title: Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity for cognitive control.
abstract: Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders.
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Kurt P
authors: KP
authors: Schulz
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychology, Purchase College of the State University of New York, Purchase, NY, USA.
authors: Suzanne M
authors: SM
authors: Clerkin
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Jeffrey H
authors: JH
authors: Newcorn
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychology, Queens College of the City University of New York, Flushing, NY, USA.
authors: Jeffrey M
authors: JM
authors: Halperin
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychology, Queens College of the City University of New York, Flushing, NY, USA.
authors: Jin
authors: J
authors: Fan
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000187:drug effects*; D000704:Analysis of Variance; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005145:Face; D005149:Facial Expression; D005260:Female; D016316:Guanfacine / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000187:drug effects; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine; D010100:Oxygen
keywords: Amygdala; Emotion; Go/no-go; Guanfacine; Prefrontal cortex; fMRI