Active Research Grants

Research event at UW

Fear and Natural Risky Decisions in Rats

Project Duration: 06/08/2018 - 02/28/2023
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Jeansok Kim
Abstract: Click to expand...
Basic fear research largely employs the Pavlovian fear conditioning paradigm in rodents. While this model systems approach simplifies behavioral and biological analyses of acquisition, maintenance and expression mechanisms of conditioned fear memories, fear conditioning studies cannot address the fact that animals and humans rely on a multitude of actions and decisions to survive the breadth of risky situations in the real world. Hence, there is a need to complement fear conditioning studies with ecologically-relevant fear research that can lead to novel translational insights. This renewal application will continue to employ and enhance our ‘approach food-avoid predator’ paradigm to investigate the naturalistic workings of the brain’s fear system. Specifically, in Aim 1, we will examine how rats adapt their fear responses, risk-assessment and foraging decisions to more realistic and diverse risky situations by simulating hidden versus visible threats and terrestrial versus aerial predators. We will also determine the functions of fear conditioning, which has never been analyzed in a naturalistic setting, under realistic prey-predator interaction scenarios. In Aim 2, we will utilize pharmacology, single unit recordings and optogenetics to further elaborate the neural mechanisms of fear in naturalistic risky conditions. Based on our earlier work, we hypothesize that the dorsal periaqueductal gray-amygdala pathway signals impending threats to elicit innate fear, that the reciprocal medial prefrontal cortex-amygdala circuits serve risk proximity assessment functions, and that the amygdala-hippocampal pathway provides the safety-danger boundary information for adaptive foraging decisions and strategies. This ethologically relevant project is significant (i) from a basic scientific perspective because it will advance a more naturalistic view of the fear system that will fill gaps in knowledge and predict new results, and (ii) from an applied perspective because it can lead to novel insights to develop more effective treatments for generalized anxiety, panic, phobia and posttraumatic stress disorders.

Creating Cultural Change in Education Systems: Can Leadership-Level Cultural Inclusion Training Reduce Achievement Gaps?

Project Duration: 06/01/2018 - 05/31/2021
Sponsor: National Science Foundatin
Dept. Investigator(s): Stephanie Fryberg
Abstract: Click to expand...
The U.S. is more racially and ethnically diverse than at any other time in the nation's history. Yet achievement gaps continue to separate racial minority and lower-income students from White and higher-income students. Research designed to reduce these achievement gaps largely focuses on student characteristics, such as motivation, belonging, and performance. The resulting interventions often aim to change the way students engage with the school context. However, eliminating achievement gaps may require more than changing individual students. It may require changing the prevailing social norms and beliefs that undermine racial minority and low-income students' success. This project examines how school leaders might be trained to build culturally inclusive and sustainable learning environments. The goal is to shape the beliefs that schools and teachers hold about diverse students and the practices they use to engage students from different racial and social class backgrounds. These culturally inclusive changes in the learning environment are expected to improve racial minority and low-income students' academic outcomes by fostering a sense of belonging and positive beliefs about learning. This project uses a district-wide intervention to create cultural change within schools. The intervention focuses on teaching educational leaders to understand and validate multiple cultural ways of being in their schools and classrooms, such that all students feel that they belong and are capable of succeeding in school. Educational leaders will learn to change their school cultures by attending week-long workshops that provide theoretical and practical information about engaging cultural differences in educational contexts. The workshop curriculum has been piloted with educators and works to bridge the gap between empirical research and real-world classroom experiences. The curriculum reflects research-based understandings of how culture influences cognitive development, motivation, and emotional expression. It also offers concrete strategies for applying empirical knowledge in educational settings. The research examines how this intervention shapes a) the policies district and school leadership enact; b) the classroom cultures teachers create and the practices they use with diverse students; and c) students' psychological and academic outcomes, particularly among racial minority and low-income students. Teaching institutional leaders to understand and validate diverse cultural backgrounds is expected to improve minority and low-income students' educational experiences and reduce racial and social class achievement gaps.

Mechanisms of adult forebrain neural circuit regeneration

Project Duration: 05/15/2018 - 02/28/2023
Sponsor: National Institute of Neurological Disorders and Stroke
Dept. Investigator(s): Eliot Brenowitz
Abstract: Click to expand...
The neural circuit that regulates birdsong, a highly precise, learned sensorimotor behavior, excels for study of fundamental mechanisms of adult circuit plasticity. The song system is a unique model of naturally occurring degeneration and compensatory regeneration in a behaviorally relevant neural circuit in adult brains. This circuit shows exaggerated seasonal degeneration and reconstruction via neurogenesis, in response to changes in circulating steroid hormone levels. Our long-term goal is to understand the fundamental mechanisms by which steroid hormones and neurotrophins interact to regulate plasticity of neural circuits and behavior. On a translational level, our goal is to understand how forebrain circuits can regenerate to support performance of complex learned motor skills. The central hypothesis of the proposed aims is that seasonal changes in hormones trigger changes in anterograde and retrograde trophic signaling that lead to remodeling of the HVC-RA circuit and changes in song behavior in adult birds.The goal of this application is to identify the trophic signaling pathways (molecular and electrophysiological) that regulate the the incorporation of newborn neurons to regenerate this circuit. This research will advance the field by elucidating fundamental issues of adult circuit plasticity. This topic is of translational relevance for exploiting endogenous or exogenous stem cells for therapeutic repair of injured or dysfunctional circuits in humans. These fundamental issues include whether new neurons added to adult circuits establish functional connections with efferent nuclei and restore behavior (Aim 1), the role of activity regulated genes in mediating retrograde trophic effects of neuronal activity on presynaptic adult neurogenesis (Aim 2), the role of calcium channels in mediating the transsynaptic neurotrophic regulation of postsynaptic activity (Aim 3), and the role of pre- and/or postsynaptic neuronal activity in maintaining a regenerated adult circuit (Aim 4).

TransYouth Project

Project Duration: 01/01/2018 - 12/31/2019
Sponsor: Arcus Foundation
Dept. Investigator(s): Kristina Olson
Abstract: Click to expand...
The TransYouth Project is the nation’s first large-scale, national, longitudinal study of transgender children’s development. This project was begun in the summer of 2013 and is spearheaded by Dr. Kristina Olson at the University of Washington. Our goal is to recruit and follow 200 transgender children across the U.S. and Canada for 25 years, starting from the time they are 3-12 years of age. Our hope is that by following these children, publishing our findings in scientific journals, and speaking and writing about their collective experiences in venues geared toward the general public, we will educate parents, teachers s, scientists, clinicians, and the public at large about the experiences of transgender children and how to best support them. Very little research has been published on the development of transgender children, and no large studies of socially-supported transgender children exist. Research to date has focused on unsupported children, often those who have received reparative therapy to alter their gender identities. Much of this work has suggested poor outcomes--high rates of anxiety and depression, suicidality, and victimization. Our cohort, on the other hand, is largely comprised of what we call “gender pioneers”--the first generation of children who are supported in their gender identities from very early ages and often socially transition (publicly presenting their gender identities, including using their authentic pronouns and names) well before puberty. We have already begun publishing our findings so that these gender pioneers can be included in the conversation about transgender children and how to care for them; our first paper, “Gender Cognition in Transgender Children,” was recently published in Psychological Science, the top empirical journal in the field of psychology and garnered considerable media and public interest. We aim to recruit a truly diverse sample: including children of all races and ethnicities, across a wide range of states in the U.S. and provinces in Canada, across all socioeconomic statuses, and within all kinds of families (e.g., adopted, biological, families with one or two moms, one or two dads, headed by grandparents, etc). To date, approximately 32% of our participants (currently 100 children) are non-White, we have had a chance to work with families from 13 states, and our sample has included families from all socio-economic quintiles. We have been contacted by an additional 120 additional eligible families in 33 states and 4 provinces who are interested in participating in our study, with a handful or more new families contacting us each week. Our study looks at a number of factors, but our main focuses are: (1) to better understand the factors (e.g., parental support) that are associated with positive mental health outcomes, gender identity, and overall well-being in transgender children (2) to document what gender development in transgender children looks like including the ways it is similar to or unique from the development of other children. (3) to better understand the ways that early support might influence later life health and well-being, and how these outcomes might differ as compared to previous or current generations of transgender children who lack early support. Early results from our sample have indicated that the gender identities of these children are authentic and deeply held, that their gender development is remarkably similar to that of cisgender children who share their gender identity, and that these supported children have dramatically lower rates of anxiety and depression than previous work with unsupported children has found. Our upcoming goals include expanding our sample geographically to increase the generalizability of our findings and to increase the types (quantitative and qualitative) and frequency of data collection. In addition, we aim to release reports of ongoing data collection more frequently. In addition, we aim to expand our work to also include studies focused on how tochange people’s understanding and support for transgender and gender nonconforming children. We believe that this work has the potential to powerfully impact standards of care for transgender children in the medical and psychological communities, to inform decision-making in future generations of families with transgender children, and to deepen the broader public’s understanding of the transgender community.

