title: Amygdala Lesions Reduce Anxiety-like Behavior in a Human Benzodiazepine-Sensitive Approach-Avoidance Conflict Test.
abstract: BACKGROUND
  Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation.
  
  
  METHODS
  In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions.
  
  
  RESULTS
  Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report.
  
  
  CONCLUSIONS
  Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior.
authors.affiliation: Division of Clinical Psychiatry Research, Psychiatric Hospital, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland. Electronic address: christoph.korn@uzh.ch.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Korn
authors.affiliation: Division of Clinical Psychiatry Research, Psychiatric Hospital, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Vunder
authors.affiliation: Epilepsy Unit, University Hospital of Bellvitge, Barcelona, Spain.
authors.forename: Júlia
authors.initials: J
authors.lastname: Miró
authors.affiliation: Cognition and Brain Plasticity Unit, Institute of Biomedicine Research of Bellvitge, Barcelona, Spain; Department of Cognition, Development, and Educational Psychology, Barcelona, Spain; Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Fuentemilla
authors.affiliation: Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Hurlemann
authors.affiliation: Division of Clinical Psychiatry Research, Psychiatric Hospital, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland; Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom.
authors.forename: Dominik R
authors.initials: DR
authors.lastname: Bach
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000473:pathology*; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001362:Avoidance Learning / Q000187:drug effects*; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D016022:Case-Control Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D008140:Lorazepam
keywords: Anxiety disorder; Double-blind; Hippocampus; Lorazepam; Placebo-controlled; Urbach-Wiethe syndrome