Deficits in dopaminergically modulated striato-thalamo-prefrontal circuits contribute to compromises in self-control and motivation in cocaine addiction (Goldstein and Volkow, 2002). Methylphenidate (MPH), a dopaminergic agonist, has been successfully used to enhance inhibitory control and salience attribution in attention-deficit hyperactivity disorder and other prefrontal psychopathologies (eg, frontotemporal dementia); indeed MPH has been suggested to improve signal-to-noise ratio (SNR) and optimize activity (eg, processing efficiency) in brain regions that modulate executive functions (Mehta et al, 2000; Volkow et al, 2008). However, in clinical trials on cocaine addiction, MPH did not reduce cocaine consumption (Volkow et al, 2004). We hypothesized that oral MPH would improve executive function in individuals with cocaine use disorders (CUDs), an effect that, when coupled with cognitive or behavioral interventions, may improve the clinical outcome.

In the current functional magnetic resonance imaging (fMRI) study, 13 CUDs (12 male subjects, mean age=46.2 years, mean duration of cocaine use, predominantly smoked=17.9 years, all meeting the current cocaine dependence criteria) matched on education and intellectual functioning with 14 healthy controls (all male, mean age=38.8, group differences statistically controlled) received 20 mg oral MPH or placebo in a randomized and counterbalanced order over two consecutive MRI sessions (separated by a mean of 14 days, MRI performed on a 4-T whole-body Varian/Siemens scanner). During peak MPH effects (60–90 min post administration), subjects performed an emotional variant of the color-word Stroop task: subjects were monetary remunerated for correct pressing for color of drug-related and matched neutral words. This task engages the prefrontal cortex in CUD (Goldstein et al, 2007). Importantly, despite lack of group differences in task engagement or performance, compared with healthy controls, CUD showed robust anterior cingulate cortex (ACC) hypoactivations, encompassing the rostroventral ACC (rvACC) (extending to the medial orbitofrontal cortex (mOFC)) and the caudal–dorsal ACC (cdACC) (Goldstein et al, 2009).

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD