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1.  Smoking and the bandit: A preliminary study of smoker and non-smoker differences in exploratory behavior measured with a multi-armed bandit task 
Advantageous decision-making is an adaptive trade-off between exploring alternatives and exploiting the most rewarding option. This trade-off may be related to maladaptive decision-making associated with nicotine dependence; however, explore/exploit behavior has not been previously investigated in the context of addiction. The explore/exploit trade-off is captured by the multi-armed bandit task, in which different arms of a slot machine are chosen to discover the relative payoffs. The goal of this study was to preliminarily investigate whether smokers differ from non-smokers in their degree of exploratory behavior. Smokers (n = 18) and non-smokers (n = 17) completed a six-armed bandit task as well as self-report measures of behavior and personality traits. Smokers were found to exhibit less exploratory behavior (i.e. made fewer switches between slot machine arms) than non-smokers within the first 300 trials of the bandit task. The overall proportion of exploratory choices negatively correlated with self-reported measures of delay aversion and nonplanning impulsivity. These preliminary results suggest that smokers make fewer initial exploratory choices on the bandit task. The bandit task is a promising measure that could provide valuable insights into how nicotine use and dependence is associated with explore/exploit decision-making.
PMCID: PMC4028629  PMID: 23245198
exploration; exploitation; smoking; tobacco; multi-armed bandit task
2.  A Pilot Study of Lis-Dexamfetamine Dimesylate (LDX/SPD489) to Facilitate Smoking Cessation in Nicotine-Dependent Adults With ADHD 
Journal of attention disorders  2012;18(2):10.1177/1087054712440320.
The goal of this study was to assess the efficacy and tolerability of lis-dexamfetamine dimesylate (LDX) as an adjunct to nicotine replacement therapy in adult smokers with ADHD who were undergoing a quit attempt.
Thirty-two regular adult smokers with ADHD were randomized to receive LDX (n = 17) or placebo (n = 15) in addition to nicotine patch concurrent with a quit attempt.
There were no differences between smokers assigned to LDX versus placebo in any smoking outcomes. Participants treated with LDX demonstrated significant reductions in self-reported and clinician-rated ADHD symptoms. LDX was well tolerated in smokers attempting to quit.
In general, LDX does not facilitate smoking cessation in adults with ADHD more than does placebo, though both groups significantly reduced smoking. LDX demonstrated efficacy for reducing ADHD symptoms in adult smokers engaging in a quit attempt.
PMCID: PMC3421044  PMID: 22508760
adult ADHD; lis-dexamfetamine dimesylate; smoking
3.  Frontoparietal Attentional Network Activation Differs Between Smokers and Nonsmokers during Affective Cognition 
Psychiatry research  2012;211(1):57-63.
Smoking withdrawal-induced disruption of affect and cognition is associated with dysregulated prefrontal brain function although little is known regarding the neural foci of smoker-nonsmoker differences during affective cognition. Thus, the current study utilized fMRI to identify smoker-nonsmoker differences in affective cognition. Thirty-four healthy volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop task (aST). The aST includes emotional cue-reactivity trials, and response selection trials that contain either neutral or negative emotional distractors. Smokers had less activation during negative cue-reactivity trials in regions subserving emotional awareness (i.e. posterior cingulate), inhibitory control (i.e. inferior frontal gyrus) and conflict resolution (i.e. anterior cingulate); whereas during response selection trials with negative emotional distractors, smokers had greater activation in a frontoparietal attentional network (i.e. middle frontal and supramarginal gyri). Exploratory analyses revealed that task accuracy was positively correlated with ACC and IFG BOLD response. These findings suggests that chronic nicotine use may reduce inhibitory control and conflict resolution of emotional distraction, and result in recruiting additional attentional resources during emotional interference on cognition.
