Human and chimpanzee shared and divergent neurobiological systems for general and specific cognitive brain functions.

A long-standing topic of interest in human neurosciences is the understanding of the neurobiology underlying human cognition. Less commonly considered is to what extent such systems may be shared with other species. We examined individual variation in brain connectivity in the context of cognitive abilities in chimpanzees (n = 45) and humans in search of a conserved link between cognition and brain connectivity across the two species. Cognitive scores were assessed on a variety of behavioral tasks using chimpanzee- and human-specific cognitive test batteries, measuring aspects of cognition related to relational reasoning, processing speed, and problem solving in both species. We show that chimpanzees scoring higher on such cognitive skills display relatively strong connectivity among brain networks also associated with comparable cognitive abilities in the human group. We also identified divergence in brain networks that serve specialized functions across humans and chimpanzees, such as stronger language connectivity in humans and relatively more prominent connectivity between regions related to spatial working memory in chimpanzees. Our findings suggest that core neural systems of cognition may have evolved before the divergence of chimpanzees and humans, along with potential differential investments in other brain networks relating to specific functional specializations between the two species.

Evaluation of a Photo Captioning Cognitive Empathy Intervention for Dementia Caregivers.

OBJECTIVES: The goal of this study was to develop and evaluate an intervention aimed at increasing cognitive empathy, improving mental health, and reducing inflammation in dementia caregivers, and to examine the relevant neural and psychological mechanisms. METHODS: Twenty dementia caregivers completed an intervention that involved taking 3-5 daily photographs of their person living with dementia (PLWD) over a period of 10 days and captioning those photos with descriptive text capturing the inner voice of the PLWD. Both before and after the intervention, participants completed questionnaires, provided a blood sample for measures of inflammation, and completed a neuroimaging session to measure their neural response to viewing photographs of their PLWD and others. RESULTS: 87% of enrolled caregivers completed the intervention. Caregivers experienced pre- to post-intervention increases in cognitive empathy (i.e. Perspective-Taking) and decreases in both burden and anxiety. These changes were paralleled by an increased neural response to photographs of their PLWD within brain regions implicated in cognitive empathy. CONCLUSION: These findings warrant a larger replication study that includes a control condition and follows participants to establish the duration of the intervention effects. CLINICAL IMPLICATIONS: Cognitive empathy interventions may improve caregiver mental health and are worthy of further investigation.

Scaling Principles of White Matter Connectivity in the Human and Nonhuman Primate Brain.

Brains come in many shapes and sizes. Nature has endowed big-brained primate species like humans with a proportionally large cerebral cortex. Comparative studies have suggested, however, that the total volume allocated to white matter connectivity-the brain's infrastructure for long-range interregional communication-does not keep pace with the cortex. We investigated the consequences of this allometric scaling on brain connectivity and network organization. We collated structural and diffusion magnetic resonance imaging data across 14 primate species, describing a comprehensive 350-fold range in brain size across species. We show volumetric scaling relationships that indeed point toward a restriction of macroscale connectivity in bigger brains. We report cortical surface area to outpace white matter volume, with larger brains showing lower levels of overall connectedness particularly through sparser long-range connectivity. We show that these constraints on white matter connectivity are associated with longer communication paths, higher local network clustering, and higher levels of asymmetry in connectivity patterns between homologous areas across the left and right hemispheres. Our findings reveal conserved scaling relationships of major brain components and show consequences for macroscale brain circuitry, providing insights into the connectome architecture that could be expected in larger brains such as the human brain.

Evolutionary expansion of connectivity between multimodal association areas in the human brain compared with chimpanzees.