Views of Gender in Early Childhood

Project Duration: 09/21/2017 - 08/31/2022
Sponsor: National Institute of Child Health & Human Development
Dept. Investigator(s): Kristina Olson
Abstract: Click to expand...
Young children’s essentialist views of gender (i.e., that gender is innate, immutable, informative, and discrete) are found to be inflexible in early childhood in all cultures studied to date, which has led researchers to construe of gender essentialism as an early-emerging cognitive default. The proposed work addresses the validity of this belief that gender essentialism is inevitable, by examining the development of gender essentialism among gender nonconforming and gender typical children. Gender nonconforming children present a unique opportunity for answering this question, as their own gender identity defies central components of an essentialist outlook on gender. Specifically, gender nonconforming children might not view gender as determined by one’s natal sex, or as discrete. Thus, gender nonconforming children’s own experiences with gender might lead to early non-essentialist beliefs about gender, different from gender typical children whose gender aligns with essentialist views of gender. If, however, gender essentialism is indeed a cognitive default, even gender nonconforming children might hold early essentialist beliefs regarding gender. We propose to study development of gender essentialism among gender nonconforming and gender typical children in 4 main ways. First, the proposed work aims to examine the similarities and differences in gender essentialism among gender nonconforming and gender typical children, and to further our current understanding of gender essentialism by studying children’s essentialism of gender and gender identity separately, which has not been previously done in the literature. Second, the project aims to understand the extent to which essentialism is a domain-general or domain-specific cognitive bias. If essentialism is a domain-general capacity, we would expect that gender nonconforming and gender typical children’s essentialism of gender will align with their essentialism of other social categories and natural kinds. However, if gender essentialism is a domain-specific capacity, we would expect to see no alignment. Third, we will examine the family environment as a context that potentially relates to children’s early essentialist beliefs. Specifically, we will examine the extent to which gender nonconforming and gender typical children’s gender essentialism mirrors the messages they receive from their parents about gender. Fourth, we aim to examine the relation between gender essentialism and prejudice against gender nonconforming children among gender typical children. The literature provides conflicting evidence regarding the relation between essentialism of social categories and prejudice. Because gender nonconforming children tend to experience high levels of discrimination and prejudice by their peers, understanding this link has crucial implications for reducing peer victimization of gender nonconforming children. Together this work will not only expand our theoretical understanding of essentialism, but will broaden our understanding of gender nonconformity in early childhood.

Gene regulatory analysis of social integration and resilience during aging

Project Duration: 09/15/2017 - 06/30/2020
Sponsor: National Institute on Aging
Dept. Investigator(s): Noah Snyder-Mackler
Abstract: Click to expand...
Almost half of American adults over 60 years old report being lonely, a condition that can have a major impact on health and mortality risk in later life. Adults with weak social relationships experience a 50% higher mortality rate than more socially integrated adults—an effect on par with that of smoking, obesity, or alcoholism. One explanation for this association is if better social integration increases resilience against stressful experiences, a hypothesis known as “stress buffering.” Yet despite the importance of social integration for human health, the behavioral and molecular mechanisms that mediate its potential role in stress buffering remain poorly understood, limiting its practical application to improving resilience during aging. The objective of the proposed study is to identify the genomic mechanisms that link social integration to stress sensitivity and inflammation during acute stress. If a main benefit of SI is to buffer against acute stress, I hypothesize that low levels of social integration will be associated with dysregulation of the gene regulatory response to acute stress. To test this hypothesis, I will leverage the advantages of studying rhesus macaques, a well-established animal model for human aging and social behavior. Work performed during the mentored phase of this award has shown that the social environment alters the epigenomic and genomic landscape of immune cells and that these changes may underlie variation in acute stress susceptibility in individuals who have more favorable vs. more adverse social environments. These findings suggest a potential mechanism, epigenomic changes, through which social adversity may accelerate the aging process. Probing how age and social experience interact to alter this mechanism will be the focus of the independent phase of this project. This project will combine studies of free-ranging macaques (Aim 1) with experimental manipulations of the social environment (Aim 2) to yield insight into the relationship between acute stress and gene regulation in a natural environment and a more controlled setting. In both contexts, I will combine genome-wide gene expression, DNA methylation, and chromatin accessibility measurements to characterize the genomic pathways associated with social integration and its relationship with the acute stress response. I will also test whether these relationships are exaggerated for older animals, and whether the presence of a close social partner can enhance resilience to psychosocial stress.

Expanding pathways to early screening and intervention for underserved toddlers with ASD (ASD-PATH)

Project Duration: 09/01/2017 - 08/31/2020
Sponsor: Health Resources and Services Administration
Dept. Investigator(s): Wendy Stone
Abstract: Click to expand...
The purpose of the ASD-PATH project is to understand barriers to early ASD screening and intervention services for Hispanic and underserved families, and to build capacity within the community to offer more diverse pathways to accessing these services. We will be conducting focus groups with caregivers and providers to guide our development of tailored workshops on evidence-based screening and intervention, as well as parent-centered discussion and decision-making. We propose that community-level improvements in early screening, referral, assessment, and intervention will result in improved outcomes for toddlers as well as their caregivers, as well as reduce current health care disparities. We will be working with providers and caregivers in 2 community health centers and 4 early intervention/home visiting programs in King County, WA. These programs were selected based on the number of children reached and their service to Hispanic and underserved families. Workshops and technical assistance for each community health center will include information on: (1) the early characteristics of ASD, (2) the use of a Level 1 ASD screen (the Modified Checklist for Autism in Toddlers – Revised with Follow-up [M-CHAT-R/F]), (3) family-centered discussion and decision making, and (4) local resources. Workshops and technical assistance for each early intervention program (which include Early Head Start and home visiting programs) will include information on: (1) the early characteristics of ASD, (2) the use of the M-CHAT-R/F, (3) the use of a Level 2 screen (the Screening Tool for Autism in Toddlers [STAT]), (4) the use of a low-cost, evidenced based, ASD-specialized behavioral intervention (Reciprocal Imitation Training [RIT]), and (5) family-centered discussion and decision making. To evaluate the effectiveness of ASD-PATH, we will collect data from caregivers and providers at multiple points before and after the ASD-PATH intervention. Caregivers will complete information about their child-related stress and efficacy, their experience of family-centered practices within provider contexts, and their child’s social-communication behavior. Providers will complete information about their practices before and after training and the acceptability and feasibility of using the tools. In addition, to evaluate changes in child’s social communication, 30 toddlers will receive direct behavioral assessments of social communication at two time points before the ASD-PATH training (i.e., pre-RIT), and a separate cohort of toddlers will receive direct assessments of social communication at two time points, once before and once after the ASD-PATH training.