PMCID: PMC3557750  PMID: 23154092
nicotine; affect; emotion; fMRI; cue-reactivity
4.  Assessing the Role of Attention-Deficit/Hyperactivity Disorder Symptoms in Smokers With and Without Posttraumatic Stress Disorder 
Nicotine & Tobacco Research  2011;14(8):986-992.
Smoking prevalence among individuals with posttraumatic stress disorder (PTSD) is elevated relative to non–PTSD smokers, and there is evidence to suggest that affect regulation may be a motivation for smoking among those with this disorder. Previous studies have also indicated that (a) PTSD is frequently comorbid with attention-deficit/hyperactivity disorder (ADHD), (b) individuals with ADHD smoke at significantly higher rates than the general population, (c) subclinical ADHD symptoms are a risk factor for smoking, and (d) affect regulation is a motivation for smoking in ADHD. The goal of this study was to assess the degree to which ADHD symptoms were uniquely associated with smoking-related affective functioning (SRAF) variables above and beyond the variance already explained by PTSD symptoms.
Smokers with (n = 55) and without PTSD (n = 68) completed measures assessing PTSD symptoms, ADHD symptoms, and SRAF.
The PTSD group endorsed significantly more severe levels of DSM-IV inattentive and hyperactive–impulsive ADHD symptoms. A series of hierarchical regressions among the entire sample indicated that, after accounting for PTSD symptoms, ADHD symptoms were associated with lower positive affect, higher negative affect, higher emotion dysregulation, higher anxiety sensitivity, and higher urges to smoke to increase positive affect.
Taken together, these findings suggest that ADHD symptoms may increase affective dysregulation difficulties already faced by smokers, particularly those with PTSD, which may, in turn, confer increased risk for smoking relapse in those with higher levels of symptomatology of both disorders.
PMCID: PMC3439866  PMID: 22180583
5.  Association between smoking and retrospectively reported attention-deficit/hyperactivity disorder symptoms in a large sample of new mothers 
Nicotine & Tobacco Research  2009;11(3):313-322.
This study investigated the association between retrospectively reported attention-deficit/hyperactivity disorder (ADHD) symptoms experienced during childhood and five cigarette smoking–related outcomes in adulthood.
A large sample (N = 1,117) of new mothers participating in an ongoing longitudinal study completed retrospective reports of their childhood ADHD symptomatology, as well as concurrent and retrospective reports of their smoking behavior. Linear regression models tested the association between ADHD symptomatology and smoking outcomes.
Childhood ADHD symptomatology was predictive of the number of cigarettes smoked per day currently and during pregnancy, as well as the age at onset of smoking. We found nonlinear associations between hyperactive–impulsive symptoms and the number of cigarettes smoked per day in pregnancy, as well as between inattentive symptoms and the number of cigarettes smoked per day currently. Women who retrospectively reported intermediate levels of ADHD symptoms during their childhood reported smoking more cigarettes per day than women who reported low or high levels of ADHD symptoms during childhood. We also found multiplicative relationship between inattentive and hyperactive–impulsive symptoms, such that inattentive symptoms were predictive of an earlier age at smoking onset only when hyperactive–impulsive symptoms were low; moreover, the magnitude of this association was stronger for Black relative to White women.
These findings demonstrate the importance of considering differential effects of ADHD symptoms and smoking outcomes as a function of sex and race. They also represent a potentially indirect means through which women who have even a moderate childhood history of ADHD symptomatology may create a set of circumstances that compromise the health and well-being of their own children.
PMCID: PMC2666380  PMID: 19307443
6.  Effects of Postnatal Parental Smoking on Parent and Teacher Ratings of ADHD and Oppositional Symptoms 
To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners’ Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.
PMCID: PMC3678953  PMID: 19525745
ADHD; smoking; disruptive behavior; nicotine dependence
7.  24-hr smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum 
Psychopharmacology  2008;204(1):25-35.
Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.
In the present study we evaluated the effect of 24-hr smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI).
Eighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-hr abstinence (abstinent condition). During scanning they viewed blocks of photographic smoking and control cues.
Following abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA 19) and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In contrast, no smoking cue > control cue activations were observed following smoking as usual. Direct comparisons between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence. In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32) and supplementary motor area (BA 6).
The present findings indicate smoking abstinence significantly potentiates neural responses to smoking-related cues in brain regions subserving visual sensory processing, attention and action planning. Moreover, greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues which is consistent with incentive-motivation models of addiction.
PMCID: PMC2810714  PMID: 19107465
cue-reactivity; craving; nicotine dependence; fMRI; smoking; dorsal striatum
8.  Neuroimaging of Nicotine Dependence: Key Findings and Application to the Study of Smoking-Mental Illness Comorbidity 
Journal of dual diagnosis  2009;5(2):168-178.
Modern neuroimaging techniques offer the opportunity to non-invasively study neuroanatomical and neurofunctional correlates of nicotine dependence and its treatment. In the present review, the most widely used neuroimaging techniques—magnetic resonance imaging (MRI), positron emission tomography (PET) and functional MRI (fMRI)—are briefly described and their strengths and limitations discussed. The use of these techniques has resulted in new insights into the neuropharmacology of tobacco addiction. Studies comparing smokers and nonsmokers have shown that smokers have less grey matter density in frontal brain regions and greater concentrations of nicotinic receptors. Research on the effects of smoking a cigarette confirms that smoking leads to the release of dopamine in brain reward areas and to nicotinic receptor binding. Studies of smoking abstinence have identified functional brain correlates of increased reactivity to smoking-related cues, and worsening of concentration. To date, neuroimaging studies of nicotine dependence among individuals with mental illness have focused almost exclusively on schizophrenia. A conceptual/methodological framework for studying dual diagnosis using neuroimaging measures is provided with the aim of spurring additional research in this area.
PMCID: PMC2743422  PMID: 19756221
MRI; fMRI; PET; nicotine; smoking; nicotine dependence; ADHD; schizophrenia; dual diagnosis; comorbidity
9.  Smoking Abstinence and Depressive Symptoms Modulate the Executive Control System During Emotional Information Processing 
Addiction Biology  2011;17(3):668-679.
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 (EIP).
Smokers (n=17) and nonsmokers (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-hr 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.
PMCID: PMC3288802  PMID: 22081878
affect; cognition; depression; emotion; fMRI; smoking
10.  Sex, ADHD symptoms, and smoking outcomes: An integrative model 
Medical Hypotheses  2012;78(5):585-593.
Both females and individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) have been found to be at increased risk for a range of smoking outcomes, and recent empirical findings have suggested that women with ADHD may be particularly vulnerable to nicotine dependence. On a neurobiological level, the dopamine reward processing system may be implicated in the potentially unique interaction of nicotine with sex and with ADHD status. Specifically, nicotine appears to mitigate core ADHD symptoms through interaction with the dopamine reward processing system, and ovarian hormones have been found to interact with nicotine within the dopamine reward processing system to affect neurotransmitter release and functioning.
This article synthesizes data from research examining smoking in women and in individuals with ADHD to build an integrative model through which unique risk for cigarette smoking in women with ADHD can be systematically explored. Based upon this model, the following hypotheses are proposed at the intersection of each of the three variables of sex, ADHD, and smoking: 1) Individuals with ADHD have altered functioning of the dopamine reward system, which diminishes their ability to efficiently form conditioned associations based on environmental contingencies; these deficits are partially ameliorated by nicotine; 2) Nicotine interacts with estrogen and the dopamine reward system to increase the positive and negative reinforcement value of smoking in female smokers; 3) In adult females with ADHD, ovarian hormones interact with the dopamine reward system to exacerbate ADHD-related deficits in the capacity to form conditioned associations; and 4) During different phases of the menstrual cycle, nicotine and ovarian hormones may interact differentially with the dopamine reward processing system to affect the type and value of reinforcement smoking provides for women with ADHD.
