James P. Morris - US grants

[unreadable] DESCRIPTION (provided by applicant): The primary goal of this training fellowship is to apply functional magnetic resonance imaging techniques to the study of the social brain. A recent endeavor of the neurosciences has been to characterized the neural circuitry associated with our ability to interact in a social world. Early brain imaging studies of social cognition were limited to the presentation of static 2 dimensional images that were often presented out of social and affective context. Current work has remedied this issue by presenting dynamic visual scenes, demonstrating how salient social cues are often reflected by meaningful biological motion. Nonetheless much of this work has employed paradigms where the subject passively views movements made in and out of social context. This proposal will test two novel designs aimed at enhancing the ability to engage subjects in a more realistic and compelling social situation. Study 1 will focus on comparing neural correlates associated with approaching a dynamic social scene with those associated with approaching a non-social scene. Study 2 has been designed to characterize neural circuitry underlying the decoding of social intentions conveyed by social signs is when humans approach ambiguous social situations. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): This is an application for an NIH Pathway to Independence Career Development Award. The candidate for this award is James P. Morris, an NRSA postdoctoral fellow at the Duke University Brain Imaging and Analysis Center. Dr. Gregory McCarthy, the former director of the Brain Imaging and Analysis Center and professor of Psychology at Yale University will serve as mentor during the mentored phase of this award. The candidate will continue his postdoctoral training with Dr. McCarthy at Yale University. The candidate's current research investigates category-specific responses in the temporal cortex, with a special emphasis on brain activity evoked by categories of stimuli with important social meaning. The candidate proposes two broad objectives for the mentored phase of this award. The first objective is to further develop the technical skills necessary to study category specific responses in the human temporal lobes with functional MRI and Intracranial ERPs. The second objective is to develop professional skills necessary to succeed as an independent investigator. These skills include the ability to present data to colleagues, mentor and guide students and collaborators, and to be able to extend knowledge to the community with the ultimate goal of fostering understanding of human disease and disorders. The independent phase of this award is focused on the development of a research program that seeks to understand the effects of both low-level stimulus factors 'as well as differences in motivation and behavior on brain activity during social perception. The successful completion of experiments proposed here will lead to a solid foundation on which to build an independent research career. The results from the proposed research will contribute to important discoveries being made regarding the neural correlates of social perception. Deficits in social perception are a striking feature of autism, schizophrenia, and anxiety disorders. An understanding of how both stimulus and behavioral factors influence social processing will provide suggestions for remediatory approaches toward the treatment of these disorders, as well as the functioning of the normal human brain. [unreadable] [unreadable] [unreadable]

Social interaction is a critical component for the formation and development of interpersonal relationships. In order to facilitate social interaction, humans have developed a specialized set of perceptual skills allowing for rapid assimilation of socially relevant information. These skills are often referred to collectively as social perception and in normal development the human brain forms specialized brain circuitry to accommodate these skills. Individual differences in social perception have a strong heritable component and therefore should be mediated by common genetic variation that impacts the structure and function of this specialized brain circuitry. However, contemporary genetic techniques focusing on the DNA sequence variation have been limited in explaining variability in complex social behavior. One potential solution to this problem is to expand the approach to consider other biological processes that impact the function of the gene without changing its sequence. These modifications are referred to as 'epigenetic' and are thought to play a critical role in healthy and disordered behavior. With support from the National Science Foundation, Drs. James Morris and Jessica Connelly of the University of Virginia are combining approaches from human neuroscience with molecular genetics to explore the role of epigenetic processes on neural circuitry supporting social perception. The project focuses on defining individual epigenetic variability along the oxytocin receptor gene. Oxytocin is a hormone that acts as a neurotransmitter in the mammalian brain and plays a critical role in social perception. Epigenetic modification of the oxytocin receptor gene influences its function and therefore should influence behaviors that are mediated by oxytocin. To test this hypothesis, subjects are assessed for epigenetic variability along the oxytocin receptor gene and then have their brains scanned while performing three common tasks that engage brain circuitry underlying social perception. The primary analysis focuses on the relationship between epigenetic variability and brain activity related to social perception. Secondary analyses consider how this relationship is related to complex behaviors such as empathy and stress reactivity.

This project establishes a new paradigm to understand how genetic variability can impact social behavior. To date, epigenetic modifications have been largely ignored when considering how genes may modulate brain activity as measured by modern neuroimaging techniques. The application of epigenetic techniques to neuroscientific investigations of social behavior will contribute to new models of personality and individual differences, and help explain vulnerability to psychiatric and developmental disorders that are defined by a wide range of individual differences. The project presents a unique opportunity for students wishing to cross-train in genetics and human neuroscience.