Thomas Jefferson Fund Award: Olfactory navigation using naturally fluctuating odor cues

Project Duration: 09/01/2017 - 08/31/2019
Sponsor: French American Cultural Exchange (FACE)
Dept. Investigator(s): David Gire
Abstract: Click to expand...
Living systems constantly make decisions based on a large array of sensory inputs that inform them of their environment. Chemical cues bear a fundamental source of information, that all domains of life extract with sophisticated mechanisms. Terrestrial and aquatic animals live in distinct physical environments, and differ in both behavioral strategies and physiological mechanisms. However in all animal species, odorants reach the receptors via an aqueous phase suggesting a common evolutionary history. Moreover, while different species use olfaction to tailor their decision-making onto specific computational needs, the neural architecture underlying the sense of smell is remarkably similar. To unravel the fundamental principles that shape olfactory driven decision-making, we target a connection between the physics of odor transport in the air and animal behavior during olfactory navigation tasks.

Collaborative: RR: Origins of Intergroup Perceptions and Attitudes Across Diverse Contexts

Project Duration: 08/01/2017 - 07/31/2020
Sponsor: National Science Foundation
Dept. Investigator(s): Kristina Olson
Abstract: Click to expand...
This collaborative project investigates the early emergence of social category knowledge with a particular focus on race and gender in children from a diverse range of racial/ethnic and geographic backgrounds throughout the United States. We focus on four core components of early social category knowledge, each with direct relevance for pressing issues of equity and discrimination: children’s attitudes towards, stereotypes about, facial recognition of, and prosocial behavior with members of different racial and gender groups. Each of these topics has previously been investigated independently and in restricted samples primarily consisting of White American children. In response to Dear Colleague Letter 16-137, a central goal of this proposal is to examine the robustness of past results in these areas, in particular the generalizability of past findings across diverse racial/ethnic and geographic samples. This will be accomplished by interviewing and testing all children on the full set of measures using a common protocol to be developed by the research team. The project involves five geographically diverse sites (Hawaii, Southern California, the Pacific Northwest, the South, and the Northeast), with each site involving two or more racial/ethnic samples of participants spanning White, Asian, Black, and Hispanic Americans, and with each racial/ethnic group sampled from at least two geographic regions.

Collaborative Proposal: Physiological Signatures of Variable Weaning Strategies in Wild Geladas (Theropithecus gelada)

Project Duration: 08/01/2017 - 07/31/2020
Sponsor: National Science Foundation
Dept. Investigator(s): Noah Snyder-Mackler
Abstract: Click to expand...
Weaning reflects a classic life history tradeoff for mammalian females. While prolonged maternal investment comes at a cost to the mother’s future reproduction, premature weaning can lead
to higher infant mortality and impaired infant development. These patterns beg the question: Under what contexts should mothers curtail parental investment at the expense of offspring fitness? In nonhuman primates, maternal dominance rank and parity appear to influence the duration of nursing, but not the timing of weaning relative to growth. True premature weaning of underdeveloped offspring is expected only under extreme conditions where infant survival
is likely to be low. For instance, in nonhuman primates, mothers are expected to prematurely wean their infants as a cost-cutting strategy against potential infanticide. To date, however,
the links between infanticide risk, maternal weaning strategies, and offspring developmental outcomes are poorly understood. In part, this is because data on growth, accurate assessments of nursing cessation, and biomarkers of potential long-term consequences (e.g., infant growth, immunity) have been difficult to obtain in wild populations. This study proposes to overcome these hurdles by using innovative techniques in stable isotope analyses, photogrammetry, and genomics to examine weaning in relation to growth, gut microbial communities, and fitness in a wild primate - the gelada (Theropithecus gelada). Geladas are an ideal model for examining such questions because male infanticide, one of the key conditions that may favor premature weaning, is common in this species. Our research focuses on three questions: (1) What is the normative trajectory of weaning in relation to growth and gut microbiome establishment? (2) What maternal attributes (dominance rank, parity) or social factors (male takeovers associated with infanticide risk) influence individual differences in nursing cessation and its timing relative to infant growth? 3) Does premature weaning negatively impact long-term health and survival?

Building and Sustaining Interventions for Children (BASIC): Task-sharing mental health care in low-resource settings

Project Duration: 08/01/2017 - 06/30/2022
Sponsor: National institute of Mental Health in collaboration with Duke University
Dept. Investigator(s): Shannon Dorsey
Abstract: Click to expand...
Eighty percent of the world’s population lives in low and middle income countries (LMIC) with few mental health resources, resulting in a substantial mental health treatment gap. Growing evidence indicates that evidence- based mental health treatments can be delivered in LMIC using a task-sharing approach, in which non- professionals deliver care under supervision. Very limited research, however, focuses on how to embed, support, and effectively deliver these treatments within existing, government-supported systems in which they could be scaled up to population-level. With LMIC governments typically spending <2% of their national budget on mental health, innovative and low-cost options are needed for intervention delivery and for implementation support. Building and Sustaining Interventions for Children (BASIC): Task-sharing mental health care in low-resource settings builds on our 15-year history of collaborations with research partners in Kenya, prior NIH-funded work that identified mental health needs of orphaned children in LMIC, and iterative and collaborative intervention adaptation and testing using a task-sharing approach, to address these needs. In BASIC, we test the implementation of Trauma-focused Cognitive Behavioral Therapy (TF-CBT), delivered via task-sharing, in two governmental sectors prioritized by our Kenyan partners as potential options for scale up— Education and Health Extension. The recent devolvement of the Kenyan government (leading to more local decision-making), the launch of a National Mental Health Policy, and our Kenyan partners’ empowerment work building enthusiasm for TF-CBT are converging to create a local climate in which BASIC could become part of the county plan, if evidence-based guidance for implementation, using mostly existing resources, existed. We test mental health treatment delivery in Education (via teacher delivery) and Health Extension (via community health volunteers) with the goal of identifying implementation practices and policies (IPPs) that explain implementation outcomes. This stepped wedge cluster randomized trial includes 40 schools and the 40 surrounding villages (120 lay counselors in each) who provide TF-CBT to 1,280 youth. We use a novel method, qualitative comparative analyses (QCA), that holds potential for substantially advancing the field of implementation science. QCA leverages the rigor of quantitative approaches and the detail of qualitative approaches, and allows for complex causality and equifinality (i.e., an outcome can be reached by multiple means). Study aims are: 1) Identify actionable IPPs that predict adoption (delivery) and fidelity (high- quality delivery) after 10 sites in sector implement TF-CBT. Use identified IPPs to (Aim 1a) guide implementation planning support for subsequent sites and to (Aim 1b) generate testable hypotheses about IPPs as causal mechanisms; 2) Test mechanisms of implementation success in both sectors; and 3) Test TF-CBT effectiveness (i.e., mental health outcomes; functioning) and cost in both sectors. This research has important implications for implementing an EBT in low-resource settings, including the US.

Effects of Blindness on Human Early Visual Pathways

Project Duration: 07/01/2017 - 06/30/2022
Sponsor: National Eye Institute
Dept. Investigator(s): Ione Fine
Abstract: Click to expand...
Early blind individuals show superior performance across a wide variety of auditory skills. However, fMRI studies examining neural plasticity resulting from blindness have almost exclusively focused on techniques that pool information across voxels. As a result, while studies have shown that differences in neural activity between early blind and sighted subjects are correlated with behavioral performance, justifications for these correlations remain at the ‘more cortex is better’ or the ‘bigger BOLD (or sometimes smaller) responses are better’ level of explanation. We will examine the widespread alterations that occur within auditory processing pathways within early blind individuals using ‘voxel‐wise encoding’ models that represent each voxel as having a tuning function along dimension(s) of interest. Simple linking models will allow us to predict behavioral performance based on the predicted cortical discriminability of stimuli. This will allow us, for the first time, to model quantitatively how neural responses to auditory stimuli might mediate the enhanced behavioral abilities observed in early blind individuals. In Aim 1 we will examine whether early blindness alters primary auditory cortex (PAC). We will begin by comparing PAC size, responsiveness and frequency tuning bandwidths across early blind and sighted individuals. We will then examine whether tuning for temporal amplitude modulations within primary auditory cortex are also affected by blindness. Computational models will be used to link primary auditory cortex neural responses to behavioral performance across a variety of auditory tasks for blind and sighted individuals. In Aim 2 we will use naturalistic stimuli to measure complex auditory spectro‐temporal tuning in both auditory and occipital cortex. Again, computational models will be used to link each individual’s neural responses to auditory performance on complex naturalistic tasks. Finally in Aim 3 we will examine auditory motion processing. Although auditory motion responses are found within visual cortical area hMT+ in early blind individuals, it is not clear how these responses help early blind subjects to perceptually segregate moving auditory objects in complex auditory environments. We will examine whether hMT+ is tuned for frequency as well as direction of motion and how hMT+ neural responses might result in enhanced behavioral performance on auditory motion tasks.

