Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not cognitive control: converging fMRI evidence from Go-Nogo and Flanker tasks

Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here, we examine the effects of nicotine dependence (trait; smokers versus non-smoking controls), and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of cognitive control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence and pharmacological manipulation. However, effects were driven entirely by conditions that required less cognitive control. When demand for cognitive control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task, or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus, findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

[1]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[2]  Robert West,et al.  Information on How to Cite Items within Roar@uel: Relapse to Smoking during Unaided Cessation: Clinical, Cognitive, and Motivational Predictors , 2022 .

[3]  Betty Jo Salmeron,et al.  Nicotine Abstinence Influences the Calculation of Salience in Discrete Insular Circuits. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[4]  E. Stein,et al.  Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial , 2017, JAMA psychiatry.

[5]  T. Lancaster,et al.  Nicotine receptor partial agonists for smoking cessation. , 2016, The Cochrane database of systematic reviews.

[6]  Thomas E. Nichols Notes on Creating a Standardized Version of DVARS , 2017, 1704.01469.

[7]  M. Munafo,et al.  The Neurobiology and Genetics of Nicotine and Tobacco , 2015, Current Topics in Behavioral Neurosciences.

[8]  S J Heishman,et al.  Effect of nicotine on brain activation during performance of a working memory task , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Nitsche,et al.  Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine , 2015, Psychopharmacology.

[10]  P. Kalivas The glutamate homeostasis hypothesis of addiction , 2009, Nature Reviews Neuroscience.

[11]  Liam Nestor,et al.  Differences in “bottom-up” and “top-down” neural activity in current and former cigarette smokers: Evidence for neural substrates which may promote nicotine abstinence through increased cognitive control , 2011, NeuroImage.

[12]  L. Elliot Hong,et al.  Individual differences in amygdala reactivity following nicotinic receptor stimulation in abstinent smokers , 2013, NeuroImage.

[13]  D. Veltman,et al.  Systematic review of ERP and fMRI studies investigating inhibitory control and error processing in people with substance dependence and behavioural addictions. , 2014, Journal of psychiatry & neuroscience : JPN.

[14]  Daniel J Fridberg,et al.  Neural correlates of performance monitoring in daily and intermittent smokers , 2014, Clinical Neurophysiology.

[15]  Giuseppe Atzori,et al.  Efficacy of a Nicotine (4 mg)-Containing Lozenge on the Cognitive Impairment of Nicotine Withdrawal , 2008, Journal of clinical psychopharmacology.

[16]  X. Geng,et al.  Large-scale functional neural network correlates of response inhibition: an fMRI meta-analysis , 2017, Brain Structure and Function.

[17]  B. Oken,et al.  Impulsivity and Stress Response in Nondependent Smokers (Tobacco Chippers) in Comparison to Heavy Smokers and Nonsmokers. , 2016, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[18]  J. Kaufman,et al.  Cingulate Hypoactivity in Cocaine Users During a GO-NOGO Task as Revealed by Event-Related Functional Magnetic Resonance Imaging , 2003, The Journal of Neuroscience.

[19]  N. Volkow,et al.  Neurocircuitry of Addiction , 2010, Neuropsychopharmacology.

[20]  Britta Hahn Nicotinic receptors and attention. , 2015, Current topics in behavioral neurosciences.

[21]  C. Lerman,et al.  Cognitive function during nicotine withdrawal: Implications for nicotine dependence treatment , 2014, Neuropharmacology.

[22]  E. Stein,et al.  Greater externalizing personality traits predict less error‐related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers , 2015, Addiction biology.

[23]  Betty Jo Salmeron,et al.  Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers , 2016, Neuropsychopharmacology.

[24]  Yang Yang,et al.  Neural Systems Underlying Emotional and Non-emotional Interference Processing: An ALE Meta-Analysis of Functional Neuroimaging Studies , 2016, Front. Behav. Neurosci..

[25]  Rachel Kozink,et al.  Smoking Withdrawal Modulates Right Inferior Frontal Cortex but not Presupplementary Motor Area Activation During Inhibitory Control , 2010, Neuropsychopharmacology.