Acquiring skills for effective social interaction is critical for infants. This project will examine the early development of brain processes that underpin successful social interactions, and identify factors that affect social functioning. The researchers will investigate social and brain development during the first year of life with a specific focus on the role of oxytocin, a neurotransmitter and hormone implicated in several social behaviors. By revealing how brain biology shapes and interacts with early infant social development, this research will fill an important gap in our knowledge and has broad implications for understanding healthy and atypical development. The project is multidisciplinary in nature as it uses a cutting-edge approach combining epigenetic, neuroscience, and behavioral methods. The findings will be broadly applicable to multiple disciplines and will inform understandings of molecular biology, neuroscience, and social psychology. The planned experiments will provide valuable research opportunities and unique training for students interested in developmental psychology, cognitive science, molecular genetics, and developmental neuroscience.

The human brain undergoes critical development during the first year of life, which allows for the effective processing of social information from faces and voices. This project will test the hypothesis that endogenous oxytocin impacts social information processing during early development by regulating levels of neural noise during face and voice processing. Oxytocin acts as a neurotransmitter in the mammalian brain and plays a critical role in many social behaviors. Oxytocin receptors (OXTR) allow the brain to respond to oxytocin, and their quantity in the brain is variable in the population. The production of these receptors is under epigenetic control, specifically through DNA methylation, and variability in OXTR prevalence is linked to variability in social information processing among adults and to the presence of neurodevelopmental disorders such as autism. The project will examine whether, from early in development, neural noise plays a predominant role in establishing the salience of social information conveyed by faces and voices, through a process governed by the oxytocin system. To this end, this project will (1) investigate longitudinal changes in neural noise across the first year of life using electroencephalography, (2) assess whether individual differences in neural noise predict social information processing and behavioral outcomes during infancy, and (3) map how epigenetic modifications in the oxytocin system impact levels of neural noise during early development. Studying neural noise in typically developing infants and identifying the processes that contribute to its individual variability will foster a deeper and more mechanistic understanding of early social and brain development.

Oxytocin is a hormone that plays a critical role in many social behaviors. Prior research suggests that natural variability in the oxytocin system affects neural systems involved in social cognition. This proposal examines whether more efficient oxytocin utilization increases sensitivity to social information. Increased sensitivity may confer an advantage when social information is relevant but may be disadvantageous in other contexts. Findings from this project are expected to provide new information about how people who differ in the way their neural systems are sensitized by this hormone respond to social information. The results will be broadly applicable to multiple disciplines spanning molecular, neural, and behavioral investigations, and may inspire new research in these disciplines. The experiments conducted are expected to provide valuable research opportunities and unique training combining molecular genetics and functional neuroimaging for students interested in psychology, cognitive science, and neurosciences.

Oxytocin receptors (OXTR) allow the body to respond to oxytocin, but its expression differs between people. These receptors are under epigenetic control, specifically through DNA methylation, which is at least in part responsible for these individual differences. OXTR methylation has been associated with brain activity supporting social cognition and with various social phenotypes in both healthy and disordered populations. Combing this reliable, endogenous epigenetic marker with functional magnetic imaging and behavioral testing, this proposal tests the hypothesis that the endogenous oxytocin system influences the degree to which an individual is sensitive to social information. Its main aims are (1) to test whether variability in OXTR methylation is associated with differential engagement of perceptual and attentional systems during social information processing; (2) to evaluate whether individuals low in OXTR methylation depend on prefrontal brain systems to suppress irrelevant social information; and (3) to assess whether the relationship between OXTR methylation and neural systems supporting attention to social information predicts self-reported sociality and independently rated social skill.

? DESCRIPTION (provided by applicant): This is an application to continue research originally started in 2001, and expanded into a longitudinal study, known as the Virginia Cognitive Aging Project (VCAP), in 2005. Over 2,300 adults 18 - 95 years old have now completed at least two longitudinal occasions, with an average of 2.7 occasions and an average time in study of 5.1 years. The research proposed in the next funding period will extend the investigation of short-term longitudinal change in a broad variety of cognitive measures, with particular emphasis on adults under the age of 80. Although previous studies have found little or no cognitive change in longitudinal comparisons involving young and middle-aged adults, this research employs three methodological innovations, variable retest intervals, measurement bursts at each occasion, and continuous recruitment of new participants, that help distinguish age effects from experience (retest) effects, and that increase sensitivity to detect change by taking into account normal short-term variability in performance. Among the primary questions to be investigated are when does normal age-related cognitive change begin, the degree to which changes in different cognitive variables are independent of one another at different periods in adulthood, the role of prior test experience on the direction and magnitude of cognitive change at different ages, the degree to which factors such as one's cognitive or physical lifestyle moderate the amount of age-related change in different cognitive abilities at various periods in adulthood, and how early can normal and pathological trajectories of cognitive aging be distinguished. Specific aims during the next grant period are to: (1) Expand the characterization of normal cognitive aging across the range from about 18 to 80 years old; (2) Extend the investigation of the role of experience effects on cognitive change; (3) Investigate the structure and nature of cognitive change across different levels of analysis and across a wide range of ages; and (4) Increase sensitivity of VCAP tests to detect early stages of cognitive pathology among VCAP participants.