Sex Differences in the Association of Cigarette Craving With Insula Structure

Diaz, Maylen Perez; Pochon, Jean‐Baptiste; Ghahremani, Dara G.; Dean, Andy C.; Faulkner, Paul; Petersen, Nicole; Tyndale, Rachel F.; Donis, Andrea; Páez, Diana; Cahuantzi, Citlaly; Hellemann, Gerhard; London, Edythe D.

doi:10.1093/ijnp/pyab015

Cited by 20 publications

(18 citation statements)

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“…The study was part of a larger investigation on the brain correlates of smoking behavior and took place between September, 2017 and February, 2020. Another report from that study is in press 52 . The study was conducted at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles (UCLA).…”

Section: Methodsmentioning

confidence: 94%

“…Neuroimaging studies have also indicated the importance of the insula in maintenance of cigarette smoking. Cortical thickness of insular sub-regions is negatively related to nicotine dependence 17–19 and cigarette craving 20 . Resting-state functional connectivity (RSFC) has been used to assess neural systems involved in nicotine dependence 21, 22 .…”

Section: Introductionmentioning

confidence: 99%

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Nicotine dependence and functional connectivity of insular cortex subregions

Pochon

et al. 2021

Preprint

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The insular cortex has been identified as a promising target in brain-based therapies for Tobacco Use Disorder, 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 has not been well understood, and therefore was the subject of this study. Forty-seven individuals (24 women; 18-45 years old) who smoked cigarettes daily rated their dependence using the Fagerström Test for Nicotine Dependence (FTND), abstained from smoking overnight (~12 h), and underwent resting-state functional MRI. Correlations between dependence and resting-state functional connectivity (RSFC) of the major insular sub-regions were evaluated using whole-brain-corrected voxel-wise analyses and post-hoc region-of-interest (ROI) analyses. Dependence was analyzed both as a unitary (FTND total score) and bivariate construct – two FTND factors (“morning smoking” and “daytime smoking”). Dependence was negatively correlated with connectivity of both the right dorsal and left ventral anterior insula with the left precuneus, and with connectivity of the left posterior insula to the left putamen. In post-hoc analyses, dependence correlated negatively with connectivity between all anterior insula subregions and the left precuneus, and with bilateral posterior insula connectivity with the left posterior putamen. The latter finding was driven by “daytime smoking”. These results suggest an anterior-posterior distinction in functional insular networks associated with different dimensions of nicotine dependence, with greater dependence linked to weaker connectivity. They may inform therapeutic approaches involving brain stimulation that may elicit differential clinical outcomes depending on the insular subnetwork targeted.

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Section: Methodsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Nicotine dependence and functional connectivity of insular cortex subregions

Pochon

et al. 2021

Preprint

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“…The current observation that insular thickness is negatively associated with craving is line with previous research in cigarette smokers. 30 , 31 Thinner insular cortex 54 , 55 , 56 and smaller insular volume 25 , 56 , 57 has furthermore been associated with heightened impulsive and compulsive behaviour. Hence, insular thinning may be a biomarker for impaired emotion regulation and, as a consequence, enhanced craving.…”

Section: Discussionmentioning

confidence: 99%

“…Although we expected these sex differences to be particularly pronounced in insular CT, these findings are in line with previous research that demonstrated that abstinence induced craving is negatively related to insular CT in nicotine dependent women, but positively related to insular CT in nicotine dependent men. 31 Lower insular volume, which is the product of insular thinning and reductions in surface area, has shown to be related to impaired attentional control in cocaine users. 25 In addition, we also found that craving related to loss of control and right insular SA was also moderated by sex: There was a positive association between right insular SA and craving related to loss of control in CU women, whereas this association was negative in CU men.…”

Section: Discussionmentioning

confidence: 99%

“…Research in nicotine dependent individuals furthermore demonstrated that cortical thickness in the right insula is negatively correlated with craving for cigarettes, 30 and recent research showed that this negative association between cortical thickness of the insula and craving may be particularly strong in women that smoke cigarettes. 31 Although these studies suggest that interventions that specially target insular function and structure, such as brain stimulation of the insula, 32 may be particularly effective in the treatment of CUD in women, 31 sex and gender differences in the association between insular morphometry and craving has not been investigated in cocaine users yet.…”

Section: Introductionmentioning

confidence: 99%

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The relationship between craving and insular morphometry in regular cocaine users: Does sex matter?

