title: Prediction Error Representation in Individuals With Generalized Anxiety Disorder During Passive Avoidance.
abstract: OBJECTIVE
  Deficits in reinforcement-based decision making have been reported in generalized anxiety disorder. However, the pathophysiology of these deficits is largely unknown; published studies have mainly examined adolescents, and the integrity of core functional processes underpinning decision making remains undetermined. In particular, it is unclear whether the representation of reinforcement prediction error (PE) (the difference between received and expected reinforcement) is disrupted in generalized anxiety disorder. This study addresses these issues in adults with the disorder.
  
  
  METHODS
  Forty-six unmedicated individuals with generalized anxiety disorder and 32 healthy comparison subjects group-matched on IQ, gender, and age performed a passive avoidance task while undergoing functional MRI. Data analyses were performed using a computational modeling approach.
  
  
  RESULTS
  Behaviorally, individuals with generalized anxiety disorder showed impaired reinforcement-based decision making. Imaging results revealed that during feedback, individuals with generalized anxiety disorder relative to healthy subjects showed a reduced correlation between PE and activity within the ventromedial prefrontal cortex, ventral striatum, and other structures implicated in decision making. In addition, individuals with generalized anxiety disorder relative to healthy participants showed a reduced correlation between punishment PEs, but not reward PEs, and activity within the left and right lentiform nucleus/putamen.
  
  
  CONCLUSIONS
  This is the first study to identify computational impairments during decision making in generalized anxiety disorder. PE signaling is significantly disrupted in individuals with the disorder and may lead to their decision-making deficits and excessive worry about everyday problems by disrupting the online updating ("reality check") of the current relationship between the expected values of current response options and the actual received rewards and punishments.
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Stuart F
authors.initials: SF
authors.lastname: White
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Marilla
authors.initials: M
authors.lastname: Geraci
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lewis
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Joseph
authors.initials: J
authors.lastname: Leshin
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Cindy
authors.initials: C
authors.lastname: Teng
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Bruno
authors.initials: B
authors.lastname: Averbeck
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Harma
authors.initials: H
authors.lastname: Meffert
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Monique
authors.initials: M
authors.lastname: Ernst
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: James R
authors.initials: JR
authors.lastname: Blair
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Christian
authors.initials: C
authors.lastname: Grillon
authors.affiliation: From the Section on Affective Cognitive Neuroscience, the Section on Fear and Anxiety, and the Unit on Learning and Decision Making, NIMH, Bethesda; and the Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Neb.
authors.forename: Karina S
authors.initials: KS
authors.lastname: Blair
mesh_terms: D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D001362:Avoidance Learning / Q000502:physiology*; D003657:Decision Making / Q000502:physiology*; D005260:Female; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D066230:Patient-Specific Modeling; D010364:Pattern Recognition, Visual / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D012016:Reference Values; D012054:Reinforcement, Psychology; D012718:Set, Psychology; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Decision-Making; Generalized Anxiety Disorder; Prediction Error; Punishment; Reward; Striatum