title: Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.
abstract: The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known.
  
  
  
  We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predict neural response to methylphenidate across multiple functional magnetic resonance imaging (fMRI) procedures.
  
  
  
  We combined neural measures from three separate procedures (two inhibitory control tasks differing in their degree of emotional salience and resting-state functional connectivity) during methylphenidate (20 mg oral, versus randomized and counterbalanced placebo) and correlated these aggregated responses with cocaine use disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity.
  
  
  
  Cocaine abusers, relative to controls, had a lower response in the dorsolateral prefrontal cortex to methylphenidate across all three procedures, driven by responses to the two inhibitory control tasks; reduced methylphenidate fMRI response in this region further correlated with more frequent cocaine use.
  
  
  
  Cocaine abuse (and its frequency), associated with lower tonic dopamine levels, correlated with a reduction in activation to methylphenidate (versus placebo). These initial results provide feasibility to the idea that multimodal fMRI tasks can be meaningfully aggregated, and that these aggregated procedures show a common disruption in addiction in a highly anticipated region relevant to cognitive control. Results also suggest that drug use frequency may represent an important modulatory variable in interpreting the efficacy of pharmacologically enhanced cognitive interventions in addiction.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. scott.moeller@mssm.edu.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. scott.moeller@mssm.edu.|, 1470 Madison Ave (Room 9-115), New York, NY, 10029, USA. scott.moeller@mssm.edu.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Moeller
authors.affiliation: Center for Neural Science, New York University, New York, NY, 10003, USA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Konova
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Parvaz
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. rita.goldstein@mssm.edu.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. rita.goldstein@mssm.edu.|, One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA. rita.goldstein@mssm.edu.
authors.forename: Rita Z
authors.initials: RZ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001921:Brain / Q000187:drug effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy; D004298:Dopamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008875:Middle Aged
chemical_list: D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D004298:Dopamine
keywords: ADHD; Addiction; Brain imaging; Cerebral cortex; Cocaine; Dopamine; FMRI; Inhibition; Psychostimulant; Working memory