Common and distinct neural targets of treatment: Changing brain function in substance addiction

Neuroimaging offers an opportunity to examine the neurobiological effects of therapeutic interventions for human drug addiction. Using activation likelihood estimation, the aim of the current meta-analysis was to quantitatively summarize functional neuroimaging studies of pharmacological and cognitive-based interventions for drug addiction, with an emphasis on their common and distinct neural targets. More exploratory analyses also contrasted subgroups of studies based on specific study and sample characteristics. The ventral striatum, a region implicated in reward, motivation, and craving, and the inferior frontal gyrus and orbitofrontal cortex, regions involved in inhibitory control and goal-directed behavior, were identified as common targets of pharmacological and cognitive-based interventions; these regions were observed when the analysis was limited to only studies that used established or efficacious interventions, and across imaging paradigms and types of addictions. Consistent with theoretical models, cognitive-based interventions were additionally more likely to activate the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in self-referential processing, cognitive control, and attention. These results suggest that therapeutic interventions for addiction may target the brain structures that are altered across addictions and identify potential neurobiological mechanisms by which the tandem use of pharmacological and cognitive-based interventions may yield synergistic or complementary effects. These findings could inform the selection of novel functional targets in future treatment development for this difficult-to-treat disorder.

[1]  J. Kaiser,et al.  Functional neuroimaging studies in addiction: Multisensory drug stimuli and neural cue reactivity , 2012, Neuroscience & Biobehavioral Reviews.

[2]  K. Zilles,et al.  Coordinate‐based activation likelihood estimation meta‐analysis of neuroimaging data: A random‐effects approach based on empirical estimates of spatial uncertainty , 2009, Human brain mapping.

[3]  Rita Z. Goldstein,et al.  Enhanced midbrain response at 6‐month follow‐up in cocaine addiction, association with reduced drug‐related choice , 2012, Addiction biology.

[4]  Brian L. Burke,et al.  The efficacy of motivational interviewing: a meta-analysis of controlled clinical trials. , 2003, Journal of consulting and clinical psychology.

[5]  Simon B Eickhoff,et al.  Investigating the Functional Heterogeneity of the Default Mode Network Using Coordinate-Based Meta-Analytic Modeling , 2009, The Journal of Neuroscience.

[6]  Rajita Sinha,et al.  Cue-Induced Brain Activity Changes and Relapse in Cocaine-Dependent Patients , 2006, Neuropsychopharmacology.

[7]  D. Meier,et al.  Insula-Specific 1H Magnetic Resonance Spectroscopy Reactions in Heavy Smokers under Acute Nicotine Withdrawal and after Oral Nicotine Substitution , 2012, European Addiction Research.

[8]  Mark B Powers,et al.  A meta-analytic review of psychosocial interventions for substance use disorders. , 2008, The American journal of psychiatry.

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

[10]  E. Murray,et al.  The amygdala and reward , 2002, Nature Reviews Neuroscience.

[11]  N. Volkow,et al.  The neural basis of addiction: a pathology of motivation and choice. , 2005, The American journal of psychiatry.

[12]  T. Robbins Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[13]  M. Buonocore,et al.  Methamphetamine users in sustained abstinence: a proton magnetic resonance spectroscopy study. , 2005, Archives of general psychiatry.

[14]  Mark Slifstein,et al.  Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment. , 2011, The American journal of psychiatry.

[15]  A. Dickinson,et al.  Parallel and interactive learning processes within the basal ganglia: Relevance for the understanding of addiction , 2009, Behavioural Brain Research.

[16]  C. Thiel,et al.  Functional brain imaging of nicotinic effects on higher cognitive processes. , 2011, Biochemical pharmacology.

[17]  Jochen Kaiser,et al.  Sensory and motor aspects of addiction , 2010, Behavioural Brain Research.

[18]  Sara E. Morrison,et al.  Representations of appetitive and aversive information in the primate orbitofrontal cortex , 2011, Annals of the New York Academy of Sciences.

