More than just mothers: The neurobiological and neuroendocrine underpinnings of allomaternal caregiving.

In a minority of mammalian species, mothers depend on others to help raise their offspring. New research is investigating the neuroendocrine mechanisms supporting this allomaternal behavior. Several hormones have been implicated in allomaternal caregiving; however, the role of specific hormones is variable across species, perhaps because allomothering independently evolved multiple times. Brain regions involved in maternal behavior in non-human animals, such as the medial preoptic area, are also critically involved in allomaternal behavior. Allomaternal experience modulates hormonal systems, neural plasticity, and behavioral reactivity. In humans, fatherhood-induced decreases in testosterone and increases in oxytocin may support sensitive caregiving. Fathers and mothers activate similar neural systems when exposed to child stimuli, and this can be considered a global "parental caregiving" network. Finally, early work on caregiving by non-kin (e.g., foster parents) suggests reliance on similar mechanisms as biologically-related parents. This article is part of the 'Parental Brain and Behavior' Special Issue.

Effects of arginine vasopressin on human anxiety and associations with sex, dose, and V1a-receptor genotype.

RATIONALE: Arginine vasopressin (AVP) has dose- and sex-specific effects on social behavior, and variation in social responses is related to variation in the V1a receptor gene in animals. Whether such complexity also characterizes AVP effects on anxiety in humans, or whether V1a genotype is related to anxiety and/or AVP's ability to affect it, remains to be determined. OBJECTIVE: To test if AVP has dose-dependent effects on anxiety in men and/or women and if a particular allele within the RS3 promoter region of the V1a receptor gene is associated with anxiety and/or AVP effects on anxiety. METHOD: Men and women self-administered 20 IU or 40 IU intranasal arginine vasopressin (AVP) and placebo in a double-blind, within-subjects design, and State (SA) and Trait (TA) anxiety were measured 60 min later. PCR was used to identify allelic variation within the RS3 region of the V1a receptor gene. RESULTS: AVP decreased SA in men across both doses, whereas only the lower dose had the same effect, across sexes, in individuals who carry at least one copy of a previously identified "risk" allele in the RS3 promoter of the V1a receptor gene. Additionally, after placebo, women who carried a copy of the allele displayed lower TA than women who did not, and AVP acutely increased TA scores in those women. CONCLUSIONS: Exogenous AVP has modest sex- and dose-dependent effects on anxiety/affect in humans. Further, allelic variation in the V1a promoter appears associated with responsiveness to AVP's effects and, at least in women, to stable levels of anxiety/affect.

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans.

Towards a neural model of infant cry perception.

Previous work suggests that infant cry perception is supported by an evolutionary old neural network consisting of the auditory system, the thalamocingulate circuit, the frontoinsular system, the reward pathway and the medial prefrontal cortex. Furthermore, gender and parenthood have been proposed to modulate processing of infant cries. The present meta-analysis (N = 350) confirmed involvement of the auditory system, the thalamocingulate circuit, the dorsal anterior insula, the pre-supplementary motor area and dorsomedial prefrontal cortex and the inferior frontal gyrus in infant cry perception, but not of the reward pathway. Structures related to motoric processing, possibly supporting the preparation of a parenting response, were also involved. Finally, females (more than males) and parents (more than non-parents) recruited a cortico-limbic sensorimotor integration network, offering a neural explanation for previously observed enhanced processing of infant cries in these sub-groups. Based on the results, an updated neural model of infant cry perception is presented.

A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

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.

Regulation of chorionic gonadotropin-alpha and chorionic somatomammotropin messenger ribonucleic acid expression by 8-bromo-adenosine 3',5'-monophosphate and dexamethasone in cultured rhesus monkey syncytiotrophoblasts.

We wished to establish an in vitro culture system to examine gene expression in the context of differentiated function with rhesus monkey syncytiotrophoblasts. Chorionic villous tissue from placentas obtained at cesarean section was dispersed with trypsin and DNase and fractionated on a 5-70% Percoll gradient. When placed in culture, cells from a mononuclear fraction demonstrated to be very highly enriched (95-97% pure) for cytotrophoblasts aggregated and began to form syncytia within 24 h in culture, reminiscent of placental syncytiotrophoblast formation. The migration and fusion of individual cytotrophoblasts to form multinuclear syncytia were documented with time-lapse video microscopy. Incorporation studies with tritiated thymidine supported the conclusion from videomicroscopy that syncytia form by the fusion of individual cells and the addition of mononuclear cells to existing syncytia, rather than by endomitosis. The syncytiotrophoblast marker pregnancy-specific beta 1-glycoprotein (SP1) was immunocytochemically identified in both intact placenta and cultured syncytiotrophoblast cells. With cells isolated from placentas obtained on day 28, 50, 70, or 140 of pregnancy, treatment with 8-bromo-cAMP increased both rhesus monkey CG alpha-subunit (mCG alpha) and chorionic somatomammotropin (mCS) mRNA levels by an average of 4-fold. Increases of up to 2.5-fold were seen with mCG alpha mRNA in as little as 2 h after treatment, with a statistically significant average response seen within 6 h. The response with mCS required at least 24 h before a significant effect was seen. Actin mRNA levels were generally unchanged or suppressed by this treatment, indicating that the effect of 8-bromo-cAMP is relatively specific for the hormone mRNAs. Treatment of syncytiotrophoblasts with dexamethasone, but not progesterone or androstenedione, resulted in an approximately 4-fold increase in mCG alpha mRNA levels within 6 h of treatment. Steroid treatment did not affect mCS mRNA levels. Treatment with 4.5-400 nM GnRH or 0.1 to 100 ng/ml basic fibroblast growth factor likewise had no effect on the level of either mRNA, suggesting that any actions of these factors on hormone secretion are not effected via changes in steady state mRNA. These results communicate that the expression of the mRNAs for rhesus monkey CG alpha and CS in syncytiotrophoblast are regulated by steroid hormone- and cAMP-mediated pathways.