Learning Complex Cognitive Skills: Bridging Neuroscience and Education through Individual Differences Research

Project Duration: 06/01/2017 - 05/31/2020
Sponsor: Office of Naval Research
Dept. Investigator(s): Chantel Prat
Abstract: Click to expand...
Vast individual differences exist in the ability to acquire new information and to master complex skill sets. Such differences must be rooted in the varying information-processing capacities of individual brains. Thus, leveraging the field of cognitive neuroscience to understand the nature of individual differences in learning allows one to move beyond characterizing ability at the behavioral level toward a more complete understanding of why an individual performs at the level he or she does. Such an understanding is critical for informing education and remediation attempts. Importantly, the current availability of affordable, consumer-grade neuroimaging equipment allows for the possibility of augmenting behavioral screening, placement, and assessment tools with the addition of relatively inexpensive measures of neural functioning. Thus, the current proposal aims to extend our previously funded line of research investigating the neural basis of individual differences in second language (L2) learning abilities, with the goal of bridging basic neuroscientific research with applications for screening and training military personnel.

Moving Beyond Changing Mindsets: Creating a Culture of Growth in Schools Phase 2

Project Duration: 06/01/2017 - 10/31/2019
Sponsor: Raikes Foundation
Dept. Investigator(s): Stephanie Fryberg
Abstract: Click to expand...
In the proposed research, we will build on our pilot study to examine a) whether training teachers to implement CIGM practices more effectively reduces racial and income achievement gaps compared to standard GM training practices and b) whether the order in which teachers learn about CI and GM affects the efficacy of the CIGM curriculum. We expect all of our curricula to narrow achievement gaps. However, we expect that the CIGM curriculum will reduce achievement gaps to a greater extent than GM curricula because the CIGM curriculum not only helps teachers to create GM cultures within their classrooms but also gives teachers aframework for understanding and validating cultural differences within the classroom. Such changes in classroom culture should create a context in which disadvantaged students feel greater belonging, are more motivated to achieve in school, are more willing to seek academic challenges, and have better academic performance.

Closed loop analysis of hippocampus-prefrontal cortex during flexible navigation

Project Duration: 05/15/2017 - 01/31/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Sheri Mizumori
Abstract: Click to expand...
While the existence of multiple memory systems in the brain is generally accepted, it is not known how these different systems interact to result in continuously adaptive memory-guided behaviors and decisions. Recent results clearly show that particular combinations of memory-related brain systems show synchronized neural activity (at the population level, for example at the theta frequency) in a task-dependent way. However the informational and behavioral significance of such co-modulation of neural activity in not known perhaps in part because such measures are not temporally or informationally refined enough to reveal the significance of this interaction. This proposal aims to develop a novel paradigm for determining whether a specific type of information in one brain area can provide a signal for a connected memory structure to engage in its well-known memory-related function. Specifically, we will test the causal relationship between neural signatures of planned behaviors in hippocampus and the regulation of flexible behaviors by the medial prefrontal cortex. Also, we will assess the subsequent impact of this neural directive on future behavioral and cognitive flexibility, as well as on future hippocampal place field integrity. These goals will be accomplished by developing a closed loop circuit between hippocampal place field activity and the prefrontal cortex: we will look on-line for a particular type of sequential activation of hippocampal place cells prior to behavioral choices made by the rat, a sequence that predicts the future path of a rat once the trial starts. This type of sequential activation is referred to as a forward sweep of place cell activity. Detection of a forward sweep will automatically and rapidly trigger the optogenetic excitation or inhibition of the prefrontal cortex, and this will also occur prior to the start of a trial. The impact of this pairing of forward sweeps with prefrontal cortical activation (or inactivation) will be measured behaviorally and neurophysiologically by quantifying behavioral flexibility and the changes in the properties of the hippocampal place fields during actual trial runs. It is postulated that prefrontal cortical normally stabilizes place fields which in turn should enable rats to more quickly adapt to changing task conditions. The successful development of this closed loop paradigm can serve as an innovative and new model for studying the functional interactions between other memory and behavioral systems of the brain, which in turn can have tremendous clinical and therapeutic benefits. It may be possible to interfere with (in cases of unwanted specific associations) or facilitate (in cases of deficient desired associations) specific types of learning or learned associations that characterize a number of mental disorders. MPI: David Gire

Closed loop analysis of hippocampus-prefrontal cortex during flexible navigation

Project Duration: 05/15/2017 - 01/31/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): David Gire
Abstract: Click to expand...
While the existence of multiple memory systems in the brain is generally accepted, it is not known how these different systems interact to result in continuously adaptive memory-guided behaviors and decisions. Recent results clearly show that particular combinations of memory-related brain systems show synchronized neural activity (at the population level, for example at the theta frequency) in a task-dependent way. However the informational and behavioral significance of such co-modulation of neural activity in not known perhaps in part because such measures are not temporally or informationally refined enough to reveal the significance of this interaction. This proposal aims to develop a novel paradigm for determining whether a specific type of information in one brain area can provide a signal for a connected memory structure to engage in its well-known memory-related function. Specifically, we will test the causal relationship between neural signatures of planned behaviors in hippocampus and the regulation of flexible behaviors by the medial prefrontal cortex. Also, we will assess the subsequent impact of this neural directive on future behavioral and cognitive flexibility, as well as on future hippocampal place field integrity. These goals will be accomplished by developing a closed loop circuit between hippocampal place field activity and the prefrontal cortex: we will look on-line for a particular type of sequential activation of hippocampal place cells prior to behavioral choices made by the rat, a sequence that predicts the future path of a rat once the trial starts. This type of sequential activation is referred to as a forward sweep of place cell activity. Detection of a forward sweep will automatically and rapidly trigger the optogenetic excitation or inhibition of the prefrontal cortex, and this will also occur prior to the start of a trial. The impact of this pairing of forward sweeps with prefrontal cortical activation (or inactivation) will be measured behaviorally and neurophysiologically by quantifying behavioral flexibility and the changes in the properties of the hippocampal place fields during actual trial runs. It is postulated that prefrontal cortical normally stabilizes place fields which in turn should enable rats to more quickly adapt to changing task conditions. The successful development of this closed loop paradigm can serve as an innovative and new model for studying the functional interactions between other memory and behavioral systems of the brain, which in turn can have tremendous clinical and therapeutic benefits. It may be possible to interfere with (in cases of unwanted specific associations) or facilitate (in cases of deficient desired associations) specific types of learning or learned associations that characterize a number of mental disorders. Contact PI: Sheri Mizumori