Understanding the bio-behavioral mechanisms underlying cigarette addiction in specific populations will be critical to developing effectively tailored smoking prevention and cessation programs for these groups. Overall, the goal of this paper is to examine the interaction of sex, smoking, and ADHD status within the context of the dopamine reward processing system not only to elucidate potential mechanisms specific to female smokers with ADHD, but also to stimulate consideration of how the examination of such individual differences can inform our understanding of smoking more broadly.
PMCID: PMC3321070  PMID: 22341778
11.  A Preliminary Analysis of Interactions Between Genotype, Retrospective ADHD Symptoms, and Initial Reactions to Smoking in a Sample of Young Adults 
Nicotine & Tobacco Research  2011;14(2):229-233.
Initial reactions to cigarettes predict later regular smoking. Symptoms of attention deficit hyperactivity disorder (ADHD) have also been shown to increase smoking risk and may moderate the relationship between genotype and smoking. We conducted an exploratory study to assess whether ADHD symptoms interact with genetic variation to predict self-reported initial reactions to smoking.
Participants were a subsample of 1,900 unrelated individuals with genotype data drawn from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. Linear regression was used to examine relationships among self-reported ADHD symptoms, genotype, and self-reported initial reactions to cigarettes (index scores reflecting pleasant and unpleasant reactions).
Polymorphisms in the DRD2 gene, SLC6A4 gene, and among males, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting pleasant initial reaction to cigarettes. Polymorphisms in the CYP2A6 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting unpleasant initial reaction to cigarettes. No main effect for any of these polymorphisms was observed nor were any interactions with DRD4 and DAT genes.
These findings suggest that genotypes associated with monoamine neurotransmission interact with ADHD symptoms to influence initial reactions to cigarette smoking. Given that an initial pleasant reaction to cigarettes increases risk for lifetime smoking, these results add to a growing body of literature that suggests that ADHD symptoms increase risk for smoking and should be accounted for in genetic studies of smoking.
PMCID: PMC3265740  PMID: 21778150
12.  Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes 
Journal of Affective Disorders  2011;136(3):1126-1134.
Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD.
A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants.
During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group.
Replication with larger samples is needed.
Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenype as a marker of MDD risk.
PMCID: PMC3272083  PMID: 22036801
Major Depressive Disorder; Remission; Reward; Anhedonia; Anticipation; Magnetic Resonance Imaging
13.  Yoga Meditation Practitioners Exhibit Greater Gray Matter Volume and Fewer Reported Cognitive Failures: Results of a Preliminary Voxel-Based Morphometric Analysis 
Hatha yoga techniques, including physical postures (asanas), breathing exercises (pranayama), and meditation, involve the practice of mindfulness. In turn, yoga meditation practices may induce the state of mindfulness, which, when evoked recurrently through repeated practice, may accrue into trait or dispositional mindfulness. Putatively, these changes may be mediated by experience-dependent neuroplastic changes. Though prior studies have identified differences in gray matter volume (GMV) between long-term mindfulness practitioners and controls, no studies to date have reported on whether yoga meditation is associated with GMV differences. The present study investigated GMV differences between yoga meditation practitioners (YMP) and a matched control group (CG). The YMP group exhibited greater GM volume in frontal, limbic, temporal, occipital, and cerebellar regions; whereas the CG had no greater regional greater GMV. In addition, the YMP group reported significantly fewer cognitive failures on the Cognitive Failures Questionnaire (CFQ), the magnitude of which was positively correlated with GMV in numerous regions identified in the primary analysis. Lastly, GMV was positively correlated with the duration of yoga practice. Results from this preliminary study suggest that hatha yoga practice may be associated with the promotion of neuroplastic changes in executive brain systems, which may confer therapeutic benefits that accrue with repeated practice.
