Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition.
ABSTRACT: Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated. Twenty adult smokers underwent functional magnetic resonance imaging scans following smoking as usual and after 24-hours abstinence. During scanning they completed a SA task with two levels of task difficulty, designed to measure both sustained (i.e. over the duration of the task) and transient (i.e. event-related) activation. Smoking abstinence significantly decreased task accuracy regardless of task difficulty. Compared to smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across dispersed cortical areas including precuneus and right superior frontal gyrus. Greater task difficulty was associated with even greater transient activation during abstinence in mostly right hemisphere regions including right inferior frontal gyrus. These findings suggest smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control (Braver, Gray & Burgess 2009) to more dispersed and transient activation reflecting reactive control.
Project description:Smoking withdrawal negatively impacts inhibitory control, and these effects are greater for smokers with preexisting attention problems, such as attention deficit/hyperactivity disorder (ADHD). The current study preliminarily evaluated changes in inhibitory control-related behavior and brain activation during smoking withdrawal among smokers with ADHD. Moreover, we investigated the role of catecholamine transmission in these changes by examining the effects of 40 mg methylphenidate (MPH) administration. Adult daily smokers with (n=17) and without (n=20) ADHD completed fMRI scanning under each of three conditions: (a) smoking as usual+placebo; (b) 24 h smoking abstinence+placebo and (c) 24 h smoking abstinence+MPH. Scan order was randomized and counterbalanced. Participants completed a modified Go/No-Go task to assess both sustained and transient inhibitory control. Voxelwise analysis of task-related BOLD signal revealed a significant group-by-abstinence interaction in occipital/parietal cortex during sustained inhibition, with greater abstinence-induced decreases in activation observed among ADHD smokers compared with non-ADHD smokers. Changes in behavioral performance during abstinence were associated with changes in activation in regions of occipital and parietal cortex and bilateral insula during sustained inhibition in both groups. MPH administration improved behavioral performance and increased sustained inhibitory control-related activation for both groups. During transient inhibition, MPH increased prefrontal activation for both groups and increased striatal activation only among ADHD smokers. These preliminary findings suggest that abstinence-induced changes in catecholamine transmission in visual attention areas (eg, occipital and superior parietal cortex) may be associated with inhibitory control deficits and contribute to smoking vulnerability among individuals with ADHD.
Project description:Smoking abstinence disrupts affective and cognitive processes. In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing. Smokers (n = 17) and non-smokers (n = 18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task-irrelevant distractors. Smokers completed two sessions: once following 24-hour abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self-reported negative affect influences brain response to images and targets. Exploratory regression analyses examined relations between baseline depressive symptoms and smoking state on brain function. Smoking state affected response to target detection in the right inferior frontal gyrus (IFG). During satiety, activation was greater in response to targets following negative versus neutral distractors; following abstinence, the reverse was observed. Withdrawal-related negative affect was associated with right insula activation to negative images. Finally, depression symptoms were associated with abstinence-induced hypoactive response to negative emotional distractors and task-relevant targets following negative distractors in frontal brain regions. Neural processes related to novelty detection/attention in the right IFG may be disrupted by smoking abstinence and negative stimuli. Reactivity to emotional stimuli and the interfering effects on cognition are moderated by the magnitude of smoking state-dependent negative affect and baseline depressive symptoms.
Project description:Among nicotine-dependent smokers, smoking abstinence disrupts multiple cognitive and affective processes including conflict resolution and emotional information processing (EIP). However, the neurobiological basis of abstinence effects on resolving emotional interference on cognition remains largely uncharacterized. In this study, functional magnetic resonance imaging (fMRI) was used to investigate smoking abstinence effects on emotion-cognition interactions.Smokers (n?=?17) underwent fMRI while performing an affective Stroop task (aST) over two sessions: once following 24-h abstinence and once following smoking as usual. The aST includes trials that serially present incongruent or congruent numerical grids bracketed by neutral or negative emotional distractors and view-only emotional image trials. Statistical analyses were conducted using a statistical threshold of p?<?0.05 cluster corrected.Smoking abstinence increased Stroop blood-oxygenation-level-dependent response in the right middle frontal and rostral anterior cingulate gyri. Moreover, withdrawal-induced negative affect was associated with less activation in frontoparietal regions during negative emotional information processing; whereas, during Stroop trials, negative affect predicted greater activation in frontal regions during negative, but not neutral emotional distractor trials.Hyperactivation in the frontal executive control network during smoking abstinence may represent a need to recruit additional executive resources to meet task demands. Moreover, abstinence-induced negative affect may disrupt cognitive control neural circuitry during EIP and place additional demands on frontal executive neural resources during cognitive demands when presented with emotionally distracting stimuli.
Project description:Relapse to smoking after initial abstinence is a major clinical challenge with significant public health consequences. At the brain and behavioral level, those who relapse to tobacco smoking have both greater cue-reactivity and lower inhibitory control than those who remain abstinent. Little is known about neural activation during inhibitory control tasks in the presence of drug-related cues. In the current study, tobacco smokers (SMK; n = 22) and non-smoking controls (CON; n = 19) completed a Go/NoGo task involving smoking cues during a functional magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were required to quit smoking, and maintenance of abstinence was evaluated as part of a 12-week smoking cessation trial. We evaluated pre-cessation brain activity during NoGo trials in smokers who were versus were not able to quit smoking. We then compared fMRI and inhibitory control measures between smokers and non-smokers. We did not find differences between SMK and CON in performance or activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK who attained biochemically-validated abstinence at the end of the smoking cessation trial had greater neural activation in the anterior insula during NoGo trials specifically with smoking-related cues. Results indicate that within SMK, decreased inhibitory control activation during direct exposure to drug-related stimuli may be a marker of difficulty quitting and relapse vulnerability.
