Susan F. Tapert, Ph.D. - US grants

The goal of this exploratory/developmental project is to investigate neurobiological mechanisms of adolescent alcohol dependence utilizing and refining functional magnetic resonance imaging (fMRI) procedures and protocol. Alcohol involvement is prevalent during adolescence, but little is known regarding its influence on cognition. Our previous studies suggested that severity of alcohol withdrawal symptoms predicts neuropsychological impairments in adolescents. fMRI is a noninvasive and safe technique for examining brain functioning. However, several challenges remain for its implementation with alcohol dependent adolescents, including minimizing motion artifact, maximizing participant compliance and comfort, and characterizing normal adolescent brain activation patterns. This project seeks to characterize neural consequences of heavy drinking during adolescence by evaluating hemodynamic changes in brain regions of alcohol dependent teens and controls during performance of cognitive challenge and alcohol cue exposure tasks. In addition, we hope to refine fMRI protocol and procedures for use with alcohol dependent adolescents. Our specific aims are: 1) to investigate activation patterns in brain regions that may be influenced by adolescent alcohol dependence and withdrawal, 2) to examine brain activation patterns associated with craving and processing alcohol-related information in teens with varied alcohol involvement histories, and 3) to optimize FMRI procedures for use with alcohol dependent adolescents. To achieve these aims, 20 alcohol dependent teens and 20 demographically matched controls will be presented with tasks designed to activate brain regions potentially involved in adolescent alcohol dependence in the fMRI environment. We hypothesize that alcohol dependent adolescents and controls will differ in brain activation patterns, both as a consequence of excessive drinking as well as in response to alcohol cues. Results will help characterize brain regions affected by heavy drinking and involved in craving states among adolescents. Resulting protocol refinement and pilot data will be used in developing a broader research program investigating neural aspects of protracted alcohol use, alcohol-related information processing, craving, etiological factors of early drinking, and predictors of future alcohol problems and problem recovery. The longer-term goal of this program of research is to develop targeted therapies for adolescents with alcohol use disorders.

DESCRIPTION (provided by applicant): The goal of this project is to better understanding brain characteristics that are premorbid to alcohol dependence by examining children at risk for alcohol problems using functional magnetic resonance imaging (fMRI) and neuropsychological (NP) testing. Our previous fMRI and NP studies suggested that protracted alcohol use during youth is associated with neurocognitive decrements in functioning. However, the extent to which these problems are caused by alcohol use cannot be ascertained until pre-existing status is well characterized. Several factors have reliably predicted the development of alcohol use disorders in youth, especially having a dense family history of alcohol dependence (FH) and meeting diagnosis for conduct disorder (CD) early in adolescence. This project will compare fMRI and NP performances in 4 groups of children with different levels of risk for developing alcohol dependence, FH+/CD+, FH+CD-, FH-/CD+, and FH-/CD-, in a 2x2 design. Each group will consist of 30 carefully screened 12-14 year olds recruited from two representative middle schools and the local juvenile justice system. NP tests will cover working memory attention, learning and retention, visuospatial, language, and executive functioning. FMRI will evaluate homodynamic changes during the performance of two challenging working memory tasks that required similar skills as NP tests that were impaired among alcohol dependent youth. These tasks produce signal contrast in brain regions that were related to FH and CD in electrophysiological and other studies. Our specific aims are to: 1) contrast neurocognition and brain functioning in FH+ (high-risk) youth to FH- (low-risk) control youth, 2) compare NP and fMRI results in CD+ (high-risk) youth to CD- (low-risk) youth, and 3) contrast the degree of abnormal neurocognition and brain functioning in each risk factor group using an interaction model. These results will be contrasted to existing fMRI and NP data on alcohol dependent teens from our current study. Further, this cohort may form the basis for a subsequent longitudinal investigation. This proposal will characterize abnormalities related to risk for alcohol dependence and help determine the extent to which neurocognitive deficits associated with alcohol dependence are due to premorbid factors.