A Lay-Led Intervention for War and Refugee Related Trauma

Project Duration: 04/07/2017 - 03/31/2020
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Lori Zoellner
Abstract: Click to expand...
Rates of PTSD, a chronic and debilitating mental disorder, are considerably higher in war-torn regions like Somalia, known for sexual violence and other human rights violations (e.g., 50.1%; Johnson et al., 2010). In the aftermath of substantial war- and refugee-related trauma, there is a clear need for effectiveness research addressing the significant, under-addressed mental health needs of Somalis and the broader Muslim community. While efficacious treatments exist for PTSD and related difficulties, such treatments typically require extensive training of providers prior to treatment delivery. Furthermore, there are significant barriers to dissemination of such treatments, particularly to the Somali community, due to Islamic beliefs that run contradictory to mental health interventions, language differences, and limited access to care (e.g., Bentley et al., 2011; Aloud & Rathur, 2009). For a population that is almost exclusively Muslim, a treatment that incorporates Islamic principles is essential. No existing trauma-focused treatments have an Islamic focus, despite the fact that almost a quarter of the world’s population practices this religion. We have developed a brief, group-based, lay-led intervention, Islamic Trauma Healing, which specifically targets healing the mental wounds of trauma within mosques. The six-session intervention combines empirically-supported exposure-based and cognitive restructuring techniques with Islamic principles central to spiritual, social, family, and work life. Core intervention components include cognitive restructuring through Prophet stories, and exposure to trauma memories through talking to Allah. Tea, incense, and supplications are included as part of each group session to promote a sense of community and spirituality. We will examine the intervention in a small RCT and to examine intervention mechanisms, specifically the effects of shifts in negative cognitions about self, world, and others and changes in connectedness with others and Allah. We also will demonstrate initial feasibility to implementing the program outside of the U.S. to an Islamic country by conducting a small pre- to post-study design. Taken together, this work will serve as the foundation for a larger scale RCT both within the U.S. Islamic refugee community and in the larger Islamic community outside of the U.S. The Islamic Trauma Healing program has the potential to provide a low-cost, self-sustaining model of faith-based intervention that can address the psychological wounds of trauma.

BRAINS: Broadening the Representation of Academic Investigators in NeuroSciences - A national program to increase the advancement of neuroscience researchers from diverse backgrounds

Project Duration: 12/01/2016 - 11/30/2021
Sponsor: National Institute of Neurological Disorders and Stroke
Dept. Investigator(s): Sheri Mizumori
Abstract: Click to expand...
Retention of highly skilled scientists from diverse and underrepresented groups is critical for creating the diverse leadership necessary for innovation in neuroscience. Unfortunately, individuals from underrepresented groups often have higher turnover rates due to a greater sense of isolation and inequitable access to networks, mentors, and key resources that affect career success. Neuroscience postdoctoral researchers and assistant professors from diverse and underrepresented backgrounds (including racial and ethnic minorities and people with disabilities) are not immune to these issues. BRAINS: Broadening the Representation of Academic Investigators in NeuroScience adopts novel approaches to diversify neuroscience such that career advancement and retention of post-Ph.D., early-career neuroscientists from underrepresented groups (URGs: racial and ethnic minorities and persons with disabilities) are increased. BRAINS explicitly seeks to plug the neuroscience early career leaky pipeline by offering a novel professional development program that addresses factors known to impact persistence and career decisions of individuals from URGs in science. Such factors include one’s sense of belonging and self-efficacy, the belief in one’s ability to perform particular behaviors to produce a specific outcome. BRAINS intentionally targets talented neuroscientists considered at risk for leaving science and academia due to lack of professional support and career self-efficacy. BRAINS has already significantly impacted the career self-efficacy, career satisfaction, and sense of belonging of 56 participants. BRAINS will next enhance the breadth and depth of its impact by tripling the number of neuroscientists participating in the program, and by introducing formal cross-cohort activities that deepen the program’s influence on participants’ career advancement. Specifically, BRAINS’ increased impact on the leaky pipeline will occur by 1. Expanding the longitudinal evaluation of all prior BRAINS participants and non-selected applicants, and growing the program by adding two new cohorts of BRAINS Fellows. 2. Foster additional synergistic networks, career skills, and the leadership potential of BRAINS Fellows through new cross-cohort activities. 3. Broadening BRAINS’ reach amongst early-career neuroscientists from URGs by introducing a BRAINS Affiliates Program.

Improving Public Response to Weather Warnings

Project Duration: 06/15/2016 - 05/31/2019
Sponsor: National Science Foundation
Dept. Investigator(s): Susan Joslyn
Abstract: Click to expand...
Despite recent improvements in lead-time and weather forecast accuracy, weather-related injury and death remain a serious problem. There is growing consensus that public response to warning forecasts, or lack thereof, is a significant contributing factor and may arise in part from distrust in the warnings themselves. This project is designed to explore three psychological issues associated with distrust that may be related to warning forecast communication. 1)Forecasts for high-impact weather events are first made days in advance to allow residents time to prepare. Subsequent forecasts for the same event may differ giving rise to the impression of inconsistency that may engender distrust. Indeed this is the assumption of forecasters who are reluctant to change forecasts even when better information becomes available, preferring to sacrifice accuracy for consistency. However, at present there is no behavioral research to support this assumption. 2) Distrust may also arise from the fact that severe weather events are usually presented as certain, because forecasters worry that admitting uncertainty will prevent residents from taking them seriously. However, evidence suggests that residents already understand that there is often considerable uncertainty, especially early on. Thus, overstated forecasts may seem implausible as well as deny residents adequate information to make decisions tailored to their own risk tolerance. 3) Importantly, distrust in warning forecasts may lead to delaying precautionary action in order to gather more information. In some cases residents may run out of time, known as delay beyond optimal stopping, a problem that may be exacerbated by time pressure.

Jacobs Foundation: Early Career Research Fellowship

Project Duration: 01/01/2016 - 12/31/2018
Sponsor: Jacobs Foundation
Dept. Investigator(s): Katie McLaughlin
Abstract: Click to expand...
My research will focus on increasing knowledge of how and why early adversity influences risk for mental health and academic problems in children and adolescents. First, I will investigate how exposure to violence influences emotional development and brain networks that support emotional processing in children. Specifically, I will examine how violence exposure alters three aspects of emotional processing: 1) emotional learning (i.e., mechanisms involved in learning about threats and rewards in the environment); 2) emotional reactivity (i.e., the intensity of emotional reactions); and 3) emotion regulation (i.e., the ability to effectively modulate the intensity and duration of emotional responses). I will determine whether disruptions in these processes following violence exposure confer risk for anxiety, depression, and aggression. Second, I will examine how early environmental deprivation influences cognitive development and brain networks that support memory, attention, and self-control. I will investigate deprivation associated with poverty in the U.S. in one study and deprivation related to prolonged institutional rearing in Eastern Europe in a separate study. I will evaluate whether deprivation-related deficits in memory, attention, and self-control increase risk for academic failure, aggression, and risky behavior. Third, I will identify factors that protect children from developing mental health problems after exposure to early adversity using cross-national population-based data from over 30 countries worldwide. My goal is to contribute to greater understanding of the role of adverse environmental experiences in shaping children’s development, so as to inform the creation of interventions, practices, and policies to promote adaptive development in society’s most vulnerable members.

IMHRO Rising Star Award: Neural Mechanisms of Stress Vulnerability Underlying Anxiety and Depression in Youth

Project Duration: 12/15/2015 - 12/31/2018
Sponsor: International Mental Health Research Organization
Dept. Investigator(s): Katie McLaughlin
Abstract: Click to expand...
Environmental experience plays a central role in the etiology of most mental disorders. Extensive research documents powerful and robust associations between exposure to stressful life events (SLEs) and the onset of virtually all common forms of psychopathology, particularly anxiety and depression. Yet the mechanisms underlying this risk remain poorly understood. In particular, research examining the mechanisms by which SLEs influence neural processes that confer risk for anxiety and depression still lacks the precision required to generate strong translational outcomes. The proposed project will employ a new methodological approach that will, for the first time, allow examination of dynamic changes in emotion, behavior, physiology, as well as neural networks underlying emotional processing following SLEs, at a sufficiently fine grained level of temporal specificity to address currently unanswered, but fundamental, questions about the mechanisms underlying the link between SLEs and anxiety and depression. This information is necessary to identify novel targets for interventions to prevent the onset of anxiety and depression in youth.