Project description:Endogenous homeostatic mechanisms can restore normal neuronal function following cocaine-induced neuroadaptations. Such mechanisms may be exploited to develop novel therapies for cocaine addiction, but a molecular target has not yet been identified. Here we profiled mouse gene expression during early and late cocaine abstinence to identify putative regulators of neural homeostasis. Cocaine activated the transcription factor, Nr4a1, and its target gene, Cartpt, a key molecule involved in dopamine metabolism. Sustained activation of Cartpt at late abstinence was coupled with depletion of the repressive histone modification, H3K27me3, and enrichment of activating marks, H3K27ac and H3K4me3. Using both CRISPR-mediated and small molecule Nr4a1 activation, we demonstrate the direct causal role of Nr4a1 in sustained activation of Cartpt and in attenuation of cocaine-evoked behavior. Our findings provide evidence that targeting abstinence-induced homeostatic gene expression is a potential therapeutic target in cocaine addiction. Overall design: mRNA profiles of mice undergo cocaine SA were generated by deep sequencing, in six replicates, using Hiseq 4000
Project description:Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia.A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26).Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia.Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia.
Project description:As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after 3 days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1-10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11-13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15-21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p=0.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments.
Project description:Most women who quit smoking during pregnancy will relapse postpartum. Interventions for sustained postpartum abstinence can benefit from understanding prenatal characteristics associated with treatment response. Given that individuals with psychiatric disorders or elevated depressive symptoms have difficulty quitting smoking and that increases in depressive symptoms prenatally are common, we examined the relevance of psychiatric diagnoses, prenatal depressive symptoms, and stress to postpartum relapse prevention intervention response.Pregnant women (N = 300) who quit smoking during pregnancy received intervention (with specialized focus on mood, weight, and stress [STARTS] or a comparison [SUPPORT]) to prevent postpartum relapse. As previously published, nearly one-third and one-quarter of women achieved biochemically-confirmed sustained abstinence at 24- and 52-weeks postpartum, with no difference in abstinence rates between the interventions. Women completed psychiatric interviews and questionnaires during pregnancy. Smoking was assessed in pregnancy, and 24- and 52-weeks postpartum.Psychiatric disorders did not predict sustained abstinence or treatment response. However, treatment response was moderated by end-of-pregnancy depressive symptoms (χ2 = 9.98, p = .002) and stress (χ2 = 6.90, p = .01) at 24- and 52-weeks postpartum and remained significant after including covariates. Women with low distress achieved higher abstinence rates in SUPPORT than in STARTS (37% vs. 19% for depressive symptoms; 36% vs. 19% for stress), with no difference for women with high symptoms.Prenatal depressive symptoms and stress predicted differential treatment efficacy in women with low symptoms, not in women with high symptoms. Diagnostic history did not predict treatment differences. Future research to address prenatal distress may help tailor postpartum relapse prevention interventions.We examined prenatal history of psychiatric disorders and psychiatric distress as moderators of response to postpartum smoking relapse prevention intervention that either included or did not include added content on mood, stress, and weight concerns. For women with lower psychiatric distress, the added focus is not necessary, as these women achieved greater sustained abstinence in the less-intensive treatment. Understanding which women need which level of care to sustain abstinence can help allocate resources for all postpartum former smokers. These findings underscore the importance of perinatal symptom monitoring and promoting behavioral health more broadly in pregnant and postpartum women.
Project description:It has been hypothesized that neural reactivity to drug cues in certain limbic/paralimbic regions of the brain is an indicator of addiction severity and a marker for likelihood of success in treatment. To address this question, in the current study, 32 participants (44 percent female) completed a functional magnetic resonance imaging cigarette cue exposure paradigm 2 hours after smoking, and then enrolled in a 9-week smoking cessation treatment program. Neural activation to smoking cues was measured in five a priori defined limbic/paralimbic regions previously implicated with cue reactivity across substances. These included regions of the ventral striatum, anterior cingulate cortex and amygdala. Cox proportional hazard modeling was conducted to predict the number of days to first smoking lapse by using neural activation in these regions. Greater neural activation during pre-treatment exposure to smoking cues in the right ventral striatum, the left amygdala, and the anterior cingulate was associated with longer periods of abstinence following cessation. A similar pattern was present for continuous abstinence for the full duration of treatment. While baseline levels of nicotine dependence were strongly associated with treatment outcome, activation in the right ventral striatum predicted duration of abstinence beyond level of nicotine dependence. These results suggest that pre-treatment reactivity to smoking cues in areas associated with cue reactivity may be associated with successfully maintaining abstinence during treatment. This is consistent with models that propose that as addiction becomes more severe, motivational processing shifts from regions that subserve reward salience and learning to regions responsible motor behavior and habit learning.
Project description:The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained attentional control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, this transient component relies on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts.