Cycles of Social Contingency: Pivotal Transitions that Shape Brain-Behavior Development in Monkeys

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PROJECT SUMMARY In humans, recent discoveries point to the importance of early-emerging and highly-conserved, quantitative mediating social phenotypes to advance understanding of the brain-behavior pathogenesis of Autism Spectrum Disorders (ASD). Thus, intact early, subcortically-guided, reflexive visual engagement performance is followed by a failed transition to cortically-guided, voluntary or reward-driven transition in early infancy. Our NHP brain- behavior studies suggest that 4-8 weeks of age (≈ 2-9 months for human infants) represents a critical period for the refinement of social skills, paralleled by fine-tuning of neural connections in social visual engagement pathways. Here, we propose a new generation of NHP studies that capitalizes on a remarkable convergence of findings yielded by current Emory ACE 2012 and related work and will include behavioral and neural measures similar to those used for human projects (P-I and P-III). 15 newborn male monkeys (Macaca mulatta) living with their mothers in large, socially complex, groups at the YNPRC Field Station will be used to: (a) characterize social visual engagement and neuromotor development (Aim 1); (b) trace development of early cycles of social contingency, adding a strong focus on mother-infant reciprocal behaviors given the apparent criticality of social contingency in moving social-communication development forward and identify early social predictors of later social competency (Aim 2); and (c) map the unfolding maturation of neural networks mediating changes in perception and attention to social stimuli, in mother-infant contingency cycles, and in the development of social competency, using longitudinal, non-invasive neuroimaging methods, and identifying early neural predictors of later social behavior outcomes (Aim 3). Data analyses will include new mathematical tools for optimal non- uniform sampling, developmental profiling, and inference of statistical causality to quantify the unfolding of social engagement between infant-mother, infant-peer, and infant-other adults (DMAC). This will allow us to (a) obtain developmental curves for each animal and detect potential outlier cases for follow up studies, (b) test temporal causality to address critical questions: Can early neurobehavioral measures in infancy predict social competency and detect abnormal social behaviors later in the juvenile period? Are the neurodevelopmental changes driving the behavioral changes, or vice-versa? The data will yield a critically needed NHP model of early social development for ASD that we will be used to (a) assess how genetic variations as well as molecular and/or experimental manipulations of social neural networks alter social development, and (b) validate efficacy of potential therapeutic treatments for attenuating social deficits in ASD.