Age‐related differences in working memory deficits during nicotine withdrawal

Abstract

Nicotine withdrawal is associated with subtle working memory deficits that predict subsequent relapse. We examined the neural substrates underlying these processes in treatment-seeking smokers, and explored the moderating influence of age on abstinence-induced alterations in brain activity and performance. Sixty-three smokers participated in two blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) scans while performing a visual N-back task on two separate occasions: smoking as usual and after 24 hours of biochemically confirmed abstinence (order counterbalanced). Abstinence (versus smoking) led to reduced accuracy, slower median correct response time, and reduced BOLD signal change in the 3 a priori regions of interest (ROIs): medial frontal/cingulate gyrus and right and left dorsolateral prefrontal cortex. Significant age x session effects were found for BOLD signal change in all three regions, as well as for withdrawal and craving; for all measures, abstinence effects were attenuated in smokers aged >50 years compared to those < 50 years old. These results suggest that abstinence effects on neurocognitive function may be more pronounced for younger smokers, and may indicate a new avenue for research exploring mechanisms underlying age differences in smoking cessation success.

Neurobiological Impact of Nicotinic Acetylcholine Receptor Agonists: An Activation Likelihood Estimation Meta-Analysis of Pharmacologic Neuroimaging Studies

“…Critically, dlPFC hypoactivation among smokers likely contributes to working memory deficits, which are predictive of smoking relapse (23, 57-59). The current results provide support for the utility of considering dlPFC activity as a potential interventional target for smoking cessation (23, 60, 61). Conversely, our results indicated that the bilateral parietal cortices, right middle frontal gyrus, and ACC were more likely to show drug-induced activity increases in studies involving nonsmokers.…”

Working Memory-Related Neural Activity Predicts Future Smoking Relapse

“…As noted above, prior work with the visual N-back task by our group (Ashare et al, 2013b;Falcone et al, 2014;Lerman et al, 2014;Loughead et al, 2009Loughead et al, , 2010 and others (Owen et al, 2005;Satterthwaite et al, 2013) has identified three task-active (right DLPFC, left DLPFC, MF/CG) and two task-negative (PCC, vmPFC) regions sensitive to abstinence challenge. ROI masks were functionally defined using the main effect of memory load (controlling for condition) in a whole-brain repeated measures condition (smoking satiety, abstinence challenge) by memory load (N-back level) ANOVA.…”

“…In addition to reducing working memory performance (Mendrek et al, 2006;Myers et al, 2008), brief abstinence is associated with reduced working memory-related activation in the dorsolateral prefrontal cortex (DLPFC) and medial frontal/ cingulate gyrus (MF/CG; Falcone et al, 2014;Loughead et al, 2010), decreased working memory-related suppression of activity in regions within the default mode network (posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC); Beaver et al, 2011;Falcone et al, 2014;Loughead et al, 2010), and dysregulated inter-network functional connectivity during task performance and at rest (Jacobsen et al, 2007;Lerman et al, 2014;Sutherland et al, 2013). FDA-approved medications, such as varenicline and bupropion, can reverse abstinence-induced working memory deficits and related neural activation in studies of abstinent smokers tested during medication vs placebo Perkins et al, 2013).…”

Integrating Ecological Momentary Assessment and Functional Brain Imaging Methods: New Avenues for Studying and Treating Tobacco Dependence

“…For instance, several studies have demonstrated that brief abstinence from nicotine alters patterns of brain activation during the performance of effortful cognitive tasks (Froeliger, Modlin, Kozink, Wang, & McClernon, 2012;Kozink, Kollins, & McClernon, 2010;Kozink, Lutz, Rose, Froeliger, & McClernon, 2010;Sweet et al, 2010;Xu et al, 2005;Xu et al, 2006), and that these effects are moderated by age (Falcone et al, 2013), genotype (Loughead et al, 2009), and individual differences in performance (Nichols, Gates, Molenaar, & Wilson, 2013). More recently, fMRI has been used to characterize the mechanisms through which nicotine replacement therapy (Beaver et al, 2011;Cole et al, 2010) and other medications for the treatment of tobacco dependence (e.g., varenicline; Loughead et al, 2010) remediate withdrawal-related cognitive deficits.…”