The neuropeptide oxytocin (OT) plays a critical role in modulating social behavior across a wide range of vertebrate species. In humans, intranasal oxytocin (INOT) has been shown to modulate various aspects of social behavior, such as empathy, trust, in-group preference, and memory of socially relevant cues. Most INOT studies employ cross-sectional designs despite the enhanced statistical power and reduction in error variance associated with individual differences characteristic of within-subject designs. Using the Prisoner Dilemma task, which models a real-life dyadic social interaction, our group has systematically explored the effect of INOT on social cooperation and non-cooperation using a cross-sectional design. In the current study, we investigated if the main findings from our cross-sectional study could be replicated in a within-subject design using the same paradigm and whether new findings would emerge. We found OT to attenuate the ventral tegmental area response to reciprocated cooperation in women, an effect that is also present in our cross-sectional sample. However, other cross-sectional findings, especially those found in men, were not observed in this within-subject study. We hypothesize that the discrepancy can be explained by differing OT effects based on the degree of stimulus novelty/familiarity. Our within-subject study also revealed new effects not found previously in our cross-sectional study. Most importantly, OT treatment on scan 2 blocked amygdala habituation to unreciprocated cooperation found in a group that received placebo on both scans among men. Our results suggest that exogenous OT reduces the salience of positive social interactions among women and prevents habituation to negative social interactions among men. These findings may have implications for the potential clinical utility of OT as a treatment for psychiatric disorders.
Our two closest living primate relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), exhibit significant behavioral differences despite belonging to the same genus and sharing a very recent common ancestor. Differences have been reported in multiple aspects of social behavior, including aggression, sex, play and cooperation. However, the neurobiological basis of these differences has only been minimally investigated and remains uncertain. Here, we present the first ever comparison of chimpanzee and bonobo brains using diffusion tensor imaging, supplemented with a voxel-wise analysis of T1-weighted images to specifically compare neural circuitry implicated in social cognition. We find that bonobos have more gray matter in brain regions involved in perceiving distress in both oneself and others, including the right dorsal amygdala and right anterior insula. Bonobos also have a larger pathway linking the amygdala with the ventral anterior cingulate cortex, a pathway implicated in both top–down control of aggressive impulses as well as bottom–up biases against harming others. We suggest that this neural system not only supports increased empathic sensitivity in bonobos, but also behaviors like sex and play that serve to dissipate tension, thereby limiting distress and anxiety to levels conducive with prosocial behavior.
Background: Diffusion MRI (dMRI) data acquisition protocols are well-established on modern high-field clinical scanners for human studies. However, these protocols are not suitable for the chimpanzee (or other large-brained mammals) because of its substantial difference in head geometry and brain volume compared with humans. Therefore, an optimal dMRI data acquisition protocol dedicated to chimpanzee neuroimaging is needed. Methods: A multi-shot (4 segments) double spin-echo echo-planar imaging (MS-EPI) sequence and a single-shot double spin-echo EPI (SS-EPI) sequence were optimized separately for in vivo dMRI data acquisition of chimpanzees using a clinical 3T scanner. Correction for severe susceptibility-induced image distortion and signal drop-off of the chimpanzee brain was performed and evaluated using FSL software. DTI indices in different brain regions and probabilistic tractography were compared. A separate DTI data set from n=34 chimpanzees (13 to 56 years old) was collected using the optimal protocol. Age-related changes in diffusivity indices of optic nerve fibers were evaluated. Results: The SS-EPI sequence acquired dMRI data of the chimpanzee brain with approximately doubled the SNR as the MS-EPI sequence given the same scan time. The quality of white matter fiber tracking from the SS-EPI data was much higher than that from MS-EPI data. However, quantitative analysis of DTI indices showed no difference in most ROIs between the SS-EPI and MS-EPI sequences. The progressive evolution of diffusivity indices of optic nerves indicated mild changes in fiber bundles of chimpanzees aged 40 years and above. Conclusion: The single-shot EPI-based acquisition protocol provided better image quality of dMRI for chimpanzee brains and is recommended for in vivo dMRI study or clinical diagnosis of chimpanzees (or other large animals) using a clinical scanner. Also, the tendency of FA decrease or diffusivity increase in the optic nerve of aged chimpanzees was seen but did not show significant age-related changes, suggesting aging may have less impact on optic nerve fiber integrity of chimpanzees, in contrast to previous results for both macaque monkeys and humans.
