Elsevier

Hormones and Behavior

Volume 61, Issue 3, March 2012, Pages 400-409
Hormones and Behavior

Review
Human neuroimaging of oxytocin and vasopressin in social cognition

https://doi.org/10.1016/j.yhbeh.2012.01.016Get rights and content

Abstract

The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using “pharmacological fMRI” and “imaging genetics”, respectively. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Highlights

► Human oxytocin and vasopressin pharmacological fMRI studies reveal acute effects on social cognition neural circuitry. ► Human oxytocin and vasopressin imaging genetics studies reveal chronic effects on brain structure and function. ► Implications for mental disorders characterized by social dysfunction are discussed.

Introduction

Oxytocin and arginine-vasopressin are highly evolutionarily conserved, molecularly similar neuropeptides known, in part, for their prominent role in mammalian social behavior and social cognition (Donaldson and Young, 2008). Historically, the social functions of oxytocin and vasopressin have primarily been elucidated in animal studies; receptor knockout, antagonism, and agonism have determined a role for oxytocin (Neumann, 2008) and vasopressin (Caldwell et al., 2008) in social affiliative and aggressive behavior (Insel, 2010), social memory and recognition (Bielsky and Young, 2004), and social stress and anxiety (Carter et al., 2008), as well as provided insight into the involvement of particular neural systems and brain regions underlying the social effects of oxytocin and vasopressin such as the amygdala, lateral septum, and nucleus accumbens (Raggenbass, 2008, Ross et al., 2009, Veenema and Neumann, 2008).

Parallel studies in humans are challenged by ethical constraints and the complexity of human sociality; however, both the discovery that the intranasal administration of neuropeptides is successful in getting them into the brain (Born et al., 2002) and advances in the mapping of human genetic variation have allowed researchers to investigate how increasing brain oxytocin and vasopressin concentrations and how genetic variation in oxytocin and vasopressin receptor genes modulate human social behavior. These investigations have revealed a role for oxytocin and/or vasopressin in a variety of human social cognitive processes, including social memory and recognition, emotion perception, empathy, trust, cooperation, fear and aggression, and social stress (for reviews see (Bartz et al., 2011, Bos et al., 2012, Ebstein et al., 2010)). While providing valuable information regarding the role of these prosocial neuropeptides in human social behavior, the aforementioned behavioral human studies do not reveal the neural systems underlying the effects of oxytocin and vasopressin on human social behavior. Given evidence that the distribution of oxytocin and vasopressin receptors in the human brain differs from that in rodents (Loup et al., 1991), as well as the species-specific differences in sensory systems critically involved in social perception/interactions (i.e., rodents rely mostly on olfactory cues, while humans rely primarily on auditory and visual cues), neural mechanisms of the influence of oxytocin and vasopressin on human sociality are likely to be, at least in part, different than in animals. As such, identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition.

The advent of non-invasive neuroimaging, and its increasing presence in mainstream human research, has enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. While several neuroimaging techniques exist, virtually all investigations pertinent to the current review (i.e., specific to understanding the impact of oxytocin and vasopressin on neural activity and morphology related to social processes in particular) have made use of structural and functional magnetic resonance imaging (MRI and fMRI, respectively). Whereas structural MRI conveys morphological information (e.g., local gray matter volume), fMRI provides regional signals representing an indirect measure of synaptic activity by virtue of activity-dependent changes in local hemodynamics (Logothetis and Wandell, 2004). Specifically, the research highlighted in the current review utilizes “pharmacological fMRI” and “imaging genetics” to assess acute or chronic influences, respectively, of oxytocin and vasopressin on neural circuitry underlying social behaviors. Pharmacological fMRI entails the combination of drug administration with fMRI to assess the influence of a drug on task-related brain activity (Honey and Bullmore, 2004). To that end, here we present pharmacological fMRI investigations of the acute effect that intranasal oxytocin and vasopressin administration has on neural activity during engagement in particular social cognitive processes. Imaging genetics is the investigation of how a particular genetic variant chronically impacts neural activity or morphology (Hariri and Weinberger, 2003). Here, we present imaging genetics studies on the consequences of human genetic variants related to oxytocin and vasopressin receptor genes on brain activity and gray matter volume in socially-relevant brain regions.

In the following sections, we review relevant pharmacological fMRI and imaging genetics studies for oxytocin and vasopressin separately, limiting our discussion to studies specifically directed at determining the influence of oxytocin/vasopressin on neural circuitry underlying some aspect of social cognition (Table 1). The studies are performed on healthy men and women, however, in a subsequent section we discuss the implications for mental disorders characterized by social dysfunction, including a review of relevant research in particular psychiatric populations. Finally, we will end with concluding remarks and a discussion of future research directions and remaining questions.

Section snippets

Pharmacological fMRI studies: Effects of intranasal oxytocin administration

To identify neural correlates underlying the influence of oxytocin on human social cognitive processes, the pharmacological fMRI studies highlighted in this section implemented double-blinded, placebo-controlled (either within and between subjects) procedures involving intranasal administration of OT at a dose of 24–32 IU, which has become the norm in human studies of OT administration (Bos et al., 2012). Despite the potential for fMRI to provide researchers with a snapshot of neural activity in

Pharmacological fMRI studies: Effects of intranasal vasopressin administration

To date, pharmacological fMRI studies investigating the effects of vasopressin on neural activity related to social cognition are far outnumbered by those of oxytocin; yet a few studies, using double-blind, placebo-controlled procedures, have demonstrated distinct neural activation patterns related to intranasal administration of vasopressin in men (Rilling et al., 2011, Zink et al., 2010, Zink et al., 2011). Despite the marked structural similarity between vasopressin and oxytocin – differing

