Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

[1]  Rita Z. Goldstein,et al.  Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction , 2009, Proceedings of the National Academy of Sciences.

[2]  M. Nader,et al.  Chronic Cocaine Self-Administration Upregulates the Norepinephrine Transporter and Alters Functional Activity in the Bed Nucleus of the Stria Terminalis of the Rhesus Monkey , 2003, The Journal of Neuroscience.

[3]  Andrew D. Blackwell,et al.  The Effects of Methylphenidate on Decision Making in Attention-Deficit/Hyperactivity Disorder , 2008, Biological Psychiatry.

[4]  T. Robbins,et al.  Neuropharmacological modulation of cognition , 2006, Current opinion in neurology.

[5]  Nicholas D. Walsh,et al.  Neural basis of the emotional Stroop interference effect in major depression , 2007, Psychological Medicine.

[6]  C. Carter,et al.  The anterior cingulate as a conflict monitor: fMRI and ERP studies , 2002, Physiology & Behavior.

[7]  Hongtu Zhu,et al.  An FMRI study of the effects of psychostimulants on default-mode processing during Stroop task performance in youths with ADHD. , 2009, The American journal of psychiatry.

[8]  S. Tiffany,et al.  The development of a cocaine craving questionnaire. , 1993, Drug and alcohol dependence.

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

[10]  Edward Nunes,et al.  Cognitive impairment, retention and abstinence among cocaine abusers in cognitive-behavioral treatment. , 2003, Drug and alcohol dependence.

[11]  Julie C. Stout,et al.  Neurocognitive insights into substance abuse , 2005, Trends in Cognitive Sciences.

[12]  D. Segal,et al.  Effects of Methylphenidate on Extracellular Dopamine, Serotonin, and Norepinephrine: Comparison with Amphetamine , 1997, Journal of neurochemistry.

[13]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[14]  T. Ernst,et al.  fMRI-acoustic noise alters brain activation during working memory tasks , 2005, NeuroImage.

[15]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[16]  M. D’Esposito,et al.  Functional Reintegration of Prefrontal Neural Networks for Enhancing Recovery After Brain Injury , 2006, The Journal of head trauma rehabilitation.

[17]  Chiang-shan R. Li,et al.  Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients , 2010, Proceedings of the National Academy of Sciences.

[18]  A. Alterman,et al.  Reliability and validity of the Cocaine Selective Severity Assessment. , 1998, Addictive behaviors.

[19]  R. Ramasubbu,et al.  Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study , 2008, Neuropsychiatric disease and treatment.

[20]  E. Butelman,et al.  Pharmacotherapy of addictions , 2002, Nature Reviews Drug Discovery.

[21]  T. Robbins,et al.  Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia , 2006, Neuropsychopharmacology.

[22]  John Suckling,et al.  Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics. , 2003, Cerebral cortex.

[23]  S. Rauch,et al.  An fMRI study of anterior cingulate function in posttraumatic stress disorder , 2001, Biological Psychiatry.

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

[25]  Y. Kim,et al.  Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study , 2006, Clinical rehabilitation.

[26]  N. Volkow,et al.  Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. , 1998, The American journal of psychiatry.

[27]  W. Sturm,et al.  Neuropsychological assessment , 2007, Journal of Neurology.

[28]  Eric Vermetten,et al.  Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder , 2004, Biological Psychiatry.

[29]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[30]  Nora D. Volkow,et al.  Methylphenidate Decreased the Amount of Glucose Needed by the Brain to Perform a Cognitive Task , 2008, PloS one.

[31]  K. Uğurbil,et al.  High contrast and fast three‐dimensional magnetic resonance imaging at high fields , 1995, Magnetic resonance in medicine.

[32]  Michael F. Green,et al.  Training and quality assurance with the structured clinical interview for DSM-IV (SCID-I/P) , 1998, Psychiatry Research.

[33]  E. Kandel,et al.  Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activity in the Amygdala , 2006, Neuron.

[34]  Karl J. Friston,et al.  Incorporating Prior Knowledge into Image Registration , 1997, NeuroImage.

[35]  A. Damasio,et al.  Insensitivity to future consequences following damage to human prefrontal cortex , 1994, Cognition.

[36]  Pearl H. Chiu,et al.  Smokers' brains compute, but ignore, a fictive error signal in a sequential investment task , 2008, Nature Neuroscience.

[37]  George Bush,et al.  The emotional counting stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division , 1998, Biological Psychiatry.

[38]  R. Gonzalez.  Applied Multivariate Statistics for the Social Sciences , 2003 .

[39]  Jean Logan,et al.  Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues , 2008, NeuroImage.

[40]  S. Brooks,et al.  Applied Multivariate Statistics for the Social Sciences , 1993 .

[41]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[42]  R. Burchfield.  Frequency Analysis of English Usage: Lexicon and Grammar. By W. Nelson Francis and Henry Kučera with the assistance of Andrew W. Mackie. Boston: Houghton Mifflin. 1982. x + 561 , 1985 .

[43]  H. Critchley.  Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[44]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[45]  C. Routledge,et al.  Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes , 2005, Psychopharmacology.

[46]  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.

[47]  M. Raichle,et al.  Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Brian W. Haas,et al.  Interference produced by emotional conflict associated with anterior cingulate activation , 2006, Cognitive, affective & behavioral neuroscience.

[49]  Adrian M. Owen,et al.  Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain , 2000, The Journal of Neuroscience.

[50]  M. Kringelbach.  The human orbitofrontal cortex: linking reward to hedonic experience , 2005, Nature Reviews Neuroscience.

[51]  Linda Chang,et al.  k-Space based summary motion detection for functional magnetic resonance imaging , 2003, NeuroImage.

[52]  K. R. Ridderinkhof,et al.  The Role of the Medial Frontal Cortex in Cognitive Control , 2004, Science.

[53]  D. Metzger,et al.  The Fifth Edition of the Addiction Severity Index. , 1992, Journal of substance abuse treatment.

[54]  Rita Z. Goldstein,et al.  Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers , 2010, PloS one.

[55]  K. Scheffler,et al.  Hyperechoes , 2001, Magnetic resonance in medicine.

[56]  T. Robbins,et al.  The Neurobiology of Attention-Deficit/Hyperactivity Disorder , 2007, Biological Psychiatry.

[57]  Rita Z. Goldstein,et al.  Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction , 2007, Neuroscience.

[58]  Yu-Shin Ding,et al.  Behavioral / Systems / Cognitive Activation of Orbital and Medial Prefrontal Cortex by Methylphenidate in Cocaine-Addicted Subjects But Not in Controls : Relevance to Addiction , 2005 .

[59]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.