Scott J Moeller1,2,3, Anna B Konova4, Dardo Tomasi5, Muhammad A Parvaz6,7, Rita Z Goldstein8,9,10. 1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. scott.moeller@mssm.edu. 2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. scott.moeller@mssm.edu. 3. , 1470 Madison Ave (Room 9-115), New York, NY, 10029, USA. scott.moeller@mssm.edu. 4. Center for Neural Science, New York University, New York, NY, 10003, USA. 5. National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA. 6. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. 7. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. 8. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. rita.goldstein@mssm.edu. 9. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. rita.goldstein@mssm.edu. 10. , One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA. rita.goldstein@mssm.edu.
Abstract
RATIONALE: The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. OBJECTIVES: 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. METHODS: 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 cocaineuse disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity. RESULTS: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 methylphenidatefMRI response in this region further correlated with more frequent cocaine use. CONCLUSIONS: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.
RCT Entities:
RATIONALE: The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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: Anna B Konova; Scott J Moeller; Dardo Tomasi; Muhammad A Parvaz; Nelly Alia-Klein; Nora D Volkow; Rita Z Goldstein Journal: Eur J Neurosci Date: 2012-07-09 Impact factor: 3.386
Authors: Rita Z Goldstein; Nelly Alia-Klein; Dardo Tomasi; Jean Honorio Carrillo; Thomas Maloney; Patricia A Woicik; Ruiliang Wang; Frank Telang; Nora D Volkow Journal: Proc Natl Acad Sci U S A Date: 2009-05-28 Impact factor: 11.205
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: Proc Natl Acad Sci U S A Date: 2010-09-07 Impact factor: 11.205
Authors: Reem K Jan; Joanne C Lin; Donald G McLaren; Ian J Kirk; Rob R Kydd; Bruce R Russell Journal: Front Psychiatry Date: 2014-03-06 Impact factor: 4.157