Marie T. Banich - US grants

[unreadable] DESCRIPTION (provided by applicant): The purpose of this application is to elucidate the brain systems that underlie the deficiencies in attentional control, most notably in the area of executive control and inhibitory processes, in individuals with attention deficit hyperactivity disorder (ADHD). Although considered core deficits (e.g., Nigg, 1999), relatively little is known about the specific neural substrates that might underlie such deficits. Using a combination of behavioral and brain mapping techniques, we propose to address these issues by investigating the hypothesis that these core attentional difficulties manifest in ADHD are a result of dysfunction of specific regions of dorsolateral and medial prefrontal cortex. Furthermore, we will examine the degree to which these neurocognitive difficulties manifest in both adolescent and adult forms of ADHD, and the degree to which they may indicate a genetic vulnerability rather than a marker for the disorder. [unreadable] [unreadable] The team investigating these issues is multi-disciplinary, consisting of a cognitive neuroscientist with a special expertise in attentional control and brain imaging methods, a clinician with expertise in classification and diagnostic issues in ADHD as well as behavioral and molecular genetic techniques, a developmental neuropsychologist with expertise in learning disabilities, and a physicist with expertise in brain imaging. The proposal builds upon the principal investigator's neural model of the brain mechanisms involved in executive aspects of attention, and integrates it with the co-investigator's state-of-the-art model of the clinical manifestations of ADHD. Moreover it employs two well-characterized clinical samples: an adult sample of college-aged individuals with ADHD, and a sample of adolescent and adult dizygotic twins discordant for ADHD, allowing us to validate our findings by testing them across distinct populations. [unreadable] [unreadable] The proposed research has the potential to shed important new light on the nature of ADHD. Elucidating which brain regions are dysfunctional has the potential 1) to increase the ability to specifically diagnose ADHD itself, as well as, providing criteria for differentiating subtypes, 2) to facilitate the development of pharmacological treatments targeting the affected regions, 3) to determine the degree to which the manifestation of ADHD is continuous from childhood through adulthood. [unreadable] [unreadable]

The catalyst center is designed to address the question: "How do people generalize knowledge?" Whether knowledge is acquired through formal schooling, technical training, or real-world experiences, its usefulness generally depends on how well it can be applied to new problems as well as new situations. Aside from very fixed and unchanging tasks where rote behaviors suffice, new circumstances routinely challenge the learner. Hence, generalization of knowledge to new situations is essential for optimal learning. Understanding generalization of knowledge is important for improving our nation's educational system as well as its ability to stay at the forefront of technological advancement. Innovation requires information learned in one domain to be applied in new and creative ways. The center will examine how we can create methods to optimize this generalization of knowledge and will test them in real-life learning situations.

The center will bring together researchers and practitioners across a wide variety of areas including psychology, education, neuroscience, computer science, cognitive science, linguistics, education, speech & hearing science, and business. The center will investigate the successes and failures of human generalization in a manner that will both extend our theoretical understanding of this issue, while at the same time supporting the development and testing of applications for optimal learning. The center will consider basic research about generalization of knowledge from four distinct approaches. The first approach examines people's behavior, considering both the situations that aid in transfer of learning, and the types of information and skills that are most easily generalized. The second approach examines the different brain systems that support learning, and considers which of them allows for the best generalization of knowledge. The third approach examines the types of information that are most easily generalized and what types of calculations can be performed on them. The fourth approach considers how generalization abilities change with development, aging, and disability.

The applied component of the center will consider generalization of knowledge across a variety of real-world domains including traditional classroom settings and informal learning situations such as museums and after-school youth programs. Practitioners in the center also utilize a variety of technological tools to aid in learning. These include educational databases for teaching about the earth and environmental sciences, computerized systems that aid school-age children in reading and writing, devices to aid individuals with who exhibit limitations due to age or disability, and virtual reality immersive environments.