Neural correlates of maternal separation in rhesus monkeys.

BACKGROUND: The neurobiological basis of stress and anxiety in primates remains poorly understood. In this study, we examined the neural response to a naturalistic social stressor: maternal separation. We used rhesus monkeys as an animal model because of their close phylogenetic affinity with humans. METHODS: Six juvenile rhesus monkeys received [(18)F]-fluorodeoxyglucose positron emission tomography scans following 1) a period together with their mothers and again after separation from their mothers 2) with or 3) without visual contact. Image subtraction revealed brain regions that exhibited altered activity during separation. In addition, plasma cortisol concentrations obtained following each condition were tested for correlations with regional brain activity. RESULTS: Maternal separation activated the right dorsolateral prefrontal cortex and the right ventral temporal/occipital lobe. There was also decreased activity in left dorsolateral prefrontal cortex associated with separation stress. Correlational analyses demonstrated these activated and deactivated regions to be positively and negatively correlated with cortisol, respectively. Additionally, correlational analyses revealed cortisol-related activation in brainstem areas previously implicated in stress and anxiety. CONCLUSIONS: In juvenile rhesus monkeys, the stress of maternal separation is associated with activation in the right dorsolateral prefrontal cortex and ventral temporal/occipital lobes and decreased activity in the left dorsolateral prefrontal cortex.

A comparative MRI study of the relationship between neuroanatomical asymmetry and interhemispheric connectivity in primates: implication for the evolution of functional asymmetries.

The authors tested the theory that hemispheric specialization evolved as a consequence of reduced interhemispheric connectivity by examining whether neuroanatomical asymmetries were associated with variation in the ratio of corpus callosum size to brain volume (CC:VOL) and to neocortical surface area (CC:NEO) in human and nonhuman primates. Magnetic resonance images were collected in a sample of 45 primates including 8 New World monkeys, 10 Old World monkeys, 4 lesser apes, 17 great apes, and 6 humans. CC:VOL and CC:NEO were determined and correlated with measures of brain asymmetry. The results indicate that brain asymmetry significantly predicted CC:VOL and CC:NEO. Subsequent analyses revealed that species variation in functional asymmetries in the form of handedness are also inversely related to CC:NEO. Taken together, these results support the hypothesis that leftward brain asymmetries may have evolved as a consequence of reduced interhemispheric connectivity.

Differential expansion of neural projection systems in primate brain evolution.

Whole brain MRI scans from 11 primate species (43 individuals) spanning more than a 50-fold range in brain volume were used to determine whether the corpus callosum keeps pace with the growth of the forebrain among living anthropoid primates. Interhemispheric connectivity via the corpus callosum and anterior commissure was reduced in larger primate brains, whereas intrahemispheric connectivity was augmented. We also show that the splenium constitutes an increasing proportion of callosal area with increasing brain size. This may function to maintain rapid integration of the left and right visual space as brain size increases. These results indicate that the evolution of larger brain size in primates results in increasingly independent hemispheres.

Planum temporale asymmetries in great apes as revealed by magnetic resonance imaging (MRI).

The planum temporale (PT), a portion of Wernicke's area, is important for linguistic functions in humans and is larger in the left compared to the right hemisphere. In this study, we assessed the presence and size of the PT in a sample of non-human primates including 21 great apes, four lesser apes, 11 Old World monkeys and eight New World monkeys using magnetic resonance imaging. The PT was measured in both the sagittal and coronal planes by use of multiplanar reformatting software. The PT could only be identified in the sample of great apes and not in the remaining non-human primate species. Within the great ape sample, the PT was larger in the left hemisphere than in the right in a statistical majority of the subjects. These results are consistent with the notion that the PT evolved as a definable structure about 15 million years ago and may have arisen as a result for selection for greater cortical folding which in turn led to greater gyrification in larger brains.