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Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study

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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 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.

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Acknowledgments

This study was supported by grants from the National Institute on Drug Abuse (to RZG: R01DA023579; to SJM: F32DA030017, K01DA037452; to ABK: F32DA039648; to MAP: F32DA033088). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We also thank Dr. Elena Shumay, whom the scientific community has lost too prematurely, for help with analyses in earlier versions of this manuscript.

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Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Scott J. Moeller, Muhammad A. Parvaz & Rita Z. Goldstein

  2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Scott J. Moeller, Muhammad A. Parvaz & Rita Z. Goldstein

  3. 1470 Madison Ave (Room 9-115), New York, NY, 10029, USA

    Scott J. Moeller

  4. Center for Neural Science, New York University, New York, NY, 10003, USA

    Anna B. Konova

  5. National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA

    Dardo Tomasi

  6. One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA

    Rita Z. Goldstein

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  1. Scott J. Moeller
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  2. Anna B. Konova
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  3. Dardo Tomasi
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  4. Muhammad A. Parvaz
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  5. Rita Z. Goldstein
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Correspondence to Scott J. Moeller or Rita Z. Goldstein.

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Moeller, S.J., Konova, A.B., Tomasi, D. et al. Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study. Psychopharmacology 233, 2559–2569 (2016). https://doi.org/10.1007/s00213-016-4307-9

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  • DOI: https://doi.org/10.1007/s00213-016-4307-9

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