To accomplish these goals, the center will support two main activities. First, it will bring together researchers across disciplines on a regular basis to exchange knowledge about how generalization of knowledge is conceptualized and addressed from their particular perspective. This program will culminate in a book, whose goal will be to provide a coherent multi-disciplinary perspective on generalization of knowledge. This book will allow what has been learned at the center to be distributed to a wider audience. The second main activity will be to take some of the ideas generated by members of the center and to try them out in real-world learning situations. The center will provide funds for these pilot projects, as well as for funds to support undergraduate and graduate students to work on the projects.

This core is designed to provide administrative oversight for the entire center and to: 1) Set the Center's overall arching goals;evaluate and ensure progress towards those goals through monthly meetings of the steering committee (consisting of project and core Principal Investigators), yearly evaluation meetings by the center membership, and a yearly meeting with the internal and external advisory boards 2) Coordinate the scientific projects through the steering committee, monthly colloquia with internal speakers, monthly colloquia with external speakers, a center wiki and website 3) Oversee the training of interdisciplinary researchers at the undergraduate, graduate, post-doctoral, and junior faculty levels as well as training in interdisciplinary project administration, which will occur through faculty mentor-mentee relationships, dual-faculty mentoring of graduate students, twice yearly professional development sessions for post-doctoral research associates and graduate students 4) Expand knowledge about executive function among center researchers through colloquia, a website and wiki, and a yearly scientific conference 5) Coordinate outreach to scientists via our website, colloquia, yearly conference and data sharing;clinicianresearchers via a half day conference;clinicians via in-service presentations;and the public via our website and an Open House 6) Disseminate the results of the center's work through scientific and lay publications, through conference presentations, and through our website and other outreach activities 7) Provide fiscal management for the center, and 8) Oversee data sharing according to NIH guidelines

The main goal of this core is to provide the brain mapping expertise, both with regards to magnetic resonance imaging and electrophysiological techniques, for use in Projects 1,2,3, and 5. This core will enable examination at both the neurobiological and psychological levels of analysis, explicitly addressing a center goal of linking levels of analysis in our understanding of executive function. The core will provide for: a)the quality control, storage, analysis and archiving of MRI and ERP data; b) documentation of data structures and processing procedures c) the incorporating of new analytic tools into the data analysis path d) support staff for running brain mapping experiments e) training in these research methods as well as the creation of materials for training purposes f) preparation of data for data sharing, and other associated functions With regards to neuroimaging, this core will also provide: a) installation of system upgrades and improvements to hardware b) the development of new acquisition and pre-processing methods, especially those that deal with susceptibility artifact and low signal-to-noise ratio. c) the application of new statistical methods to data analysis d) clinical expertise should any structural abnormalities be observed in participants With regards to electrophysiological techniques, this core will also provide: a) standardization of data collection across high-density array recording system b) expand methods and approaches for the integration of data from fMRI and ERP experiments that have been designed in parallel. More specifically it will examine various ways in which fMRI data can be used to seed dipole sources for ERP data, and the ways in which these sources can be disentangled. Understanding the relationship between neurobiological markers and psychological functioning has large implications for mental health. It provides a potential avenue for new procedures for diagnosis and assessment for the efficacy of treatment for executive dysfunction associated with psychiatric disorders.

DESCRIPTION (provided by applicant): The goal of the proposed center is to address two fundamental questions about executive function: 1. What are the component mental processes that contribute to executive control? 2. How does the brain support and enable executive function? Executive function is a broad term that encompasses many critical skills and cognitive functions, including those that guide, control, inhibit, and monitor behavior. Because of its broad nature, there is no clear consensus on exactly what constitutes executive function, nor is there clear agreement on what neural, structures support executive control. In this proposal we argue that executive function is an emergent and modulatory function that represents an interaction among many different cognitive processes and also among many different brain regions. To investigate this issue we have organized the center around core processes that we posit contribute to executive function, as well as factors influencing the variability in executive function. The core processes are: (a) control processes, (b) learning processes, (c) memory retrieval processes, (d) emotional processes, and (e) language processes. We examine the first of these four processes each in a separate project, while the fifth, language processes, is examined across projects. We further posit that these processes co-contribute to executive function through their shared reliance on working memory and prefrontal cortex. The two sources of variability in executive function that we focus on are: (a) developmental variability and (b) genetic variability. To examine these issues, we have two projects that examine the development of executive function - one focused on childhood and the other focused on adolescence - and another project that examines genetic influences on executive function. The approaches taken within the center are highly interdisciplinary drawing from cognitive and clinical psychology, behavior genetics, cognitive neuroscience, physics, computer science, and child and adolescent development. Increased understanding of executive function is highly relevant for mental health, as aspects of it are compromised across a wide variety of psychiatric disorders, including schizophrenia, depression, mania, obsessive compulsive disorder, and attention deficit hyperactivity disorder, among others.