PMCID: PMC3525089  PMID: 23304217
14.  Smoking Withdrawal Symptoms Are More Severe Among Smokers With ADHD and Independent of ADHD Symptom Change: Results From a 12-Day Contingency-Managed Abstinence Trial 
Nicotine & Tobacco Research  2011;13(9):784-792.
Smokers with attention deficit hyperactivity disorder (ADHD) have greater difficulty quitting than those without ADHD, but preliminary data (McClernon, Kollins, Lutz, Fitzgerald, Murray, Redman, et al., 2008) suggest equivalent severity of withdrawal symptoms following brief abstinence. The objective of this study was to characterize the differential effects of intermediate term smoking abstinence on self-reported withdrawal and ADHD symptoms in adult smokers with and without ADHD.
Forty adult (50% female), nontreatment seeking moderate-to-heavy smokers with and without ADHD were enrolled in a 12-day quit study in which monetary incentives were provided for maintaining biologically verified abstinence. Self-reported withdrawal, mood, and ADHD symptoms were measured pre- and post-quitting.
ADHD and controls did not vary on smoking or demographic variables. Significant Group × Session interactions were observed across a broad range of withdrawal symptoms and were generally characterized by greater withdrawal severity among ADHD smokers, particularly during the first 5 days of abstinence. In addition, Group × Sex × Session interactions were observed for craving, somatic symptoms, negative affect, and habit withdrawal; these interactions were driven by greater withdrawal severity among females with ADHD. Group × Session interactions were not observed for ADHD symptom scales.
The results of this study suggest that smokers with ADHD, and ADHD females in particular, experience greater withdrawal severity during early abstinence—independent of effects on ADHD symptoms. Whereas additional research is needed to pinpoint mechanisms, our findings suggest that smoking cessation interventions targeted at smokers with ADHD should address their more severe withdrawal symptoms following quitting.
PMCID: PMC3203401  PMID: 21571687
15.  Understanding the Phenotypic Structure of Adult Retrospective ADHD Symptoms During Childhood in the United States 
Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous disorder, and the phenotypic structure comprising inattentive and hyperactive-impulsive type symptoms has been the focus of a growing body of recent research. Methodological studies are needed to better characterize phenotypes to advance research as well as clinical practice. A large U.S. population-based sample of young adults (N = 14,307, aged 17–28 years, 52.8% female) retrospectively reported their experiences of childhood ADHD symptoms. Factor analysis, latent class analysis, and factor mixture modeling of ADHD symptoms were compared to determine which underlying structure best fit the data. Fit statistics as well as substantive criteria compared models within and across model subtypes. Analyses supported a two-factor two-class structure for both male and female subjects. The two latent factors represented inattentive and hyperactive-impulsive symptom dimensions. The two latent classes divided people into a smaller affected class and a larger unaffected class. Individuals who reported having been diagnosed with ADHD were more likely to be in the affected class (OR male subjects = 4.03, 95% CI [2.65, 6.13]; OR female subjects = 5.65, 95% CI [3.15, 10.10]). This work aids in the understanding of ADHD symptomatology within the population; a majority of people experience very low symptom severity, whereas a minority of people experience high symptom severity. Within this high symptom group, however, variability in symptom experiences exists. Empirical models can be helpful in clarifying ADHD phenotypic structure that has the potential to advance research on the etiology and consequences of ADHD symptoms.
