Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.
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.
['Moeller|Scott J|SJ|', 'Konova|Anna B|AB|', 'Tomasi|Dardo|D|', 'Parvaz|Muhammad A|MA|', 'Goldstein|Rita Z|RZ|']
D000328:Adult D001289:Attention Deficit Disorder with Hyperactivity D001921:Brain D019970:Cocaine-Related Disorders D003071:Cognition D003072:Cognition Disorders D004298:Dopamine D018765:Dopamine Uptake Inhibitors D004644:Emotions D005240:Feasibility Studies D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008774:Methylphenidate D008875:Middle Aged
FMRI Cocaine Dopamine Working memory Addiction ADHD Brain imaging Cerebral cortex Inhibition Psychostimulant