The International Journal of Neuropsychopharmacology

Rapid Communication

Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex

Chandra Sekhar Sripadaa1 c1, K. Luan Phana1a2a3, Izelle Labuschagnea4, Robert Welsha1a5, Pradeep J. Nathana4a6 and Amanda G. Wooda7a8

a1 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

a2 Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA

a3 Neuroscience Program, University of Michigan, Ann Arbor, MI, USA

a4 School of Psychology and Psychiatry, Monash University, Australia

a5 Department of Radiology, University of Michigan, Ann Arbor, MI, USA

a6 Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK

a7 School of Psychology University of Birmingham, Edgbaston, UK

a8 Critical Care and Neurosciences, Murdoch Childrens Research Institute, Melbourne, Australia


The neuropeptide oxytocin (OXT) plays an important role in complex socio-affective behaviours such as affiliation, attachment, stress and anxiety. Previous studies have focused on the amygdala as an important target of OXT's effects. However, the effects of OXT on connectivity of the amygdala with cortical regions such as medial frontal cortex, an important mediator of social cognition and emotion regulation, remain unexplored. In a randomized, double-blind, cross-over design, 15 volunteers received intranasal OXT or placebo prior to resting-state functional magnetic resonance imaging. OXT significantly increased connectivity between both amygdalae and rostral medial frontal cortex (rmFC), while having only negligible effects on coupling with other brain regions. These results demonstrate that OXT is a robust and highly selective enhancer of amygdala connectivity with rmFC, a region critical to social cognition and emotion regulation, and add to our understanding of the neural mechanisms by which OXT modulates complex social and cognitive behaviours.

(Received July 25 2011)

(Reviewed September 13 2011)

(Revised March 09 2012)

(Accepted April 16 2012)

(Online publication May 30 2012)

Key words

  • Amygdala;
  • fMRI;
  • medial prefrontal cortex;
  • oxytocin;
  • resting-state connectivity.


c1 Address for correspondence: C. S. Sripada, MD, PhD, Department of Psychiatry, University of Michigan, Rachel Upjohn Building, Room 2743, 4250 Plymouth Road, Ann Arbor, MI 48109-2700, USA. Tel.: (734) 936-9527 Fax: (734) 936-7868 Email: or