[19]  A. Bonci,et al.  Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation , 2012, Neuropsychopharmacology.

[20]  D. Linden,et al.  How psychotherapy changes the brain – the contribution of functional neuroimaging , 2006, Molecular Psychiatry.

[21]  B. Everitt,et al.  Direct Interactions between the Basolateral Amygdala and Nucleus Accumbens Core Underlie Cocaine-Seeking Behavior by Rats , 2004, The Journal of Neuroscience.

[22]  D. Veltman,et al.  Neuroscience and Biobehavioral Reviews Effects of Non-invasive Neurostimulation on Craving: a Meta-analysis , 2022 .

[23]  N. Volkow,et al.  Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications , 2011, Nature Reviews Neuroscience.

[24]  M. Mandelkern,et al.  Smoking-induced change in intrasynaptic dopamine concentration: Effect of treatment for Tobacco Dependence , 2010, Psychiatry Research: Neuroimaging.

[25]  Jonathan D. Cohen,et al.  Anterior Cingulate Conflict Monitoring and Adjustments in Control , 2004, Science.

[26]  Marc N. Potenza,et al.  An Initial Study of Neural Responses to Monetary Incentives as Related to Treatment Outcome in Cocaine Dependence , 2011, Biological Psychiatry.

[27]  Nora D Volkow,et al.  Neurocircuitry of Addiction , 2010, Neuropsychopharmacology.

[28]  T. Robbins,et al.  Impulsivity, Compulsivity, and Top-Down Cognitive Control , 2011, Neuron.

[29]  Rachel Kozink,et al.  Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis , 2010, Psychopharmacology.

[30]  A. Venneri,et al.  Reduced grey matter in the posterior insula as a structural vulnerability or diathesis to addiction , 2012, Brain Research Bulletin.

[31]  Donna J. Calu,et al.  Opiate versus psychostimulant addiction: the differences do matter , 2011, Nature Reviews Neuroscience.

[32]  A. Bonci,et al.  Synaptic plasticity in the mesolimbic system , 2010, Annals of the New York Academy of Sciences.

[33]  Jin Fan,et al.  The activation of attentional networks , 2005, NeuroImage.

[34]  K. Carroll,et al.  Behavioral therapies for drug abuse. , 2005, The American journal of psychiatry.

[35]  Dardo Tomasi,et al.  Effects of methylphenidate on resting-state functional connectivity of the mesocorticolimbic dopamine pathways in cocaine addiction. , 2013, JAMA psychiatry.

[36]  T. Robbins,et al.  Neurobehavioral mechanisms of impulsivity: Fronto-striatal systems and functional neurochemistry , 2008, Pharmacology Biochemistry and Behavior.

[37]  R. Spanagel,et al.  New pharmacological treatment strategies for relapse prevention. , 2013, Current topics in behavioral neurosciences.

[38]  Tim Lancaster,et al.  Nicotine receptor partial agonists for smoking cessation. , 2010, The Cochrane database of systematic reviews.

[39]  M. Pérez-García,et al.  What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance? , 2011, Neuroscience & Biobehavioral Reviews.

[40]  Young T. Hong,et al.  Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement , 2007, Science.

[41]  Y. Shaham,et al.  Context-induced relapse to drug seeking: a review , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[42]  Marc N. Potenza,et al.  Pretreatment Brain Activation During Stroop Task Is Associated with Outcomes in Cocaine-Dependent Patients , 2008, Biological Psychiatry.

[43]  Neuroimaging in Addiction , 2011 .

[44]  A. Brody,et al.  In vivo brain imaging of human exposure to nicotine and tobacco. , 2009, Handbook of experimental pharmacology.

[45]  M. Potenza,et al.  Neuroscience of Behavioral and Pharmacological Treatments for Addictions , 2011, Neuron.