DESCRIPTION (provided by applicant): The goal of this exploratory developmental project is to better understand the degree to which use of +/- 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and cannabis during late adolescence affect brain functioning. Marijuana and MDMA are used relatively widely in the United States and Western Europe with rates increasing particularly for adolescents. Animal models have suggested adverse brain changes associated with MDMA use. Although some human studies have shown neurocognitive deficits among MDMA users, these reports have been challenged by inadequately matched comparison groups, particularly with regards to other substance use, and recent substance use. Additionally, it is unknown how use of these substances during adolescent neuromaturational processes affect brain functioning and thinking abilities. Since most users of MDMA take other substances as well, a drug-using comparison group appears appropriate. The current proposal compares brain functioning using functional magnetic resonance imaging (fMRI) and neuropsychological (NP) performance between 3 groups of 16 to 18 year old adolescents: 1) users of MDMA and marijuana, 2) users of marijuana only, and 3) nonusers. Youth will be recruited from local high schools (N=9000) during twice-annual school-wide surveys conducted as part of another ongoing research project. Testing will take place after >28 days of abstinence from MDMA, cannabis, and other substance, confirmed by frequent toxicology screening in the four weeks before assessment. Results from this study will also be compared to those of alcohol use disordered adolescents in our current fMRI and NP studies. Based on animal models and existing data in humans, it is hypothesized that the MDMA+marijuana group will show a greater degree of abnormality on these measures than the marijuana only group or the non-using control group. We predict that cognitive performances related to serotonergic functioning, such as memory and impulsivity, will be particularly abnormal, with corresponding fMRI response decreases in prefrontal, orbitofrontal, and medial temporal cortices during tasks requiring these areas. A secondary aim of this project is to refine assessment methods by developing procedures for establishing 28 days of sobriety in youth and validating measures of intoxication and post-intoxication effects to help ascertain the pharmacology of drugs taken by teens.

[unreadable] DESCRIPTION (provided by applicant): Relevance: Marijuana is the most commonly used illicit drug in the U.S., and 6 percent of high school seniors report using marijuana >20 times per month. Neuromaturation continues during adolescence in the form of gray matter decreases and white matter increases, including in regions with dense distributions of cannabinoid receptors (e.g., frontal lobe, hippocampus, striatum, and cerebellum). However, few studies have examined the relationship between heavy marijuana use during adolescence and subsequent brain development. Longitudinal studies are essential to determine if previously observed abnormalities predate cannabis use or are caused by cannabinoid exposure. Description: In this application, we propose to recruit 78 adolescents to add to a cohort of 90 adolescents recruited in project R21 DA15228 (PI: Tapert), and follow these 168 teens with the same neuropsychological tests, functional magnetic resonance imaging (FMRI; working memory, inhibition, and learning tasks), MRI (to examine brain volume), and diffusion imaging (to probe white matter integrity) 1.5 and 3 years after the initial assessment. Brief interviews will be conducted each 6 months over the 3-year follow-up period to assess marijuana, alcohol, nicotine, and other drug use and academic involvement. Participants will be 126 heavy marijuana users and 42 non-users, recruited through two local school districts using the same approach as in R21 DA15228. At baseline, all participants will be age 16-18, free from psychiatric, learning, neurological, and medical disorders, and with limited exposure to alcohol, nicotine, and other drugs. Among users, late onset (after age 16) current users, early onset (less than or equal to 15) current users, and early onset (less than or equal to 15) former users will be targeted for recruitment. Prior to each imaging session, youths will undergo a 28-day monitored abstinence period by providing urine samples every 3-4 days and a hair sample for drug toxicology (as in R21 DA15228). Aims: Aims of the current application are to: (1) replicate preliminary findings of CNS differences between chronic heavy marijuana users and demographically similar non-users after 28 days of abstinence; (2) determine whether early onset (as opposed to duration) of heavy marijuana use is associated with abnormal CNS functioning; (3) determine if frequency and intensity of marijuana use predicts changes in brain imaging and cognitive test measures over a 3-year period; and (4) evaluate if FMRI response patterns during executive functioning tasks can predict subsequent substance use. All analyses will control for premorbid factors (i.e., family history of substance use disorders and personality), educational involvement (i.e., attendance), and other substance use (i.e., alcohol, nicotine, and other drugs). [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Relevance: Alcohol and other drug use are common among U.S. adolescents. Our prior studies found that adolescents with alcohol use disorders (AUD) show abnormalities on indices .of brain functioning, including neuropsychological testing, hippocampal volume, and functional magnetic resonance imaging (FMRI) response to cognitive tasks. We also found abnormalities on some of these measures related to risk factors for adolescent alcohol involvement. Thus, it is unclear if abnormalities observed in adolescents with AUD are caused by alcohol exposure, or predated the onset of heavy drinking. Description: This renewal project will follow youth initially characterized in the first funding period of R01 AA13419. At baseline, these youth are 12-14 year-olds free from any psychiatric disorder with, on average, one alcohol use experience, and half are at risk for AUD based on a family history of alcohol dependence. Baseline assessment includes neuropsychological testing, high resolution MRI, and FMRI acquisition during spatial working memory and inhibition tasks. In this competing renewal, we will expand the baseline sample from 128 to 285 youth, and follow these adolescents quarterly with interviews on substance use and general functioning. Each subject who initiates heavy drinking (defined as consuming >5 drinks on an occasion >5 times in a month), as well as a non-user matched for age, gender, and family history status, will be invited back to repeat the protocol on an annual basis for the duration of the 5-year project. Based on surveys in the school districts we recruit from (A/=5420), we anticipate that >20% (n>50) will initiate heavy drinking and 50% (n>125) will remain non-users as of the 4-year follow-up (i.e., by age 16-18). Aims: The goal of this study is to ascertain if indices of brain functioning (i.e., neuropsychological testing;hippocampal, prefrontal cortex, and cerebellar volumes;and FMRI response to spatial working memory and inhibition tasks in prefrontal and parietal regions) change after the onset of heavy drinking to a different degree than would be accounted for by normal adolescent neurodevelopment. We hypothesize that initiation of heavy drinking during adolescence will be associated with changes in brain structure and function, and that family history of AUD and gender will moderate this relationship. Other substance use (marijuana and nicotine) and other risk factors for SUD (externalizing behaviors, level of response to alcohol, and alcohol expectancies) will be evaluated as potential contributors to change in brain functioning. Based on our previous studies, we further hypothesize that baseline brain response patterns will significantly predict substance involvement in the following year.