Neuroimaging of oxytocin and vasopressin in psychiatric disorders

Accumulating evidence suggests a role of oxytocin and/or vasopressin in a host of neuropsychiatric disorders, particularly those with aspects of social dysfunction, including autism spectrum disorder, social anxiety disorder, obsessive–compulsive disorder, depression, schizophrenia, and attachment disorders (Heinrichs et al., 2009, McCarthy and Altemus, 1997). Up to this point, the oxytocin and vasopressin pharmacological fMRI and imaging genetics studies highlighted in this review have been

Conclusions and future directions

As intricate as human social behavior is, the influence of oxytocin and vasopressin on the neural circuitry underlying social cognitive processes is also undeniably complex. While in the last several years oxytocin and vasopressin pharmacological fMRI and imaging genetics research has produced multiple promising findings, they are often diverse and disparate, limiting their generalizability and conclusiveness. Oxytocin and vasopressin effects on social-related neural responses are strongly

Acknowledgments

C.F.Z. acknowledges support from the Intramural Research Program of the National Institute of Mental Health during the preparation of this manuscript. A.M.-L. acknowledges grant support from the Deutsche Forschungsgemeinschaft (DFG; SFB 636), Bundesministerium für Bildung und Forschung (BMBF; NGFN-MooDs, Bernstein-Programme), European Union (NEWMEDS, OPTIMIZE and EU-GEI) and National Alliance for Research on Schizophrenia and Depression (NARSAD; Distinguished Investigator Award) during the

References (87)

  • G. Domes et al.

    Oxytocin improves “mind-reading” in humans

    Biol. Psychiatry

    (2007)
  • G. Domes et al.

    Effects of intranasal oxytocin on emotional face processing in women

    Psychoneuroendocrinology

    (2010)
  • R.P. Ebstein et al.

    Genetics of human social behavior

    Neuron

    (2010)
  • Y. Fan et al.

    Is there a core neural network in empathy? An fMRI based quantitative meta-analysis

    Neurosci. Biobehav. Rev.

    (2011)
  • M. Fischer-Shofty et al.

    The effect of intranasal administration of oxytocin on fear recognition

    Neuropsychologia

    (2010)
  • D.J. Furman et al.

    Variant in oxytocin receptor gene is associated with amygdala volume

    Psychoneuroendocrinology

    (2011)
  • M.I. Gobbini et al.

    Neural systems for recognition of familiar faces

    Neuropsychologia

    (2007)
  • J.L. Goodson et al.

    Nonapeptide mechanisms of social cognition, behavior and species-specific social systems

    Curr. Opin. Neurobiol.

    (2010)
  • A.J. Guastella et al.

    Oxytocin increases gaze to the eye region of human faces

    Biol. Psychiatry

    (2008)
  • A.J. Guastella et al.

    Intranasal arginine vasopressin enhances the encoding of happy and angry faces in humans

    Biol. Psychiatry

    (2010)
  • U. Habel et al.

    Amygdala activation and facial expressions: explicit emotion discrimination versus implicit emotion processing

    Neuropsychologia

    (2007)
  • A.R. Hariri et al.

    The amygdala response to emotional stimuli: a comparison of faces and scenes

    NeuroImage

    (2002)
  • A.R. Hariri et al.

    Neocortical modulation of the amygdala response to fearful stimuli

    Biol. Psychiatry

    (2003)
  • J.V. Haxby et al.

    The distributed human neural system for face perception

    Trends Cogn. Sci.

    (2000)
  • M. Heinrichs et al.

    Oxytocin, vasopressin, and human social behavior

    Front. Neuroendocrinol.

    (2009)
  • G. Honey et al.

    Human pharmacological MRI

    Trends Pharmacol. Sci.

    (2004)
  • H. Inoue et al.

    Association between the oxytocin receptor gene and amygdalar volume in healthy adults

    Biol. Psychiatry

    (2010)
  • T.R. Insel

    The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior

    Neuron

    (2010)
  • S. Jacob et al.

    Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism

    Neurosci. Lett.

    (2007)
  • R. Landgraf et al.

    Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication

    Front. Neuroendocrinol.

    (2004)
  • X. Liu et al.

    Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

    J. Hum. Genet.

    (2010)
  • F. Loup et al.

    Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study

    Brain Res.

    (1991)
  • M.M. McCarthy et al.

    Central nervous system actions of oxytocin and modulation of behavior in humans

    Mol. Med. Today

    (1997)
  • M. Mikolajczak et al.

    Oxytocin not only increases trust when money is at stake, but also when confidential information is in the balance

    Biol. Psychol.

    (2010)
  • M. Raggenbass

    Overview of cellular electrophysiological actions of vasopressin

    Eur. J. Pharmacol.

    (2008)
  • M.M. Riem et al.

    Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial

    Biol. Psychiatry

    (2011)
  • R. Saxe et al.

    Making sense of another mind: the role of the right temporo-parietal junction

    Neuropsychologia

    (2005)
  • J.L. Stein et al.

    A validated network of effective amygdala connectivity

    NeuroImage

    (2007)
  • R. Thompson et al.

    The effects of vasopressin on human facial responses related to social communication

    Psychoneuroendocrinology

    (2004)
  • H. Tost et al.

    Neurogenetic Effects of OXTR rs2254298 in the Extended Limbic System of Healthy Caucasian Adults

    Biol. Psychiatry

    (2011)
  • A.H. Veenema et al.

    Central vasopressin and oxytocin release: regulation of complex social behaviours

    Prog. Brain Res.

    (2008)
  • L.M. Williams et al.

    Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording

    NeuroImage

    (2001)
  • S. Wu et al.

    Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population

    Biol. Psychiatry

    (2005)
  • Cited by (143)

    View all citing articles on Scopus
    View full text