ADHD, Smoking Withdrawal, and Inhibitory Control: Results of a Neuroimaging Study with Methylphenidate Challenge

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.

[1]  Russell A. Poldrack,et al.  Engagement of large-scale networks is related to individual differences in inhibitory control , 2010, NeuroImage.

[2]  L. Hawk,et al.  Effects of smoking abstinence on impulsive behavior among smokers high and low in ADHD-like symptoms , 2011, Psychopharmacology.

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

[4]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

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

[6]  C. Green,et al.  Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial. , 2010, The Journal of clinical psychiatry.

[7]  Rachel Kozink,et al.  Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability , 2017, JAMA psychiatry.

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

[9]  Frank Telang,et al.  Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. , 2007, Archives of general psychiatry.

[10]  F. J. McClernon,et al.  Effects of smoking abstinence on smoking-reinforced responding, withdrawal, and cognition in adults with and without attention deficit hyperactivity disorder , 2013, Psychopharmacology.

[11]  F. J. McClernon,et al.  Smoking abstinence and neurocognition: implications for cessation and relapse. , 2015, Current topics in behavioral neurosciences.

[12]  Andrew Zalesky,et al.  Altered Functional Brain Connectivity in a Non-Clinical Sample of Young Adults with Attention-Deficit/Hyperactivity Disorder , 2012, The Journal of Neuroscience.

[13]  Richard E. Carson,et al.  Clinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo , 2010, Biological Psychiatry.

[14]  T. Fukuda The world federation of societies of biological psychiatry , 1995, Biological Psychiatry.

[15]  E. Willcutt The Prevalence of DSM-IV Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review , 2012, Neurotherapeutics.

[16]  John A. Dani,et al.  Withdrawal from Chronic Nicotine Exposure Alters Dopamine Signaling Dynamics in the Nucleus Accumbens , 2012, Biological Psychiatry.

[17]  Bart Rypma,et al.  White matter tract integrity predicts visual search performance in young and older adults , 2012, Neurobiology of Aging.

[18]  Miao‐kun Sun,et al.  Trends in cognitive sciences , 2012 .

[19]  F. J. McClernon,et al.  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. , 2011, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[20]  R. Halari,et al.  A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with Attention Deficit Hyperactivity Disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention , 2012, Cortex.

[21]  R. Barkley Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. , 1997, Psychological bulletin.

[22]  Maurizio Fava,et al.  Neural Substrates of Attentional Bias for Smoking-Related Cues: An fMRI Study , 2010, Neuropsychopharmacology.

[23]  Yu-Shin Ding,et al.  Imaging the Effects of Methylphenidate on Brain Dopamine: New Model on Its Therapeutic Actions for Attention-Deficit/Hyperactivity Disorder , 2005, Biological Psychiatry.

[24]  Mei-Chen Hu,et al.  Divergence by ADHD subtype in smoking cessation response to OROS-methylphenidate. , 2011, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[25]  Andrew T. Morgan,et al.  Behavioral/systems/cognitive Striatal Dopamine D 2 /d 3 Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans Impulsive Behavior Is Thought to Reflect a Traitlike Characteristic That Can Have Broad Consequences for an Individual's Success and Well-be , 2022 .

[26]  J. Swanson,et al.  Evaluating dopamine reward pathway in ADHD: clinical implications. , 2009, JAMA.

[27]  W. Pelham,et al.  Childhood predictors of adolescent substance use in a longitudinal study of children with ADHD. , 2003, Journal of abnormal psychology.

[28]  Hiroki M. Morimoto,et al.  Functional dissociation in right inferior frontal cortex during performance of go/no-go task. , 2009, Cerebral cortex.

[29]  Kazunori Sato,et al.  The Human Prefrontal and Parietal Association Cortices Are Involved in NO-GO Performances: An Event-Related fMRI Study , 2002, NeuroImage.

[30]  G H Glover,et al.  Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  V. Glauche,et al.  Visual cortex abnormalities in adults with ADHD: A structural MRI study , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[32]  R. Kessler,et al.  The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. , 2006, The American journal of psychiatry.

[33]  F. J. McClernon,et al.  A Pilot Study of Lis-Dexamfetamine Dimesylate (LDX/SPD489) to Facilitate Smoking Cessation in Nicotine-Dependent Adults With ADHD , 2014, Journal of attention disorders.

[34]  E. Bullmore,et al.  Neuroanatomical Abnormalities and Cognitive Impairments Are Shared by Adults with Attention-Deficit/Hyperactivity Disorder and Their Unaffected First-Degree Relatives , 2014, Biological Psychiatry.

[35]  C. Pomerleau,et al.  Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. , 1995, Journal of substance abuse.

[36]  T. Moore,et al.  CONTROL OF VISUAL CORTICAL SIGNALS BY PREFRONTAL DOPAMINE , 2011, Nature.

[37]  R. Poldrack,et al.  Common neural substrates for inhibition of spoken and manual responses. , 2008, Cerebral cortex.

[38]  A. Kelley,et al.  Methylphenidate Preferentially Increases Catecholamine Neurotransmission within the Prefrontal Cortex at Low Doses that Enhance Cognitive Function , 2006, Biological Psychiatry.

[39]  Robert West,et al.  Relapse to smoking during unaided cessation: clinical, cognitive and motivational predictors , 2010, Psychopharmacology.

[40]  F. J. McClernon,et al.  Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes , 2015, Neuropsychopharmacology.

[41]  Hinderk M. Emrich,et al.  Neuronal correlates of ADHD in adults with evidence for compensation strategies – a functional MRI study with a Go/No-Go paradigm , 2010, German medical science : GMS e-journal.

[42]  F. Xavier Castellanos,et al.  Large-scale brain systems in ADHD: beyond the prefrontal–striatal model , 2012, Trends in Cognitive Sciences.

[43]  S. Shiffman,et al.  Smoking withdrawal symptoms in two weeks of abstinence , 1976, Psychopharmacology.

[44]  J. Pruessner,et al.  Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate , 2008, Current neuropharmacology.

[45]  Marlene Behrmann,et al.  Visuotopic Cortical Connectivity Underlying Attention Revealed with White-Matter Tractography , 2012, The Journal of Neuroscience.

[46]  S. Hall,et al.  Preliminary evidence of the association between the history of childhood attention-deficit/hyperactivity disorder and smoking treatment failure. , 2005, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[47]  Yong He,et al.  Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood. , 2011, Archives of general psychiatry.

[48]  F. J. McClernon,et al.  Sex, ADHD symptoms, and smoking outcomes: an integrative model. , 2012, Medical hypotheses.

[49]  H. Hart,et al.  Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. , 2013, JAMA psychiatry.

[50]  F. J. McClernon,et al.  Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study , 2008, Psychopharmacology.

[51]  S. Faraone,et al.  ADHD is associated with early initiation of cigarette smoking in children and adolescents. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[52]  J. Huston,et al.  Dopamine activity in the occipital and temporal cortices of rats: Dissociating effects of sensory but not pharmacological stimulation , 2007, Synapse.

[53]  David J. Madden,et al.  Brain Connectivity and Visual Attention , 2013, Brain Connect..

[54]  F. J. McClernon,et al.  ADHD and Smoking , 2008, Annals of the New York Academy of Sciences.