Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers
Introduction
In contrast to most mammalian species, humans have been characterized as an alloparental species in which mothers typically receive help from other adults in raising their children (Hrdy, 2009). In some societies and cultures, the primary helper is the father, and in this situation, paternal involvement is associated with reduced child mortality and morbidity (Gaudino et al., 1999, Weitoft et al., 2003), as well as improved social, psychological, and educational outcomes (Cabrera et al., 2000, Sarkadi et al., 2008). Yet, despite these facts, there is remarkable variation in paternal involvement (Hrdy, 2009) and father absence has increased precipitously over the last half of the 20th century (Cabrera et al., 2000), highlighting the importance of understanding the neurobiological influences on paternal caregiving.
Oxytocin (OT) is a naturally occurring endogenous neuropeptide that is produced in the paraventricular and supraoptic nuclei of the hypothalamus and released into both the brain and the peripheral circulation (Meyer-Lindenberg et al., 2011). Peripherally, it promotes both uterine contractions during labor and milk letdown during nursing, while centrally, it promotes maternal caregiving (Rilling and Young, 2014) and other forms of attachment. In rats, OT acts on the mesolimbic dopamine (DA) system to facilitate the motivation to approach and nurture offspring (Numan, 2007). The mesolimbic DA system may also motivate caregiving in humans. For example, nucleus accumbens activation scales to the degree of “baby schema” (i.e., cuteness) of child pictures, as well as with the self-reported motivation to care for the children among women (Glocker et al., 2009a, Glocker et al., 2009b). Moreover, OT has been shown to augment activation within the mesolimbic DA system as women view pictures of unknown crying infants (Gregory et al., 2015). Thus, humans and rodents may share core neural mechanisms that motivate maternal behavior (Rilling and Young, 2014).
Recent work suggests that maternal and paternal behavior rely on similar neural substrates. For example, the medial preoptic area of the hypothalamus is now known to be a critical node for parental behavior in both sexes (Wu et al., 2014). Perhaps, like maternal caregiving, paternal caregiving is mediated by OT acting in the mesolimbic DA system. Married fathers have higher levels of plasma OT than unmarried non-fathers (Mascaro et al., 2014b), and plasma OT levels increase over the first 6 months of fatherhood (Gordon et al., 2010). Moreover, paternal plasma OT levels are correlated with father-infant affect synchrony and with stimulatory touch in father-infant play sessions (Feldman et al., 2011, Gordon et al., 2010). In addition, intranasal OT treatment increases paternal stimulatory and exploratory play with toddlers and increases the duration of episodes of father-infant touch and social reciprocity. These augmented paternal behaviors in turn alter the infant's behavior, increasing the duration of infant gaze to the father and infant object manipulation, as well as infant salivary oxytocin (Weisman et al., 2012). Overall, OT appears to motivate paternal behaviors that facilitate father-infant bonding. Collectively, these findings lead to the prediction that intranasal OT will augment activation within the mesolimbic DA system as men view pictures of their children.
Infants solicit parental caregiving not only by their appearance but also through crying. In mice, OT in the left auditory cortex accelerates maternal retrieval of crying pups (Marlin et al., 2015). Infant crying can also be an aversive stimulus and parents must often regulate their initial negative emotional reaction to it in order to deliver appropriate care. In female rats, OT acts via the medial preoptic area (MPOA) to inhibit an avoidance system that includes the amygdala (Numan, 2007). Intranasal OT also attenuates the amygdala response to unknown infant cries among nulliparous women (Riem et al., 2011), consistent with inhibition of an avoidance pathway. The same study also found that intranasal OT augmented the anterior insula response to unknown infant cries, suggesting that OT may also enhance empathic responses to infant cries. The effect of OT on the neural response to infant cries in fathers has not yet been investigated.
Vasopressin (AVP), which differs from OT by only two amino acids, has also been implicated in paternal behavior. AVP injections into the lateral septum elicit paternal behavior in male prairie voles (Wang et al., 1994), and AVP-immunoreactive staining in bed nucleus of stria terminalis (BNST) terminals predicts paternal behavior in California mice (Bester-Meredith and Marler, 2003). In primates, marmoset monkey fathers have increased V1a vasopressin receptor density as well as increased dendritic spine density on neurons in prefrontal cortex (Kozorovitskiy et al., 2006). Finally, intranasal AVP administration increased attention to virtual baby-related avatars in human fathers-to-be (Cohen-Bendahan et al., 2015). However, the role of AVP in human parental behavior, as well as its neural mechanism, has not been investigated.
