William Hopkins - US grants

This is a Shannon Award providing partial support for research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. Further scientific data for the CRISP System are unavailable at this time.

The proposed studies serve to investigate differences and similarities in cognitive processes related to hemispheric specialization among primate species including chimpanzees with language-training. This population of chimpanzees offer the unique opportunity to examine whether symbols which have acquired meaning are lateralized in a manner similar to those observed in humans. The objectives of the proposed research are as follows: a) To examine lateralized processing of meaningful and nonmeaningful symbols in human and chimpanzee subjects who use and comprehend visual-graphics symbols with age, sex, species, matched controls. To contrast language-trained chimpanzees patterns of lateralized processing on a variety of tasks with those who have not been reared in a similar environment. b) To assess hemispheric advantages in the processing of facial stimuli and performance on mental rotation tasks in three species"of primate including monkeys, chimpanzees and humans using a visual half-field paradigm designed to test neurologically intact subjects. c) To test hand preference, using multiple measures requiring different manipulation and postural demands, in 100 adult chimpanzees and monkeys. The task are designed so that direct comparative analysis between species can be performed. Moreover, the proposed study will examine cross-sectionally hand preference in chimpanzees and monkeys from different age classes. Finally, heritability of hand preference among related and unrelated chimpanzees and monkeys will be examined. The proposed studies are presented within a neuropsychological framework and will serve to advance our understanding of comparative cognition between species as well as brain-behavior relationships which may accompany different underlying cognitive processes.

During the past year, several non-invasive techniques were developed and employed for the study of neuroanatomical asymmetries and cerebral blood flow in chimpanzees in relation to cognitive functions. Specifically, magnetic resonance imaging (MRI) was used to assess asymmetries in the planum temporale and in petalia patterns in great apes and monkeys. In a subsequent study, asymmetries in Sylvian fissure length were examined as they pertain to the expression of handedness in a sample of chimpanzees. To assess cerebral blood flow, chimpanzees were trained to present their ears which allowed for assessment of temperature changes in the tympanic membrane. Temperature changes were then correlated with performance on a variety of cognitive tasks. With respect to the MRI results, these data suggest that the neurobiological basis of language is evident in great apes. Moreover, the MRI results as well as the blood flow results indicate the presence of structural and physiolog ical manifestations of hemispheric specialization in nonhuman primates. Taken together, the existing results and further development of these methodologies will foster a greater understanding of the biological and environmental factors which govern the development of cognitive functions in primates, including humans.

Further studies examining genetic and environmental contributions to the expression of hand preference were performed in chimpanzees. Furthermore, the possible consequences and neuroanatomical correlates of hand preference were examined in the chimpanzees. The findings from this year indicate a) individual variation in hand preference can be explained by variation in prenatal hormones b) birth order has a significant effect on hand preference and c) variation in prenatal hormone exposure has a significant impact on maternal outcome and neonatal fatalities. Additionally, the chimpanzees exhibit neuroanatomical asymmetries that are human-like in pattern and are related to variation in the size of the corpus callosum. Taken together, the results of this study further our understanding of the role of laterality as a marker of reduced fitness in humans. FUNDING NIH / NS-29574 $65,000 12/01/98 - 11/31/03 PUBLICATIONS Hopkins, W. D. The evolutionary and genetic (possibly?) basis of hand preference in humans What can the great apes tell us. Current Psychology of Cognition 3:234-238, 1998. Hopkins, W.D. Heritability of hand preference in chimpanzees Evidence from a interspecies partial cross-fostering study, Journal of Comparative Psychology (In press). Hopkins, W.D. Statistical issues in the assessment and interpretation of hand preference data in nonhuman primates, International Journal of Primatology (In press). Hopkins, W.D. Chimpanzees hand preferences Task specific or true handedness? Journal of Comparative Psychology (In press). Leavens, D.A. and Hopkins, W.D. Gestural communication in chimpanzees Implication for theories regarding social cognition. Journal of Comparative Psychology (In press). Parr, L.A., Hopkins, W.D. and deWaal, F.B.M. The perception of facial expression by chimpanzees. Evolution of Communication (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center

DESCRIPTION (adapted from applicant's abstract): The long term goals of the proposed studies are a) to determine factors which influence the expression of handedness in primates and b) to examine the reproductive and immunological correlates of behavioral lateralization in primates. The specific aims are a) to assess environmental and genetic factors as determinants of hand preference b) to determine whether measures of developmental stability can explain individual differences in phenotypic expressions of hand preference and c) to determine whether handedness is predictive of compromised immunological functioning and/or reproductive biology. The role of genetic and environmental factors on the expression of hand preference will be determined by comparing the concordance in hand preference in parent/offspring dyads who were either conspecific-reared or cross-fostered. Measures of fluctuating asymmetry (FA), specifically dermatoglyphics, will be used to assess developmental instability in the chimpanzees. The FA data will be used to determine whether chimpanzees who do not show the predicted phenotypic expression of hand preference have larger FA than comparison subjects. Larger FA values would reflect a greater effect of prenatal perturbations in certain hand preference groups. Finally, the relationship between hand preference and immunological functioning and reproductive biology will be assessed in left-, ambidextrous and right-handed chimpanzees matched on age and rearing history. These data will provide valuable information on whether non-right-handedness is associated with increased risks for health related problems and potentially reflects decreased survival fitness.

DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to understand the neurobiological basis of complex cognitive, perceptual and motor processes from the standpoint of neurophysiological and neuroanatomical specializations of the left and right cerebral hemispheres. The aims are to evaluate neural systems involved in the expression of communicative behaviors, execution and perception of motor actions and social behaviors that are hypothesized to be homologs to the evolution of complex human cognition including expressive and receptive language. Positron emission tomography (PET) will be used to assess the neurobiology of gestural and vocal communication in chimpanzees. Additional PET studies will be conducted to evaluate whether the "mirror-neuron" system of motor action and perception previously described in monkeys underlies the execution and perception of complex motor processes, such as imitation, in chimpanzees. PET studies will also be used to evaluate evolutionary hypotheses of language origins that are rooted in the social functions of language. Of specific interest is the link between the evolution of language and the function of social grooming in primates. To test these hypotheses, PET will be used to evaluate the neural systems involved in grooming by chimpanzees. The neurobiology of handedness, one of the most pronounced manifestations of hemispheric specialization, will also be evaluated in the proposed studies. PET will be used to assess where the hand is represented in the primary motor cortex in chimpanzees and these data will be mapped to known neuroanatomical landmarks on the motor strip of chimpanzees. Hand regions will then be mapped and quantifed in the left and right cerebral hemispheres from magnetic resonance images (MRI) and asymmetries in this region will be correlated with various measures of hand preference and skill. The overall studies will contribute to our understanding of factors that influence individual and species differences in the expression of hemispheric specialization.

communication; cerebral dominance; Primates; animal colony; animal communication behavior;

Incubation of eggs is a critical part of reproduction in birds. Optimal growth and development of embryos takes place within a narrow range of incubation temperatures, and parents must balance the competing demands of maintaining good body condition while caring for developing eggs. The importance of incubation has often been overlooked in studies of avian reproductive costs, but incubation costs can limit both current and future reproductive success. Time and energy demands can be especially important in species where only one sex incubates. Reduced attendance by incubating parents makes it more likely that egg temperatures will deviate from that needed for optimal development. Low egg temperatures can slow development and lead to longer incubation periods, which results in greater predation risk and potentially influences the amount of energy used by developing embryos and ultimately neonate phenotype. This research with wood ducks will have 3 main components. First, previous experimental work has shown that incubation temperature influenced both incubation period and neonate phenotype of wood ducks. This project will use incubation temperature to manipulate phenotypes of neonates and then return day-old ducklings to foster mothers to raise. Effects of these temperature-induced changes to duckling phenotype on growth and development, survival, recruitment to the breeding population, and subsequent reproductive success will be examined. Second, effects of incubation temperature on metabolic rates and total energy expended by wood duck embryos will be estimated. Later, ability of ducklings incubated at different temperatures to thermoregulate and the energetic costs of thermoregulation also will be examined. Third, incubation costs of adults will be manipulated and effects of these manipulated costs on body mass dynamics, incubation behavior, within- and between-season reproductive performance, and survival of females will be examined. The project will use a life history framework to examine fitness consequences of maternal reproductive decisions. Results should re-invigorate studies of incubation patterns and their functional consequences in birds, and make new contributions to our understanding of the evolution of vertebrate life history strategies. Integration of research and education will be an important goal of the project. This will be accomplished by (1) incorporating new research findings in undergraduate and graduate courses, (2) recruiting undergraduate and graduate students to work on the project, (3) hosting a workshop for NSF-sponsored undergraduates at the Savannah River Ecology Laboratory to demonstrate field research and data management methods, and (4) integrating a K-12 activity on waterfowl reproduction, conservation and education with the Virginia Tech's Science Outreach Program (SOuP) which brings science research to broader audiences, especially K-12 teachers and students.

Recent research demonstrates that in wood ducks (Aix sponsa) less than 1¢ªC variation in average incubation temperatures affects duckling growth, body condition, thermoregulatory ability, immune function, stress endocrinology, and locomotor performance. Many of these effects persist until at least several weeks after hatching. The proposed research will continue to explore the role incubation temperature plays in defining characteristics of hatchling wood ducks that are important to their development. Specifically, this research will investigate whether incubation temperature drives trade-offs between physiological processes critical to early survival in birds, their thermoregulatory ability and the immune system. The proposed research will also explore a potential underlying mechanism responsible for meditating effects of incubation temperature on avian phenotype.

