Kathleen M. Thomas, Ph.D. - US grants

DESCRIPTION (provided by applicant): This revised Research Career Award application will provide the applicant with the additional training and mentoring necessary to pursue an independent career using functional neuroimaging techniques to examine issues in developmental cognitive neuroscience. The applicant is an Instructor of Psychology in Psychiatry with doctoral training in child psychology and postdoctoral training in anatomical and functional magnetic resonance imaging (MRI) techniques with children. Her work focuses on the brain bases of learning and memory skills across childhood, in particular, the development of implicit sequence learning. The current proposal seeks to build on this developmental expertise and to further the candidate's theoretical thinking in cognitive science and advanced technical skills in the area of functional MRI, and the integration of behavioral, electrophysiological and fMRI approaches to examining the neural bases of sequence learning in children. She will be mentored in the design, conduct, and analysis of behavioral and neuroimaging studies that attempt to address gaps in the literature examining the development and neural bases of implicit learning across childhood. Studies will address normative development and will include 1) development of an eye movement based sequence learning task that is appropriate for all age ranges; 2) behavioral experiments that probe the constraints of child learning systems by manipulating characteristics of the information to be learned, and 3) parallel electrophysiological and neuroimaging studies to assess the temporal and spatial dynamics of the neural systems subserving sequence learning across development. The overall purpose of the proposedstudies is to further our understanding of the neural systems underlying the development of various forms of learning and memory. Ultimately, the long-term goal of this work is to lay the critical foundation for understanding how disruptions in the development of these neural systems may give rise to developmental disorders.

0-11 years old; Address; Ammon Horn; Anatomic; Anatomical Sciences; Anatomy; Area; Behavioral; CRISP; Child; Child Youth; Children (0-21); Computer Retrieval of Information on Scientific Projects Database; Cornu Ammonis; Corpus Striatum; Corpus striatum structure; Environment; Fe element; Functional Magnetic Resonance Imaging; Funding; Gestation; Goals; Grant; Hippocampus; Hippocampus (Brain); Human, Child; Institution; Intermediary Metabolism; Investigators; Iron; METBL; MR Imaging; MR Tomography; MRI; MRI, Functional; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Magnetic Resonance Imaging, Functional; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Memory; Metabolic; Metabolic Processes; Metabolism; NIH; NMR Imaging; NMR Tomography; National Institutes of Health; National Institutes of Health (U.S.); Nature; Neurocognitive; Neuropsychologies; Neuropsychology; Nuclear Magnetic Resonance Imaging; Outcome; Performance; Population Study; Pregnancy; Public Health; Research; Research Personnel; Research Resources; Researchers; Resources; Sampling; School-Age Population; Schools; Science of Anatomy; Source; Striate Body; Striatum; United States National Institutes of Health; Zeugmatography; anatomy; children; cognitive function; cohort; elementary school; fMRI; fetal; hippocampal; infant of diabetic mother; maternal diabetes; neural circuit; neural circuitry; neuropsychologic; prenatal; public health medicine (field); school age; striatal; substantia alba; unborn; white matter; youngster

