Stephen EP Smith, PhD - US grants

? DESCRIPTION (provided by applicant): The major technological and analytical advances in human brain imaging achieved as part of the Human Connectome Projects (HCP) enable examination of structural and functional brain connectivity at unprecedented levels of spatial and temporal resolution. This information is proving crucial to our understanding of normative variation in adult brain connectivity. It is now timely to use the tools and analytical approaches developed by the HCP to understand how structural and functional wiring of the brain develops. Using state-of-the art HCP imaging approaches will allow investigators to push our currently limited understanding of normative brain development to new levels. This knowledge will critically inform prevention and intervention efforts targeting well known public health concerns (e.g., neurological and psychiatric disorders, poverty). The majority of developmental connectivity studies to date have used fairly coarse resolution, have not been multi-modal in nature, and few studies have used comparable methods to assess individuals across a sufficiently wide age range to truly capture developmental processes (e.g., early childhood through adolescence). Here we propose a consortium of five sites (Harvard, Oxford, UCLA, University of Minnesota, Washington University), with extensive complimentary expertise in brain imaging and neural development, including many of the investigators from the adult and pilot lifespan HCP efforts. Our synergistic integration of advances from the HARVARD-MGH and WU-MINN-OXFORD HCPs with cutting edge expertise in child and adolescent brain development will enable major advances in our understanding of the normative development of human brain connectivity. The resultant unique resource will provide rich, multimodal data on several biological and cognitive constructs that are of critical importance to health and well-being across this age range and allow a wide range of investigators in the community to gain new insights about brain development and connectivity. Aim 1 will be to optimize existing HCP Lifespan Pilot project protocols on the widely available Prisma platform to respect practical constraints in studying healthy children and adolescents over a wide age range and will also collect a matched set of data on the original Skyra and proposed Prisma HCP protocols to serve as a linchpin between the past and present efforts. Aim 2 will be to collect 1500 high quality neuroimaging and associated behavioral datasets on healthy children and adolescents in the age range of 5-21, using matched protocols across sites, enabling robust characterization of age-related changes in network properties including connectivity, network integrity, response properties during tasks, and behavior. Aim 3 will be to collect and analyze longitudinal subsamples, task, and phenotypic measures that constitute intensive sub-studies of inflection points of health-relevant behavioral changes within specific developmental phases. Aim 4 will capitalize on our success in sharing data in the HCP, and use established tools, platforms and procedures to make all data publically available through the Connectome Coordinating Facility (CCF).

? DESCRIPTION (provided by applicant): The major technological and analytical advances in human brain imaging achieved as part of the Human Connectome Projects (HCP) enable examination of structural and functional brain connectivity at unprecedented levels of spatial and temporal resolution. This information is proving invaluable for enhancing our understanding of normative variation in young adult brain connectivity. It is now timely to use the tools and analytical approaches developed by the HCP to understand how structural and functional wiring of the brain changes during the aging process. Using state-of-the art HCP imaging approaches will allow investigators to push our currently limited understanding of normative brain aging to new levels. We propose an effort involving a consortium of five sites (Massachusetts General Hospital, University of California at Los Angeles, University of Minnesota, Washington University in St. Louis, and Oxford University), with extensive complementary expertise in human brain imaging and aging and including many investigators associated with the original adult and pilot lifespan HCP efforts. This synergistic integration of advances from the MGH and WU-MINN-OXFORD HCPs with cutting-edge expertise in aging provides an unprecedented opportunity to advance our understanding of the normative changes in human brain connectivity with aging. Aim 1 will be to optimize existing HCP Lifespan Pilot project protocols to respect practical constraints in studying adults over a wide age range, including the very old (80+ years). Aim 2 will be to collect high quality neuroimaging, behavioral, and other datasets on 1200 individuals in the age range of 36 - 100+ years, using matched protocols across sites. This will enable robust cross-sectional analyses of age-related changes in network properties including metrics of connectivity, network integrity, response properties during tasks, and behavior. Aim 3 will be to collect and analyze longitudinal data on a subset of 300 individuals in three understudied and scientifically interesting groups: ages 36-44 (when late maturational and early aging processes may co-occur); ages 45-59 (perimenopausal, when rapid hormonal changes can affect cognition and the brain); and ages 80 - 100+ (the `very old', whose brains may reflect a `healthy survivor' state). The information gained relating to these important periods will enhance our understanding of how important phenomena such as hormonal changes affect the brain and will provide insights into factors that enable cognitively intact function into advanced aging. Aim 4 will capitalize on our success in sharing data in the Human Connectome Project (HCP), and will use these established tools, platforms, and procedures to make this data publicly available through the Connectome Coordination Facility.