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

社会偶然事件的循环：塑造猴子大脑行为发展的关键转变

• 批准号: 10005485
• 负责人: JOCELYNE H BACHEVALIER
• 金额: $ 44.97万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005485
• 关键词: Address; Adolescent; Adult; Age; Amygdaloid structure; Animals; Anterior; Attention; Attenuated; Automobile Driving; Behavior; Behavior assessment; Behavioral; Biological; Biological Models; Birth; Brain; Code; Competence; Complex; Corticospinal Tracts; Data; Data Analyses; Development; Dorsal; Etiology; Follow-Up Studies; Foundations; Functional Magnetic Resonance Imaging; Generations; Genetic; Genetic Variation; Goals; Human; Human Development; Infant; Insula of Reil; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Maps; Mathematics; Measurement; Measures; Mediating; Methods; Modeling; Molecular; Monkeys; Mothers; Motor; Neonatal; Network-based; Newborn Infant; Nucleus Accumbens; Pathogenesis; Pathway Analysis; Pathway interactions; Perception; Performance; Phenotype; Prefrontal Cortex; Primates; Publishing; Reflex action; Research; Rest; Rewards; Role; Sampling; Scanning; Screening procedure; Sensory; Shapes; Social Behavior; Social Development; Social Environment; Social Network; Socialization; Stimulus; Structure; Techniques; Testing; Therapeutic; Videotape; Visual; Visual attention; Work; autism spectrum disorder; behavior measurement; behavioral outcome; behavioral study; brain behavior; brain shape; cingulate cortex; critical period; disability; gaze; graph theory; infancy; interdisciplinary approach; male; neural network; neurobehavioral; neurodevelopment; neuroimaging; nonhuman primate; novel; object motion; peer; relating to nervous system; response; skills; social; social attention; social communication; social deficits; social engagement; social skills; tool; visual tracking

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.

项目概要 在人类中，最近的发现指出了早期出现的、高度保守的、定量的重要性 调节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 疾病（自闭症谱系障碍）。因此，遵循完整的早期、皮质下引导、反射性视觉参与表现 由于婴儿早期未能成功过渡到皮质引导、自愿或奖励驱动的过渡。我们的 NHP 大脑 - 行为研究表明，4-8 周龄（对于人类婴儿来说约为 2-9 个月）是发育的关键时期。 社交技能的完善，同时微调社交视觉参与中的神经连接 途径。在这里，我们提出了新一代 NHP 研究，该研究利用了 当前 Emory ACE 2012 和相关工作得出的结果将包括行为和神经测量 类似于用于人类项目的那些（P-I 和 P-III）。 15 只新生雄性猴子（Macaca mulatta）与它们生活在一起 他们的母亲在YNPRC野外站的大型、社会复杂的群体中将被用来：(a) 社交视觉参与和神经运动发育（目标 1）； (b) 追踪社会早期周期的发展 考虑到社交的明显重要性，增加了对母婴互动行为的强烈关注 推动社会传播发展的偶然因素并确定后来的早期社会预测因素 社会能力（目标 2）； (c) 绘制介导变化的神经网络的逐渐成熟过程 在母婴应急周期以及社会发展中对社会刺激的感知和关注 能力，使用纵向、非侵入性神经影像方法，并识别早期神经预测因素 后来的社会行为结果（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、发展分析和统计因果关系推断，以量化社会发展 婴儿与母亲、婴儿与同伴以及婴儿与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后续研究的潜在异常情况，(b) 测试时间 因果关系解决关键问题：婴儿期早期神经行为测量能否预测社交能力 并在青少年时期发现异常的社会行为？神经发育变化是驱动因素吗 行为改变，或者反之亦然？这些数据将产生一个急需的早期社会 NHP 模型 ASD 的开发，我们将用于 (a) 评估遗传变异以及分子和/或 社交神经网络的实验操作改变了社会发展，并且（b）验证了 减轻自闭症谱系障碍社交缺陷的潜在治疗方法。