[46]  Manuel Gómez-Río,et al.  Neural correlates of hot and cold executive functions in polysubstance addiction: Association between neuropsychological performance and resting brain metabolism as measured by positron emission tomography , 2012, Psychiatry Research: Neuroimaging.

[47]  H. Gu,et al.  Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits. , 2009, Archives of general psychiatry.

[48]  M. Sofuoglu,et al.  Cognitive enhancement as a pharmacotherapy target for stimulant addiction. , 2010, Addiction.

[49]  K. Lynch,et al.  A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms. , 2006, Drug and alcohol dependence.

[50]  C. Roncero,et al.  Efficacy of psychostimulant drugs for cocaine dependence. , 2010, The Cochrane database of systematic reviews.

[51]  Marc A Schuckit,et al.  Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. , 2005, Archives of general psychiatry.

[52]  David Couper,et al.  Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. , 2006, JAMA.

[53]  E. Stamatakis,et al.  Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study , 2012, PloS one.

[54]  Miguel Ángel García-Cabezas,et al.  Distribution of the dopamine innervation in the macaque and human thalamus , 2007, NeuroImage.

[55]  L. Stead,et al.  Nicotine receptor partial agonists for smoking cessation (Review) , 2007 .

[56]  Jason M. White,et al.  Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence. , 2010, Addiction.

[57]  K. Lynch,et al.  A Double-Blind, Placebo-Controlled Trial of Modafinil for Cocaine Dependence , 2005, Neuropsychopharmacology.

[58]  M. Mandelkern,et al.  Effects of Treatment for Tobacco Dependence on Resting Cerebral Glucose Metabolism , 2010, Neuropsychopharmacology.

[59]  A. Lindgren,et al.  Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review. , 2006, Addiction.

[60]  L. Ray,et al.  Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials. , 2009, Journal of studies on alcohol and drugs.

[61]  Hidenao Fukuyama,et al.  Quantification of human nicotinic acetylcholine receptors with 123I-5IA SPECT. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[62]  A. Laird,et al.  The Neural Basis of Drug Stimulus Processing and Craving: An Activation Likelihood Estimation Meta-Analysis , 2011, Biological Psychiatry.

[63]  D. Hommer,et al.  Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study. , 2010, Archives of general psychiatry.

[64]  E. Sokhadze,et al.  Neurofeedback Effects on Evoked and Induced EEG Gamma Band Reactivity to Drug-related Cues in Cocaine Addiction. , 2010, Journal of neurotherapy.

[65]  Michael J. Martinez,et al.  Bias between MNI and Talairach coordinates analyzed using the ICBM‐152 brain template , 2007, Human brain mapping.

[66]  Gladys N. Pachas,et al.  Brain Reactivity to Smoking Cues Prior to Smoking Cessation Predicts Ability to Maintain Tobacco Abstinence , 2010, Biological Psychiatry.

[67]  H. Flor,et al.  Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics , 2004, Psychopharmacology.

[68]  D. Zald,et al.  Reconsidering anhedonia in depression: Lessons from translational neuroscience , 2011, Neuroscience & Biobehavioral Reviews.

[69]  J S Fowler,et al.  Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: implications in addiction. , 1999, The American journal of psychiatry.

[70]  D. Veltman,et al.  Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research , 2012, Brain and behavior.

[71]  M. Jung,et al.  Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review , 2006, Neuroscience & Biobehavioral Reviews.

[72]  Rita Z. Goldstein,et al.  Addiction: Pulling at the Neural Threads of Social Behaviors , 2011, Neuron.

[73]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[74]  Lianne Schmaal,et al.  N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study , 2012, Neuropsychopharmacology.

[75]  P. Goldman-Rakic,et al.  Sustained Mnemonic Response in the Human Middle Frontal Gyrus during On-Line Storage of Spatial Memoranda , 2002, Journal of Cognitive Neuroscience.

[76]  J. Swanson,et al.  Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder , 2012, The Journal of Neuroscience.

[77]  Colin Camerer,et al.  Self-control in decision-making involves modulation of the vmPFC valuation system , 2009, NeuroImage.