The goal of this project is to utilize brain mapping methods, both fMRI and ERPs, as well as computational modeling, to examine the neural mechanisms involved in cognitive control, which include processes requiring the selection, manipulation, inhibition, and evaluation of information. There are two main aims. The first main aim is to test the validity of our neural model of cognitive control using fMRI, ERPs, and computational modeling as a way to elucidate the organization of prefrontal cortex for executive function. We will test the hypothesis that control occurs via a cascade of processing involving distinct regions of prefrontal cortex, each of which is involved in selection of a distinct type of mental representation. We will do so via empirical studies in which fMRI and ERP data are collected in parallel and via computational model that is structured to represent the interdependences between prefrontal brain regions that play a role in the cascade. The second main aim is to to investigate the hypothesis that the neural substrates involved in the inhibition or suppression of internal mental representations are distinct from those involved in amplification or maintenance of internal mental representations. These studies will use fMRI to investigate the neural substrates involved in the selection, amplification, and suppression of thoughts using two novel paradigms. This project addresses both of the major questions that the center is examining, namely the nature of the organization of prefrontal cortex for executive function and the cognitive underpinnings of executive function. The work to be performed in in this project is designed to interface with parallel investigations regarding the organizaiton of prefrontal cortex in Projects 2 3, and 5, and parallel investigations about the cognitive components of executive function in Projects 2,3, 4 and 5. Of note, as with all other projects in the center, it examines these quesitons at the neurobiological, psychological and computational levels of analysis. Results from this project will expand our understanding of how cognitive control processes can be implemented by the brain. Such findings have large-ranging implications for psychiatric disorders involving: (i) attentional dysfunction, such as attention-deficit hyperactivity disorder,(ii) ruminative thought patterns, such as obsessive-compulsive disorder, (iii) the intrusion of unwanted thoughts and images, such as posttraumatic stress disorder, and (iv) disorders in which the attribution of thoughts as self-generated as compared to emanating from others is blurred, such as schizophrenia.

DESCRIPTION (provided by applicant): The goal of the present project is to understand the effects in early adulthood of interpersonal trauma experienced during childhood. In particular, the project will examine the hypothesis that long-lasting changes are observed in cognitive processes and the brain systems that support such processes as a result of childhood interpersonal trauma (CIT). The project has two specific aims. The first specific aim is to examine the hypothesis that neural systems involved in attentional control and in the selection of information in working memory will be compromised in individuals with a history of CIT (T+) as compared to those without (T-). In particular, the prediction is that individuals with a history of childhood interpersonal trauma will have a poorer ability to ignore distracting information, both of an emotional and non-emotional nature, and that this will be accompanied with reduced activity in regions of dorsolateral prefrontal cortex that are associated with top- down attentional control. An additional prediction is that individuals with a history of childhood interpersonal trauma will have a reduced ability to control the contents of working memory, especially when such information must be inhibited or "cleared" out. These effects will be accompanied by reduced activity in regions of dorsolateral prefrontal cortex associated with control over the contents of working memory. The second aim is to investigate the hypothesis that the compromise of functioning of these neural control mechanisms will increase with severity of symptomatology related to trauma. In particular, an increase in the degree of intrusive thoughts is predicted to be associated with more compromise of these cognitive functions and neural systems. There is one exploratory aim, which is to examine the hypothesis that individuals with a history of childhood interpersonal trauma as compared to those without will show alterations in brain anatomy, most notably in prefrontal regions and the corpus callosum. These hypotheses will be investigated in one study in which individuals will participate in two 1.25 hour sessions. The first session is designed to obtain information about the trauma history of the individual while also obtaining related information such as their degree of anxiety, worry, depression and intrusive thoughts. The second session involves functional and anatomical brain scanning. In this session individuals will perform two tasks, an attention task and a working memory task while their brain activity is assessed using functional magnetic resonance imaging (fMRI). In addition, a high- resolution anatomical scan and a diffusion tensor imaging scan will be obtained so that brain anatomy can be compared between the two groups and also related to symptomatology within the childhood interpersonal trauma (T+) group. The proposed research will provide information on how specific experiences (i.e., trauma) during the childhood period impact both cognitive and neural development. Such knowledge is critical for designing early intervention and treatments aimed at countering and ameliorating the effects of trauma.