This core will provide the basic infrastructure that supports the operational plan and day-to-day functioning of the center. The components of the core are structured so that each support function has a circumscribed focus, which will be implemented by the director and co-director, Drs. Tapert and Schulteis. The unique expertise of Dr. Tapert in recruitment and assessment suggested a logical integration of these support functions into an Administrative Core to best service the needs of the Center. The specific aims of this Core are: (1) to provide the administrative infrastructure across all projects and center functions; (2) to establish a uniform, validated, and reliable recruitment, screening, and assessment pathway; and (3) to provide the database and information technology infrastructure that will support efficient data analysis for all projects, communication between center members, and information distribution. By accomplishing these aims, the core will (1) enable efficient administrative support to CIDIA investigators through the provision of coordinated grants management, human subjects protections procedures, human resources assistance, and other administrative functions; (2) disseminate information about CIDIA research activities and programs within UCSD and with potential outside collaborators to encourage new collaborations and mentorship of new investigators who will do translational research relevant to interoceptive dysregulation in drug addiction; and (3) provide timely recruitment and accurate yet efficient clinical assessment functions for the human studies. Administrative functions to assure smooth operation of the Center include organizing meetings, seminars, and visits from consultants and advisors; organizing documentation to IRB, lACUC, and other entities, purchasing, and travel arrangements for Projects 1, 2, and 3. Recruitment and assessment will serve Projects 1 and 2. Information technology functions include set up and maintenance of secure and accurate data entry systems, maintenance of data security, data backup, and software maintenance for Projects 1, 2, and 3.