The development of complex cognitive functions during human evolution coincides with pronounced encephalization and expansion of white matter, the brain's infrastructure for region-to-region communication. We investigated adaptations of the human macroscale brain network by comparing human brain wiring with that of the chimpanzee, one of our closest living primate relatives. White matter connectivity networks were reconstructed using diffusion-weighted MRI in humans (n = 57) and chimpanzees (n = 20) and then analyzed using network neuroscience tools. We demonstrate higher network centrality of connections linking multimodal association areas in humans compared with chimpanzees, together with a more pronounced modular topology of the human connectome. Furthermore, connections observed in humans but not in chimpanzees particularly link multimodal areas of the temporal, lateral parietal, and inferior frontal cortices, including tracts important for language processing. Network analysis demonstrates a particularly high contribution of these connections to global network integration in the human brain. Taken together, our comparative connectome findings suggest an evolutionary shift in the human brain toward investment of neural resources in multimodal connectivity facilitating neural integration, combined with an increase in language-related connectivity supporting functional specialization.

Perception of male and female infant cry aversiveness by adult men.

Objective: The study aimed to determine why male infants are abused more frequently than female infants.Background: Infant crying is a well-known trigger for Shaken Baby Syndrome or Abusive Head Trauma (SBS/AHT). For unknown reasons, male infants are more often victims of SBS/AHT than female infants. We hypothesised that this sex difference in victimisation was attributable to either acoustic or movement differences between male and female infants when crying, or to gender stereotypes about infant crying (e.g. 'boys don't cry').Methods: Adult male participants rated auditory and video cry stimuli from male and female infants for aversiveness. Each infant was rated while wearing both blue and pink clothing to denote male or female gender.Results: In two experiments, male infants spent more time producing expiratory phonations than did female infants, and this variable was positively correlated with aversiveness ratings. Including visual stimuli increased male but not female infant cry aversiveness compared with audio stimuli alone. Finally, dressing infants in blue did not increase cry aversiveness.Conclusions: These findings suggest that both the tendency of male infants to produce more expiratory phonations when crying, as well as their visual appearance when crying, may contribute to their increased vulnerability to abuse.

The neural correlates of grandmaternal caregiving.

In many societies, grandmothers are important caregivers, and grandmaternal investment is often associated with improved grandchild well-being. Here, we present, to our knowledge, the first study to examine grandmaternal brain function. We recruited 50 grandmothers with at least one biological grandchild between 3 and 12 years old. Brain function was measured with functional magnetic resonance imaging as grandmothers viewed pictures of their grandchild, an unknown child, the same-sex parent of the grandchild, and an unknown adult. Grandmothers also completed questionnaires to measure their degree of involvement with and attachment to their grandchild. After controlling for age and familiarity of stimuli, viewing grandchild pictures activated areas involved with emotional empathy (insula and secondary somatosensory cortex) and movement (motor cortex and supplementary motor area). Grandmothers who more strongly activated areas involved with cognitive empathy (temporo-parietal junction and dorsomedial prefrontal cortex) when viewing pictures of the grandchild desired greater involvement in caring for the grandchild. Finally, compared with results from an earlier study of fathers, grandmothers more strongly activated regions involved with emotional empathy (dorsal anterior cingulate cortex, insula and secondary somatosensory cortex), and motivation (nucleus accumbens, ventral pallidum and caudate nucleus). All in all, our findings suggest that emotional empathy may be a key component of grandmaternal responses to their grandchildren.

Quantitative assessment of prefrontal cortex in humans relative to nonhuman primates.

Humans have the largest cerebral cortex among primates. The question of whether association cortex, particularly prefrontal cortex (PFC), is disproportionately larger in humans compared with nonhuman primates is controversial: Some studies report that human PFC is relatively larger, whereas others report a more uniform PFC scaling. We address this controversy using MRI-derived cortical surfaces of many individual humans, chimpanzees, and macaques. We present two parcellation-based PFC delineations based on cytoarchitecture and function and show that a previously used morphological surrogate (cortex anterior to the genu of the corpus callosum) substantially underestimates PFC extent, especially in humans. We find that the proportion of cortical gray matter occupied by PFC in humans is up to 1.9-fold greater than in macaques and 1.2-fold greater than in chimpanzees. The disparity is even more prominent for the proportion of subcortical white matter underlying the PFC, which is 2.4-fold greater in humans than in macaques and 1.7-fold greater than in chimpanzees.

The neural correlates of paternal consoling behavior and frustration in response to infant crying.

