Chet C. Sherwood - US grants

The human brain is distinguished by costly energetic demands and enhanced plasticity. This combination of factors underlies some of the most unique cognitive capacities of our species. The brain's capacity for learning is greatest during childhood and involves the formation and refinement of new neuronal connections. This process is driven by high rates of energy consumption. This research project will identify the genetic changes during evolution that brought about the human brain and explore the causal link between the development of brain plasticity and metabolism.

A major aim of this project involves charting the changes in the brain's energy utilization during the different maturational stages of humans. To accomplish this goal, the interdisciplinary team is using positron emission tomography scans of brain glucose consumption over the course of development from birth to adult stages. These results will be integrated with the patterns presented by RNA and protein data on the thousands of genes that are expressed at changing levels in different brain regions across the same developmental stages. Comparative data on the developmental expression of proteins and neuron morphology in great apes and macaque monkeys are also being obtained to determine whether the progression of molecular and cellular changes in human brain development are distinctively different from our close relatives. The investigators expect to find coordinated expression patterns in brain energetic and brain plasticity genes showing evidence that adaptive evolution occurred in their regulatory machinery during the origin of humans. The results should provide important clues about the organization and function of the molecular machinery that underpins the type of human brain plasticity that gives our species its exceptional capacity to incorporate experience and learning into the production of culture.

By focusing attention on brain energetic and brain plasticity genes that show adaptive evolution during recent human ancestry but are currently fixed across human populations, this project's focus on shared genes that define human cognitive abilities reinforces the conclusion of a common humanity. Thus the results of this project should be of interest to the general public and to scientists across a wide variety of disciplines, including anthropology, neuroscience, molecular evolution, bioenergetics, endocrinology and pediatrics. Experimental determination of total brain energetics during growth will enhance our ability to understand the age-specific tradeoffs that the acquisition of larger brains would have required during human evolutionary history, while also providing a new context in which to understand metabolic diseases such as diabetes. Furthermore, this project will advance research and education by providing training opportunities for individuals at the undergraduate, graduate and postdoctoral levels.

This Integrative Graduate Education and Research Training (IGERT) award focuses on the evolution of the human brain, cognition, and related behavioral responses to environmental change. The program integrates cross-disciplinary research training in a unique mix of disciplines, namely archeology, biomechanics and engineering, cognitive science, comparative and experimental functional morphology, ecology, evolutionary and developmental biology, genetics, geochemistry, morphometrics, life history, molecular biology, neuroscience, and paleoclimatology. Innovative educational and training aspects include an emphasis on collaboration via group problem-based learning approaches, required laboratory rotations in two different disciplines, and seminars in ethics and professional conduct. The program combines George Washington University?s PhD program in Hominid Paleobiology with the Howard University PhD in Physiology and Biophysics, together with faculty from the Smithsonian Institution and Johns Hopkins University?s Center for Functional Anatomy and Evolution, The collaboration with Howard University (an HBCU) and existing and planned internship programs for undergraduates will increase the recruitment of underrepresented minorities. Outreach activities include a required internship in the public understanding of science, in conjunction with area institutions such as the National Geographic Society, USA Today, NPR, the National Academy of Sciences, American Anthropological Association, local schools and others. The program offers research-training opportunities at major international institutions in Europe (e.g., Max Planck Institut für evolutionäre Anthropologie (MPIEA); Swedish Museum of Natural History; Università degli Studi di Firenze?s Laboratori di Antropologia; University of Bordeaux), China and Africa. IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries.

Despite numerous hypotheses concerning language evolution, the neurobiological origins of the human capacity to speak remain little understood. Studies suggest that the striatum, a subcortical structure forming complex connections with the cerebral cortex, may be important in the evolution of vocal learning - the capacity to modify vocalizations in response to social experience - which is necessary to acquire speech during development. The striatum also is a key site of expression of FOXP2, a gene that underwent positive selection in modern humans, and, in a mutated form, is responsible for a hereditary disorder affecting language production. To date, however, evidence indicating a role of the striatum in the evolution of speech and language mainly comes from experimental species, such as birds and mice, which are evolutionarily distant from humans.

The aim of the current project by doctoral student Serena Bianchi (George Washington University), under the guidance of Dr. Chet Sherwood, is to identify neural features of the non-human primate striatum that may have been associated with the evolution of the capacity for vocal learning that characterizes human speech. To this end, this project uses non-invasive neuroimaging techniques, and post-mortem histological and molecular analyses, to examine the striatum of captive chimpanzees for which the use of learned, voluntarily controlled vocalizations produced to attract the attention of the experimenter (attention-getting vocalizations) has been documented. Specific aims include assessing whether the striatum of chimpanzees who produce attention-getting vocalizations differs from chimpanzees that do not exhibit this vocal phenotype in 1) morphology, and pattern of connections with motor and language-related regions of the cerebral cortex; and 2) neuronal plasticity and expression of proteins associated with synaptic functions and FOXP2. Investigating the neurobiology of vocal communication in an animal model evolutionarily close to humans may help identify precursors to speech production within a Darwinian framework of language origins as 'descent with modifications' of existing neural structures in the non-human primate brain.

