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: Rita Z Goldstein, Patricia A Woicik, Thomas Maloney, Dardo Tomasi, Nelly Alia-Klein, Juntian Shan, Jean Honorio, Dimitris Samaras, Ruiliang Wang, Frank Telang, Gene-Jack Wang, Nora D Volkow
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 38 Pg. 16667-72 (Sep 21 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 20823246 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Dopamine Uptake Inhibitors
• Methylphenidate

Topics

• Administration, Oral
• Adult
• Case-Control Studies
• Cocaine-Related Disorders (drug therapy, physiopathology, psychology)
• Cognition (drug effects)
• Dopamine Uptake Inhibitors (administration & dosage)
• Female
• Gyrus Cinguli (drug effects, physiopathology)
• Humans
• Magnetic Resonance Imaging
• Male
• Methylphenidate (administration & dosage)
• Middle Aged
• Neuropsychological Tests
• Task Performance and Analysis