The goal of the proposed center is to address two fundamental questions about executive function: 1. What are the component mental processes that contribute to executive control? 2. How does the brain support and enable executive function? Executive function is a broad term that encompasses many critical skills and cognitive functions, including those that guide, control, inhibit, and monitor behavior. Because of its broad nature, there is no clear consensus on exactly what constitutes executive function, nor is there clear agreement on what neural, structures support executive control. In this proposal we argue that executive function is an emergent and modulatory function that represents an interaction among many different cognitive processes and also among many different brain regions. To investigate this issue we have organized the center around core processes that we posit contribute to executive function, as well as factors influencing the variability in executive function. The core processes are: (a) control processes, (b) learning processes, (c) memory retrieval processes, (d) emotional processes, and (e) language processes. We examine the first of these four processes each in a separate project, while the fifth, language processes, is examined across projects. We further posit that these processes co-contribute to executive function through their shared reliance on working memory and prefrontal cortex. The two sources of variability in executive function that we focus on are: (a) developmental variability and (b) genetic variability. To examine these issues, we have two projects that examine the development of executive function - one focused on childhood and the other focused on adolescence - and another project that examines genetic influences on executive function. The approaches taken within the center are highly interdisciplinary drawing from cognitive and clinical psychology, behavior genetics, cognitive neuroscience, physics, computer science, and child and adolescent development. Increased understanding of executive function is highly relevant for mental health, as aspects of it are compromised across a wide variety of psychiatric disorders, including schizophrenia, depression, mania, obsessive compulsive disorder, and attention deficit hyperactivity disorder, among others.

The Center for Research Computing (CRC) at the University of Colorado Boulder (CU-Boulder) will acquire, deploy and maintain an expandable petascale storage instrument, the CU-Boulder petaLibrary. This instrument, consisting on an integrated disk and tape system, will enable faculty, staff, postdocs, graduate and undergraduate students to build, store, share and merge large and growing data collections. The petaLibrary will be made available to all CU-Boulder researchers at no usage charge other than the cost of the media.

The petaLibrary will serve as the infrastructure for a number of data services provided by the University Libraries, the Museum, the National Snow and Ice Data Center (NSIDC) and the CRC to the CU-Boulder campus community. The services will include the deposit and discovery of a wide range of digital resources, including digital surrogates of archives and special collections materials owned by libraries and museums on campus, openly accessible resources, digital media only library resources and the scholarly output of the campus. Data-intensive projects include digital collections; high fidelity, high definition recordings of human interaction; global-scale land remote sensing; bio-digitization efforts by the Museum; as well as research programs utilizing CU-Boulder's computational resources.

The broader impacts of the project include the development of workshops on data archival and long-term data formats for researchers, research projects and educational opportunities with the CRC for graduate and undergraduate students. Other efforts will include working with The Colorado Coalition for Gender and IT (CCGIT) and the National Center for Women and Technology (NCWIT) to address the limited diversity in IT, specifically in the area of cyberinfrastructure by providing summer internship opportunities for female faculty in data management related topics.