Human fathers often form strong attachments to their infants that contribute to positive developmental outcomes. However, fathers are also the most common perpetrators of infant abuse, and infant crying is a known trigger. Research on parental brain responses to infant crying have typically employed passive listening paradigms. However, parents usually engage with crying infants. Therefore, we examined the neural responses of 20 new fathers to infant cries both while passively listening, and while actively attempting to console the infant by selecting soothing strategies in a video game format. Compared with passive listening, active responding robustly activated brain regions involved in movement, empathy and approach motivation, and deactivated regions involved in stress and anxiety. Fathers reporting more frustration had less activation in basal forebrain areas and in brain areas involved with emotion regulation (e.g., prefrontal cortex and the supplementary motor area). Successful consolation of infant crying activated regions involved in both action-outcome learning and parental caregiving (anterior and posterior cingulate cortex). Overall, results suggest that active responding to infant cries amplifies activation in many brain areas typically activated during passive listening. Additionally, paternal frustration during active responding may involve a combination of low approach motivation and low engagement of emotion regulation.

Evolutionary modifications in human brain connectivity associated with schizophrenia.

The genetic basis and human-specific character of schizophrenia has led to the hypothesis that human brain evolution may have played a role in the development of the disorder. We examined schizophrenia-related changes in brain connectivity in the context of evolutionary changes in human brain wiring by comparing in vivo neuroimaging data from humans and chimpanzees, one of our closest living evolutionary relatives and a species with which we share a very recent common ancestor. We contrasted the connectome layout between the chimpanzee and human brain and compared differences with the pattern of schizophrenia-related changes in brain connectivity as observed in patients. We show evidence of evolutionary modifications of human brain connectivity to significantly overlap with the cortical pattern of schizophrenia-related dysconnectivity (P < 0.001, permutation testing). We validated these effects in three additional, independent schizophrenia datasets. We further assessed the specificity of effects by examining brain dysconnectivity patterns in seven other psychiatric and neurological brain disorders (including, among others, major depressive disorder and obsessive-compulsive disorder, arguably characterized by behavioural symptoms that are less specific to humans), which showed no such associations with modifications of human brain connectivity. Comparisons of brain connectivity across humans, chimpanzee and macaques further suggest that features of connectivity that evolved in the human lineage showed the strongest association to the disorder, that is, brain circuits potentially related to human evolutionary specializations. Taken together, our findings suggest that human-specific features of connectome organization may be enriched for changes in brain connectivity related to schizophrenia. Modifications in human brain connectivity in service of higher order brain functions may have potentially also rendered the brain vulnerable to brain dysfunction.

Comparative Primate Connectomics.

A connectome is a comprehensive map of neural connections of a species nervous system. While recent work has begun comparing connectomes across a wide breadth of species, we present here a more detailed and specific comparison of connectomes across the primate order. Long-range connections are thought to improve communication efficiency and thus brain function but are costly in terms of energy and space utilization. Methods for measuring connectivity in the brain include measuring white matter volume, histological cell counting, anatomical tract tracing, diffusion-weighted imaging and tractography, and functional connectivity in MRI. Comparisons of global white matter connectivity suggest that larger primate brains are less well connected than smaller primate brains, but that humans have more connections than expected for our cortical neuron number, which may be concentrated in the prefrontal cortex. Although there is significant overlap in structural connectivity between humans and nonhuman primates, human-specific connections are found in cortical areas involved with language, imitation, and tool use. Similar to structural connectivity, there is also widespread overlap between humans and macaques in resting state functional connectivity. However, there are again a number of human-specific connections in cortical regions involved in language, tool use, and empathy. Comparative connectomics also offers the opportunity to detect specializations of connectivity in other primate species besides humans. Future research should capitalize on the ability of diffusion tractography to measure connectivity in postmortem brains that could expand the representation of species beyond humans, chimpanzees, and rhesus macaques, and facilitate identification of connectivity-based adaptations to different social and ecological niches. This work will require careful attention to establishing cortical homologies across species and to improving tractography methods to limit detection of false-positive and false-negative connections. Finally, it will be important to attempt to establish the functional significance of variation in connectivity profiles by examining how these covary with behavior and cognition both across and within species.