0-6 weeks old; Age-Years; Auditory; Behavior assessment; CRISP; Computer Retrieval of Information on Scientific Projects Database; Diabetic mother; Event-Related Potentials; Fe element; Funding; Grant; Impairment; Infant; Infant, Newborn; Institution; Investigation; Investigators; Iron; Medial; Mediating; Memory; NIH; National Institutes of Health; National Institutes of Health (U.S.); Newborn Infant; Newborns; Protocol; Protocols documentation; Recognition (Psychology); Research; Research Personnel; Research Resources; Researchers; Resources; Risk; Sampling; Source; Structure; Temporal Lobe; Testing; United States National Institutes of Health; Visual; behavioral assessment; event related potential; fetal hypoxia; fetus hypoxia; memory recognition; newborn human (0-6 weeks); temporal cortex; temporal lobe/cortex; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stress has been shown to alter the development of neural systems involved in learning (particularly contextual, cued, and extinction learning) and cognitive control. Emerging evidence in the human and mouse suggests that stressful experiences result in region-specific alterations in BDNF levels. The overarching goal of this project is to test the hypothesis that the Val66Met polymorphism in the BDNF gene will moderate the effects of early life stress (in the form of institutional/orphanage rearing) on the structure and function of the hippocampus, amygdala and ventromedial prefrontal cortex (including orbital prefrontal cortex). Participants will be 12-14 year old children adopted internationally between the ages of 4 months and 5 years after having lived for 75% or more of their pre-adoption lives in institutions (hospitals, orphanage). We will test the hypothesis that the BDNF Val66Met polymorphism will moderate the impact of early life stress (dose/duration of institutional care) on structure and function of these regions. We will also examine whether these effects are diminished with time in the adoptive home. This project is part of an NIMH Center grant that includes additional projects addressing the impact of BDNF genotype on learning and cognitive control in typical development from 8-18 years of age (Sackler Institute, New York) and a knock-in gene model of the Val66Met polymorphism in the mouse, including early postnatal stress and behavioral measures of mouse learning.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Participants will be 14 adults between the ages of 20-22 years and 16 teens between the ages of 13-14 years. The scanning session will begin with a sagittal scout for purposes of prescribing subsequent images. Sagittal T1 MPRAGE images will be aquired for coregistration of functional images. Whole brain EPI BOLD images will be acquired in three runs while subjects perform the behavioral task below. An EPI fieldmap will be acquired at the same resolution and slice locations to allow for offline correction of field inhomogeneities. The behavioral combines a go/nogo task with emotionally arousing background images selected from the International Affective Picture System. In this task, letters are presented sequentially in a small box at the center of the computer screen. Subjects are asked to respond as quickly as possible with a button press to every one of a series of letters except for a specific target: an 'X'. The Xs appear on 25% of trials such that participants acquire a prepotent tendency to press and need to actively inhibit their response during nogo trials. The behavioral task consists of three runs of twelve blocks. Responses (press or no press) and reaction times will be recorded using an MRI compatible button box. We anticipate the entire session taking one hour per subject. This estimate includes 15 minutes for equipment setup and positioning of the participant, 11 minutes of structural scanning, 30 minutes of functional scanning and 10 minutes of clean-up and data transfer.

? 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).

The effectiveness of social buffering in regulating stress appears to wane for a period with puberty at the same time that stress-reactivity increases and young adolescents become more vulnerable to stress-related affective pathology. However, there is a dearth of knowledge regarding the neural underpinnings of social buffering in children and the changes in neural responses to potential social buffers with puberty. Two of the proposed experiments address this gap in knowledge. In addition, to date, the loss of social buffering effectiveness with puberty has primarily been examined using activity of the hypothalamic-pituitary-adrenocortical (HPA) axis as the stress measure. All three proposed experiments will examine the pervasiveness of the effect by examining sympathetic and parasympathetic responses, in addition to salivary cortisol. Urinary oxytocin will also be examined because of its role as an anti-stress hormone. Finally, the effectiveness of parents and friends as social buffers during the peripubertal period has only been examined for social evaluative stressors. The proposed experiments will determine whether the loss of social buffering also extends to threat stimuli as it does in adults and to situations in which two friends are both experiencing the stressful event together. Finally, all three proposed studies will explore whether puberty is associated with an emergence of sex differences in social buffering by parents and friends. Participants will be 11-14 years old and Tanner staging by nurse exam along with self-report and testosterone and DHEA will index pubertal status. Our prior research uncovered the waning of the effectiveness of parents to serve as social buffers of the HPA axis over the pubertal transition and the concomitant failure of friends to ?step in? as stress buffers. The proposed experiments are the logical extension of this work. The results will have the potential to drive significant attention to the role of developmental disruptions in social stress buffering as possible contributing factors in the rise of affective problems in the early teen years.