title: Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task.
abstract: 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.
authors.affiliation: Department of Medical Research, Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. rgoldstein@bnl.gov
authors.forename: Rita Z
authors.initials: RZ
authors.lastname: Goldstein
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Woicik
authors.forename: Thomas
authors.initials: T
authors.lastname: Maloney
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.forename: Nelly
authors.initials: N
authors.lastname: Alia-Klein
authors.forename: Juntian
authors.initials: J
authors.lastname: Shan
authors.forename: Jean
authors.initials: J
authors.lastname: Honorio
authors.forename: Dimitris
authors.initials: D
authors.lastname: Samaras
authors.forename: Ruiliang
authors.initials: R
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D003071:Cognition / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D008875:Middle Aged; D009483:Neuropsychological Tests; D013647:Task Performance and Analysis
chemical_list: D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate
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