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

项目摘要 在人类中，最近的发现指出了早期出现的和高度保守的，定量的 介导社会表型，以促进对自闭症谱系的大脑行为发病机制的理解 自闭症（ASD）。因此，完整的早期，皮层下引导的，反射性的视觉参与表现如下 在婴儿早期，大脑皮层引导的、自愿的或奖励驱动的过渡失败。我们的大脑- 行为研究表明，4-8周龄（人类婴儿为12 -9个月）是一个关键时期， 社交技能的完善，以及社交视觉参与中神经连接的微调 途径。在这里，我们提出了新一代的NHP研究，利用一个显着的收敛， 当前Emory ACE 2012和相关工作产生的结果，将包括行为和神经测量 类似于用于人类项目（P-I和P-III）。15只新生雄性猴子（Macaca mulatta）， 他们的母亲在大型，社会复杂，群体在YNPRC外地站将被用来：（a）表征 社会视觉参与和神经运动发育（目标1）;（B）跟踪社会视觉参与早期周期发育 偶然性，增加了对母婴互惠行为的强烈关注，因为社会的明显关键性 在推动社会沟通发展的偶然性，并确定早期的社会预测，后来 社会能力（目标2）;（c）映射神经网络介导的变化的展开成熟， 知觉和注意力的社会刺激，在母婴应急周期，并在发展的社会 能力，使用纵向，非侵入性神经影像学方法，并确定早期神经预测因子， 社会行为结果（目标3）。数据分析将包括新的数学工具，用于优化非 统一抽样，发展概况，统计因果关系的推断，以量化社会的发展， 婴儿-母亲、婴儿-同伴和婴儿-其他成人之间的互动（DMAC）。这将使我们能够（a）获得 每只动物的发育曲线，并检测用于后续研究的潜在离群值情况，（B）测试时间 解决关键问题的因果关系：婴儿期早期神经行为测量能否预测社会能力 并在青少年时期发现异常的社会行为是神经发育的变化 行为的改变，还是相反这些数据将产生一个急需的NHP模型， ASD的发展，我们将用于（a）评估遗传变异以及分子和/或 社会神经网络的实验操作改变了社会发展，以及（B）验证了 用于减轻ASD中的社会缺陷的潜在治疗性治疗。

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.