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Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control

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Abstract

Rationale

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.

Objectives

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.

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Acknowledgements

This research was supported by Grant No. MH070892 to KPS from the National Institute of Mental Health and by a pilot grant to KPS from the Mount Sinai School of Medicine General Clinical Research Center, which is funded by grant MO1RR00071 from the National Center for Research Resources, a component of the National Institutes of Health. Development of the MacBrain Face Stimulus Set (NimStim) was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at nimtottenham@ucla.edu for more information concerning the stimulus set. Thanks to our volunteers for participating in this study and to Hanna Oltarzewska and Frank Macaluso for their invaluable support in data acquisition.

Financial disclosures

Dr. Newcorn is a recipient of grants for research support from Eli Lilly & Co., Ortho-McNeil-Janssen, and Shire and is or has been an advisor/consultant for Alcobra, Eli Lilly & Co., NEOS, Ortho-McNeil-Janssen, Shire, and BioBehavioral Diagnostics Company. No other authors have financial interests or potential conflicts of interest to declare.

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Correspondence to Kurt P. Schulz.

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This research was supported by National Institutes of Health (NIH) Grant K01MH070892 and Grant MO1RR00071 from the National Center for Research Resources, a component of the NIH. Dr. Newcorn is a recipient of research grants from Eli Lilly, Ortho-McNeil-Janssen and Shire; and is or has been an advisor/consultant for Alcobra, Biobehavioral Diagnostics, Eli Lilly, Ortho-McNeil-Janssen, and Shire. No other authors have financial interests or potential conflicts of interest to declare.

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Schulz, K.P., Clerkin, S.M., Fan, J. et al. Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control. Psychopharmacology 226, 261–271 (2013). https://doi.org/10.1007/s00213-012-2893-8

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  • DOI: https://doi.org/10.1007/s00213-012-2893-8

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