PMCID: PMC3354630  PMID: 22394329
16.  Monetary Incentives Promote Smoking Abstinence in Adults With Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with attention deficit hyperactivity disorder (ADHD) smoke at rates significantly higher than the general population and have more difficulty quitting than nondiagnosed individuals. Currently, there are no evidence-based approaches for reducing smoking specifically in individuals with ADHD. Adult regular smokers with or without ADHD participated in a study of extended smoking withdrawal where monetary incentives were used to promote abstinence. Participants were paid according to an escalating schedule for maintaining abstinence measured as self-report of no smoking and an expired air carbon monoxide (CO) level of ≤4 parts per million. Sixty-four percent (14/22) of smokers with ADHD and 50% (11/22) of smokers without ADHD maintained complete abstinence for the 2-week duration of the study. Twenty-two percent (5/22) and 9% (2/22) of smokers with ADHD and without ADHD, respectively, maintained continued abstinence for up to 10 days following the removal of the contingencies. Though abstinence rates were higher for the smokers with ADHD, the group differences were not statistically significant. Results suggest that monetary incentives may be a useful approach for promoting abstinence in adult smokers with ADHD, perhaps owing to altered reinforcement processes in these individuals.
PMCID: PMC3354633  PMID: 20545386
ADHD; smoking; nicotine dependence; contingency management
17.  Cognitive enhancers for the treatment of ADHD 
Attention-deficit hyperactivity disorder (ADHD) is associated with multiple cognition-related phenotypic features in both children and adults. This review aims to clarify the role of cognition in ADHD and how prevailing treatments, which are often highly effective at reducing the clinical symptoms of the disorder, fare in modulating ADHD-related cognitive processes. First, we consider how the broad construct of cognition can be conceptualized in the context of ADHD. Second, we review the available evidence for how a range of both pharmacological and non-pharmacological interventions have fared with respect to enhancing cognition in individuals affected by this pervasive disorder. Findings from the literature suggest that the effects across a broad range of pharmacological and non-pharmacological interventions on the characteristic symptoms of ADHD can be distinguished from their effects on cognitive impairments. As such the direct clinical relevance of cognition enhancing effects of different interventions is somewhat limited. Recommendations for future research are discussed, including the identification of cognition-related end ophenotypes, the refinement of the ADHD clinical phenotype, and studying the difference between acute and chronic treatment regimens.
PMCID: PMC3353150  PMID: 21596055
ADHD; Cognition; Pharmacological treatment
18.  The Effect of Nicotine and Trauma Context on Acoustic Startle in Smokers with and without Posttraumatic Stress Disorder 
Psychopharmacology  2010;215(2):379-389.
Exaggerated startle response is a prominent feature of posttraumatic stress disorder (PTSD) although results examining differences in the acoustic startle response (ASR) between those with and without PTSD are mixed. One variable that may affect ASR among persons with PTSD is smoking. Individuals with PTSD are more likely to smoke and have greater difficulty quitting smoking. While smokers with PTSD report that smoking provides significant relief of negative affect and PTSD symptoms, the effects of smoking or nicotine deprivation on startle reactivity among smokers with PTSD are unknown.
The purpose of the current study were to: 1) examine baseline acoustic startle response (ASR) in smokers with and without PTSD under conditions of overnight abstinence; 2) evaluate the effect of smoking on ASR; and 3) evaluate the contextual effects of trauma versus neutral script presentations.
ASR was measured among 48 smokers with and without PTSD in the context of a 2 (Group: PTSD vs. non-PTSD) X 2 (Context: trauma vs. neutral) X 3 (Smoking Condition: usual brand cigarette vs. denicotinized cigarette vs. no smoking) design.
Effects of modest size indicated: 1) PTSD participants demonstrated higher ASR; 2) compared to non-PTSD participants, PTSD participants reported greater negative affect following a trauma related script; and 3) following a trauma related script and smoking a usual brand cigarette, PTSD participants demonstrated higher ASR.
Although many smokers with PTSD report that smoking reduces PTSD symptoms, results suggest that smoking may actually potentiate or maintain an exaggerated startle response.
