The human brain is distinct from those of other species in terms of size, organization, and connectivity. How do structural evolutionary differences drive patterns of neural activity enabling brain function? Here, we combine brain imaging and biophysical modeling to show that the anatomical wiring of the human brain distinctly shapes neural dynamics. This shaping is characterized by a narrower distribution of dynamic ranges across brain regions compared with  that of chimpanzees, our closest living primate relatives. We find that such a narrow dynamic  range distribution supports faster integration between regions, particularly in transmodal systems. Conversely, a broad dynamic range distribution as seen in chimpanzees facilitates brain processes relying more on neural interactions within specialized local brain systems. These findings suggest that human brain dynamics have evolved to foster rapid associative processes in  service of complex cognitive functions and behavior.

Despite our close genetic relationship with chimpanzees, there are notable differences between chimpanzee and human social behavior. Oxytocin and vasopressin are neuropeptides involved in regulating social behavior across vertebrate taxa, including pair bonding, social communication, and aggression, yet little is known about the neuroanatomy of these systems in primates, particularly in great apes. Here, we used receptor autoradiography to localize oxytocin and vasopressin V1a receptors, OXTR and AVPR1a respectively, in seven chimpanzee brains. OXTR binding was detected in the lateral septum, hypothalamus, medial amygdala, and substantia nigra. AVPR1a binding was observed in the cortex, lateral septum, hypothalamus, mammillary body, entire amygdala, hilus of the dentate gyrus, and substantia nigra. Chimpanzee OXTR/AVPR1a receptor distribution is compared to previous studies in several other primate species. One notable difference is the lack of OXTR in reward regions such as the ventral pallidum and nucleus accumbens in chimpanzees, whereas OXTR is found in these regions in humans. Our results suggest that in chimpanzees, like in most other anthropoid primates studied to date, OXTR has a more restricted distribution than AVPR1a, while in humans the reverse pattern has been reported. Altogether, our study provides a neuroanatomical basis for understanding the function of the oxytocin and vasopressin systems in chimpanzees.

The neural mechanisms supporting social bonds between adult men remain uncertain. In this double-blind, placebo-controlled study, we investigate the impact of intranasally administered oxytocin (OT) and vasopressin (AVP) on behavior and brain activity among men in the context of an iterated Prisoner’s Dilemma game, which models a real-life social situation. fMRI results show that, relative to both AVP and placebo, OT increases the caudate nucleus response to reciprocated cooperation, which may augment the reward of reciprocated cooperation and/or facilitate learning that another person can be trusted. OT also enhances left amygdala activation in response to reciprocated cooperation. Behaviorally, OT was associated with increased rates of cooperation following unreciprocated cooperation in the previous round compared with AVP. AVP strongly increased cooperation in response to a cooperative gesture by the partner compared with both placebo and OT. In response to reciprocated cooperation, AVP increased activation in a region spanning known vasopressin circuitry implicated in affiliative behaviors in other species. Finally, both OT and AVP increase amygdala functional connectivity with the anterior insula relative to placebo, which may increase the amygdala’s ability to elicit visceral somatic markers that guide decision making. These findings extend our knowledge of the neural and behavioral effects of OT and AVP to the context of genuine social interactions.

Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals.

Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1-2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers had significantly higher levels of plasma oxytocin and lower levels of plasma testosterone. In response to child picture stimuli, fathers showed stronger activation than non-fathers within regions important for face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo-parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex [mOFC]). On the other hand, non-fathers had significantly stronger neural responses to sexually provocative images in regions important for reward and approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone levels were negatively correlated with responses to child stimuli in the MFG. Surprisingly, neither testosterone nor oxytocin levels predicted neural responses to sexual stimuli. Our results suggest that the decline in testosterone that accompanies the transition to fatherhood may be important for augmenting empathy toward children.

Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled "Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction." This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.

