Archival ReportRisky Decision Making in Neurofibromatosis Type 1: An Exploratory Study

BackgroundNeurofibromatosis type 1 (NF1) is a monogenic disorder affecting cognitive function. About one third of children with NF1 have attentional disorders, and the cognitive phenotype is characterized by impairment in prefrontally mediated functions. Mouse models of NF1 show irregularities in gamma-aminobutyric acid release and striatal dopamine metabolism. We hypothesized that youths with NF1 would show abnormal behavior and neural activity on a task of risk taking reliant on prefrontal-striatal circuits.MethodsYouths with NF1 (n = 29) and demographically comparable healthy control subjects (n = 22), aged 8 to 19 years, were administered a developmentally sensitive gambling task in which they chose between low-risk gambles with a high probability of obtaining a small reward and high-risk gambles with a low probability of obtaining a large reward. We used functional magnetic resonance imaging to investigate neural activity associated with risky decision making as well as age-associated changes in these behavioral and neural processes.ResultsBehaviorally, youths with NF1 tended to make fewer risky decisions than control subjects. Neuroimaging analyses revealed significantly reduced neural activity across multiple brain regions involved in higher-order semantic processing and motivation (i.e., anterior cingulate, paracingulate, supramarginal, and angular gyri) in patients with NF1 relative to control subjects during the task. We also observed atypical age-associated changes in neural activity in patients with NF1 such that during risk taking neural activity tended to decrease with age in control subjects, whereas it tended to increase with age in patients with NF1.ConclusionsFindings suggest that developmental trajectories of neural activity during risky decision making may be disrupted in youths with NF1.