This research will integrate research with education primarily by targeting K-12 teachers and students and undergraduates in wildlife sciences and biology. The K-12 education approach aims both to raise awareness of waterfowl natural history and conservation as well as the scientific process. In teaming with the Virginia Tech Science and Outreach Program, 12 elementary schools, 4 middle schools, 4 high schools, and 4 special education programs will have access to color-printed cards highlighting the natural history and conservation status of Virginia waterfowl. The schools will also have access to lesson plans pertaining to avian incubation and reproductive ecology that incorporate Virginia standards of learning. Education of undergraduates involves a new program that facilitates reciprocal learning by pairing a graduate student with an undergraduate researcher conducting a senior thesis project. The goal of the program is to prepare undergraduates for their upcoming transition to graduate school by giving them hands-on training with all major aspects of academic research, while simultaneously preparing graduate students for their eventual transition into a faculty position.

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 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.

Project Summary Alzheimer's disease (AD) is a major health concern defined by pathologic changes in the brain that coincide with altered behavior and cognitive function. Animal models have advanced our understanding of AD, but these models artificially induce neuropathy to simulate the human disease. For instance, while amyloid- beta (A?) deposition occurs in most mammals, tau-positive neurofibrillary tangles (NFT) have only been identified in a few nonhuman species studied to date. Our research team recently discovered that chimpanzees, one of our closest genetic relatives, naturally develop both A? plaques and NFT, the pathological hallmarks of AD. In addition to AD pathology, elderly chimpanzees also develop cerebral amyloid angiopathy (CAA), a neurovascular condition found in 80% of AD patients associated with cognitive decline. Therefore, additional studies in chimpanzees could shed new light on the etiology of AD and CAA, leading to potentially new directions for therapeutic interventions. The overall goals of the proposed studies are to further examine the pathologic, epigenetic, and cognitive characteristics of aging, CAA, and AD in chimpanzees. In Aim 1, we will perform comprehensive pathologic analyses aimed at quantifying biomarkers of CAA and AD, including A?40 and A?42 plaque and vessel volumes, NFT density, pericyte and smooth muscle cell vessel volumes, neuron and synapse densities, and mitochondrial dysfunction. The collective neuropathologic measures will be examined in a sample of chimpanzees for which antemortem cognitive data is available, and the main focus will be determining which pathologic markers best predict individual variation in cognition. Moreover, we will test the correlation of AD and CAA pathologies with inflammatory processes, such as microglial activation and astrogliosis. In Aim 2, we will quantify epigenetic age in the chimpanzee population and evaluate whether chimpanzees with CAA or AD lesions demonstrate accelerated epigenetic aging in the brain relative to apes without pathology. We also will determine if epigenetic age is a better predictor than chronological age of changes in cognition, region-specific gray matter volume, and white matter integrity and connectivity. Finally, though previous studies have found cross-sectional age differences in cognition in chimpanzees, we will determine whether chimpanzees show longitudinal changes in cognition and whether any age-related loss in performance predicts the subsequent expression of AD pathology in this proposal. All biomaterials and cognitive data obtained in the proposed studies will be added to the National Chimpanzee Brain Resource and made publicly available to the scientific community through a web portal. The proposed studies, in their entirety, will fill an important gap in our knowledge about the comparative biology of aging and disease in chimpanzees and may provide critical translational insight into how those processes contribute to the progression of CAA and AD in humans. This information will provide crucial direction for future translational studies using rodent and nonhuman primate models.

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.

The COVID-19 pandemic has exposed vulnerabilities in global supply-chains and in the production of manufactured goods, with social and environmental impacts. Through collaborations that explore practices to increase connections among sustainable consumption, sustainable production, and sustainable development, the VR(Ex)Change Network increases efficiency and sustainability of global manufacturing and supply chains. This highly interactive network offers early-career fora, teaching incubators, webinar series, training and leadership opportunities, to engage diverse, underrepresented, and early-career individuals from around the world. Diverse perspectives, from across different regions, fields, and sectors inform opportunities for applied research and collaboration. The VR(Ex)Change enhances the competitiveness of U.S. researchers and professionals within the global sustainability and circular economy transformation. <br/><br/>The VR(Ex)Change Network produces research and analysis to support viable and sustainable human communities, and tackles questions of resource scarcity, environmental degradation, and human well-being. Members utilize scenario analysis, case studies, landscape studies, and other methods to investigate key themes: (1) Universal Development, Livelihoods, and Resilient Communities; (2) Moving from Circular Economy to Circular Society; (3) Digital Technology to Enable Sufficiency; (4) Design and Cultural Change as Drivers of Secure Lifestyle; and (5) Future of Work and the Role of Consumption. The collaboration provides a solutions-focused, stakeholder-driven approach that produces research and applications from a unified approach to studying sustainable consumption and production. Using a systems-approach focused on mutuality and higher-order learning, the team produces outputs that include a strategic roadmap for transformative integration of production and consumption that facilitates future development of the network.<br/><br/>The Accelerating Research through International Network-to-Network Collaborations (AccelNet) program is designed to accelerate the process of scientific discovery and prepare the next generation of U.S. researchers for multiteam international collaborations. The AccelNet program supports strategic linkages among U.S. research networks and complementary networks abroad that will leverage research and educational resources to tackle grand scientific challenges that require significant coordinated international efforts. This project is funded by the Office of International Science and Engineering (OISE).<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.