Nicotine dependence and insula subregions: functional connectivity and cue-induced activation

Abstract

Nicotine dependence is a major predictor of relapse in people with Tobacco Use Disorder (TUD). Accordingly, therapies that reduce nicotine dependence may promote sustained abstinence from smoking. The insular cortex has been identified as a promising target in brain-based therapies for TUD, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence is not well understood, and therefore was the focus of this study. Sixty individuals (28 women; 18–45 years old), who smoked cigarettes daily, rated their level of nicotine dependence (on the Fagerström Test for Nicotine Dependence) and, after abstaining from smoking overnight (~12 h), underwent functional magnetic resonance imaging (fMRI) in a resting state. A subset of these participants (N = 48) also completing a cue-induced craving task during fMRI. Correlations between nicotine dependence and resting-state functional connectivity (RSFC) and cue-induced activation of the major insular sub-regions were evaluated. Nicotine dependence was negatively correlated with connectivity of the left and right dorsal, and left ventral anterior insula with regions within the superior parietal lobule (SPL), including the left precuneus. No relationship between posterior insula connectivity and nicotine dependence was found. Cue-induced activation in the left dorsal anterior insula was positively associated with nicotine dependence and negatively associated with RSFC of the same region with SPL, suggesting that craving-related responsivity in this subregion was greater among participants who were more dependent. These results may inform therapeutic approaches, such as brain stimulation, which may elicit differential clinical outcomes (e.g., dependence, craving) depending on the insular subnetwork that is targeted.

Genetic and environmental influence on resting state networks in young male and female adults: a cartographer mapping study

“…It is noted that smoking and alcohol usage have been suggested to have an impact on chronological brain age (Ning et al, 2020 ). Similar to as described before, but specific to rsFC, there are differing effects of acute nicotine and chronic nicotine exposure, and with the anterior cingulate, prefrontal cortex, eDMN, and insular cortex particularly involved (although more regions may be implicated), which may relate in differing ways to the results in this study (e.g., insular and frontal opercular cortex was one noted region influenced by genetic effects found; Cheng et al, 2019 ; Fedota & Stein, 2015 ; Ghahremani et al, 2023 ; Sutherland et al, 2012 ). Additionally, the effects of time‐period of quitting from cigarette, alcohol, or other substances used, or time of last substance use (ignoring other effects such as tiredness or time of day of scan, elaborated on in a comment in Cheng et al, 2019 ), and rsfMRI acquisition periods in relation to these events can have differing effects on rsFC (albeit, concatenating the rsfMRI time series across multiple time points may help with generalizability in this respect; Sweitzer et al, 2016 ).…”

Increased ventral anterior insular connectivity to sports betting availability indexes problem gambling

“…Accordingly, by using a whole brain approach, we expected to observe increased vAI PPI with the orbitofrontal cortex and the ventral striatum during sports betting availability. Based on existing evidence, we expect a positive and negative vAi coupling with these regions (especially with the orbitofrontal cortex) 10–17 . In addition, based on previous fMRI findings obtained with our sports betting availability task, negative PPI could be expected.…”

“…Based on existing evidence, we expect a positive and negative vAi coupling with these regions (especially with the orbitofrontal cortex). 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 In addition, based on previous fMRI findings obtained with our sports betting availability task, negative PPI could be expected. These positive and negative dynamics of brain connectivity likely reflect the complex nature of the interactions between the insula and the so‐called bottom‐up impulsive and top‐down reflective systems.…”

“…Indeed, the insular cortex constitutes a ‘gating system’ in the interplay between neurocognitive processes 10–13 . Specifically, the insula has been divided into three major subregions that serve distinct functions, with the posterior insula (PI) specializing in the processing of afferent bodily information, the dorsal anterior insula (dAI) in higher‐order executive control cognitive processes and the vAI in emotional and reward‐based processes 10–17 . Importantly, several functional connectivity studies provided evidence for the hypothesis that the insular cortex is a key hub for identifying interactions among the brain networks involved in the processing of salient‐motivational cues (for a review, see previous works 10,11 ).…”

“… 10 , 11 , 12 , 13 Specifically, the insula has been divided into three major subregions that serve distinct functions, with the posterior insula (PI) specializing in the processing of afferent bodily information, the dorsal anterior insula (dAI) in higher‐order executive control cognitive processes and the vAI in emotional and reward‐based processes. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 Importantly, several functional connectivity studies provided evidence for the hypothesis that the insular cortex is a key hub for identifying interactions among the brain networks involved in the processing of salient‐motivational cues (for a review, see previous works 10 , 11 ). For instance, Zhao et al 13 highlighted that during monetary‐based decision‐making, the PI is connected to brain regions involved in sensorimotor motor processes (e.g., supplementary motor area), the dAI is predominately connected with brain regions commonly involved in higher cognition and executive control processes (e.g., dorsolateral prefrontal cortex), and the vAI is preferentially connected to regions from the reward‐brain system, including the ventral striatum and the orbitofrontal cortex (i.e., the fronto‐striatal pathway; e.g., Weber et al 18 ).…”