INSPIRE: Neural and Genetic Factors Underlying Individual and Phylogenetic Variation in Communication

该INSPIRE奖部分由社会、行为和经济科学理事会行为和认知科学部的感知、行动和认知项目和生物人类学项目以及综合活动办公室资助。人类自然地学会说话和使用语言。这是人类的特征之一。了解这种非凡能力的生物学与神经科学、语言学、遗传学、心理学和人类学等领域有关。人类的言语和语言涉及相互交织的过程，包括对信号的感知（即声音、单词、手势、手语中的符号），对嘴、舌头和喉头的阶段性运动的学习，以产生声音元素的组合，以及对词义、语言结构的更高层次的认知方面，以及对发生交流的话语的理解。由于这些组成部分中的每一个都可能有单独的神经和遗传基础，因此关注语言的各个方面有助于剖析这种复杂的社会认知行为。对人类言语和语言障碍的研究提供了对候选基因（FOXP2和KIAA0319）和涉及语言功能不同要素的大脑结构的深入了解。然而，在非人类动物中，这些语言的遗传和神经构建块的存在程度和变化程度尚不清楚。这项研究项目采用了一种创新的跨学科方法，在人类最亲近的亲戚黑猩猩中调查这个问题。更好地理解这些复杂的相互作用将进一步加深我们对影响人类语言障碍的神经发育基础的认识，如自闭症谱系障碍、阅读障碍和言语运动障碍。该项目包括多方面的个体差异在声乐学习，运动控制，和声音符号学习与遗传变异，神经解剖结构和大脑中的分子表达。黑猩猩在面部运动控制方面表现出明显的差异，这使得一些个体（而不是其他个体）能够灵活地学习新的发声方式。为了了解黑猩猩与声音学习能力相关的神经生物学差异，该项目将使用几种尖端的分析方法，结合详细的MRI脑成像，精密的显微解剖结构和细胞组成测量（来自现有的组织学收集），以及创新的基于计算机科学的方法。此外，基因组分析将包括FOXP2基因，该基因在建立人类语言发展所需的大脑回路中起着关键作用。然而，在灵长类动物中，FOXP2在交流和口面运动控制方面的功能基本上是未知的：该项目将首次表征黑猩猩中FOXP2的变异，并检查其与大脑结构、基因表达和声音学习的个体差异之间的联系（行为测试包括对黑猩猩的最小鼓励和用食物奖励的强化，不涉及任何麻醉、疼痛或痛苦）。人类语言的另一个重要方面是在听觉和视觉两方面理解单词及其含义的能力。在人类中，与大脑发育和阅读障碍有关的KIAA0319基因被认为在这种声音符号学习中起着关键作用。该项目将研究KIAA0319基因的变异是如何影响黑猩猩大脑组织和声音符号学习的差异的（安置在耶基斯国家灵长类动物中心和MD安德森癌症中心）。研究中使用的所有DNA样本、核磁共振扫描和脑组织都已事先获得。这些多种技术的结合将产生独特的数据集，这将改变我们比较黑猩猩和人类与语言和大脑功能相关的大脑结构和行为能力的能力。

This INSPIRE award is partially funded by the Perception, Action, and Cognition Program and the Biological Anthropology Program in the Division of Behavioral and Cognitive Sciences in the Directorate for Social, Behavioral, and Economic Sciences, and the Office of Integrative Activities.Humans naturally learn to speak and use language. It is one of the defining features of our species. Understanding the biology of this extraordinary capacity is relevant to the fields of neuroscience, linguistics, genetics, psychology, and anthropology. Human speech and language involve intertwined processes, including the perception of signals (i.e., sounds, words, manual gestures, signs in sign language), the learning of phased movements of the mouth, tongue, and larynx to produce combinations of sound elements, as well as the higher-level cognitive aspects of word meaning, language structure, and the understanding of the discourse in which communication occurs. As each of these components may have separate neural and genetic bases, a focus on individual aspects of language helps dissect this complex socio-cognitive behavior. Studies of humans with speech and language disorders have provided insight into candidate genes (FOXP2 and KIAA0319) and brain structures implicated in different elements of language function. However, it is not yet understood the degree to which these genetic and neural building blocks of language are present and vary in nonhuman animals. This research project encompasses an innovative and interdisciplinary approach to investigate this question among humans' closest living relatives, the chimpanzees. A better understanding of these complex interactions will further our knowledge of the neurodevelopmental foundation of disorders affecting language in humans, such as autism spectrum disorder, dyslexia, and verbal dyspraxia.The project includes a multifaceted examination of individual differences in vocal learning, motor control, and sound-symbol learning in relation to genetic variation, neuroanatomical structure, and molecular expression in the brain. Chimpanzees show marked variation in orofacial motor control that allows some individuals, but not others, to flexibly learn novel vocalizations. To understand the neurobiological differences among chimpanzees related to vocal learning ability, this project will use several cutting-edge analytic approaches, combining detailed MRI brain imagery, sophisticated measurements of microanatomical structure and cellular composition (from an existing histological collection), and innovative computer science-based methods. In addition, genomic analyses will include FOXP2, a gene that plays a critical role in establishing the brain circuitry required for the development of language in humans. However, the function of FOXP2 in communication and orofacial motor control is essentially unknown in primates: this project will be the first to characterize variation in FOXP2 across chimpanzees and examine associations with individual differences in brain structure, gene expression, and vocal learning (behavioral tests that involve minimal encouragement of the chimpanzees and reinforcement with food rewards, without involving any anesthesia, pain, or distress). Another important dimension of human language is the ability to understand words and their meaning, in both the auditory and visual domains. In humans, the gene KIAA0319, which is involved in brain development and dyslexia, is thought to play a key role in this sound-symbol learning. This project will examine how variation in KIAA0319 underlies differences in brain organization and sound-symbol learning in chimpanzees (housed at the Yerkes National Primate Center and the MD Anderson Cancer Center). All DNA samples, MRI scans, and brain tissue to be used in the study has previously been acquired. The combination of these multiple techniques will result in unique data sets that will transform our ability to compare brain structures and behavioral abilities relevant to language and brain function in chimpanzees and humans.