? 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 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 Twin Hub of the ABCD-USA Consortium is in response to RFA-DA-15-015; the proposal includes the University of Minnesota (hub leader), Virginia Commonwealth University, Washington University, and the University of Colorado to prospectively determine neurodevelopmental and behavioral predictors and consequences of substance use on children and adolescents. A representative community sample of 800 twin pairs, ages 9-10 years, from four sites whose researchers are leaders in twin research, SU and abuse, and neuroimaging of cognitive and emotional functioning will be tested, together with 700 singletons, contributing to the sample of 11,111 to be collected from 11 hubs across the ABCD-USA Consortium. 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) effects of substance use patterns on the adolescent brain; 2) effects of substance use on behavioral and health outcomes; 3) bidirectional relationships between psychopathology and substance use patterns; 4) effects of individual genetic, behavioral, neurobiological, and environmental differences on risk profiles and substance use outcomes; and 5) gateway interactions between use of different substances. The Twin Hub proposes to use classic and co-twin control designs to study genetic vs. environmental contributions to adolescent brain/behavioral development and how these contributions predict SU propensity. Using sophisticated growth trajectory modeling techniques, we will also identify the genetic and environmentally- determined consequences of substance use on brain and behavioral development, including the assessment of gene-by-environment interactions. In addition, we will develop biospecimen resources for future studies of genomic, epigenomic, metabolomics and microbiome changes that may influence substance use and its broad health consequences. Specific to this Twin-Hub, we will obtain baseline and follow-up serum, saliva, and in some cases gut microbiota from biological samples. This work enriches the full ABCD-USA Consortium given that disentangling G and E contributions to individual risk for addiction and sensitivity to SU's neurocognitive effects has highly significant public policy and prevention-based implications.

? DESCRIPTION (provided by applicant): Adolescence is an important developmental period characterized by rapid changes in multiple domains, including maturation of the brain's prefrontal cortex, increases in planning and cognitive control, and also a large increase in rates of anxiety and depression. Deficits in control and planning have been identified as a risk factor for mental illness, including depression and anxiety. One aspect of control that is understudied but likely affects risk for depression and anxiety, is the ability to quickly and efficiently selec among competing options when planning or working towards a goal. Such selection can be difficult for anyone, but is especially so for individuals with elevated levels of anxiety or depression, leading to problems in planning and decision-making. To date, these issues have primarily been studied in adults. However, it is important to understand how these abilities develop during adolescence because that is the developmental time period in which many aspects of mental illness first appear. The proposed research builds upon an innovative and integrative model of how such selection abilities are accomplished. It examines this issue at multiple units of analysis, linking a) neurochemistry of the brain, to b) activation of specific brin regions, to c) behavioral performance on tasks requiring selection to d) self-report of the ability to select amongst alternatives in daily life. This proposal brings together a multi-disciplinary team of scientists that articulated and tested the original model in adults (cognitive and developmental neuroscientists, and a physicist with expertise in brain imaging) with a clinical scientist with expertise in development of anxiety and depression during adolescence. The project leverages a highly retained sample of youth and their caregivers who have been prospectively followed for 5 years with extensive evaluation of psychopathology, but have not previously undergone neuroimaging or evaluation of planning or control. The project will test 144 youth (72 middle and 72 older adolescents) and 72 adults both at an initial time point and then two years later. This project aims to determine the development of biobehavioral mechanisms for selection in adolescence and adulthood (Aim 1), associations between selection mechanisms and anxiety and depression (Aim 2), and how these selection mechanisms over time may predict changes in psychopathology and/or vice versa (Aim 3). The proposed research will make a significant, innovative impact by providing information about important processes that develop during adolescence, and their relationship to the onset of mental illness. The data provided by the project will help break new ground and advance the field's understanding of developmental changes in the interplay of control and planning with mental health during the critical adolescent period.

? DESCRIPTION (provided by applicant): The overall objective of the current project is to understand the neural mechanisms that allow us to remove information from our current thoughts. For the last half century, it has been known that we have a limited capacity to concurrently keep information in mind at one time, typically considered to be about 7 items. This capacity is often referred to as working memory. Surprisingly, what is not known, however, is how we remove information from working memory, so as to either allow other items in or to clear it entirely. Understanding how information is removed from working memory, and which brain systems allow one to do so, is important not only from the perspective of obtaining a better understanding of how the brain influences the way we think, but also because such an understanding has important implications for psychological disorders. Many psychological disorders are characterized by an inability to remove certain types of information from working memory. For example, individuals with obsessive-compulsive disorder have difficulty not thinking about what harm might befall them or others, and individuals with depression have difficulty not ruminating on negative ideas and feelings. One of the reasons that it has been so hard to understand how information is removed from working memory is the large challenge involved in determining what a person might be thinking of at a particular point in time, and/or knowing whether indeed thoughts have been cleared from working memory. The goal of this project is to leverage brain-imaging techniques to overcome this problem. Recent techniques drawn from computer science allow one to characterize the pattern of brain activity associated with particular items (e.g., apples, pears, grapes, melons) or particular categories of items (frui, tools, faces, buildings). The project will utilize such methods to verify, via a pattern of brain activity, on which occasions individuals have either cleared their mind of certain items, or replaced them with other thoughts (e.g., switched from thinking about an apple to thinking about a pear, switched from thinking about an apple to thinking about a hammer). Then, the study will test the hypothesis that a certain set of brain regions in the prefrontal cortex plays a central roe in successfully changing the nature of the information held in working memory. In addition, the proposed research will examine how these neural mechanisms vary depending on differences across individuals. In particular, the project is designed to gather information both on how much difficulty an individual reports in controlling his or her thoughts, and also on the topics and characteristics of an individual's everyday thoughts (e.g., they are usually about things that happened in the past, negative, vague in scope, etc.). It is predicted that individuals who have difficulty controlling their thoughts and who have vague and over general thoughts will have more difficulty removing information from working memory, and they will show less activity in brain regions that control such thoughts. If this hypothesis is confirmed, it could provide new avenues for therapeutic intervention for psychological disorders characterized by repetitive thought.

PROJECT SUMMARY PROJECT III: FUNCTIONAL AND ANATOMICAL INVESTIGATIONS OF DOMAIN-SPECIFIC AND DOMAIN-GENERAL ALTERATIONS IN NEURAL SYSTEMS UNDERLYING MATH & READING DIFFICULTY The goal of this high-risk/high-reward project will be to investigate, using a new and novel perspective, the neural underpinnings of reading and math difficulties. In particular, in a novel theoretical conceptualization, this project links specific neural systems to specific behavioral characteristics exhibited by individuals with learning disabilities. The center within which this project is embedded focuses on three types of behaviors proposed to be altered in reading and math disability: processing speed, domain-specific processes that are needed to enable a given ability (e.g., word recognition for reading; numerical sense for math), and executive processes that aid in selecting and prioritizing specific information to support domain-specific processes. This project tests a model which posits that alterations of each of these three behaviors is associated with alterations in each of three specific aspects of neural function. The project will examine whether slowed processing speed, which is observed trans-diagnostically across reading and math disability, is associated with poorer overall integration and coordination of information across the brain. Brain organization will be assessed by state-of-the art methods. In one method drawn from graph theory, the brain is conceptualized as consisting as a set of nodes or regions, with the connections between them acting as a route for information flow (much like an airline network). The hypothesis to be tested argues that the first behavioral characteristic, slowed processing speed, will be associated with reduced efficiency of information flow through the brain. In the other method, the brain is divided into intrinsic connectivity networks, where brain regions whose activity co-varies together over time are grouped together (much as the world is composed of different alliances such as the European Union and North American Free Trade Association). From this perspective, it is proposed that in individuals with slowed processing speed, processing within these networks is not well insulated from one another. The project will also test the hypothesis that the second behavioral characteristic, domain-specific deficits (i.e., math difficulties, reading difficulties) are reflected in altered processing in brain regions critical to a given domain. In the case of reading, such critical areas include the language-related superior temporal/inferior parietal regions along with inferior frontal regions of the left hemisphere. For math, the critical region is the intraparietal sulcus. Finally, the project will test the hypothesis that those individuals with learning difficulty who also exhibit executive dysfunction, the third behavioral characteristic, will show alterations in function of lateral prefrontal regions, as well as disrupted connectivity of this region to posterior regions involved in domain-specific (e.g., math, reading) processing. So as to increase relevance for the identification and treatment of individuals with learning disability, an additional project goal will be to determine whether these neural markers can be used together with one another to predict the level of reading (or math) difficulties exhibited on an individual-by-individual basis. To meet these ambitious goals, the project brings together scientists with requisite areas of expertise.