PMCID: PMC3270823  PMID: 21188354
Acoustic Startle Response; posttraumatic stress disorder; nicotine; cigarette smoking
19.  Meditation-State Functional Connectivity (msFC): Strengthening of the Dorsal Attention Network and Beyond 
Meditation practice alters intrinsic resting-state functional connectivity (rsFC) in the default mode network (DMN). However, little is known regarding the effects of meditation on other resting-state networks. The aim of current study was to investigate the effects of meditation experience and meditation-state functional connectivity (msFC) on multiple resting-state networks (RSNs). Meditation practitioners (MPs) performed two 5-minute scans, one during rest, one while meditating. A meditation naïve control group (CG) underwent one resting-state scan. Exploratory regression analyses of the relations between years of meditation practice and rsFC and msFC were conducted. During resting-state, MP as compared to CG exhibited greater rsFC within the Dorsal Attention Network (DAN). Among MP, meditation, as compared to rest, strengthened FC between the DAN and DMN and Salience network whereas it decreased FC between the DAN, dorsal medial PFC, and insula. Regression analyses revealed positive correlations between the number of years of meditation experience and msFC between DAN, thalamus, and anterior parietal sulcus, whereas negative correlations between DAN, lateral and superior parietal, and insula. These findings suggest that the practice of meditation strengthens FC within the DAN as well as strengthens the coupling between distributed networks that are involved in attention, self-referential processes, and affective response.
PMCID: PMC3320106  PMID: 22536289
20.  Neurocognitive correlates of the effects of yoga meditation practice on emotion and cognition: a pilot study 
Mindfulness meditation involves attending to emotions without cognitive fixation of emotional experience. Over time, this practice is held to promote alterations in trait affectivity and attentional control with resultant effects on well-being and cognition. However, relatively little is known regarding the neural substrates of meditation effects on emotion and cognition. The present study investigated the neurocognitive correlates of emotion interference on cognition in Yoga practitioners and a matched control group (CG) underwent fMRI while performing an event-related affective Stroop task. The task includes image viewing trials and Stroop trials bracketed by neutral or negative emotional distractors. During image viewing trials, Yoga practitioners exhibited less reactivity in right dorsolateral prefrontal cortex (dlPFC) to negative as compared to neutral images; whereas the CG had the opposite pattern. A main effect of valence (negative > neutral) was observed in limbic regions (e.g., amygdala), of which the magnitude was inversely related to dlPFC activation. Exploratory analyses revealed that the magnitude of amygdala activation predicted decreased self-reported positive affect in the CG, but not among Yoga practitioners. During Stroop trials, Yoga practitioners had greater activation in ventrolateral prefrontal cortex (vlPFC) during Stroop trials when negative, compared to neutral, emotional distractor were presented; the CG exhibited the opposite pattern. Taken together, these data suggest that though Yoga practitioners exhibit limbic reactivity to negative emotional stimuli, such reactivity does not have downstream effects on later mood state. This uncoupling of viewing negative emotional images and affect among Yoga practitioners may be occasioned by their selective implementation of frontal executive-dependent strategies to reduce emotional interference during competing cognitive demands and not during emotional processing per se.
PMCID: PMC3405281  PMID: 22855674
mindfulness; fMRI; emotion-cognition
21.  Smoking Withdrawal Modulates Right Inferior Frontal Cortex but not Presupplementary Motor Area Activation During Inhibitory Control 
Neuropsychopharmacology  2010;35(13):2600-2606.
Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of this study was to investigate the neural basis of these effects in critical substrates of IC—right inferior frontal cortex (rIFC) and presupplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-h smoking abstinence. During scanning they completed a Go/No-Go task that required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1 vs 24.8% in the satiated condition, p<0.001) while having no effects on GO trial accuracy or reaction time (RT). In rIFC, smoking abstinence was associated with a significantly increased event-related BOLD signal (p=0.026). Pre-SMA was unaffected by smoking condition. The results of this preliminary study suggest that successful IC during withdrawal is associated with increased processing demands on a cortical center associated with attention to inhibitory signals.
