Trends in Cognitive Sciences
ReviewRevisiting the role of the insula in addiction
Section snippets
Revisiting the role of the insula in addiction
The IC has been known for a while as a receiver of interoceptive signals, and a necessary substrate for experiencing emotion and self-awareness 1, 2, 3. More recently, its role in attention and decision-making has been gathering increased attention 4, 5, 6. A growing body of research indicates that the decision process is a dynamic interplay between an implicit or automatic appetitive system, which promotes cue-induced habitual behaviors, and the executive control and/or inhibitory prefrontal
Heterogeneity of the IC and its role in addiction
Based on its internal structure, three major subdivisions of the IC have been identified: (i) the granular insula, which is located in the posterior dorsal portion of the IC; (ii) the agranular insula, located in the anterior ventral portion of the IC; and (3) the dysgranular insula, a large band occupying the middle portion of the IC [17]. Although these anatomical subdivisions have been identified in both humans and animals, in the addiction literature their use has been limited to animal
Evidence from lesions
The essential role of the IC in drug addiction is evident in the animal literature. Many of these studies used the conditioned place preference paradigm (CPP), in which rodents experience a drug administration in an environment that they do not normally prefer, and quickly develop a preference for this environment. A similar method is the conditioned place aversion (CPA) paradigm, where an environment is paired with aversive stimuli.
In a CPP experiment with mice, the preference for the
Evidence from neuroimaging studies
Structural imaging studies examining gray matter volume and density differences between addicted individual and healthy controls showed lower volume in the IC in cocaine users 40, 41, 42, heroin users [40], cannabis users [43], methamphetamine users 42, 44, and smokers 45, 46. The degree of this brain volume reduction seemed to increase as a function of the number of years of drug use 41, 47. Among these studies, nearly all of those that allowed for inspection of the subdivisions of IC found
An insight from the functional connectivity literature
The network-based approach considers the brain as a set of cohesive interconnected networks, as opposed to a collection of components. From examining the insula-centered networks, it has been proposed that the IC, together with the ACC, form a salience network (SN) that is responsible for coordinating resources between default mode (DMN: VMPFC and posterior cingulate cortex) and central executive (CEN: dorsolateral prefrontal cortex and posterior parietal cortex) networks [63]. Moreover, it has
Open questions
There are several potential avenues for future research that could help address this apparent inconsistency between lesion and neuroimaging studies. Although many studies have shown decreased gray matter in the insula of substance-dependent individuals, as reviewed above 40, 41, 42, 43, 44, 45, 46, there are no studies that have attempted to look at an increase or decrease in the white matter associated with the IC itself. Also, studies that address the structural connectivity of the IC are
Concluding remarks
It is tempting to consider parsimonious theories, such as ‘desensitized interoceptive insula system’ or ‘more efficient insula system’; both of which are consistent with reduced activation, but the latter can also be used to explain why insula lesions often lead to loss of addiction. However, we must consider the fact that the IC is part of a neural network, and its damage or lesion leads to changes in the network configuration that could alter its function. It is also likely that the changes
Acknowledgments
This manuscript was supported in part by NIDA Grant Number R01DA031626 to S.J.R. and NCI Grant Number R01CA152062 to A.B.
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