As part of this project, dissemination of knowledge about the evolution of the brain and language will be fostered through collaboration with the outreach program of the Smithsonian National Museum of Natural History, and the development of on-line resources and teaching materials. In addition, the histological collection created by this project will be made available to other researchers.

During human evolution there have been large- and small-scale changes in underlying anatomical structures of the brain. Studying this reorganization is important for understanding the link between structure and function in the brain, and how this relationship may affect cognition and behavior. This project will look at changes in the interconnectedness and anatomy of a region of the brain related to planning and carrying out complex tool making, in humans and a number of non-human primate species. The findings will advance our scientific knowledge about how distinctive human behaviors originated and developed, ultimately contributing to our overall understanding of the origins of modern human behavior and culture. In addition, the project will support a female graduate student in the STEM sciences, provide science outreach to the public, and potentially inform future research on degenerative neurological diseases.

The parietal region of the brain, particularly the inferior parietal lobe (IPL), experienced reorganization in the human lineage based on studies of fossil endocasts and neuroimaging scans. The IPL is particularly active in observing, planning and executing tool-use and skilled tool-making. The proposed project will integrate histological analyses of IPL microanatomy and a neuroimaging-based study of function and connectivity between the IPL and other brain regions to investigate reorganization. These methods will be applied consistently across a sample of primate species and humans to address reorganization of the IPL in human evolution. Such an integrative approach will reveal the anatomy of the human and non-human primate IPL and will show how the IPL operates within large-scale functional networks. This study will provide a detailed investigation of human-specific changes in brain evolution within a comparative and evolutionary framework, and can aid in answering questions about the origins of distinctive human behaviors, such as complex tool-making and symbolic behaviors. Thus, studying patterns of brain reorganization in the hominin lineage ultimately contributes to our overall understanding of the origins of human behavior and culture.

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.

The hippocampus is a brain structure that is critical for the storage and recall of long-term memory as well as spatial navigation. It is also one of the only brain structures that maintains the ability to generate new neurons throughout one's lifetime, a feature necessary for effective long-term memory. This project will investigate the origins of human memory by comparing the hippocampus of humans to those of our closest living non-human primate relatives at the levels of neuroanatomy, gene expression, and genetics. This research will provide novel insights into the neurobiological basis of certain human-specific memory-related abilities and the ecological factors that may have driven their emergence. Furthermore, this project will identify neurobiological targets that may render humans uniquely susceptible to certain neurological diseases and disorders known to affect the hippocampus (e.g., Alzheimer's disease, Autism spectrum disorder). Data from this project may inform further research and discoveries on human brain form and function. The project will support undergraduate mentoring and research experiences, and the investigators will engage in public science outreach to promote understanding of neuroscience, genetics and human evolution.

While the hippocampus is central to long-term memory in all mammals, only in humans is it known to additionally mediate episodic memory, the capacity to recall specific personal experiences and imagine future events. This may have first emerged in our hominin ancestors to meet the demands of increasingly challenging environments, expanded home ranges, and novel hunting/foraging strategies. Recent evidence suggests that the human whole-hippocampus has become evolutionarily specialized compared to those of other primates in terms of relative size, neuronal structure and distribution, and gene expression. However it is well known that the hippocampus is composed of molecularly and functionally distinct subfields. This project will therefore investigate the evolution of the hippocampus in humans and non-human primates in terms of neuroanatomy, gene expression, and genotype. Volumetric proportions of hippocampal subfields and degree of adult hippocampal neurogenesis will be estimated, and ecological variables will be correlated with neuroanatomical measures to test for neuroecological relationships. Whole-transcriptome gene expression data of hippocampal subfields will be generated and used to identify genes that are differentially expressed in humans. Protein-coding and regulatory regions of genes will be tested for positive selection.

Our species is distinguished from other primates and mammals by our large brains and impressive cognitive abilities. Prolonged brain growth through development, along with a particularly long life, are essential to the emergence of human cognition, but may also lead to greater susceptibility to psychiatric and aging-related neurodegenerative disorders, like Alzheimer's disease. This project will characterize molecular changes in the brains of humans and other primates across the adult lifespan to identify features that distinguish the human pattern of brain development and aging. The results of this project will help pinpoint the genetic mechanisms underlying dynamic lifespan changes that are unique to human neurobiology and may improve our understanding of common medical conditions. The project will involve mentoring and building the analytical skills of trainees at different career stages (postdoctoral, graduate, undergraduate), and communicating results of this study to members of the public through accessible educational programming.