PMCID: PMC2978758  PMID: 20861830
inhibitory control; smoking; fMRI; withdrawal; inferior frontal cortex; pre-supplementary motor area; Addiction & Substance Abuse; Psychiatry & Behavioral Sciences; Cognition; Psychopharmacology; inhibitory control; smoking, fMRI; withdrawal; inferior frontal cortex; presupplementary motor area
22.  Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition 
Addiction biology  2010;15(4):480-490.
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-hr 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 the smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across disperse 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.
Smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control (Braver et al., 2009) to more disperse and transient activation reflecting reactive control.
PMCID: PMC2996612  PMID: 21040240
attention; fMRI; mixed-design; nicotine dependence; prefrontal cortex; smoking
23.  “Bringing the real world into the laboratory: Personal smoking and nonsmoking environments” 
Drug and alcohol dependence  2010;111(1-2):58-63.
Pictorial representations of specific environments related to smoking can evoke robust craving to smoke, even in the absence of any proximal cues to smoke (e.g., cigarettes, lighters.) To evaluate the salience of smoking environment cues, we developed a novel procedure for bringing smokers’ real world smoking and nonsmoking environments into the laboratory to compare them with standard (i.e. not personalized) environments within a cue-reactivity paradigm. Seventy-two smokers used digital cameras to take pictures of the environments in which they do and do not smoke. They then completed a cue-reactivity session during which they viewed and rated pictures of smoking and nonsmoking environments, half personal and half standard, all devoid of proximal smoking cues. As hypothesized, personal environments led to a significantly larger smoking-nonsmoking difference in craving, compared with the standard environments. Personalization also enhanced stimuli vividness, relevance, positive affect, and excitement, as well as heart rate changes from baseline. Implications of these findings for exposure-based research and treatment for addiction, as well as other psychological disorders, are discussed.
PMCID: PMC2930143  PMID: 20510552
tobacco; cue reactivity; context; conditioning
24.  Smoking withdrawal modulates right inferior frontal cortex but not pre-supplementary motor area activation during inhibitory control 
Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of the current study was to investigate the neural basis of these effects in critical substrates of IC—right inferior frontal cortex (rIFC) and pre-supplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-hrs smoking abstinence. During scanning they completed a Go/No-Go task which required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1% versus 24.8% in satiated condition, p<.001) while having no effects on GO trial accuracy or reaction time (RT). In rIFC, smoking abstinence was associated with significantly increased event-related BOLD signal (p=.026). Pre-SMA was unaffected by smoking condition. The results of this preliminary study suggest that successful IC during withdrawal is associated with increased processing demands on a cortical center associated with attention to inhibitory signals.
PMCID: PMC2978758  PMID: 20861830
inhibitory control; smoking; fMRI; withdrawal; inferior frontal cortex; presupplementary motor area
25.  Proximal Versus Distal Cues to Smoke: The Effects of Environments on Smokers’ Cue-Reactivity 
Smokers are highly reactive to smoking-related cues that are directly linked, or most proximal, to actual smoking behavior (e.g., lit cigarettes). However, over the course of smoking, proximal cues may not be the only stimuli to become strongly associated with smoking. Distal cues, such as the environments in which smoking occurs (e.g., bar) might also gain associative properties and come to evoke robust reactivity from smokers. To test this, a pilot study was first conducted to develop standard pictorial stimuli of smoking and nonsmoking environments, all of which were completely devoid of proximal smoking cues. A comparison set of smoking and nonsmoking proximal cues was then created. Using the 12 total pictorial cues developed, 62 adult smokers participated in a cue-reactivity study during which they viewed and rated pictorial smoking and nonsmoking environment and proximal cues. Results demonstrate that, similar to proximal cues, environments associated with smoking can alone function as stimuli capable of evoking strong subjective reactivity from smokers. This work supports a broader conceptualization of drug-related cues in cue-based research and treatment development that includes proximal and distal cues as distinct categories.
PMCID: PMC2963185  PMID: 18540780
craving; cue reactivity; proximal and distal stimuli; environments; smoking

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