title: An fMRI examination of developmental differences in the neural correlates of uncertainty and decision-making.
abstract: BACKGROUND
  Maturation of prefrontal circuits during adolescence contributes to the development of cognitive processes such as decision-making. Recent theories suggest that these neural changes also play a role in the shift from generalized anxiety disorder (GAD) to depression that often occurs during this developmental period. Cognitive models of the development of GAD highlight the role of intolerance of uncertainty (IU), which can be characterized behaviorally by impairments in decision-making. The present study examines potential developmental differences in frontal regions associated with uncertain decision-making, and tests the impact of IU on these circuits.
  
  
  METHODS
  Twelve healthy adults (ages 19-36) and 12 healthy adolescents (ages 13-17) completed a decision-making task with conditions of varied uncertainty while fMRI scans were acquired. They also completed measures of worry and IU, and a questionnaire about their levels of anxiety and certainty during the task.
  
  
  RESULTS
  Combined group analyses demonstrated significant linear effects of uncertainty on activity within anterior cingulate cortex (ACC). Region of interest (ROI)-based analysis found a significant interaction of group and IU ratings in ACC. Increased IU was associated with robust linear increases in ACC activity only in adolescents. An ROI analysis of feedback-related processing found that adolescents demonstrated greater activation during incorrect trials relative to correct trials, while the adults showed no difference in neural activity associated with incorrect and correct feedback.
  
  
  CONCLUSIONS
  This decision-making task was shown to be effective at eliciting uncertainty-related ACC activity in adults and adolescents. Further, IU impacts ACC activity in adolescents during uncertain decision-making, providing preliminary support for a developmental model of GAD.
authors.affiliation: NYU Child Study Center, NYU School of Medicine, New York, NY 10016, USA. amy.krain@med.nyu.edu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Krain
authors.forename: Sara
authors.initials: S
authors.lastname: Hefton
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Monique
authors.initials: M
authors.lastname: Ernst
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Klein
authors.forename: Michael P
authors.initials: MP
authors.lastname: Milham
mesh_terms: D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology; D003657:Decision Making; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011795:Surveys and Questionnaires