Many war veterans struggle with depression and suicidality, and separation from the military is a time of particularly high risk. Based on research in non-human animals, we hypothesized that reduced oxytocin signaling would mediate symptoms of depression and suicidality in war veterans recently separated from their close comrades. We also hypothesized that veterans with more frequent contact with comrades would have fewer symptoms of depression and suicidality. In this cross-sectional study, male veterans from the Iraq and Afghanistan wars (n = 86) provided blood and urine samples for measurement of peripheral oxytocin (OT) levels, as well as saliva samples for DNA extraction followed by genotyping of oxytocin receptor gene (OXTR) Single Nucleotide Polymorphisms, and CpG-methylation assessment. Participants also completed a series of mental health questionnaires and interviews. Veterans reported feeling very close to their comrades during war, and missing them greatly upon returning home. Neither peripheral OT levels nor OXTR genotypes were related to symptoms of depression or suicidality. On the other hand, methylation at OXTR CpG −924 was negatively correlated with depressive symptomology, after controlling for possible confounds. Veterans who socialized with comrades more frequently had higher levels of urinary, but not plasma OT, as well as less depressive symptomology. Social connectedness was a strong negative predictor of symptoms of both depression and suicidality, eclipsing the predictive power of other variables such as post-deployment social support, the degree to which participants reported missing their comrades, and the frequency with which they socialized with comrades. Our results suggest that veteran mental health is more impacted by lack of social connectedness than by separation from close comrades per se. While there is some evidence that OXTR methylation relates to depressive symptomology, decreased OT signaling does not appear to mediate the relationship between social disconnectedness and depression or suicidality. Sleep quality and anxiety disorders were also significantly associated with mental health symptoms, independent of social connectedness. Our findings suggest that efforts aimed at alleviating the burden of depression and suicidality in returning war veterans should focus on re-integrating veterans into society and establishing a feeling of social connectedness, as well as on treating anxiety disorders and sleep problems.
The evolution of neurocranial morphology in Homo sapiens is characterized by bulging of the parietal region, a feature unique to our species. In modern humans, expansion of the parietal surface occurs during the first year of life, in a morphogenetic stage which is absent in chimpanzees and Neandertals. A similar variation in brain shape among living adult humans is associated with expansion of the precuneus. Using MRI-derived structural brain templates, we compare medial brain morphology between humans and chimpanzees through shape analysis and geometrical modeling. We find that the main spatial difference is a prominent expansion of the precuneus in our species, providing further evidence of evolutionary changes associated with this area. The precuneus is a major hub of brain organization, a central node of the default-mode network, and plays an essential role in visuospatial integration. Together, the comparative neuroanatomical and paleontological evidence suggest that precuneus expansion is a neurological specialization of H. sapiens that evolved in the last 150,000 years that may be associated with recent human cognitive specializations.
Objectives: Testosterone (T) has an integral, albeit complex, relationship with social behavior, especially in the domains of aggression and competition. However, examining this relationship in humans is challenging given the often covert and subtle nature of human aggression and status-seeking. The present study aimed to investigate whether T levels and genetic polymorphisms in the AR gene are associated with social behavior assessed via natural language use. Methods: We used unobtrusive, behavioral, real-world ambulatory assessments of men in partnered heterosexual relationships to examine the relationship between plasma T levels, variation in the androgen receptor (AR) gene, and spontaneous, everyday language in three interpersonal contexts: with romantic partners, with co-workers, and with their children. Results: Men's T levels were positively correlated with their use of achievement words with their children, and the number of AR CAG trinucleotide repeats was inversely correlated with their use of anger and reward words with their children. T levels were positively correlated with sexual language and with use of swear words in the presence of their partner, but not in the presence of co-workers or children. Conclusions: Together, these results suggest that T may influence social behavior by increasing the frequency of words related to aggression, sexuality, and status, and that it may alter the quality of interactions with an intimate partner by amplifying emotions via swearing.