[78]  Paul M. Matthews,et al.  Nicotine replacement in abstinent smokers improves cognitive withdrawal symptoms with modulation of resting brain network dynamics , 2010, NeuroImage.

[79]  M. Srisurapanont,et al.  Naltrexone for the treatment of alcoholism: a meta-analysis of randomized controlled trials. , 2005, The international journal of neuropsychopharmacology.

[80]  J. O'Loughlin,et al.  Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials , 2008, Canadian Medical Association Journal.

[81]  D. Ciraulo,et al.  Modafinil for the treatment of cocaine dependence. , 2009, Drug and alcohol dependence.

[82]  S. Kühn,et al.  Common biology of craving across legal and illegal drugs – a quantitative meta‐analysis of cue‐reactivity brain response , 2011, The European journal of neuroscience.

[83]  Y. Zang,et al.  Methylphenidate Normalizes Resting-State Brain Dysfunction in Boys With Attention Deficit Hyperactivity Disorder , 2013, Neuropsychopharmacology.

[84]  J. Swanson,et al.  Dopamine in drug abuse and addiction: results from imaging studies and treatment implications , 2004, Molecular Psychiatry.

[85]  Elliot A. Stein,et al.  Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans , 2014, Neuropharmacology.

[86]  Angela M. Uecker,et al.  ALE meta‐analysis: Controlling the false discovery rate and performing statistical contrasts , 2005, Human brain mapping.

[87]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[88]  Orin C. Davis,et al.  Amygdala volume associated with alcohol abuse relapse and craving. , 2008, The American journal of psychiatry.

[89]  J. Kaiser,et al.  Brain Regions Related to Tool Use and Action Knowledge Reflect Nicotine Dependence , 2009, The Journal of Neuroscience.

[90]  Rita Z. Goldstein,et al.  The Neurocircuitry of Impaired Insight in Drug Addiction , 2009, Trends in Cognitive Sciences.

[91]  Katsuyuki Sakai,et al.  Reactive mechanism of cognitive control system. , 2010, Cerebral cortex.

[92]  D. Sulzer,et al.  How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission , 2011, Neuron.

[93]  Bridget A. Martell,et al.  Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population. , 2006, Archives of general psychiatry.

[94]  R. V. van Holst,et al.  Drug-related decrease in neuropsychological functions of abstinent drug users. , 2011, Current drug abuse reviews.

[95]  A. Feingold,et al.  Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients. , 2003, Drug and alcohol dependence.

[96]  Guinevere F. Eden,et al.  Meta-Analysis of the Functional Neuroanatomy of Single-Word Reading: Method and Validation , 2002, NeuroImage.

[97]  D. Zald,et al.  Dopaminergic Mechanisms of Individual Differences in Human Effort-Based Decision-Making , 2012, The Journal of Neuroscience.

[98]  C. Luhmann Temporal Decision-Making: Insights from Cognitive Neuroscience , 2009, Front. Behav. Neurosci..

[99]  F. J. McClernon,et al.  IMAGING STUDY: Selectively reduced responses to smoking cues in amygdala following extinction‐based smoking cessation: results of a preliminary functional magnetic resonance imaging study , 2007, Addiction biology.

[100]  G. Di Chiara,et al.  Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[101]  Mathias Pessiglione,et al.  Separate Valuation Subsystems for Delay and Effort Decision Costs , 2010, The Journal of Neuroscience.

[102]  B. Balleine,et al.  Annals of the New York Academy of Sciences the Orbitofrontal Cortex, Predicted Value, and Choice , 2022 .

[103]  R. See Neural substrates of cocaine-cue associations that trigger relapse. , 2005, European journal of pharmacology.

[104]  Linda Chang,et al.  Adaptation of Brain Glutamate Plus Glutamine during Abstinence from Chronic Methamphetamine Use , 2008, Journal of Neuroimmune Pharmacology.

[105]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.