Tracy Riggins - US grants

DESCRIPTION (provided by applicant): Project Summary (abstract) Drug abuse among women of child-bearing age is an enduring public health problem because exposure to drugs during the prenatal period can directly alter the course of fetal development and adversely impact later outcomes. Our research aims to characterize effects of prenatal drug exposure (PDE) on neurobehavioral outcomes in adolescence. Effects of PDE may be especially significant during this developmental period due to unbalanced development of brain regions associated with responsiveness to rewards and behavioral control and the accumulation of social and environmental risk factors. The objective of this application is to identify how PDE relates to adolescents'own risk-taking propensity at both the behavioral and neural level. We will use functional magnetic resonance imaging (fMRI) to examine brain activation in a well-characterized sample of adolescents with a history of PDE who have been followed since birth while they complete an established, ecologically valid, computer-based assessment tool for risk-taking behavior. We hypothesize that PDE will lead to 1) direct alterations in neural structure and function associated with reward pathways due to disrupted neurodevelopment, and 2) indirect effects by altering the baseline activity of neural systems, increasing vulnerability to socio-environmental risk factors, and altering the individuals'own assessment of and engagement in risk-taking behavior. Results of this investigation will advance the field as it brings the power and tools of cognitive neuroscience to bear on long-term effects of drug abuse and addiction. Understanding how PDE affects functioning at the neural level in adolescents is crucial for understanding behavioral effects, including the development of risk-taking and other problem behaviors. These outcomes will have an important impact as they will demonstrate the long-term consequences of PDE on development and highlight relations with the environment. Research that integrates neural and behavioral measures in public health relevant topics is innovative. The outcomes of the proposed experiment have important public health significance because they can be used to develop targeted prevention strategies to interrupt this intergenerational cycle of risk behavior.

DESCRIPTION (provided by applicant): Memory is a cornerstone ability upon which we build knowledge of ourselves and the world around us. Failures in memory, no matter how small, can significantly impact life success and mental health (including anxiety and depression). In adults, recognition memory is subserved by two processes, recollection and familiarity, which rely on partially distinct brain circuitry in the medial temporal lobe (MTL) and prefrontal cortex (PFC). Familiarity is the process that allows for the global assessment of memory strength. Recollection is the process that allows for the retrieval of distinct features associated with the context of the event. Recollection preferentially involves the hippocampus, a MTL structure characterized by its protracted developmental course. Neuroanatomical data illustrates that structural development of the hippocampus continues at least through the 5th year postnatally, which has been theoretically linked to functional changes observed in behavioral memory performance (e.g., improvements in autobiographical memory and episodic memory that occur during early childhood). However, this link has not yet been examined empirically. Thus, despite all we know about memory processes and associated neural circuitry in adults, the systematic study of its functional maturation early in life is notably absent. What remains relatively unexplored are age-related changes in the basic processes that underlie memory improvement in early childhood. This poses not only a gap in scientific understanding but also a barrier to development of intervention techniques that would facilitate or improve memory, particularly in those at-risk for impairment. Our goal is to elucidate mechanisms of change in memory development by systematically investigating changes in memory behavior and neural activity. Towards this end, the proposed research seeks to indentify windows during which memory processes develop that are informed by neurodevelopment. Specifically, we will examine familiarity and recollection processes during a memory retrieval task using a unique combination of electrophysiological and behavioral measures in early childhood. We hypothesize that electrophysiological and behavioral correlates of recollection (which rely on the hippocampus) will show substantial developmental change from 3 to 5 years of age, compared to changes in familiarity processes. Systematic study of memory development in humans has important implications for understanding memory in general and will ultimately further our understanding of disorders of memory (e.g., developmental amnesia), populations where memory is affected (e.g., individuals with depression), and disorders in which abnormalities of memory circuitry have been reported (e.g., depression, autism, and schizophrenia). PUBLIC HEALTH RELEVANCE: Memory impairment has been linked to learning disabilities in childhood and mental health disorders such as depression and schizophrenia in adolescence and adulthood. Our research aims to characterize the functional development of memory circuitry in the medial temporal lobe (MTL) by using event-related potentials to identify hippocampally-mediated recollective processes in early childhood and examine their development during a window of significant structural brain development. Knowledge gained from the outcomes of the proposed research will allow for the development of targeted prevention strategies for populations at-risk for memory impairment and those diagnosed with neurodevelopmental disorders known to affect MTL circuitry.