2022

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While it has been suggested that cocaine use and relapse in women is more strongly related to stress-relief craving, whereas cocaine use in men is more strongly related to reward craving, the neural mechanisms that underlie these differences are poorly understood. The aim of this study was to investigate sex-dependent differences in insular morphometry and associations with craving, in a sample of regular cocaine users (CUs) and non-drug using controls (non-CUs). It was hypothesized that insular volume, thickness and surface area would be lower in CU women, compared with CU men and non-CUs. It was furthermore hypothesized that insular morphometry, particularly insular thickness, would be negatively associated to reward craving in CU men, while being negatively associated with stress-relief craving in CU women. In contrast to the hypothesis, we did not find evidence of sex-specific differences in insular morphometry in CUs. However, sex-specific association between stress-relief craving and insular morphometry were found: Right insular volume was negatively associated with stress-relief craving in CU women, whereas this association was positive in CU men. Additionally, right insular surface area was negatively associated with stress-relief craving in cocaine-using men, whereas this association was positive in cocaine-using women. In conclusion, the current study provides first evidence of sexspecific differences in the association between craving and insular morphometry in a sample of regular cocaine users. Although speculative, these sex-specific alterations in insular morphometry may underlie higher stress-induced craving and relapse in CU women compared with CU men.cocaine use disorder, craving, insula, sex and gender differences, stress | INTRODUCTIONCocaine is one of the most commonly used illicit drug in Europe, and the prevalence of (high-risk) use has been increasing in the past decade. 1 While the prevalence of cocaine use is approximately two to three times higher in men than in women (in the Netherlands, 1.2% of men, and 0.4% of women report recent use of cocaine) this gap is slowly closing. 2 Research furthermore suggests that women progress more rapidly to cocaine use disorders (CUDs) than men and show greater rates of relapse. 3 Nonetheless, very little is known about sex

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Functional connectivity gradients of the insula to different cerebral systems

Shen

et al. 2022

Human Brain Mapping

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The diverse functional roles of the insula may emerge from its heavy connectivity to an extensive network of cortical and subcortical areas. Despite several previous attempts to investigate the hierarchical organization of the insula by applying the recently developed gradient approach to insula‐to‐whole brain connectivity data, little is known about whether and how there is variability across connectivity gradients of the insula to different cerebral systems. Resting‐state functional MRI data from 793 healthy subjects were used to discover and validate functional connectivity gradients of the insula, which were computed based on its voxel‐wise functional connectivity profiles to distinct cerebral systems. We identified three primary patterns of functional connectivity gradients of the insula to distinct cerebral systems. The connectivity gradients to the higher‐order transmodal associative systems, including the prefrontal, posterior parietal, temporal cortices, and limbic lobule, showed a ventroanterior‐dorsal axis across the insula; those to the lower‐order unimodal primary systems, including the motor, somatosensory, and occipital cortices, displayed radiating transitions from dorsoanterior toward both ventroanterior and dorsoposterior parts of the insula; the connectivity gradient to the subcortical nuclei exhibited an organization along the anterior–posterior axis of the insula. Apart from complementing and extending previous literature on the heterogeneous connectivity patterns of insula subregions, the presented framework may offer ample opportunities to refine our understanding of the role of the insula in many brain disorders.

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Sex Differences in the Association of Cigarette Craving With Insula Structure

Cited by 20 publications

References 72 publications

Nicotine dependence and functional connectivity of insular cortex subregions

Nicotine dependence and functional connectivity of insular cortex subregions

The relationship between craving and insular morphometry in regular cocaine users: Does sex matter?

Functional connectivity gradients of the insula to different cerebral systems

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