In the current double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT on one scan and placebo on the other (n = 15) or 20 IU intranasal AVP on one scan and placebo on the other (n = 15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listed to unknown infant cry stimuli. Fathers also rated their subjective reactions to cry stimuli. Our aim was to evaluate the effect of intranasal OT and AVP on paternal brain function and subjective ratings of cry stimuli. We also sought to determine if any such effects were modulated by attachment security or early life experience, as has been reported previously (Bakermans-Kranenburg and van IJzendoorn, 2013, Bartz et al., 2011). We hypothesized that intranasal OT would augment activation within the mesolimbic DA system as men viewed pictures of their children, and that it would also augment activation in auditory cortex and anterior insula in response to baby cries, while suppressing activation to baby cries in the amygdala. We further hypothesized that intranasal OT would attenuate negative subjective reactions to cry stimuli through inhibition of the avoidance pathway. Finally, we expected these effects of OT to be stronger among fathers with supportive family backgrounds (Bakermans-Kranenburg and van IJzendoorn, 2013) and high levels of attachment anxiety (De Dreu, 2012b). Given the much more limited body of research on AVP and paternal behavior, we did not have a-priori hypotheses as to how it would influence brain function in fathers.
Section snippets
Subjects
Thirty-one biological fathers of 1–2 year old children were recruited by posting flyers around the Emory University campus, at local parks and daycare centers. Fathers were required to be currently cohabitating with their committed partner and child. Enrollment in the study required participation by the father, his adult partner and their child. All enrolled fathers had female partners. The study was approved by the Emory Institutional Review Board, and all participants gave written informed
Main effects of child picture stimuli under placebo treatment
Viewing own children, compared with viewing adults, yielded widespread activation, including the caudate nucleus, putamen, substantia nigra, thalamus, medial prefrontal cortex (MPFC) and visual cortex, as well as deactivation in subgenual ACC (Fig. S3a, Supplementary Table 1). The contrast between own and unknown child pictures yielded a very similar pattern of activation (Fig. S3b; Supplementary Table 1). There was no significant activation for the contrast between unknown child and adult
Discussion
As outlined in the introduction, considerable evidence suggests that OT facilitates multiple aspects of paternal caregiving (Feldman et al., 2011, Gordon et al., 2010, Mascaro et al., 2014b, Weisman et al., 2012). Our study was designed to investigate the neural mechanism for this effect. Our main finding is that intranasal OT increases the caudate nucleus, dACC and visual cortex response in fathers viewing pictures of their toddlers. In contrast, AVP had no effect on paternal neural responses
Conclusion
While it has long been known that pregnancy hormones prime mammalian females for parental caregiving (Rilling and Young, 2014), only recently has it become clear that males of some mammalian species, including our own, also experience hormonal changes that may prime them for parental caregiving. These changes include decreases in testosterone and increases in oxytocin (Gettler et al., 2011, Gordon et al., 2010, Gray et al., 2002, Mascaro et al., 2014b). Here, in a sample of fathers of 1–2 year
Acknowledgements
This study was supported by National Institute of Child Health and Human Development [grant R21HD078778] and the National Center for Advancing Translational Sciences of the National Institutes of Health [award number UL1TR000454]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
We thank Lynnet Richey for assistance with making figures and Elissar Andari for many helpful comments on the manuscript.
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2022, Hormones and BehaviorCitation Excerpt :On a neural level, administration of vasopressin increased neural activation in response to infant cry sounds accompanied by emotional (versus neutral) contextual information (Thijssen et al., 2018). In a different sample, administration of vasopressin had no effects on neural responses to infant cry sounds in fathers in the postnatal period (Li et al., 2017). In the same sample as Thijssen et al. (2018), expectant fathers used more handgrip force after vasopressin administration (as compared to placebo) in reaction to viewing an image of an unknown infant versus viewing an image of their own infant, possibly indicating that vasopressin administration reduces empathy for an unknown crying infant (Alyousefi-van Dijk et al., 2019).
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2022, PsychoneuroendocrinologyCitation Excerpt :A previous study indicated that nulliparous women receiving intranasal oxytocin (as compared to placebo) showed increased insula and inferior frontal gyrus reactivity during exposure to infant cry sounds and decreased activation of the amygdala, suggesting that oxytocin stimulates sensitive responses to infant crying by enhancing empathy and decreasing anxiety and aversion (Riem et al., 2011). However, oxytocin administration did not affect neural responses to infant cry sounds (versus control stimulus) in 15 fathers with 1–2-year-old first-born and non-first-born children (Li et al., 2017). The effects of oxytocin administration on infant cry perception in the first year of fatherhood (between 2 and 12 months after the birth of their first child) is currently unknown.