Preliminary evidence that androgen signaling is correlated with men's everyday language.

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.

Intranasal oxytocin modulates neural functional connectivity during human social interaction.

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.

Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques.

Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in-group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT-and AVP-containing neurons project into the cortex. Here, we demonstrate the existence of OT- and AVP-containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT-immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT-immunoreactive fibers were found in macaque cortex. AVP-immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non-human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions.

Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers.

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1-2year old children to receive either 24IU intranasal OT before one scan and placebo before the other scan (n=15) or 20IU intranasal AVP before one scan and placebo before the other scan (n=15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage.

The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans.

The human default mode network (DMN), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. The DMN and social cognitive networks overlap significantly in humans. We previously demonstrated that chimpanzees (Pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human DMN. Human DMN is defined by task-induced deactivations, not absolute resting metabolic levels; ergo, resting activity is insufficient to define a DMN in chimpanzees. Here, we assessed the chimpanzee DMN's deactivations relative to rest during cognitive tasks and the effect of social content on these areas' activity. Chimpanzees performed a match-to-sample task with conspecific behavioral stimuli of varying sociality. Using [(18)F]-FDG PET, brain activity during these tasks was compared with activity during a nonsocial task and at rest. Cortical midline areas in chimpanzees deactivated in these tasks relative to rest, suggesting a chimpanzee DMN anatomically and functionally similar to humans. Furthermore, when chimpanzees make social discriminations, these same areas (particularly precuneus) are highly active relative to nonsocial tasks, suggesting that, as in humans, the chimpanzee DMN may play a role in social cognition.

Testicular volume is inversely correlated with nurturing-related brain activity in human fathers.

Despite the well-documented benefits afforded the children of invested fathers in modern Western societies, some fathers choose not to invest in their children. Why do some men make this choice? Life History Theory offers an explanation for variation in parental investment by positing a trade-off between mating and parenting effort, which may explain some of the observed variance in human fathers' parenting behavior. We tested this hypothesis by measuring aspects of reproductive biology related to mating effort, as well as paternal nurturing behavior and the brain activity related to it. Both plasma testosterone levels and testes volume were independently inversely correlated with paternal caregiving. In response to viewing pictures of one's own child, activity in the ventral tegmental area--a key component of the mesolimbic dopamine reward and motivation system--predicted paternal caregiving and was negatively related to testes volume. Our results suggest that the biology of human males reflects a trade-off between mating effort and parenting effort, as indexed by testicular size and nurturing-related brain function, respectively.

Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome.

With the mapping of macroscale connectomes by means of in vivo diffusion-weighted MR Imaging (DWI) rapidly gaining in popularity, one of the necessary steps is the examination of metrics of connectivity strength derived from these reconstructions. In the field of human macroconnectomics the number of reconstructed fiber streamlines (NOS) is more and more used as a metric of cortico-cortical interareal connectivity strength, but the link between DWI NOS and in vivo animal tract-tracing measurements of anatomical connectivity strength remains poorly understood. In this technical report, we communicate on a comparison between DWI derived metrics and tract-tracing metrics of projection strength. Tract-tracing information on projection strength of interareal pathways was extracted from two commonly used macaque connectome datasets, including (1) the CoCoMac database of collated tract-tracing experiments of the macaque brain and (2) the high-resolution tract-tracing dataset of Markov and Kennedy and coworkers. NOS and density of reconstructed fiber pathways derived from DWI data acquired across 10 rhesus macaques was found to positively correlate to tract-tracing based measurements of connectivity strength across both the CoCoMac and Markov dataset (both P < 0.001), suggesting DWI NOS to form a valid method of assessment of the projection strength of white matter pathways. Our findings provide confidence of in vivo DWI connectome reconstructions to represent fairly realistic estimates of the wiring strength of white matter projections. Our cross-modal comparison supports the notion of in vivo DWI to be a valid methodology for robust description and interpretation of brain wiring.

Process versus product in social learning: comparative diffusion tensor imaging of neural systems for action execution-observation matching in macaques, chimpanzees, and humans.

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.