetically defined neural circuitry elements or connectivity can be interrogated with activity readouts and/or activity manipulations in behaviorally relevant contexts. Exploiting translational and back-translational approaches between clinical and preclinical studies would finally enhance understanding of the causal role for the insula in higher brain function, at multiple levels spanning from the gene, molecule, cell, circuitry, physiology to behavior. DMN: default mode network; SN: salience network; CEN: central executive network; PCC: posterior cingulate cortex; VMPFC: ventromedial prefrontal cortex; ACC: anterior cingulate cortex; AI: anterior insula; PPC: posterior parietal cortex; DLPFC: dorsolateral prefrontal cortex; ChR2: channelrhodopsin-2; NpHR: halorhodopsin.