Background: The neuropeptides oxytocin and vasopressin have been repeatedly implicated in social decision making by enhancing social salience and, generally, cooperation. The iterated and sequential version of the prisoner’s dilemma (PD) game is a social dilemma paradigm eliciting strategies of cooperation versus competition. Aims: We aimed to characterise the role of PD players’ sex, game partner type (computer vs. human) and oxytocin or vasopressin inhalation on the player’s strategy preference. Methods: Participants (153 men; 151 women) were randomised to intranasal 24 IU oxytocin, 20 IU vasopressin or placebo, double-blind, and played the PD. We examined main and interactive effects of sex, drug and partner type on strategy preference. Results: We found a pervasive preference for a tit-for-tat strategy (i.e. general sensitivity to the partner’s choices) over unconditional cooperation, particularly when against a human rather than a computer partner. Oxytocin doubled this sensitivity in women (i.e. the preference for tit-for-tat over unconditional cooperation strategies) when playing against computers, which suggests a tendency to anthropomorphise them, and doubled women’s unconditional cooperation preference when playing against humans. Vasopressin doubled sensitivity to the partner’s previous choices (i.e. for tit-for-tat over unconditional cooperation) across sexes and partner types. Conclusions: These findings suggest that women may be more sensitive to oxytocin’s social effects of anthropomorphism of non-humans and of unconditional cooperation with humans, which may be consistent with evolutionary pressures for maternal care, and that vasopressin, irrespective of sex and partner type, may be generally sensitising humans to others’ behaviour.
Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment.
Social learning varies among primate species. Macaques only copy the product of observed actions, or emulate, while humans and chimpanzees also copy the process, or imitate. In humans, imitation is linked to the mirror system. Here we compare mirror system connectivity across these species using diffusion tensor imaging. In macaques and chimpanzees, the preponderance of this circuitry consists of frontal–temporal connections via the extreme/external capsules. In contrast, humans have more substantial temporal–parietal and frontal–parietal connections via the middle/inferior longitudinal fasciculi and the third branch of the superior longitudinal fasciculus. In chimpanzees and humans, but not in macaques, this circuitry includes connections with inferior temporal cortex. In humans alone, connections with superior parietal cortex were also detected. We suggest a model linking species differences in mirror system connectivity and responsivity with species differences in behavior, including adaptations for imitation and social learning of tool use.
Recent studies have identified brain correlates of placebo analgesia, but none have assessed how accurately patterns of brain activity can predict individual differences in placebo responses. We reanalyzed data from two fMRI studies of placebo analgesia (N β 47), using patterns of fMRI activity during the anticipation and experience of pain to predict new subjects' scores on placebo analgesia and placebo-induced changes in pain processing. We used a cross-validated regression procedure, LASSO-PCR, which provided both unbiased estimates of predictive accuracy and interpretable maps of which regions are most important for prediction. Increased anticipatory activity in a frontoparietal network and decreases in a posterior insular/temporal network predicted placebo analgesia. Patterns of anticipatory activity across the cortex predicted a moderate amount of variance in the placebo response (̃12% overall,̃40% for study 2 alone), which is substantial considering the multiple likely contributing factors. The most predictive regions were those associated with emotional appraisal, rather than cognitive control or pain processing. During pain, decreases in limbic and paralimbic regions most strongly predicted placebo analgesia. Responses within canonical pain-processing regions explained significant variance in placebo analgesia, but the pattern of effects was inconsistent with widespread decreases in nociceptive processing. Together, the findings suggest that engagement of emotional appraisal circuits drives individual variation in placebo analgesia, rather than early suppression of nociceptive processing. This approach provides a framework that will allow prediction accuracy to increase as new studies provide more precise information for future predictive models.