DESCRIPTION (provided by applicant): Memory is a cornerstone ability upon which we build knowledge of ourselves and the world around us. Failures in memory, no matter how small, can significantly impact life success and mental health. A large body of research exists regarding the neural bases of memory in adults. This work indicates episodic memory relies on a distributed network of brain regions within temporal, parietal and prefrontal cortices, with the hippocampus playing a critical and irreplaceable role. In contrast, very few studies have examined neural mechanisms underlying memory development in early childhood. This is particularly unfortunate as behavioral research suggests this is a time of significant and rapid development in episodic memory. Additionally, neuroanatomical data from non-human primates have shown that structural development of the hippocampus continues at least through the 5th year postnatally. Although this finding has been theoretically linked to functional development and improvements in behavioral memory performance, it has not yet been examined empirically. Thus, despite all we know about memory processes and associated neural circuitry in adults, the systematic study of its functional maturation early in life is notably absent. This not only poses a gap in scientific understanding but also a barrier to development of intervention techniques that would facilitate or improve memory in those at-risk for impairment. The goal of this proposal is to characterize changes in the structure and function of the hippocampally-mediated episodic memory network during early childhood, when gains in episodic memory are greatest. The primary hypothesis is that episodic memory development results from changes in the hippocampus and its progressive, integrative participation and segregation with cortical areas. In order to test this hypothesis, we will 1) determine how changes in sub regions of the hippocampus contribute to age-related improvements in memory ability during early childhood, 2) determine how the hippocampus becomes integrated with cortical areas to establish a mature memory network and stabilize memory performance in early childhood and 3) identify neural changes that precede behavioral improvements in episodic memory, which will serve as targets for memory intervention in early childhood. To achieve this goal, we will acquire data from ultra-high resolution structural MRI, high resolution resting-state functional MRI, and behavioral assessments of episodic memory ability from a sample of 175 4-to 8-year-old using a cohort-sequential design. This multimodal and longitudinal approach will allow for the identification of neural trajectories that lead to age- related changes in behavior. Systematic study of memory development in childhood has important implications for understanding memory in general and will provide critical information for targeted intervention (and prevention) strategies for populations at-risk for memory impairment and those diagnosed with neurodevelopmental disorders known to affect the hippocampus and memory.

PROJECT SUMMARY Naps benefit learning and memory in young children. However, children transition out of naps during the preschool years (~3-5 yrs). Whether naps should be encouraged in preschools or eliminated to provide more time for early learning is not clear. Reflecting this uncertainty, there are currently no formal recommendations regarding napping in childhood (e.g., from American Academy of Pediatrics). Our recent pilot study suggests the the transition out of naps may reflect maturation of the hippocampus, such that as this structure matures it allows for memories to be held in this short-term memory store across the day without detrimental interference. The specific objective of the proposed research is to examine the role of sleep and hippocampal development on memory during early childhood, specifically when children transition out of naps. The central hypothesis of this proposal is that maturation of the hippocampus during this period results in more information being retained without interference, reducing the need for frequent consolidation, which we posit underlies the transition out of naps. Preschool age participants will include both habitual nappers and habitual non-nappers. Using a within-subjects design, children will either be nap-promoted or wake-promoted mid-day. Children will participate in a visuospatial memory task prior to the nap/wake interval and recall will subsequently be reassessed. We will use an innovative combination of techniques to measure hippocampal volume and functional connectivity and sleep physiology during the nap. Aim 1 is to examine how the shift from biphasic to monophasic sleep is related to hippocampal structure and function. We hypothesize that, compared to habitual nappers, non-nappers will have better memory performance overall, less memory decay over intervals of wake, larger hippocampal volumes, and stronger connectivity within the hippocampal-cortical network. Aim 2 is to establish the relation between brain maturation and sleep on memory consolidation in early childhood. We hypothesize that brain maturation predicts memory consolidation over the nap. Importantly, we posit that brain maturation increases sleep spindles and slow wave activity which, in turn, increase nap-dependent memory consolidation. The translational significance may be seen in new policies regarding preschool nap opportunities and pediatric nap guidelines for preschool children. The theoretical significance is that these outcomes will drive an entirely new research dimension for educational sciences (sleep as a novel target to enhance learning) and spur further studies in the interaction of sleep and brain development on cognition.

Project Summary/Abstract Neurodevelopmental processes are shaped by dynamic interactions between genes and environments. Maladaptive experiences early in life can alter developmental trajectories, leading to harmful and enduring developmental sequelae. Pre- and postnatal hazards include maternal substance exposure, toxicant exposures in pregnancy and early life, maternal health conditions, parental psychopathology, maltreatment, structural racism, and excessive stress. To elucidate how various environmental hazards impact child development, it is imperative that a normative template of developmental trajectories over the first 10 years of life be established based on a sufficiently large and demographically diverse sample of the US population. To accomplish this, the Healthy Brain and Child Development National Consortium (HBCD-NC) has been formed to deploy a harmonized, optimized, and innovative set of neuroimaging (MRI, EEG) measures complemented by an extensive battery of behavioral, physiological, and psychological tools, and biospecimens to understand neurodevelopmental trajectories in a sample of 7,500 mothers and infants enrolled at 24 sites across the United States (US). The HBCD-NC will carry out a common research protocol under direction of the HBCD-NC Administrative Core (HCAC) and will assemble and distribute a comprehensive and well-curated research dataset to the scientific community at large under the direction of the HBCD-NC Data Coordinating Center (HDCC). The overarching goal of the HBCD-NC is to create a comprehensive, harmonized, and high- dimensional dataset that will characterize typical neurodevelopmental trajectories in US children and that will assess how biological and environmental exposures affect those trajectories. A special emphasis will be placed on understanding the impact of pre- and postnatal exposure to opioids, marijuana, alcohol, tobacco and/or other substances. To address these broad objectives, the sample of women enrolled will include: 1) a racially, ethnically, and socioeconomically diverse cohort that is representative of the US population; 2) pregnant woman with use of targeted substances (opioids, marijuana, alcohol, tobacco); and 3) demographically and behaviorally similar women without substance use in pregnancy to enable valid causal inferences. In addition, the HBCD-NC will identify key developmental windows during which both harmful and protective environments have the most influence on later neurodevelopmental outcomes. The large, multi-modal, longitudinal, and generalizable dataset that will be produced for the first time by this study will provide novel insights into child development using state- of-the-art methods. The HBCD-NC study will inform public policy to improve the health and development of children across the nation.