Effect of Indoor Compared with Outdoor Location during Gestation on the Incidence of Diarrhea in Indoor-Reared Rhesus Macaques (Macaca mulatta).

Behavior and health, including the incidence of chronic idiopathic diarrhea, can vary widely among NHP reared indoors. We hypothesized that factors during gestation account for some of the variability in chronic diarrhea risk that cannot be explained by postnatal environment, genes, or known physiologic deficits. We hypothesized that, among macaques reared indoors postnatally, outdoor housing during gestation (when the dam engaged with a large, species-typical social group) would be protective against diarrhea as compared with gestation experienced in an indoor setting. We also hypothesized that exposure to routine husbandry and veterinary care in utero would increase diarrhea rates in offspring. We built models to test the influence of specific events during pregnancy as well as their interactions with anxiety-related genotype as a way of understanding gene×environment interaction on the development of diarrhea in indoor-reared rhesus macaques. Although previous reports have suggested that rearing by the mother in an indoor environment is preferable to nursery rearing, we found that whether gestation occurred indoors (in single or pair housing) or outdoors (in a large social group) better explained the variability in diarrhea rate in our study population of indoor-reared macaques. Furthermore, the diarrhea incidence was associated with nervous temperament and serotonin transporter promoter genotype. Several significant interactions indicated that some of these effects were specific to subsets of animals. Our results demonstrate that the prenatal environment can have unexpected lasting health consequences.

Familial aggregation of chronic diarrhea disease (CDD) in rhesus macaques (Macaca mulatta).

Chronic diarrheal disease (CDD) is a critical problem for breeders of captive rhesus macaque (Macaca mulatta), as it results in significant levels of morbidity and death annually. As with other inflammatory disorders, CDD is thought to be caused by environmental and/or genetic factors. Although correspondence between the characters defined as Mendelian by pedigree or segregation analysis and functional genes is difficult to establish, such analyses provide essential entry points into understanding CDD in captive bred rhesus macaques. To investigate the familial aggregation of CDD in captive rhesus macaque, we performed pedigree, segregation and heritability analyses on genealogical data from 55 severely affected individuals (probands) through whom relatives with a history of CDD were ascertained from routine computerized colony records comprising vital and demographic statistics of 10,814 rhesus macaques. We identified 175 rhesus macaques with CDD and estimated its incidence as approximately 2% in the colony. The disease strongly clustered in eight multi-generation pedigrees. Inspection of the pedigrees, segregation analysis and heritability estimate of CDD suggest that susceptibility to the disease is under strong genetic control. Identification of the locations of susceptibility genes in the rhesus macaque genome could facilitate the reduction of their frequency in captive breeding facilities.

Effect of menstrual cycle on resting brain metabolism in female rhesus monkeys.

Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we use 18F-fluorodeoxyglucose positron emission tomography to monitor changes in resting brain glucose metabolism across the menstrual cycle in female rhesus monkeys. Results showed greater activity in right lateral orbitofrontal cortex, a region involved in processing negatively valenced emotional stimuli, in the follicular compared with luteal phase. Estradiol levels were negatively correlated with activity in cortical and brainstem regions involved in emotional processing, and positively correlated with activity in areas involved in cognitive control and emotion regulation. In summary, the data suggest that in primates, fluctuations of ovarian hormones across the menstrual cycle influence activity in brain areas involved in emotion and its regulation.

The neural correlates of the affective response to unreciprocated cooperation.

Humans excel at reciprocal altruism in which two individuals exchange altruistic acts to their mutual advantage. The evolutionary stability of this system depends on recognition of and discrimination against non-reciprocators, and the human mind is apparently specialized for detecting non-reciprocators. Here we investigate the neural response to non-reciprocation of cooperation by imaging human subjects with fMRI as they play an iterated Prisoner's dilemma game with two assumed human partners. Unreciprocated cooperation was associated with greater activity in bilateral anterior insula, left hippocampus and left lingual gyrus, compared with reciprocated cooperation. These areas were also more responsive to unreciprocated cooperation than to unsuccessful risk taking in a non-social context. Finally, functional connectivity between anterior insula and lateral orbitofrontal cortex (OFC) in response to unreciprocated cooperation predicted subsequent defection. The anterior insula is involved in awareness of visceral, autonomic feedback from the body and, in concert with the lateral orbitofrontal cortex, may be responsible for negative feeling states that bias subsequent social decision making against cooperation with a non-reciprocating partner.

Neural correlates of social cooperation and non-cooperation as a function of psychopathy.

BACKGROUND: Psychopathy is a disorder involving a failure to experience many emotions that are necessary for appropriate social behavior. In this study, we probed the behavioral, emotional, and neural correlates of psychopathic traits within the context of a dyadic social interaction. METHODS: Thirty subjects were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma game with human confederates who were outside the scanner. Subjects also completed two self-report psychopathy questionnaires. RESULTS: Subjects scoring higher on psychopathy, particularly males, defected more often and were less likely to continue cooperating after establishing mutual cooperation with a partner. Further, they experienced more outcomes in which their cooperation was not reciprocated (cooperate-defect outcome). After such outcomes, subjects scoring high in psychopathy showed less amygdala activation, suggesting weaker aversive conditioning to those outcomes. Compared with low-psychopathy subjects, subjects higher in psychopathy also showed weaker activation within orbitofrontal cortex when choosing to cooperate and showed weaker activation within dorsolateral prefrontal and rostral anterior cingulate cortex when choosing to defect. CONCLUSIONS: These findings suggest that whereas subjects scoring low on psychopathy have emotional biases toward cooperation that can only be overcome with effortful cognitive control, subjects scoring high on psychopathy have an opposing bias toward defection that likewise can only be overcome with cognitive effort.