Thesis defense Marianne Oldehinkel (Donders series 242)

3 October 2016

Promotors: prof. dr. J. Buitelaar and prof. dr. C. Beckmann,
copromotor: dr. M. Mennes

Investigation of cortico-striatal network dysfunciton in ADHD using applications of resting state fMRI

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neuropsychiatric disorder, yet little is known about its underlying neurobiological mechanisms. Next to symptoms of inattention, hyperactivity and impulsivity, many patients with ADHD also experience impairments in cognitive control, motor function and reward processing. These functions rely on several striatal and cortical regions in the brain that together form the cortico-striatal networks. This thesis was aimed at investigating whether ADHD can be related to abnormal functional connectivity, i.e., communication, within these brain networks.

To this end, innovative applications of resting state functional magnetic resonance imaging (R-fMRI) were used to investigate functional connectivity in a large cohort of 444 participants, including patients with ADHD, their unaffected siblings as well as control participants. In addition to classical categorical analyses comparing the ADHD group with the control group, also dimensional analyses based on continuous ADHD symptom measures were conducted. These dimensional analyses take the large inter-individual symptom differences among ADHD patients into account. The studies conducted in this thesis demonstrated the significance of advanced methodology and revealed important insights into the functional connectivity architecture of cortico-striatal networks in ADHD: ADHD-related abnormalities were observed in the cortico-striatal networks underlying motor function and cognitive control, but not in the cortico-striatal network underlying reward processing. Furthermore, these results were mainly revealed by the dimensional and not the categorical analyses. These findings highlight the important contribution of dimensional characteristics to ADHD as well as the huge potential of dimensional analyses in revealing the neurobiological correlates of ADHD.