Citation

Jonas RK, Roh E, Montojo CA, Pacheco LA, Rosser T, Silva AJ, Bearden CE. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2017; 2(2): 170-179.

Affiliation

Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles.

Copyright

(Copyright © 2017, Society of Biological Psychiatry, Publisher Elsevier Publishing)

DOI

10.1016/j.bpsc.2016.12.003

PMID

28736755

PMCID

PMC5518467

Abstract

BACKGROUND: Neurofibromatosis 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 GABA release and striatal dopamine metabolism. We hypothesized that youth with NF1 would show abnormal behavior and neural activity on a task of risk-taking reliant on prefrontal-striatal circuits.

METHODS: Youth with NF1 (N=29) and demographically comparable healthy controls (N=22), ages 8-19, 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 (fMRI) to investigate neural activity associated with risky decision making, as well as age-associated changes in these behavioral and neural processes.

RESULTS: Behaviorally, youth with NF1 tended to make fewer risky decisions than controls. 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 controls 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 controls, whereas it tended to increase with age in patients with NF1.

CONCLUSIONS: Findings suggest that developmental trajectories of neural activity during risky decision-making may be disrupted in youth with NF1.

Language: en

Keywords

Decision-Making; Development; Functional MRI; Neurofibromatosis Type I; Phenotype-Genotype; Psychiatric Disorders