ReviewHuman neuroimaging of oxytocin and vasopressin in social cognition
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)
- et al.
Role of the amygdala in processing visual social stimuli
Prog. Brain Res.
(2006) - et al.
Social effects of oxytocin in humans: context and person matter
Trends Cogn. Sci.
(2011) - et al.
Oxytocin shapes the neural circuitry of trust and trust adaptation in humans
Neuron
(2008) - et al.
Oxytocin, vasopressin, and social recognition in mammals
Peptides
(2004) - et al.
The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study
Neuron
(2005) - et al.
Vasopressin: behavioral roles of an “original” neuropeptide
Prog. Neurobiol.
(2008) Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders?
Behav. Brain Res.
(2007)- et al.
Oxytocin, vasopressin and sociality
Prog. Brain Res.
(2008) Sex differences in vasopressin and oxytocin innervation of the brain
Prog. Brain Res.
(2008)- et al.
Oxytocin attenuates amygdala responses to emotional faces regardless of valence
Biol. Psychiatry
(2007)
Oxytocin improves “mind-reading” in humans
Biol. Psychiatry
Effects of intranasal oxytocin on emotional face processing in women
Psychoneuroendocrinology
Genetics of human social behavior
Neuron
Is there a core neural network in empathy? An fMRI based quantitative meta-analysis
Neurosci. Biobehav. Rev.
The effect of intranasal administration of oxytocin on fear recognition
Neuropsychologia
Variant in oxytocin receptor gene is associated with amygdala volume
Psychoneuroendocrinology
Neural systems for recognition of familiar faces
Neuropsychologia
Nonapeptide mechanisms of social cognition, behavior and species-specific social systems
Curr. Opin. Neurobiol.
Oxytocin increases gaze to the eye region of human faces
Biol. Psychiatry
Intranasal arginine vasopressin enhances the encoding of happy and angry faces in humans
Biol. Psychiatry
Amygdala activation and facial expressions: explicit emotion discrimination versus implicit emotion processing
Neuropsychologia
The amygdala response to emotional stimuli: a comparison of faces and scenes
NeuroImage
Neocortical modulation of the amygdala response to fearful stimuli
Biol. Psychiatry
The distributed human neural system for face perception
Trends Cogn. Sci.
Oxytocin, vasopressin, and human social behavior
Front. Neuroendocrinol.
Human pharmacological MRI
Trends Pharmacol. Sci.
Association between the oxytocin receptor gene and amygdalar volume in healthy adults
Biol. Psychiatry
The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior
Neuron
Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism
Neurosci. Lett.
Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication
Front. Neuroendocrinol.
Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population
J. Hum. Genet.
Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study
Brain Res.
Central nervous system actions of oxytocin and modulation of behavior in humans
Mol. Med. Today
Oxytocin not only increases trust when money is at stake, but also when confidential information is in the balance
Biol. Psychol.
Overview of cellular electrophysiological actions of vasopressin
Eur. J. Pharmacol.
Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial
Biol. Psychiatry
Making sense of another mind: the role of the right temporo-parietal junction
Neuropsychologia
A validated network of effective amygdala connectivity
NeuroImage
The effects of vasopressin on human facial responses related to social communication
Psychoneuroendocrinology
Neurogenetic Effects of OXTR rs2254298 in the Extended Limbic System of Healthy Caucasian Adults
Biol. Psychiatry
Central vasopressin and oxytocin release: regulation of complex social behaviours
Prog. Brain Res.
Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording
NeuroImage
Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population
Biol. Psychiatry
Cited by (143)
Four-week intranasal oxytocin administration reduces attachment avoidance in older women
2023, Hormones and BehaviorDifferences in Diffusion-Weighted Imaging and Resting-State Functional Connectivity Between Two Culturally Distinct Populations of Prairie Vole
2022, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingThe importance of pro-social processing, and ameliorating dysfunction in schizophrenia. An FMRI study of oxytocin
2022, Schizophrenia Research: Cognition