The genetic and physiological basis of human brain development and aging are not fully understood. Changes in methylation are important in development and aging, and plasticity of methylation appears to play a key role in the brain, contributing to processes like the formation of neuronal connections. Previous studies have identified differences in brain methylation patterns among primate species, and the investigators' prior work suggests that genes acting in the nervous system undergo alterations in methylation with advancing age. This project will specifically investigate DNA methylation in four brain regions. The work will build on existing research by taking a comparative approach to identify differences in the trajectories of methylation change in several distinct brain regions across adulthood among four primate species, including humans. Identifying differences among primate brains in age-related change could help us understand the origins of traits distinguishing human brains, including aspects of neurobiological aging.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

The proposed research will examine naturally occurring molecular variation in the brains of humans and other primates to understand how modifications to the function of genes in the brain relate to differences in developmental and social experience across species. The proposal is highly interdisciplinary, incorporating methods and perspectives from molecular biology, anthropology, neuroscience and psychology, and will advance fundamental knowledge about mechanistic processes underlying gene-environment interactions in the brains of highly social species. In addition to offering interdisciplinary training for graduate and undergraduate students during the proposed research, the PIs will integrate research opportunities with outreach efforts for high school students, high school teachers, and also for broader public audiences, including children. Comparative studies of primates offer great educational and outreach potential due to their deep implications for understanding humans? place in nature. Furthermore, the brain is the most widely studied organ in genetic and psychological studies, making the datasets this project will generate especially worthwhile as open resources for the scientific community. All research conducted will be published in peer-reviewed scientific journals and disseminated in scientific meetings.

Nonhuman primates have been important model species for the study of mechanisms underlying the biological, genetic and neural basis of a variety of behavioral and cognitive functions. Many aspects of primate brains, including size, structural variation and rate of maturation are tightly associated with life history traits such as cognition, gestation length and life span. These differences are also associated with different developmental rates of primate brains. For example, human brains are extremely immature at birth, followed by slow development, providing ample opportunities for interaction between genome and environment to occur. This research project aims to study the molecular record of such genome-environment interaction in the context of primate brain development. Specifically, the investigators will examine DNA methylation, which functions as cellular memory of environmental input and thus moderates genome-environment interactions, and hypothesize that natural variation in brain size and development of primate species will be reflected in variation of DNA methylation, and in turn, gene expression. Several primate species will be included, encompassing naturally occurring variation in life history traits and brain size. Neocortical areas with distinctive developmental patterns, at cellular resolution, will be compared. In addition to phylogenetic variation, the research will utilize a unique opportunity to investigate how early social experiences have shaped DNA methylation and gene expression within species, using archived samples from chimpanzees and baboon colonies. The proposed research will generate novel opportunities to correlate molecular data with brain and cognitive phenotypes across multiple scales of biology.

This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Humans have remarkably plastic brains; adaptations for learning are perhaps the hallmark evolutionary trait of our species. This project will examine learning-related aspects of brain organization in great ape species that are close evolutionary relatives of humans – bonobos and chimpanzees – using noninvasive tests and archived brain samples and images. The work focuses on two learned skills that were important factors in human evolution: tool use and language. One analysis will use archived brain images from previous studies combined with new behavioral tests of skill learning. Apes will receive training in evolutionarily-relevant, naturalistic tool use skills, and the investigators will measure how individual variation in brain organization is related to skill learning. Another analysis will examine brain organization in apes that have and have not undergone training to use language-like systems, including hand signs and pictogram boards. The investigators will examine how language training is related to learning-related changes in the brain. Results are expected to shed light on probable brain changes during the evolution of the human species, provide insight on neural mechanisms of real-world skill learning in primate species closely related to humans, and facilitate understanding of how individual variation in brain structure is related to individual variation in behavior and cognition.<br/> <br/>This project will use a cross-disciplinary, comparative, integrative approach to examine how individual variation in brain anatomy influences learning trajectories in the context of real-world, evolutionarily relevant skills. It also examines the interaction between acquired, plastic changes in the brain resulting from learning during an individual’s lifetime, and evolved, heritable changes resulting from natural selection across generations. The project brings together methodological and theoretical approaches from neuroscience and neuroimaging, anthropology, archaeology, and animal behavior. Identification of plastic changes resulting from language training in great apes will provide a new window on the evolution of language circuits in our own species and will for the first time add crucial neurobiological information to landmark, long-running language-training studies in apes. Additionally, individual variation in chimpanzee and bonobo brain anatomy will be linked to differences in learning trajectories in two evolutionarily-relevant, real-world skills: simple stone tool knapping and nut cracking. Together, this research will provide important new insight on brain changes underlying acquisition of learned skills both on the timescale of individual lifetimes (plasticity) and the timescale of evolved, species-level change (adaptation).<br/><br/>This project is funded by the Integrated Strategies for Understanding Neural and Cognitive Systems (NCS) program, which is jointly supported by the Directorates for Computer and Information Science and Engineering (CISE), Education and Human Resources (EHR), Engineering (ENG), and Social, Behavioral, and Economic Sciences (SBE).<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.