Project 1: Adolescents'use of amphetamine drugs is a major public health concern, as 11% of high school seniors have used methamphetamine or a pharmaceufical amphetamine taken other than for prescribed purposes (MTF, 2008). Interoception refers to sensing and processing the internal body state via afferent Cfibers, which is integrated in the insular cortex. Previous invesfigafions have linked insular cortex functioning to aspects of addiction. However, the precise role of the interoceptive system and insular cortex in the development of substance dependence is unclear. Here, we hypothesize that the insular cortex is hyporesponsive to interoceptive stimulation, but hyper-reactive to drug cues in adolescents at risk for substance dependence based on repeated experimentation during youth. In this project, we will compare activity of the interoceptive system in response to positively and negatively valenced interoceptive and drug cue stimuli between: (1) at-risk adolescents who are current users of amphetamines, (2) resilient adolescents who are former users of amphetamines but stopped without ever meeting dependence criteria, and (3) control adolescents with no history of amphetamines use. The aims are: (1) to determine the role of the insula in processing interoceptive information in teens at risk for amphetamine dependence, teens who appear resilient to amphetamine dependence, and healthy control adolescents;(2) to determine the role of the insula in processing cue-related informafion in teens at risk for amphetamine dependence, teens who have been resilient to amphetamine dependence, and healthy control adolescents;(3) to modify neuroimaging paradigms in response to Project 3 (animal studies) to better characterize the role of interoceptive circuitry in the direct posifive (high) versus negafive (withdrawal/hangover) effects among teens at risk for amphetamine dependence;and (4) examine the development of the interoceptive system in adolescence by comparing adolescent controls and adult controls (from Project 2) on activation patterns to interoceptive and drug cue tasks. Together, these studies will help determine how interoceptive dysregulation plays a role in putting adolescents at risk for amphetamine use. These insights will be used in future studies aimed at altering the reactivity of the insular cortex as a way of preventing or treating substance dependence. Combining results from Projects 1 and 2 will yield important insights into the role of the insular cortex and interocepfive functioning in risk for amphetamine dependence in general. Finally, the outcome of this study will prepare us for longitudinal studies of interoceptive dysfunction in a P50 extension of this Center.

DESCRIPTION (provided by applicant): In response to RFA-AA-12-006, this application proposes the Administrative Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA), located at UCSD, to determine the effects of alcohol use on the developing adolescent brain. This consortium was designed to provide a nationally representative sample of adolescents and to integrate the diverse scientific expertise and research experience with youth represented by researchers at each site. As such, the following applications should be considered jointly: N-CANDA: Administrative Component, UCSD (PI: Sandra Brown PhD (Contact), Susan Tapert PhD) N-CANDA: Data Component, SRI (PI: Adolf Pfefferbaum, M.D.) N-CANDA: Duke (PI: Michael DeBellis, M.D.) N-CANDA: Pittsburgh (PI: Duncan Clark, Ph.D., M.D.) N-CANDA: SRI (PIs: Ian Colrain, Ph.D. (Contact) and Fiona Baker, Ph.D.) N-CANDA: UCSD (PI: Susan Tapert, Ph.D.) Recruited at ages 12 through 21, a high-risk enhanced community sample of 680 subjects will complete a baseline assessment then undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal MRI protocol, comprehensive neuropsychological battery, and assessment of alcohol use and related problems, along with other substance involvement, mental health symptoms, and other risk factors, will be measured. Brain imaging uses state-of-the-art high-resolution structural MRI (sMRI), diffusion tensor imaging (DTI), resting state MRI (rsMRI), and an anti-saccade or Stroop functional MRI task to capitalize on local expertise. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that are actively developing during adolescence, involved in psychological regulation, responsive to rewards, and thought to be vulnerable to toxic alcohol effects. Five aims specified in the RFA will be systematically tested with a focus on adolescent substance use and neuromaturational trajectories. Each of the four Research Components will collaborate with another site on two additional aims. Examined in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at greater risk for an alcohol use disorder.

PROJECT SUMMARY During young adulthood, drinking dramatically increases, with binge-level drinking peaking at age 22 and nearly half of individuals reporting binge-level alcohol use. Frequent binge alcohol use during the protracted neuromaturation spanning into the mid-20s may result in greater brain and cognitive effects than similar alcohol use in later adulthood. In response to RFA-AA-17-003, this application proposes a Research Project Site of the National Consortium on Alcohol and Neurodevelopment in Adolescence second phase (NCANDA-2) to determine the predictors and effects of heavy adolescent alcohol use in adolescence and young adulthood. To achieve this, the UCSD site of NCANDA-2 will continue to follow a cohort of 211 San Diego-area (n=831 across all 5 sites) participants (ages 12-21 at baseline visit) to acquire the necessary data to advance our understanding of adolescent development and the effects of alcohol use during adolescence on the adult brain. NCANDA-2 will use multimodal neuroimaging, cognitive testing, behavioral assessment, biospecimen collection, and multimodal assessments in the natural environment. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence and young adulthood, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, the UCSD site will collaborate with the Duke and OHSU sites to study recovery of these abnormalities. Specifically, we will examine the degree to which targeted heavy drinking related neurocognitive and brain integrity deficits remit over 4 weeks of monitored abstinence. UCSD will also collaborate with the SRI site to collect the Stroop task in the fMRI environment to evaluate changes in the cognitive control system for youth who increase drinking versus those who do not. Sex differences in development, alcohol use patterns and history, impact of alcohol use on the brain, and sex-differentiating psychosocial factors (e.g., depression symptoms) will be considered in analyses. With the additional longitudinal data provided by this renewal, we will determine the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities and resiliencies that may alter adolescents? and young adults? risk for alcohol or other substance use disorder and other mental health and developmental outcomes.