Deprivation and Threat: Dimensions of Early Experience and Neural Development

Project Duration: 12/10/2015 - 11/30/2020
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Katie McLaughlin
Abstract: Click to expand...
The proposed research examines the impact of child trauma and deprivation on the development of neural networks involved in emotion regulation and cognitive control in a unique, well characterized NIH-funded longitudinal cohort of children where exposure to environmental adversity has been precisely quantified. We will test a conceptual model based on extensive preliminary data suggesting that different types of environmental experience have distinct effects on neural development by examining the influence of trauma and deprivation on neural structure, including cortical thickness and white matter microstructure, and neural function in Negative Valence Systems (function and connectivity in amygdala-ventromedial PFC network during fear conditioning and extinction) and Cognitive Control Systems (function and connectivity in frontoparietal networks during cognitive control tasks). Elucidating these mechanisms will not only build knowledge of how adverse environments alter neural development in ways that might increase risk for psychopathology, but will also suggest possible targets for preventive interventions aimed at reducing psychopathology risk in children exposed to environmental adversity.

Collaborative Research: Mechanisms of Sound Source Localization Underlying an Ancestral Mode of Vertebrate Hearing

Project Duration: 08/15/2015 - 07/31/2019
Sponsor: National Science Foundation
Dept. Investigator(s): Joseph Sisneros
Abstract: Click to expand...
The proposed research investigates the mechanisms of sound source localization underlying an ancestral mode of hearing in fishes. Evidence suggests that the capacity for sound source localization is common to mammals, birds reptiles, and amphibians, but surprisingly it is not known whether fishes locate sound sources in the same manner or what computational strategies fish use for successful source localization. Sound source localization by fishes continues to be an important topic in animal behavior and in the hearing sciences but the specific mechanisms that enable sound source localization by fishes remain a mystery. In the proposed experiments, the plainfin midshipman fish (Porichthys notatus) will be used as a general model to investigate the mechanisms that are common and essential for all vertebrates to mediate sound source localization. A strength of the midshipman fish as a model for sound source localization is that gravid females exhibit a very robust phonotactic response to a relatively simple acoustic signal (the male?s mate call). The investigation will take an integrated behavioral, anatomical, and brain activational approach to determine the extent that the fish inner ear end organs (saccule, lagena, and utricle) and lateral line system are used in sound source localization by fishes. The following hypotheses will be tested: 1) all three endorgans (saccule, lagena and utricle) are required for source localization while the use of lateral line is not required for sound localization, and 2) auditory afferents from the three putative auditory endorgans (saccule, lagena and utricle) have convergent input to the same auditory processing regions (and potentially the same principal cells) in the auditory hindbrain and midbrain forming maps that contain directional and frequency information from each end organ. To test the first hypothesis, a series of behavioral sound playback experiments will be performed to characterize the phonotaxic responses of female fish that have undergone the systematic removal of specific organs (saccule, lagena, utricle, and lateral line organs) in order to determine the role of each organ in sound-source localization. To test the second hypothesis, the central projections of endorgans by bulk labeling each endorgan separately with neurobiotin or simultaneously with different fluorescent-labeled dextran amine tracers will be performed to delineate the auditory pathways for each organ. Brain activation patterns specific to each endorgan of the inner ear will be characterized by using the expression of the immediate early gene product c-Fos in response to controlled auditory directional stimuli after systematically removing auditory input from two of the three end organs (saccule, lagena and utricle). Thus, the input from one end organ will remain intact during each recording session while the others will be ablated or removed.

Effectiveness of PTSD treatment for suicidal and multi-diagnostic clients

Project Duration: 04/01/2015 - 03/31/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Melanie Harned
Abstract: Click to expand...
The public health impact of posttraumatic stress disorder (PTSD) is enormous. PTSD greatly increases the risk of suicidal ideation and attempts as well as the likelihood of developing multiple, often severe comorbid disorders. Although several evidence-based treatments for PTSD have been found to be effective in community settings and are increasingly available to consumers, only a select group of clients with PTSD are offered these treatments. In particular, suicidal and severely comorbid individuals with PTSD who are likely to incur among the highest individual and societal costs are the least likely to have access to effective PTSD treatment. The Dialectical Behavior Therapy Prolonged Exposure (DBT PE) protocol, which is designed to be integrated into standard Dialectical Behavior Therapy (DBT) to treat PTSD among suicidal, severe, and multi-diagnostic clients, has shown evidence of efficacy when implemented in research settings. In particular, the integrated DBT+DBT PE treatment significantly improves PTSD while simultaneously reducing suicidal and self-injurious behavior, depression, anxiety, dissociation, guilt, shame, and social and global impairment. The present pilot project aims to evaluate the feasibility, acceptability, safety, and effectiveness of this intervention when implemented in community agencies, as well as develop and test the methods needed to successfully transfer the intervention into routine clinical practice. The project will be conducted in collaboration with Community Behavioral Health (CBH), a large, nonprofit managed care organization that manages behavioral health services for Philadelphia County’s more than 400,000 Medicaid recipients. During an initial strategic planning phase, researchers and key stakeholders in the CBH system will collaboratively assess agency, provider, and client needs and work to identify and address potential barriers to implementation. This feedback will then be used to tailor the intervention, training materials, and research procedures to the needs of the target system. Finally, these training and implementation procedures will be evaluated in a pilot feasibility study conducted in four CBH agencies and outcomes will be benchmarked to those obtained in prior studies of DBT+DBT PE conducted in research settings. Organizational-, provider-, and client-level predictors of training outcomes, as well as affective mechanisms of treatment outcome, will also be evaluated. Information gathered during the pilot feasibility study will be used to inform the design and conduct of a subsequent full-scale effectiveness trial. This research has the potential to significantly impact public health by increasing access to effective PTSD treatment for some of the most high-risk and severe consumers of mental health services.

Inhibitory dysfunction in autism

Project Duration: 03/15/2015 - 02/29/2020
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Scott Murray
Abstract: Click to expand...
Autism spectrum disorder (ASD) is a complex disorder of brain development characterized by difficulties in social interaction, communication, and repetitive behaviors and can be accompanied by intellectual disability and disruptions of sensory processing. One recent and potentially unifying neurobiological explanation posits that ASD is caused by disruptions in the excitatory/inhibitory (E/I) balance within the brain. Consistent with the E/I explanation, recent genetic and neuroscience research in animal models suggest that inhibitory neurotransmitter gamma-aminobutyric acid (GABA) signaling may be significantly disrupted in ASD. However, the role of GABA in ASD remains largely untested in humans. We propose to test the hypothesis that changes in cortical levels of GABA give rise to over- and under- responsiveness of neural circuits leading to key sensory and motor symptoms of ASD. Critically, GABA signaling is highly amenable to pharmacological treatment. Thus, understanding how GABA signaling is altered in ASD will open up new pharmacological treatment possibilities. We will use state-of-the-art magnetic resonance spectroscopy (MRS) techniques to measure levels of GABA in adults with an ASD and neurotypical control subjects in visual, motor, and auditory cortices. We will use fMRI measures of evoked sensory and motor responses to characterize neural responsiveness in these regions along with clinical measures of sensory-sensitivity and motor-related symptoms. Finally, we will use fMRI to measure the strength of a well-established inhibitory neural circuit in the visual system: surround suppression. By elucidating the functioning of inhibitory signaling our results will significantly advance our understanding of the neurobiological causes of ASD.