Crying is the principal means by which newborn infants shape parental behavior to meet their needs. While this mechanism can be highly effective, infant crying can also be an aversive stimulus that leads to parental frustration and even abuse. Fathers have recently become more involved in direct caregiving activities in modern, developed nations, and fathers are more likely than mothers to physically abuse infants. In this study, we attempt to explain variation in the neural response to infant crying among human fathers, with the hope of identifying factors that are associated with a more or less sensitive response. We imaged brain function in 39 first-time fathers of newborn infants as they listened to both their own and a standardized unknown infant cry stimulus, as well as auditory control stimuli, and evaluated whether these neural responses were correlated with measured characteristics of fathers and infants that were hypothesized to modulate these responses. Fathers also provided subjective ratings of each cry stimulus on multiple dimensions. Fathers showed widespread activation to both own and unknown infant cries in neural systems involved in empathy and approach motivation. There was no significant difference in the neural response to the own vs. unknown infant cry, and many fathers were unable to distinguish between the two cries. Comparison of these results with previous studies in mothers revealed a high degree of similarity between first-time fathers and first-time mothers in the pattern of neural activation to newborn infant cries. Further comparisons suggested that younger infant age was associated with stronger paternal neural responses, perhaps due to hormonal or novelty effects. In our sample, older fathers found infant cries less aversive and had an attenuated response to infant crying in both the dorsal anterior cingulate cortex (dACC) and the anterior insula, suggesting that compared with younger fathers, older fathers may be better able to avoid the distress associated with empathic over-arousal in response to infant cries. A principal components analysis revealed that fathers with more negative emotional reactions to the unknown infant cry showed decreased activation in the thalamus and caudate nucleus, regions expected to promote positive parental behaviors, as well as increased activation in the hypothalamus and dorsal ACC, again suggesting that empathic over-arousal might result in negative emotional reactions to infant crying. In sum, our findings suggest that infant age, paternal age and paternal emotional reactions to infant crying all modulate the neural response of fathers to infant crying. By identifying neural correlates of variation in paternal subjective reactions to infant crying, these findings help lay the groundwork for evaluating the effectiveness of interventions designed to increase paternal sensitivity and compassion.

The gene-culture coevolution (GCC) framework has gained increasing prominence in the social and biological sciences. While most studies on human GCC concern the evolution of low-level physiological traits, attempts have also been made to apply GCC to complex human traits, including social behavior and cognition. One major methodological challenge in this endeavor is to reconstruct a specific biological pathway between the implicated genes and their distal phenotypes. Here, we introduce a novel approach that combines data on population genetics and expression quantitative trait loci to infer the specific intermediate phenotypes of genes in the brain. We suggest that such “neuroendophenotypes” will provide more detailed mechanistic insights into the GCC process. We present a case study where we explored a GCC dynamics between the oxytocin receptor gene (OXTR) and cultural tightness–looseness. By combining data from the 1000 Genomes project and the Gene-Tissue-Expression project (GTEx), we estimated and compared OXTR expression in 10 brain regions across five human superpopulations. We found that OXTR expression in the anterior cingulate cortex (ACC) was highly variable across populations, and this variation correlated with cultural tightness and socio-ecological threats worldwide. The mediation models also suggested possible GCC dynamics where the increased OXTR expression in the ACC mediates or emerges from the tight culture and higher socio-ecological threats. Formal selection scans further confirmed that OXTR alleles linked to enhanced receptor expression in the ACC underwent positive selection in East Asian countries with tighter social norms. We discuss the implications of our method in human GCC research.

While a variety of meditation techniques are increasingly employed as health interventions, the fact that meditation requires a significant commitment of time and effort may limit its potential widespread utility. In the current study, we ask whether baseline subjective reports or brain activity in response to a "Pain for Self and Others" paradigm predicts subsequent engagement in mindfulness and compassion meditation. The study also investigated whether compassion training would impact neural responses when compared to an active health education control group. Prior to training, activation of the left and right anterior insula, an area thought to be important for empathy, in response to the Other pain task was positively related to engagement with compassion meditation as measured by practice time (n = 13). On the other hand, activity in the left amygdala during the Self pain task was negatively correlated with mindfulness practice time. Following the study intervention, there was no difference between the compassion group (n = 13), and the control group (n = 8), in brain responses to either the Self or Other task. These results are the first to indicate that baseline neural responses may predict engagement with meditation training and suggest that pre-existing neurobiological profiles differentially predispose individuals to engage with disparate meditation techniques. © 2012 Elsevier Inc.