? DESCRIPTION (provided by applicant): Adolescence is a critical neurodevelopmental period associated with dramatic increases in rates of substance use. Identifying the pathways to substance use and its effects on child and adolescent development is critically important, as the effects of substance use during ongoing maturation likely have long-lasting effects on brain functioning and behavioral, health, and psychological outcomes. This Research Project Site application from the University of California, San Diego and Laureate Institute for Brain Research is in response to RFA-DA-15-015 as part of the ABCD-USA Consortium (5/13), to prospectively determine the neurodevelopmental and behavioral predictors and consequences of substance use on children and adolescents. A representative community sample of 1086 9-10 year olds enriched for high- risk characteristics will be recruited, contributing to the sample f 11,111 to be collected from 11 hubs across the ABCD- USA Consortium. All participants will undergo a comprehensive baseline assessment, including state-of-the-art brain imaging, comprehensive neuropsychological testing, bioassays, mobile monitoring and careful assessment of substance use, environment, psychopathological symptoms, and social functioning every 2 years. Interim annual interviews and quarterly web-based assessments will provide refined temporal resolution of behaviors, development, and life events with minimal participant burden. These Consortium-wide data obtained during the course of this project will elucidate: 1) the effects of substance use patterns on the adolescent brain; 2) the effects of substance use on behavioral and health outcomes; 3) the bidirectional relationship between psychopathology and substance use patterns; 4) the effects of individual genetic, behavioral, neurobiological, and environmental differences on risk profiles and substance use outcomes; and 5) the gateway interactions between use of different substances. This hub's Research Project focuses on mechanisms of substance use disorder, special populations with high use prevalence, and the use of drugs other than marijuana. (1) We will determine whether individual differences in neural processing of antireward (i.e., negative reinforcement mechanisms) in amygdala, insula, and anterior cingulate are associated with increased negative emotionality and pain, predict initiation of use and problem use, and are in turn further dysregulated by substance use. (2) We will determine whether protective environment factors and ethnic identification in minority youth are linked to healthier antireward processing and better substance use outcomes. (3) We will determine whether antireward neural processing predicts increased use of illicit drugs other than MJ including misuse of prescription drugs, if such use predicts subsequent exaggerated antireward processing, and if gateway interactions exist between substances. Finally, we will use machine learning approaches to develop a youth-specific risk calculator that will enable us to identify individually- based modifiable risk factor, providing brain-based targets of future novel prevention and intervention approaches.

Project Summary/Abstract This is a competitive renewal of an alcohol research training program (T32) currently in its 14th year to continue an exceptional track record of training alcohol researchers by supporting four predoctoral and four postdoctoral fellows per year, with each being appointed to the training grant for two years. This training program is directed by Dr. Edward Riley of San Diego State University (SDSU) and co-directed by Dr. Susan Tapert from the University of California San Diego (UCSD). The training faculty consists primarily of researchers affiliated with the SDSU/UCSD Joint Doctoral Program (JDP) in Clinical Psychology. The JDP provides a unique opportunity for the training of doctoral students in the Science/Practitioner (Boulder) model and is consistently ranked as one of the top clinical psychology doctoral programs in the U.S. The model is guided by the conviction that a solid foundation in the science of psychology is essential for the modern clinical psychologist. Further, a rigorous scientific core, including the commitment to empirically based knowledge and the development of research skills, is regarded to be fundamental in educating clinical psychologists. Finally, given that trainees acquire both scientific and clinical skills, this model is consistent with the NIH goal of translating research to the clinic. The environment for this training at both SDSU and UCSD is rich with resources, skilled mentors, ample research funding, and a collegial atmosphere that encourages collaborative studies. This training program is designed to prepare fellows for careers in academic settings with specialization in the alcohol research field. The specific training encompasses a broad range of alcohol-related research, including areas such as neural risk factors and consequences of alcohol exposure, fetal alcohol spectrum disorders, and adolescent substance use. Predoctoral students receive didactic training in the behavioral sciences and in alcohol and other substance use and related disorders. The postdoctoral fellows receive similar types of varied training with a more individualized approach, tailored to their needs and expectations within the broad field of alcohol research. Since this training program began in 2002, it has undergone constant refinement, and will continue to do so, to meet the needs of the trainees and the evolving addictions research field. Importantly, its graduates are making their way in the academic world with considerable success. Their experience as fellows on this T32 has provided the trainees with the scientific discipline necessary to be successful academic researchers and the clinical skills to ask applicable and relevant questions regarding alcohol and other substance use and use disorders.

