Pharmacological fMRI with Methylphenidate

Methylphenidate is a dopamine agonist traditionally used to treat attention deficit/hyperactivity disorder (ADHD). We reasoned that oral methylphenidate, administered at low doses, could help ameliorate deficits in prefrontal and other dopamine-modulated brain regions commonly observed in stimulant dependent individuals.

Results have supported our hypotheses. For example, functional hypoactivations in the anterior cingulate cortex to an emotionally salient task in cocaine addicted individuals (Goldstein et al., 2009) were normalized with single-dose methylphenidate (Goldstein et al., 2010); methylphenidate similarly normalized activity in the dorsolateral prefrontal cortex when subjects performed a classical task of executive function (i.e., the Stroop task) (Moeller et al., 2012). In another study, healthy non-addicted individuals (but not cocaine users) showed increased activity in the dopaminergic midbrain during mental fatigue, presumably boosting motivation to complete the task; oral methylphenidate rescued this midbrain response in the cocaine users (Moeller et al., 2012). More recently, we have examined the effects of methylphenidate on the brain at rest (resting-state functional connectivity). Methylphenidate reduced an abnormally strong connectivity, or cross-talk, of the ventral striatum with the dorsal striatum (putamen/globus pallidus), regions crucial for habit formation that may underlie core addiction symptomatology (Konova et al., 2013).

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