Cognitive control and decision making in ADHD

The overall aim of this thesis was to address how aspects of cognitive control and decision making contribute to ADHD symptoms. As the disorder is characterized by heterogeneous symptoms, investigating the neurobiology of the disorder is difficult. The use of endophenotypes may help to address this problem: a quantifiable component between biology and behavior reduces the heterogeneity of the disorder and will help in investigating the bio-behavioral pathways underlying it. In Part 1 (chapters 2, 3 & 4) we addressed whether deficits in brain activity during different aspects of cognitive control are vulnerable to familial risk for ADHD. By doing so, we were able to identify candidate endophenotypes for ADHD research. We found changes in brain activity in both fronto-striatal and fronto-cerebellar circuits in subjects with ADHD and their unaffected siblings. Furthermore, functional connectivity between regions of these circuits was also affected. These data suggest that impairments in fronto-striatal and fronto-cerebellar circuits are suitable as an endophenotype for ADHD research. In Part 2 (chapters 5 & 6), we investigated whether cognitive deficits in ADHD are limited to higher-order processes, or if basic perceptual decisions are also affected. Furthermore, we addressed where in the brain basic decisions are biased by reward expectations. We found that subjects with ADHD were impaired in adjusting the balance between speed and accuracy, and as such were disabled in optimizing their behavior to task demands. In addition, we found BOLD correlates of reward-related bias in the inferior frontal gyrus, a region implicated in cognitive control and ADHD. These findings suggest that impairments in such basic processes might have a larger contribution to the phenotype of this disorder than has been thought up until now.