title: Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control.
abstract: BACKGROUND
  Functional interactions between limbic regions that process emotions and frontal networks that guide response functions provide a substrate for emotional cues to influence behavior. Stimulation of postsynaptic α₂ adrenoceptors enhances the function of prefrontal regions in these networks. However, the impact of this stimulation on the emotional biasing of behavior has not been established.
  
  
  OBJECTIVE
  This study tested the effect of the postsynaptic α₂ adrenoceptor agonist guanfacine on the emotional biasing of response execution and inhibition in prefrontal cortex.
  
  
  METHODS
  Fifteen healthy young adults were scanned twice with functional magnetic resonance imaging while performing a face emotion go/no-go task following counterbalanced administration of single doses of oral guanfacine (1 mg) and placebo in a double-blind, cross-over design.
  
  
  RESULTS
  Lower perceptual sensitivity and less response bias for sad faces resulted in fewer correct responses compared to happy and neutral faces but had no effect on correct inhibitions. Guanfacine increased the sensitivity and bias selectively for sad faces, resulting in response accuracy comparable to happy and neutral faces, and reversed the valence-dependent variation in response-related activation in left dorsolateral prefrontal cortex (DLPFC), resulting in enhanced activation for response execution cued by sad faces relative to happy and neutral faces, in line with other frontoparietal regions.
  
  
  CONCLUSIONS
  These results provide evidence that guanfacine stimulation of postsynaptic α₂ adrenoceptors moderates DLPFC activation associated with the emotional biasing of response execution processes. The findings have implications for the α₂ adrenoceptor agonist treatment of attention-deficit hyperactivity disorder.
authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. kurt.schulz@mssm.edu
authors.forename: Kurt P
authors.initials: KP
authors.lastname: Schulz
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Clerkin
authors.forename: Jin
authors.initials: J
authors.lastname: Fan
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Halperin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003463:Cues; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D005260:Female; D016316:Guanfacine / Q000494:pharmacology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine