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

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.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Moeller SJ,Konova AB,Tomasi D,Parvaz MA,Goldstein RZ

doi

10.1007/s00213-016-4307-9

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

2559-69

issue

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-016-4307-9

journal_volume

233

pub_type

杂志文章,随机对照试验

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