[26]  E. Stein,et al.  Chronic Exposure to Nicotine Is Associated with Reduced Reward-Related Activity in the Striatum but not the Midbrain , 2012, Biological Psychiatry.

[27]  Edythe D London,et al.  Smoking Reduces Conflict-Related Anterior Cingulate Activity in Abstinent Cigarette Smokers Performing a Stroop Task , 2010, Neuropsychopharmacology.

[28]  D. Veltman,et al.  The role of dopamine in inhibitory control in smokers and non-smokers: A pharmacological fMRI study , 2013, European Neuropsychopharmacology.

[29]  N. Volkow,et al.  Neurobiologic Advances from the Brain Disease Model of Addiction. , 2016, The New England journal of medicine.

[30]  S. Eickhoff,et al.  Neuroscience and Biobehavioral Reviews Three Key Regions for Supervisory Attentional Control: Evidence from Neuroimaging Meta-analyses , 2022 .

[31]  E. Stein,et al.  Cognitive Mechanisms of Nicotine on Visual Attention , 2002, Neuron.

[32]  E. Stein,et al.  Networks Associated with Reward , 2016 .

[33]  Kathleen M. Gates,et al.  The first day is always the hardest: Functional connectivity during cue exposure and the ability to resist smoking in the initial hours of a quit attempt , 2017, NeuroImage.

[34]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[35]  N. Volkow,et al.  Neurobiology of addiction: a neurocircuitry analysis. , 2016, The lancet. Psychiatry.

[36]  C. Eriksen,et al.  Effects of noise letters upon the identification of a target letter in a nonsearch task , 1974 .

[37]  Donald W. Pfaff,et al.  Neuroscience in the 21st Century , 2013, Springer New York.

[38]  L. Tanoue Quitting Smoking Among Adults — United States, 2001–2010 , 2012 .

[39]  John R. Fedota,et al.  Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers , 2015, Neuropsychopharmacology.

[40]  Stephen M. Stahl,et al.  Rationale, pharmacology and clinical efficacy of partial agonists of α4β2 nACh receptors for smoking cessation , 2007 .

[41]  R. Chan,et al.  Effects of nicotine on response inhibition and interference control , 2017, Psychopharmacology.

[42]  J. Palca Nicotine addiction , 1988, Nature.

[43]  R. Mattick,et al.  Deficits in behavioural inhibition in substance abuse and addiction: a meta-analysis. , 2014, Drug and alcohol dependence.

[44]  Justin L. Vincent,et al.  Distinct brain networks for adaptive and stable task control in humans , 2007, Proceedings of the National Academy of Sciences.

[45]  E. Stein,et al.  Acute Nicotine Differentially Impacts Anticipatory Valence- and Magnitude-Related Striatal Activity , 2013, Biological Psychiatry.

[46]  Stephen M Stahl,et al.  Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. , 2007, Trends in pharmacological sciences.

[47]  Daniel M. Roberts,et al.  The N2 ERP component as an index of impaired cognitive control in smokers , 2014, Neuroscience Letters.

[48]  K. Kiehl,et al.  Neural correlates of response inhibition in current and former smokers , 2017, Behavioural Brain Research.

[49]  Britta Hahn,et al.  Performance effects of nicotine during selective attention, divided attention, and simple stimulus detection: an fMRI study. , 2009, Cerebral cortex.

[50]  E. Stein,et al.  Down-Regulation of Amygdala and Insula Functional Circuits by Varenicline and Nicotine in Abstinent Cigarette Smokers , 2013, Biological Psychiatry.

[51]  Adam R. Walczak,et al.  At the heart of the ventral attention system: The right anterior insula , 2009, Human brain mapping.

[52]  C. Bullen,et al.  Nicotine replacement therapy versus control for smoking cessation. , 2018, The Cochrane database of systematic reviews.

[53]  J. Pekar,et al.  Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent , 2008, Neuropsychologia.

[54]  Rita Z. Goldstein,et al.  Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. , 2002, The American journal of psychiatry.

[55]  M. Luijten,et al.  Deficits in Inhibitory Control in Smokers During a Go/NoGo Task: An Investigation Using Event-Related Brain Potentials , 2011, PloS one.