Insula’s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving

Abstract

Rationale Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking. Objectives We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC). Methods Overnight-deprived smokers (n=24) and non-smokers (n=20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC. Results Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI–vmPFC circuit fully mediated this alexithymia–craving relation. That is, elevated alexithymia predicted decreased aI–vmPFC rsFC and, in turn, decreased aI–vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI–vmPFC mediational effect was not observed following drug administration. Conclusions These results suggest that a weakened right aI–vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI–vmPFC functional coupling may be relevant factors for smoking cessation success.

Error monitoring is related to processing internal affective states

“…A recent study using concurrent electroencephalogram and functional imaging found that cognitive control as measured by the congruency effect is related to activity in the more dorsally located SMA, whereas error monitoring is related to activity in a larger portion extending from the SMA over the aMCC to more rostrally located rostral anterior cingulate cortex (Iannacone, Hauser, Staempfli, Walitza, & Brem, 2015). The rostral anterior cingulate cortex shows altered activity in alexithymia (Bertoz et al, 2002;Frewen et al, 2008;Paradiso, Vaidyia, Cormick, Jones, & Robinson, 2008;Sutherland, Carroll, Salmeron, Ross, & Stein, 2013), and the present results indicate a reduced impact of emotions on error monitoring in alexithymia. Given the stronger involvement of the rostral anterior cingulate cortex in error monitoring than in interference control, our findings could suggest a role of this brain region in information transfer between the more dorsally located aspects of the errormonitoring system and the affective system.…”

Revisiting the role of the insula in addiction

“…Abstinent users demonstrated stronger connectivity than active recent users. These findings, together with prior evidence that the insula plays a key role in monitoring and regulating homeostasis of bodily states [2,61,68], supports the hypothesis that the insula's influence on goal-directed drug seeking is achieved by increased synchronization of its activity with the amygdala, and by disrupting the salience network functionality [69]. When the goal is successfully achieved (drug is consumed), this imbalance is re-adjusted back to normal.…”

Disrupted Resting-State Brain Functional Architecture in Amphetamine-Type Stimulant Abusers

“…Our findings are consistent with these previous studies. Similar to our findings, abnormal insula-MPFC functional connectivity has also been reported in smoking studies, e.g., a weakened right anterior insula-ventral MPFC functional circuit in smoking abstinent subjects [85]. This similarity suggests that amphetamine-type stimulants may interfere with functional networks similar to smoking.…”

“…Rs-fMRI involves analysis of spontaneous brain function using blood oxygen level-dependent contrasts in the absence of a task, rendering it suitable for clinical applications [11]. Rs-fMRI has been successfully applied to the characterization of brain function disturbances in substance-dependent populations, including individuals addicted to heroin [12][13][14][15], nicotine [16][17][18][19], and cocaine [20,21]. These rs-fMRI findings provide evidence that regions related to reward, memory and learning, cognitive control, motivation, and salience evaluation are involved in addiction [22].…”