+ Models PNEC-2288; No. of Pages 13 Please cite this article in press as: Bethlehem, R.A.I., et al., Oxytocin, brain physiology, and functional connectivity: A review of intranasal oxytocin fMRI studies. Psychoneuroendocrinology (2012), http://dx.doi.org/10.1016/j.psyneuen.2012.10.011 REVIEW Oxytocin, brain physiology, and functional connectivity: A review of intranasal oxytocin fMRI studies Richard A.I. Bethlehem a,c, * , Jack van Honk a,b , Bonnie Auyeung c , Simon Baron-Cohen c a Department of Experimental Psychology, Utrecht University, Heidelberglaan 2, 3584CS Utrecht, The Netherlands b Department of Psychiatry and Mental Health, University of Cape Town, J-Block Groote Schuur Hospital Observatory, Cape Town, South Africa c Autism Research Centre, Department of Psychiatry, University of Cambridge, Trumpington Road 18b, Cambridge CB2 8AH, United Kingdom Received 28 August 2012; received in revised form 10 October 2012; accepted 10 October 2012 Psychoneuroendocrinology (2012) xxx, xxx—xxx KEYWORDS Oxytocin; fMRI; Amygdala; Functional connectivity; Neural communication; Social brain Summary In recent years the neuropeptide oxytocin (OT) has become one of the most studied peptides of the human neuroendocrine system. Research has shown widespread behavioural effects and numerous potential therapeutic benefits. However, little is known about how OT triggers these effects in the brain. Here, we discuss some of the physiological properties of OT in the human brain including the long half-life of neuropeptides, the diffuse projections of OT throughout the brain and interactions with other systems such as the dopaminergic system. These properties indicate that OT acts without clear spatial and temporal specificity. Therefore, it is likely to have widespread effects on the brain’s intrinsic functioning. Additionally, we review studies that have used functional magnetic resonance imaging (fMRI) concurrently with OT administration. These studies reveal a specific set of ‘social’ brain regions that are likely to be the strongest targets for OT’s potential to influence human behaviour. On the basis of the fMRI literature and the physiological properties of the neuropeptide, we argue that OT has the potential to not only modulate activity in a set of specific brain regions, but also the functional connectivity between these regions. In light of the increasing knowledge of the behavioural effects of OT in humans, studies of the effects of OT administration on brain function can contribute to our understanding of the neural networks in the social brain. # 2012 Elsevier Ltd. All rights reserved. * Corresponding author at: Department of Experimental Psychology, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands. Tel.: +31 030 253 4368. E-mail address: r.a.i.bethlehem@uu.nl (R.A.I. Bethlehem). Available online at www.sciencedirect.com j our na l h omepa g e: www.e lse vie r.c om/l oca te/ psyne ue n 0306-4530/$ — see front matter # 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psyneuen.2012.10.011