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 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.

Concomitant Drug Use among Opioid-Dependent Patients with and without Attention Deficit Hyperactivity Disorder: Does Methylphenidate Merit a Trial?

“…At best, there is inconsistent evidence for stimulants and other pharmacotherapies in patients with cocaine dependence [12, 19, 21, 26]. These findings are supported by an MRI study demonstrating reduced activation of the dorsolateral prefrontal cortex in response to MPH intake in cocaine-using patients in comparison to controls [43]. Thus, MPH may cause beneficial but generally modest effects in cocaine users.…”

Meta‐analysis of aberrant post‐error slowing in substance use disorder: implications for behavioral adaptation and self‐control

“…It is plausible that developing novel strategies to improve PES in laboratory settings via training or medication [e.g. the dopaminergic agonist methylphenidate, which has shown initial promise in modulating behavior during tasks of response inhibition reported here (Li et al ., ; Moeller et al ., , )] could lead to corresponding improvements in behavioral adaption in those diagnosed with SUD. Supporting this view are a small number of studies that reported correlations between PES and adaptive change in task performance, although these findings have been mixed (see Table ) and at times nuanced [e.g.…”