The influence of stimulant therapy and comorbidity on decisions in ADHD

Current research shows that approximately half of the children with ADHD continue to have ADHD as adults. Adults with ADHD must, differently then children, make independent decisions for which they might be less equipped than healthy adults. We hypothesi ze that because decision making and learning from experience depends on dopamine, the neurotransmitter also know to play an important role in ADHD, these functions should be impaired in adults with ADHD, especially if they are not under the influence of d opamine-modulating medication like methylphenidate. To investigate the cognitive and brain processes underlying decision making in adults with ADHD, we conduct a placebo controlled randomized trial in which we compare patients taking their medication or a placebo with each other and with healthy controls. In the behavioral arm of the study, we use mathematical models of decision making to determine if differences in decision making depend on differences in decision speed (impulsivity), the ability to rap idly and accurately process reward information, or both. The key aim of the fMRI study is to identify which brain processes of decision making, like for instance representation of rewards or cost-benefit comparison, are influenced by ADHD and its medicati on. The fMRI study is complemented by a pharmacological MRI study examining how medication modulates blood flow in dopaminergic regions of the brain, in particular the basal ganglia.

Attention Deficit Hyperactivity Disorder (ADHD) is often considered a childhood disorder. However, ADHD frequently persists into adulthood. As in children, the best therapy for adult ADHD is central-stimulant phenethylaminedrugs (e.g. methylphenidate), wh ich results in increased pre-frontal and sub-cortical dopamine and noradrenalin levels in the brain. Therefore, ADHD and methylphenidate therapy also influence learning and decision-making, functions strongly relying on sub-cortical and pre-frontal brain processes. Our goal is to explain learning and decision making deficits in adult ADHD patients by describing the underlying affective and cognitive processes including their neural implementation as well as to examine their modulation through through met hylphenidate therapy. In this context we will put particular focus on the influence of comorbidities. From an applied perspective the project provides a first step in the development of new diagnostic methods to improve treatment of. From the perspective of patients and their relatives, the description of decision mechanisms in can help to understand bad decision and to develop coping strategies. These goals are pursued through three studies: A behavioral experiment will compare how healthy controls and A DHD patients on and off methylphenidate perform during instrumental learning and cost/benefit decision-making and use computational modeling to explain differences in task performance. A second experiment shall combine functional magnetic resonance imagin g (fMRI) with mathematical modeling to investigate the brain processes underlying task performance and their modulation by methylphenidate. (3) A third pharmacological MRI experiment shall investigate methylphenidate treatment effects in terms of changes in tonic cerebral blood flow. To tie in the project with tasks more typically used in ADHD research, we will also use a classic neuropsychological test of attention (continuous performance test (CPT)).