DESCRIPTION (provided by applicant): Alcohol and other drug use are common in adolescence. Our prior studies found that adolescents with alcohol use disorders (AUD), and even binge drinking in the absence of a diagnosis, show abnormalities on indices of brain functioning, including neuropsychological test performance; hippocampal, prefrontal, and cerebellar volumes; white matter microstructural integrity; and functional magnetic resonance imaging (FMRI) response to cognitive and alcohol cue tasks. However, some of these indices are related to risk factors for adolescent alcohol involvement, such as family history of AUD. Thus, it is unclear if abnormalities observed in adolescent heavy drinkers are caused by alcohol exposure, or predated the onset of heavy drinking. Description: This renewal project will follow 296 youth previously characterized in R01 AA13419 prior to the onset of substance use. At baseline, these youth were 12-14 year-olds free from any psychiatric disorder with, on average, one alcohol use experience, and nearly half at risk for AUD based on family history. Baseline assessments, now complete, included neuropsychological testing and brain imaging with high resolution MRI, FMRI acquisition during working memory and alcohol cue presentation tasks, and diffusion tensor imaging (DTI). In this competing renewal, we will continue to follow these adolescents with quarterly interviews on substance use and general functioning. Each subject who initiates heavy drinking (defined as at least monthly binge drinking episodes), as well as a non-user matched for age, gender, and family history, will be invited back to repeat the protocol 3 times during this 5-year period (independent of whether they remain heavy drinkers or transition out during the duration of the project). As of Year 09, 29% (n=86) have initiated heavy drinking (most typically at age 17), and 61% (n=181) have remained non-drinkers/users (28 fall into neither group). Aims: The goal of this project now is to ascertain if indices of brain functioning (i.e., neuropsychological testing; hippocampal, prefrontal cortex, and cerebellar volumes; white matter microstructural integrity in frontoparietal and fronto-cerebellar tracks, and FMRI response to working memory in frontal and parietal regions and to alcohol cues in reward networks changes after the onset of heavy drinking to a different degree than observed in typically developing adolescents of the same age who do not use substances. We hypothesize that initiation of heavy drinking during adolescence will be associated with alternations in brain structure and function, and that gender will moderate this relationship. Other substance use (marijuana and nicotine) and other risk factors for AUD (externalizing behaviors, level of response to alcohol, and alcohol expectancies) will be evaluated as potential contributors to change in brain functioning. Based on our previous studies, we further hypothesize that baseline brain response patterns will significantly predict substance use involvement and outcomes. Pilot analyses will begin to look at normalization of these neural abnormalities, as some young adults transition out of heavy drinking.

Abstract Adolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and child health in the United States. The ABCD Research Consortium consists of 21 research sites across the country, a Coordinating Center, and a Data Analysis and Informatics Resource Center. In its first five years, under RFA-DA-15-015, ABCD enrolled a diverse sample of 11,878 9-10 year olds from across the consortium, and will track their biological and behavioral development through adolescence into young adulthood. All participants received a comprehensive baseline assessment, including state-of-the-art brain imaging, neuropsychological testing, bioassays, careful assessment of substance use, mental health, physical health, and culture and environment. A similar detailed assessment recurs every 2 years. Interim in-person annual interviews and mid-year telephone or mobile app assessments provide refined temporal resolution of developmental changes and life events that occur over time with minimal burden to participating youth and parents. Intensive efforts are made to keep the vast majority of participants involved with the study through adolescence and beyond, and retention rates thus far are very high. Neuroimaging has expanded our understanding of brain development from childhood into adulthood. Using this and other cutting-edge technologies, ABCD can determine how different kinds of youth experiences (such as sports, school involvement, extracurricular activities, videogames, social media, unhealthy sleep patterns, and vaping) interact with each other and with a child's changing biology to affect brain development and social, behavioral, academic, health, and other outcomes. Data, securely and privately shared with the scientific community, will enable investigators to: (1) describe individual developmental pathways in terms of neural, cognitive, emotional, and academic functioning, and influencing factors; (2) develop national standards of healthy brain development; (3) investigate the roles and interaction of genes and the environment on development; (4) examine how physical activity, sleep, screen time, sports injuries (including traumatic brain injuries), and other experiences influence brain development; (5) determine and replicate factors that influence mental health from childhood to young adulthood; (6) characterize relationships between mental health and substance use; and (7) specify how use of substances such as cannabis, alcohol, tobacco, and caffeine affects developmental outcomes, and how neural, cognitive, emotional, and environmental factors influence the risk for adolescent substance use.

