The human brain faces a variety of computational dilemmas, including the flexibility/stability, the speed/accuracy and the labor/leisure tradeoff. I will argue that striatal dopamine is particularly well suited to dynamically regulate these computational tradeoffs depending on constantly changing task demands. This working hypothesis is grounded in evidence from recent studies on learning, motivation and cognitive control in human volunteers, using chemical PET, psychopharmacology, and/or fMRI. These studies also begin to elucidate the mechanisms underlying the huge variability in catecholaminergic drug effects across different individuals and across different task contexts. For example, I will demonstrate how effects of the most commonly used psychostimulant methylphenidate on learning, Pavlovian and effortful instrumental control depend on fluctuations in current environmental volatility, on individual differences in working memory capacity and on opportunity cost respectively.

Drug addiction is a chronically relapsing disorder characterized by compulsive drug use despite catastrophic personal consequences (e.g., loss of family, job) and even when the substance is no longer perceived as pleasurable. In this talk, I will present results of human neuroimaging studies, utilizing a multimodal approach (neuropsychology, functional magnetic resonance imaging, event-related potentials recordings), to explore the neurobiology underlying the core psychological impairments in drug addiction (impulsivity, drive/motivation, insight/awareness) as associated with its clinical symptomatology (intoxication, craving, bingeing, withdrawal). The focus of this talk is on understanding the role of the dopaminergic mesocorticolimbic circuit, and especially the prefrontal cortex, in higher-order executive dysfunction (e.g., disadvantageous decision-making such as trading a car for a couple of cocaine hits) in drug addicted individuals. The theoretical model that guides the presented research is called iRISA (Impaired Response Inhibition and Salience Attribution), postulating that abnormalities in the orbitofrontal cortex and anterior cingulate cortex, as related to dopaminergic dysfunction, contribute to the core clinical symptoms in drug addiction. Specifically, our multi-modality program of research is guided by the underlying working hypothesis that drug addicted individuals disproportionately attribute reward value to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli, with a concomitant decrease in the ability to inhibit maladaptive drug use. In this talk I will also explore whether treatment (as usual) and 6-month abstinence enhance recovery in these brain-behavior compromises in treatment seeking cocaine addicted individuals. Promising neuroimaging studies, which combine pharmacological (i.e., oral methylphenidate, or RitalinTM) and salient cognitive tasks or functional connectivity during resting-state, will be discussed as examples for using neuroimaging for empirically guiding the development of effective neurorehabilitation strategies (encompassing cognitive reappraisal and transcranial direct current stimulation) in drug addiction.