Neural circuit mechanisms of odor localization in mice

Project Duration: 01/01/2015 - 05/31/2019
Sponsor: National Institute on Deafness and Other Communication Disorders
Dept. Investigator(s): David Gire
Abstract: Click to expand...
One of the primary functions of the brain is to integrate and process sensory input into a form that can guide the behavior of an animal within its environment. Combining sensory information in such a way that the source of a given stimulus can be located is a key aspect of this function. I propose to study the integration and processing of bilateral sensory information as it applies to odor localization in mice. Mice are macrosmotic creatures, and employ their sense of smell to detect conspecifics, food, and predators at a distance. Odor source localization is thus a vital ability for mice. Despite its ethological importance, the neural mechanisms that support odor localization are largely unknown. Research in this proposal will focus upon a cortical structure, the anterior olfactory nucleus (AON), which has been hypothesized to play a central role in odor localization by processing bilateral olfactory information and transmitting this information across the two hemispheres of the brain. Work performed during the mentored phase of this award has shown that mice use airborne odor plumes to locate the source of odors in the environment. These results suggest a functional role for neural processing of the spatiotemporal cues present in airborne plumes. The mechanisms that support this processing will be examined in awake, behaving mice during the independent phase of this project. This will be accomplished by monitoring the odor responses of AON neurons that send feedback axons to the olfactory bulbs and controlling their activity during odor localization tasks. Selective monitoring of AON feedback projections in awake mice will be accomplished through cutting edge multi-photon imaging techniques, and the role of these neurons in odor localization will be directly tested using optogenetic strategies. Work during the independent phase will also elucidate the mechanisms through which bilateral input is processed in the AON, focusing upon the role of inhibitory neurons. Taken together, the results of these studies will define how feedback from the cortex and local cortical inhibitory processing work together to combine bilateral sensory information in such a way that the source of an odor can be located. By defining the mechanisms used to integrate sensory information in support of an ethologically relevant function, this work will provide a firm basis for the general understanding of information processing within neural circuits as it occurs during natural sensory-driven behavior. Defining such fundamental mechanisms of neural circuit processing will be instrumental for the understanding and treatment of disorders that alter sensory integration, such as schizophrenia and autism spectrum disorders.

Child Trauma and the Development of Neural Systems Underlying Emotion Regulation

Project Duration: 09/17/2014 - 08/31/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Katie McLaughlin
Abstract: Click to expand...
Childhood trauma exposure is strongly associated with psychopathology onset in children, adolescents, and adults, accounting for a substantial proportion of mental disorders in the population. However, the neurodevelopmental mechanisms that explain the association between child trauma (CT) and psychopathology remain poorly characterized. In particular, research examining how CT influences brain development remains in its infancy. Yet understanding the neurodevelopmental processes that are disrupted as a result of CT exposure will provide critical information about the pathways linking adverse environments to psychopathology. To that end, the proposed project examines the impact of CT on the development of neural networks involved in emotion regulation, a plausible neurobiological pathway linking CT to psychopathology. The proposed research addresses Objective 1 of the NIMH Strategic Plan by examining how specific types of early environmental experience—child physical or sexual abuse and domestic violence—alter neural structure and function in ways that might increase risk for psychopathology. We hypothesize that CT exposure disrupts the development of the prefrontal cortex (PFC) and amygdala, resulting in atypical patterns of neural function and reduced structural and functional connectivity between these regions. We aim to build knowledge of how environmental experience shapes development in Negative Valence Systems by applying a neurobiological model distinguishing between emotional reactivity and both implicit and explicit emotion regulation to investigate this hypothesis. Specifically, we propose that a) CT exposure leads to heightened amygdala reactivity and that reactivity is positively associated with trauma severity and chronicity, and b) chronicity of exposure to CT is additionally associated with deficits in emotion regulation, involving poor PFC modulation of amygdala reactivity resulting from low structural and functional connectivity between these regions. The conceptual model will be tested by acquiring structural and functional MRI data in a sample of 8-16 year olds; half with exposure to child maltreatment or domestic violence and half without exposure to CT or interpersonal violence. The sample will be recruited to ensure variation in CT chronicity and severity and to allow us to examine associations of CT with neural structure and function in children with and without pre-existing internalizing psychopathology. The proposed study builds on existing research examining the influence of early deprivation on brain development by examining how experiences of threat influence neural structure and function in children. Study findings will provide critical information regarding the specific aspects of emotional reactivity and regulation that are disrupted following CT exposure. Elucidating these mechanisms will not only build knowledge of how adverse environments alter neural development in ways that might increase risk for psychopathology, but will also suggest possible targets for preventive interventions aimed at reducing psychopathology risk in children exposed to trauma.

The Effects of Attention in Human Visual Cortex

Project Duration: 09/01/2014 - 08/31/2019
Sponsor: National Eye Institute
Dept. Investigator(s): Geoffrey Boynton
Abstract: Click to expand...
Humans are excellent at selecting the relevant part of a cluttered visual scene or the relevant conversation at a noisy party. In contrast, humans are often not so successful at dividing attention over multiple stimuli. One cannot read two books at once and is it is not wise to talk on a phone and drive at the same time. Much has been learned about the effects of attention on physiological responses in the human and monkey visual cortex. However nearly all of this work has addressed selective attention, which is when attention is directed to one source of information over another. In general, studies of selective attention have shown that activity in many areas of the brain is greater for a stimulus that is relevant to the current task compared to a stimulus that is not relevant. Surprisingly, very little is known about the effects of divided attention - paying attention to more than one thing on a time - on neuronal responses. This lack of a physiological literature is particularly surprising given the long history of research on the effects of divided attention on behavioral performance. Interestingly. these behavioral studies show a wide range of effects: for discrimination of simple features there can little cost to attended to multiple stimuli at a time, whereas for higher–level perceptual tasks such as reading words it may impossible to attend to more than one stimulus at a time. Here we propose a series of behavioral and imaging studies to examine the physiological basis of divided attention. We will (1) examine what factors in a task result in a cost when dividing attention. In particular we will examine whether it is the complexity of the stimulus or the task that is the critical factor for both a simple grating task (Specific Aim 1) and complex lexical task (Specific Aim 2). Second we will determine the cause of reduced neural responses and impaired behavioral performance when attentional capacity is limited. In particular, we will determine whether attentional limitations are due to attenuation of attentional gain, a shift to serial processing or suppressive interactions between stimuli. Finally we will examine the spatial profile of attentional modulations during divided attention: whether it is spread broadly across space and/or features or allocated discretely. This gap in the literature is of clinical importance. Individuals with autism spectrum disorder and ADHD show differential divided attention effects: a deeper understanding of the mechanism underlying divided attention is likely to prove critical in linking these behavioral differences to underlying neurophysiological mechanisms.

Double Isolation: Social Pressure and Gender Disparities in Computer Science

Project Duration: 09/01/2014 - 02/28/2019
Sponsor: National Science Foundation
Dept. Investigator(s): Sapna Cheryan
Abstract: Click to expand...
This is a middle-stage project focusing on broadening participation in computer science. The current proposal builds on my previously funded work (NSF CAREER Award; DRL-0845110) by proposing a novel mechanism for why women are less interested in computer science than their male peers. We investigate whether women perceive social pressure from their peers to conceal an interest in the field. We further investigate how to alleviate this social pressure and increase women’s participation in computer science. Taken together with my previous findings, this proposal would show that women considering computer science face an unfortunate “double isolation” in that they anticipate isolation not only from those within the field of computer science but also from their peers outside it. The current work develops and tests a theoretical model that identifies the sources of social pressure on women and the consequences of this social pressure on women’s interest and performance in computer science. To test our theory, we will conduct two surveys in Year 1 and seven behavioral experiments in Years 1 to 3. In Year 1, we examine whether women perceive more social pressure than men in computer science but not in other fields (e.g., English), and the effects of perceived social pressure on interest and performance in computer science. In Year 2, we examine how to reduce social pressure by using private learning mechanisms and broadening stereotypes. In Year 3, we partner with the Computer Science Teachers Association to conduct a large-scale field experiment across multiple high schools that tests whether exposure to female computer science role models who are portrayed with their friends reduces perceived social pressure on women and increases their interest in computer science.