The coronavirus pandemic has affected children and families worldwide. In the US, schools and closed, yet there is variability across states and cities regarding pandemic recommendation on social distancing. The situation likely affects different children in different ways, due to varying levels of familial financial impact, self or family COVID-19 illness, mental health effects of social distancing and stress, online activity, scholastic activity, adult supervision, and indirect health influences of altered physical activity, sleep, and access to nutrition. The Adolescent Brain Cognitive Development project (ABCD) is a longitudinal study of 11,878 diverse youth enrolled at ages 9-10 in 2016-2018 (birth years 2006-2009) at 21 research sites around the United States. This RAPID project will design and implement a new survey, to assess personal impact of COVID-19 on ABCD participants and families. With this new information, we can leverage existing ABCD data to examine perturbations in developmental trajectories of brain functioning, neurocognition, mental health, substance use, academic achievement, and social functioning. By immediately collecting a unique set of measures that characterize the pandemic?s effects, we can make use of the existing ABCD protocol and design in this large, diverse, national sample. Results from this study will provide substantially improved guidelines for future epidemics and pandemics, and indicate potential targets for interventions when other traumas affect children.

The ABCD cohort is being followed until at least age 20, with: biennial state-of-the-art neuroimaging, epigenetics/genetics, and physical activity tracking; annual cognitive testing and assessments with youth and parents on mental and physical health and development, life events and trauma exposure, culture and environment, substance use, sleep, and screen time; and biannual brief assessments of mental health and substance use. The proposed research would immediately characterize the impacts of the COVID-19 pandemic on each child via a youth and parent self-assessment that characterizes their personal level of family disruption, social distancing and its impact, attitudes, adherence to public health directives, and media exposure. This crisis provides a unique opportunity to make use of ABCD?s elaborate infrastructure and rigorous scientific processes to discern critical dimensions of behavior not previously envisioned. The impending severity of this unanticipated pandemic may result in significant influences on school-age youth for decades, and this RAPID will be critical to characterizing factors that protect and exacerbate its effects. This research will immediately examine COVID-19 related effects on youth, and how their practices around virus transmission and prevention vary as a function of family and social factors, external influences, and other characteristics.

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 broader impact/commercial potential of this I-Corps project is the development of a pain-free, lab-under-the-skin wearable technology for continuous, and real-time monitoring of multiple biomarkers of significance such as alcohol, glucose, lactate, ketone bodies, testosterone, cortisol, insulin, and more. The proposed lab-under-the-skin device may potentially promote public health for the treatment and prevention of alcohol misuse, more effective management of diabetes in the ever-growing population of people affected with diabetes, and timely diagnosis, treatment, and recovery of infectious diseases such as sepsis in hospitals or at-home settings. In addition, the device may be adopted for performance, health, and fitness use cases, which may aid in educating individuals in understanding their own physiology and metabolism, and personalized nutrition.

This I-Corps project is based on the development of a wearable sensor for continuous monitoring of model analytes namely alcohol, glucose, and lactate. The proposed technology is based on a quarter-sized electrochemical sensor that uses a microneedle array with wireless communication to the wearer’s smartphone. The barely visible micron-scale array of microneedles enables continuous access to the molecular information-rich biofluid beneath the skin in a pain- and discomfort-free manner. The preliminary results of continuous monitoring were promising for all investigated biomarkers, with the sensors’ data being in perfect correlation with those obtained from gold-standard metrics. Product and market validation activities by the interviews with potential end-users, decision-makers, and influencers throughout this I-Corps project will bring increased certainty and focus during the product development efforts on the choice of biomarkers that are immediate needs of the prospect market segments. In addition, the goal is to address the true need of the end-user, and to develop what has tangible commercial value and a broader impact on society.

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.