Abstract Neuroimaging has expanded our understanding of brain development from childhood into early adulthood. Adolescent substance use trends have shifted over time, but use of cannabis, alcohol, and tobacco remain prevalent, typically starting during teenage years, when serious mental health conditions also tend to emerge. Although physical health is at its lifetime peak, emerging concerns for teens include increasing rates of depression, anxiety, social isolation, suicidal ideation, and excessive use of screen media. The extent to which early substance use and other environmental exposures may place youth at risk for altered neurodevelopment and adverse outcomes remains poorly understood. A diverse sample of 11,878 9-10 year olds was enrolled from 21 sites across the ABCD Study consortium under RFA-DA-15-015. All participants underwent a comprehensive baseline assessment, including state-of- the-art brain imaging, comprehensive neuropsychological testing, bioassays, careful assessment of substance use, mental health, physical health, culture and environment, and mobile monitoring every 2 years. Interim in- person annual interviews and biannual telephone or mobile app assessments provide refined temporal resolution of behaviors, development, and life events with minimal participant burden. Intensive efforts are made to retain the vast majority of participants through adolescence and beyond and retention rates thus far are very high. Data, securely and privately shared with the scientific community, will enable investigators to: (1) describe individual developmental trajectories 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 affect brain development; (5) determine and replicate factors that influence the onset, course, and severity of mental illnesses; (6) characterize the relationship between mental health and substance use; and (7) specify how use of different substances (e.g., cannabis, alcohol, tobacco, caffeine) affects developmental outcomes, and how neural, cognitive, emotional, and environmental factors influence substance use risk.

PROJECT SUMMARY The overall objective of the current project is to understand how emotional thoughts can be removed from one's mind. Most psychiatric disorders are characterized by an inability to remove negative, intrusive, and maladaptive thoughts from mind. Previously examining whether an individual has purged a thought from mind has relied mainly on self-report measures (e.g., ?Yes, I stopped thinking about the car crash?). In the proposed research, the research team will use a combination of brain imaging approaches with machine learning techniques drawn from computer science to provide an objective neural marker of whether indeed a thought has been removed from mind. This approach builds on proven success with this technique pioneered by the research team. This prior work focused on the removal of (emotionally neutral) information from mind and demonstrated that suppressing a specific thought and clearing one's mind of all thought rely on different neural mechanisms. Moreover, the prior findings indicated that these mental operations differentially affect one's ability to take in new information after the old information has been removed. The focus of the proposed project will be to examine how emotional information is removed from current thought. The project will ask three main questions. First, it will examine whether the emotional valence of information affects the engagement and effectiveness of neural systems involved in removing information from mind. A series of parallel studies, one involving neuroimaging and the other examining people's behavior, are designed to examine whether these removal operations are affected by a) the emotional valence (positive, negative) of the information to be removed, b) the emotional valence of the information that should now be brought to mind and c) the match (e.g., positive, positive) or mismatch (positive, negative) between the valence of the information being removed and that which replaces it. Expectations are that negative information will be harder to remove and easier to be brought into current thought than positive information. Second, the project will examine whether the effectiveness of these removal operations varies across individuals. It will assess the degree to which individuals report that they have difficulty controlling their thoughts, the degree to which they have symptoms related to depression and anxiety, and their ability to hold and manipulate information in working memory. Expectations are that individuals who report difficulty in controlling their thoughts will have difficulty in removing information from mind, and that people with higher levels of depression will have specific difficulties in removing negative thoughts. Third, the project will examine whether individuals can be trained, using real-time feedback about brain function during neuroimaging, to effectively remove thoughts from mind by providing them with a sense of what it feels like to successfully remove a thought. The results of the proposed project will have important implications both for understanding the recurrent and intrusive thoughts that characterize psychopathology and for providing insights on how they might be reduced.