Abstract
RationaleDysregulation of dopaminergic neurotransmission, specifically altered reward processing assessed via the reward anticipation in the MID task, plays a central role in the etiopathogenesis of neuropsychiatric disorders.ObjectivesWe hypothesized to find a difference in the activity level of the reward system (measured by the proxy reward anticipation) under drug administration versus placebo, in that amisulpride reduces, and L-DOPA enhances, its activity.MethodsWe studied the influence of dopamine agonist L-DOPA and the antagonist amisulpride on the reward system using functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task in n = 45 healthy volunteers in a randomized, blinded, cross-over study.ResultsThe MID paradigm elicits strong activation in reward-dependent structures (such as ventral striatum, putamen, caudate, anterior insula) during reward anticipation. The placebo effect demonstrated the expected significant blood oxygen level–dependent activity in reward-dependent brain regions. Neither amisulpride nor L-DOPA led to significant changes in comparison with the placebo condition. This was true for whole-brain analysis as well as analysis of a pre-defined nucleus accumbens region-of-interest mask.ConclusionThe present results cast doubt on the sensitivity of reward anticipation contrast in the MID task for assessing dopamine-specific changes in healthy volunteers by pharmaco-fMRI. While our task was not well-suited for detailed analysis of the outcome phase, we provide reasonable arguments that the lack of effect in the anticipation phase is not due to an inefficient task but points to unexpected behavior of the reward system during pharmacological challenge. Group differences of reward anticipation should therefore not be seen as simple representatives of dopaminergic states.
Highlights
Rewards are crucial things in life: whether we strive for food, sex, social signals, or illicit drugs, we experience features of our sensory perception as more salient than others and approach towards them
Dysregulation in the reward system has been discussed in disorders ranging from schizophrenia to attention-deficit hyperactivity disorder (ADHD) and has been most often interpreted as a dysfunction of the dopaminergic neurotransmission (Der-Avakian et al 2016)
We did not find evidence that reward anticipation contrast tested in our monetary incentive delay (MID) task is modulated by a challenge of the dopamine system using an antagonist or agonist
Summary
Rewards are crucial things in life: whether we strive for food, sex, social signals, or illicit drugs, we experience features of our sensory perception as more salient than others and approach towards them. The task has been used in several variants which can lead to different effects depending on task methodology like contingency rate of the reward (Plichta and Scheres 2015). This MID task has been demonstrated to have good test reliability (Plichta et al 2012). Several findings in psychiatric patients, like a blunted BOLD response during anticipation in patients with ADHD (Plichta and Scheres 2014) or schizophrenia as well as first-degree relatives (Grimm et al 2012, 2014), were interpreted in the context of dopaminergic theories
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