The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate‐precuneus pathway

Abstract

IntroductionPerturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus.MethodsUsing functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting-state functional connectivity analysis using the anterior cingulate cortex as a seed.ResultsIndependent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed-based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60–0.76; P < 0.05).ConclusionsIn concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting-state functional connectivity in this pathway increases during nicotine withdrawal in correlation with the intensity of withdrawal-induced craving. These findings suggest that smoking triggers structural and functional neural adaptations in the brain that support withdrawal-induced craving.

Smoking Abstinence-Induced Changes in Resting State Functional Connectivity with Ventral Striatum Predict Lapse During a Quit Attempt

“…However, these results are consistent with previous studies demonstrating that connectivity within this network is strengthened during smoking withdrawal (Cole et al, 2010;Huang et al, 2014;Sutherland et al, 2013); but also that connectivity between similar regions is attenuated among smokers compared with nonsmokers (Hong et al, 2010), and is negatively correlated with nicotine dependence (Hong et al, 2009) and likelihood of relapse (Addicott et al, 2015;Janes et al, 2010). Thus, enhanced connectivity across regions including the insula, cingulate, and striatum appears to be protective when assessed as a trait-level marker independent of abstinence state, whereas state-based increases in connectivity strength co-occur with increases in subjective craving and withdrawal (Huang et al, 2014;Sutherland et al, 2013), similar to that observed here. The present findings build upon this prior research to highlight the importance of individual differences in the effects of abstinence on connectivity strength and suggest that withdrawal-induced modulation of connectivity may be associated with better cessation outcomes.…”

“…If increased VS connectivity with the cingulo-insular network reflects a stronger degree of cognitive control over motivationally relevant stimuli, thereby enhancing the ability to inhibit the impulse to smoke, then it is somewhat surprising that such regulatory pathways were increased during abstinence among non-lapsers, particularly as tobacco withdrawal is associated with diminished ability to resist smoking (Roche et al, 2014). However, these results are consistent with previous studies demonstrating that connectivity within this network is strengthened during smoking withdrawal (Cole et al, 2010;Huang et al, 2014;Sutherland et al, 2013); but also that connectivity between similar regions is attenuated among smokers compared with nonsmokers (Hong et al, 2010), and is negatively correlated with nicotine dependence (Hong et al, 2009) and likelihood of relapse (Addicott et al, 2015;Janes et al, 2010). Thus, enhanced connectivity across regions including the insula, cingulate, and striatum appears to be protective when assessed as a trait-level marker independent of abstinence state, whereas state-based increases in connectivity strength co-occur with increases in subjective craving and withdrawal (Huang et al, 2014;Sutherland et al, 2013), similar to that observed here.…”

Dorsal anterior cingulate glutamate is associated with engagement of the default mode network during exposure to smoking cues

“…For instance, stronger dACC-precuneus structural and functional interactions are associated with greater nicotine physical dependence (Huang et al, 2013, 2014) and such functional dACC-precuneus interactions increase during withdrawal (Huang et al, 2014). As the dACC and precuneus are primary nodes of the SN and DMN respectively, the work of Haung et al is consistent with the finding that SN-DMN interactions also increase during withdrawal (Lerman et al, 2014).…”

Nicotine and Resting-State Functional Connectivity: Effects of Intermittent Doses

“…rsFC in many of these areas is affected by nicotine in humans, such as the anterior cingulate cortex, insula, caudate, putamen, and the prefrontal cortex. 12,13 The site exhibiting functional connectivity alterations with the widest number of other regions is the interpeduncular nucleus. Interestingly, this brain region reportedly plays a key role in nicotine withdrawal symptoms (reviewed in Dani et al 14 …”