A Screen-Refer-Treat (SRT) Model to Promote Earlier Access to ASD Intervention

Project Duration: 08/25/2014 - 06/30/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Wendy Stone
Abstract: Click to expand...
Although caregivers often become concerned about their child by 17-19 months of age, children do not typically receive a diagnosis of autism spectrum disorder (ASD) until they are 4½ years old, or older for Hispanic families. It is now well documented that early participation in ASD-specialized intervention can lead to significant improvements in skills and behavior for toddlers with ASD. However, despite the availability of publicly funded Part C early intervention (EI) services, long waits for a formal ASD diagnosis can prevent toddlers from receiving appropriately specialized intervention during the critical birth-to-three years. In addition, caregivers concerned about ASD experience high levels of uncertainty and stress during this waiting period. This project will implement and evaluate an innovative healthcare service delivery model designed to promote earlier access to specialized intervention for toddlers with ASD. The Screen-Refer-Treat (SRT) model provides a coordinated and cost-effective approach to early identification and intervention by involving both medical and EI providers, and represents a practical and sustainable strategy for bridging the gap between ASD concerns and ASD intervention. The SRT model, which builds on the availability of validated ASD screening tools and low-cost behaviorally-based ASD interventions, will be implemented in four diverse communities across Washington State to evaluate changes in service delivery practices for toddlers with Hispanic as well as Non-Hispanic backgrounds. The SRT model comprises three components: (1) universal ASD screening at 16-20 months and prompt referral to EI programs by primary care physicians (PCPs); (2) expedited ASD assessments within EI programs; and (3) use of an inexpensive, evidence-based ASD-specialized intervention by EI providers. An electronic version of the Modified Checklist for Autism (M-CHAT) with automated scoring that incorporates relevant follow-up questions will be provided to PCP practices, and distance coaching via telemedicine will be available to EI providers to support their ASD assessment and intervention activities. A stepped wedge cluster RCT design will be used to evaluate implementation and outcomes of the SRT model. Data on screening, referral, assessment, and intervention practices will be collected from 40 PCPs and 80 EI providers across the state prior to and following SRT implementation to identify practice changes. In addition, separate samples of caregivers of toddlers with ASD concerns (n=245) will be recruited from communities before and after SRT implementation and followed prospectively to measure differences and changes over time in caregiver well-being, parenting efficacy, satisfaction with healthcare systems, and toddler’s social-communicative behaviors. We predict that implementation of the SRT model will be associated with higher rates of ASD screening by PCPs, earlier referral to EI programs, earlier initiation of ASD-specialized intervention, reduced time between ASD concerns and diagnosis, and improved caregiver and child outcomes.

Advancing Human Brain to Brain Communication Capabilities

Project Duration: 07/01/2014 - 07/31/2019
Sponsor: W.M. KECK Foundation
Dept. Investigator(s): Andrea Stocco
Abstract: Click to expand...
In August of 2013, the researchers involved in this proposal were the first in the world to successfully develop a brain-to-brain interface (BBI) in humans. This demonstration involved the transfer of the intention to move the right hand from a “Sender” brain to a “Receiver” brain located across campus (see http://goo.gl/ceqkG9). The goal of the current proposal is to advance the methods and science that made this first BBI possible, with the goal of systematically increasing the complexity of thoughts, intentions, and mental states that can reliably be transferred from one human brain to another. To do so, advances in computer science and neuroscience must be made to enhance the “neural bridge” connecting the brains to one another. We have organized our efforts in building this bridge into four aims: (1) To reverse-engineer the neural code for representing complex thoughts, (2) To improve thought decoding capabilities, (3) To advance brain stimulation protocols, and (4) To characterize the unique and invariant features of information representation necessary for translating a meaningful code from one brain to another. Advancing BBI capabilities will have vast implications for transmitting nonverbal information from one mind to another, with possible revolutionary applications in neuroscience, education, and health care.

Developmental changes and individual differences in sensitivity to fairness in infancy

Project Duration: 08/01/2013 - 05/31/2019
Sponsor: National Institute of Child Health & Human Development
Dept. Investigator(s): Jessica Sommerville
Abstract: Click to expand...
The ability to recognize social and moral norms, and use them to guide behavior, is fundamental to social cohesion and harmony. One prominent norm that guides adults’ and children’s actions and evaluations of events is the norm of a fair distribution of goods based on the “principle of equality”: that, all other things considered, goods should be divided equally to recipients. The goal of the proposed experiments is to test a new developmental model regarding the development of fairness sensitivity within infancy, that stresses infants’ interactions with caregivers in the context of sharing games as the source of age-related changes and individual differences in infants’ acquisition of equality norms. The proposed research has 3 specific aims, 1) to characterize the development origins and trajectory of infants’ burgeoning acquisition of equality norms, 2) to investigate the causal role of sharing experience infants’ responses to inequality, 3) to investigate the nature of infants’ responses to inequality, and, more specifically, whether and when such responses become moral intuitions. We test 3 central hypotheses regarding infants’ developing sensitivity to fairness in the context of resource distribution tasks. The first hypothesis is that developmental changes occur between 6 and 9 months of age in infants’ ability to detect inequality, coincident with the onset of sharing experience. The second hypothesis is that individual differences in infants’ inequality responses arise from individual differences in parental dispositional empathy that influence the ways in which parents emphasize principles of equality and reciprocity in infant-caregiver interactions. The third hypothesis is that infants’ inequality responses incrementally, and over time, begin to encompass various affective and cognitive components of more mature moral judgments. Across 10 experiments 6 to 24-month-old infants take part in both implicit tasks (based on looking times and pupil dilation) and explicit tasks (based on infants’ overt social behavior) to investigate developmental changes and individual differences in responses to inequality. The proposed experiments are conceptually innovative because they 1) test a novel theoretical model with respect to infants’ burgeoning fairness concerns that stresses the role of both parental attitudes and everyday experience in early social cognition, 2) seek to establish criteria for investigating the origins of moral judgment in infancy, and 3) investigate the origins of individual differences in early social cognition. The proposed work is also methodologically innovative as it introduces 3 novel experimental tasks and a novel dependent measure (pupil dilation) to study infants’ acquisition of socio-moral norms; the introduction of these methods will have broad-ranging effects on the field or early perceptual and cognitive development by increasing the armory of tools and techniques available to developmental scientists. Finally, the proposed work may have import in the diagnosis and remediation of developmental disorders, such as autism, that are characterized by social deficits, including a recognition and understanding of social norms.

Fear and Natural Risky Decisions in Rats

Project Duration: 07/15/2013 - 03/31/2019
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Jeansok Kim
Abstract: Click to expand...
While fear plays a fundamental, protective role in our lives, irrational and uncontrollable fear responses are common features of various anxiety disorders that are detrimental to one’s quality of daily life. Most contemporary views on fear ascribe preeminent importance to learning, and decades of animal research using the Pavlovian fear conditioning paradigm have made tremendous progress in identifying the neural circuits and mechanisms responsible for the acquisition, maintenance and expression of conditioned fear memories, with a general focus on the amygdala. In contrast to learned fear, innate fear and its effects on risky decisions have largely been overlooked in preclinical and clinical fear research despite its evolutionarily-conserved role in survival. We have recently found that the amygdala regulates both innate fear responses and risky behavior in rats foraging in a seminaturalistic environment with a ‘predator-like’ robot that is programmed to surge toward the animal as it seeks food. By applying naturalistic ‘prey-predator’ interactions, the long-term goal of this research is to construct a general experimental and theoretical basis for understanding the functions of fear in ecologically-relevant situations that closely reflect the environments in which fear responses and risky decisions naturally occur. We will incorporate this in a systems-level model that can fill the gaps in knowledge, predict new results, and provide insights into the basic approach-avoid conflicts that are thought to underlie human psychopathologies. There are three specific aims of the project: (1) a BEHAVIORAL ANALYSIS will investigate the basic rules of the rat’s natural foraging decision in highly quantifiable ‘approach food-avoid predator’ situations; (2) a SYSTEMS-LEVEL ANALYSIS will reveal the specific roles that the amygdala, medial prefrontal cortex, and hippocampus play in mediating innate fear and risky foraging behavior; and (3) a SINGLE UNIT ANALYSIS will relate specific components of the animal’s behavior to a neural representation of dynamic, affective evaluation in real time. Information generated from this project would be of significance (1) from a basic scientific perspective, providing a more complete picture of fearful behavior in an ecologically-realistic environment; and (2) from an applied perspective, providing insights into developing (and screening the safety of) drug and cognitive-behavioral therapies for generalized anxiety, panic, phobia and posttraumatic stress disorders.