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null (Ed.)Abstract Background How the brain develops accurate models of the external world and generates appropriate behavioral responses is a vital question of widespread multidisciplinary interest. It is increasingly understood that brain signal variability—posited to enhance perception, facilitate flexible cognitive representations, and improve behavioral outcomes—plays an important role in neural and cognitive development. The ability to perceive, interpret, and respond to complex and dynamic social information is particularly critical for the development of adaptive learning and behavior. Social perception relies on oxytocin-regulated neural networks that emerge early in development. Methods We tested the hypothesis that individual differences in the endogenous oxytocinergic system early in life may influence social behavioral outcomes by regulating variability in brain signaling during social perception. In study 1, 55 infants provided a saliva sample at 5 months of age for analysis of individual differences in the oxytocinergic system and underwent electroencephalography (EEG) while listening to human vocalizations at 8 months of age for the assessment of brain signal variability. Infant behavior was assessed via parental report. In study 2, 60 infants provided a saliva sample and underwent EEG while viewing faces and objects and listening to human speech and water sounds at 4 months of age. Infant behavior was assessed via parental report and eye tracking. Results We show in two independent infant samples that increased brain signal entropy during social perception is in part explained by an epigenetic modification to the oxytocin receptor gene ( OXTR ) and accounts for significant individual differences in social behavior in the first year of life. These results are measure-, context-, and modality-specific: entropy, not standard deviation, links OXTR methylation and infant behavior; entropy evoked during social perception specifically explains social behavior only; and only entropy evoked during social auditory perception predicts infant vocalization behavior. Conclusions Demonstrating these associations in infancy is critical for elucidating the neurobiological mechanisms accounting for individual differences in cognition and behavior relevant to neurodevelopmental disorders. Our results suggest that an epigenetic modification to the oxytocin receptor gene and brain signal entropy are useful indicators of social development and may hold potential diagnostic, therapeutic, and prognostic value.more » « less
In humans, satisfying sexual activity within a pair‐bond plays a significant role in relationship quality and maintenance, beyond reproduction. However, the neural and genetic correlates for this basic species‐supporting function, in response to a pair‐bonded partner, are unknown.
We examined the neural correlates of oxytocin‐ (
Oxtrrs53576) and vasopressin‐ ( Avpr1a rs3) receptor genotypes with sexual satisfaction and frequency, among a group of individuals in pair‐bonds (M relationship length = 4.1 years). Participants were scanned twice (with functional MRI), about 1‐year apart, while viewing face images of their spouse and a familiar, neutral acquaintance. Results
Sex satisfaction scores showed significant interactions with
Oxtrand Avprvariants associated with social behaviors in a broad network of regions involved in reward and motivation (ventral tegmental area, substantia nigra [SN], and caudate), social bonding (ventral pallidum), emotion and memory (amygdala/hippocampus), hormone control (hypothalamus); and somatosensory and self‐other processing (SII, frontal, and temporal lobe). Sexual frequency interactions also showed activations in the SN and paraventricular hypothalamus for Avpr, and the prefrontal cortex for Oxtr. Conclusions
Satisfying sexual activity in pair‐bonds is associated with activation of subcortical structures that support basic motivational and physiological processes; as well as cortical regions that mediate complex thinking, empathy, and self‐other processes highlighting the multifaceted role of sex in pair‐bonds.
Oxtrand Avprgene variants may further amplify both basic and complex neural processes for pair‐bond conservation and well‐being.
Joint attention (JA) is an important milestone in human infant development and is predictive of the onset of language later in life. Clinically, it has been reported that children at risk for or with a diagnosis of autism spectrum disorder (ASD) perform more poorly on measures of JA compared to neurotypical controls. JA is not unique to humans but has also been reported in great apes and to a lesser extent in more distantly related monkeys. Further, individual differences in JA among chimpanzees are associated with polymorphisms in the vasopressin and oxytocin genes,
AVPR1Aand OXTR. Here, we tested whether individual variation in DNA methylation of OXTRand AVPR1Awere associated with performance on JA tasks in chimpanzees. We found that individual differences in JA performance was associated with AVPR1Amethylation, but not OXTRmethylation in the chimpanzees. The collective results provide further evidence of the role of AVPR1Ain JA abilities in chimpanzees. The results further suggest that methylation values for AVPR1Amay be useful biomarkers for identifying individuals at risk for ASD or related neurodevelopmental disorders associated with impairments in JA abilities.
A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor (
Oxtr) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species ( n= 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.
Positive emotions play a critical role in guiding human behavior and social interactions. This study examined whether and how genetic variability in the oxytocin system is linked to individual differences in expressing positive affect in human infants. Our results show that genetic variation in CD38 (rs3796863), previously linked to increased release of oxytocin, was associated with higher rates of positive affective displays among a sample of 7-month-old infants, using established parent-report measures. Moreover, infants displaying increased levels of positive affect (smiling and laughter) also showed enhanced brain responses in the right inferior frontal cortex, a brain region previously linked to perception–action coupling, when viewing others smile at them. These findings suggest that, from early in development, genetic variation in the oxytocin system is associated with individual differences in expressed positive affect, which in turn are linked to differences in perceiving positive affect. This helps uncover the neurobiological processes accounting for variability in the expression and perception of positive affect in infancy.