Signatures of alcohol use in the structure and neurochemistry of insular cortex: a correlational study

Abstract

Rationale Insular cortex supports the representation of motivational feelings through the integration of interoceptive information concerning bodily physiology. Compromised insular integrity is implicated in alcohol and drug use disorders. Alcohol-associated insular dysfunction may arise through aberrant glutamatergic neurotransmission associated with selective neuronal death and atrophy. Objective In a sample of alcohol users, we combined magnetic resonance spectroscopy (MRS) with voxel and surface-based morphometry (VBM, SBM) to test the hypothesis that the neurochemical and structural properties of the insula relate to alcohol use. Methods Twenty-three healthy individuals were characterized by measures of alcohol use and subjective craving. Right mid-insula glutamate/glutamine (Glx) and total N-acetylaspartate/N-acetyl-aspartylglutamate (TNAA) concentrations were measured using MRS. Right insular structure was quantified using VBM and SBM parameters. We tested for predictive associations between these neuroimaging and behavioral/psychometric measures using Bayesian statistics. Results Reduced insular Glx concentration was associated with increased alcohol compulsions and, to a lesser extent, with greater alcohol use severity. Anecdotal evidence for a negative relationship between alcohol use severity and levels of insular gyrification was also observed. Conclusions This study is, to date, the first characterization of the neurochemical and morphological integrity of insular cortex in alcohol users. Our data seem to reveal a negative relationship between alcohol use and the neurochemical and structural integrity of the insula, a critical substrate for motivational behavior. These neurobiological characteristics might contribute to loss of control toward compulsive drinking with prolonged and excessive alcohol use. Electronic supplementary material The online version of this article (10.1007/s00213-019-05228-w) contains supplementary material, which is available to authorized users.

Gray and white matter morphology in substance use disorders: a neuroimaging systematic review and meta-analysis

“…It has been proposed that the insula and the anterior cingulate cortex form the salience network (SN), that coordinates between the default mode network (DMN) and the central executive network (CEN) 50 . In our study we found lower volume of the insula, a region whose morphology has been associated with substance use compulsion and severity 51 . The insula plays a major role in interoception by integrating information from the internal physiological state, and projecting information to the ACC, ventral striatum and prefrontal cortex to initiate adaptive responses 52 .…”

Deter the emotions: Alexithymia, impulsivity and their relationship to binge drinking

“…Additionally, high alexithymia scores predict earlier age of alcohol use onset, longer duration of alcohol misuse, and increased amount of alcohol consumed ( Kopera et al, 2015 ). Correspondingly, high alexithymia scores, together with impulsivity, predict heavy alcohol drinking among university students ( Betka et al, 2019 , Lyvers et al, 2019 ). Thus, alexithymia may specifically increase the risk of developing AUD ( Cruise and Becerra, 2018 , Uzun et al, 2003 ).…”

It’s more than just interoception: The insular cortex involvement in alcohol use disorder

“…Together these findings suggest that insular activity is down-regulated during abstinence and abstinenceassociated negative affective states in individuals with alcohol use disorder. From a mechanistic perspective, compulsive alcohol use reduces insular glutamate-glutamine concentrations suggesting that perhaps an excitatory insular pathway may be driving this behaviour (Betka et al, 2019). Additionally, Laukkanen et al (Laukkanen et al, 2019) showed increased [ 3 H]quisqualic acid binding (a group I mGlu receptor agonist) in post-mortem anterior insular cortex brain tissue of individuals with alcohol use disorder compared to control brains.…”

“…Indeed, the insular has connections with the ventral striatum, particularly the nucleus accumbens core, and the ventral tegmental area/ substantia nigra (Allen et al, 1991;Ohara et al, 2003;Wright & Groenewegen, 1996). Importantly, dopamine, gamma-aminobutyric acid (GABA) and glutamate appear to be key neurotransmitters involved in the function of the insular cortex (Betka et al, 2019;Ohara et al, 2003). One class of disorders where motivated behaviours are augmented include substance use disorders.…”