Active Research Grants

Research event at UW

A cultural growth-mindset approach to interest: Implications for gender gaps in computer science participation

Project Duration: 12/01/2019 - 11/30/2022
Sponsor: National Science Foundation
Dept. Investigator(s): Sapna Cheryan
Abstract: Click to expand...
This proposal builds on the PI's previously funded work (NSF CAREER Award: DRL-0845110; NSF REAL: DRL-1420351) showing that women are discouraged from computer science courses because stereotypes cause them to believe that computer science is not one of their academic interests. In the current proposal, we investigate whether a mindset that does not seem gendered on its surface - the cultural belief that academic interest is fixed - contributes to gender gaps in computer science participation. We further examine whether changing educational environments to foster a growth mindset about interest - a belief that academic interest is malleable - and pairing it with information about a welcoming local computer science culture reduces gender gaps in computer science. This research is extremely applicable to educational policies and practices. The research we propose suggests that women may be forsaking important learning opportunities before trying them because of a fixed mindset about academic interest in combination with perceptions of an unwelcoming culture in computer science. However, relatively simple changes to educational environments such as showcasing peers' stories and changing the structure of advising meetings can prevent many women from eliminating computer science as an option. Like classic growth mindset research, this research is well-suited to education and dissemination.

Disrupted stimulus offset responses in autism spectrum

Project Duration: 11/01/2019 - 10/31/2021
Sponsor: Simons Foundation Autism Research Initiative
Dept. Investigator(s): Scott Murray
Abstract: Click to expand...
This proposal seeks to investigate the hypothesis that there is a disruption to the stimulus neural offset response in autism spectrum disorder (ASD). This hypothesis is motivated by a striking observation we made in fMRI measurements to simple sensory stimuli in adults with ASD compared to neurotypical (NT) controls. Specifically, we observed an fMRI undershoot (the fMRI response goes negative before returning to baseline) in our NT population, as is typically observed. However, the fMRI undershoot was virtually absent in the ASD participants. Recent findings that have simultaneously measured EEG and fMRI responses have demonstrated that the fMRI undershoot: 1) reflects neural responses, 2) correlates with the magnitude of EEG stimulus offset responses, and 3) is tied to inhibitory processing. Thus, our fMRI observation of a lack of an undershoot in the ASD population suggests disrupted neural inhibition that is specifically tied to removal of input. To test this hypothesis, we propose to measure EEG/ERP stimulus offset responses, the fMRI undershoot, and psychophysical measures of visual sensitivity following stimulus removal in an adult population with ASD compared to matched neurotypical controls. Together these experiments seek to establish a novel measure of altered neural inhibitory processing in ASD.

Acceptability of Sustained-Release Antiretrovirals for Treatment in the US and sub-Saharan Africa

Project Duration: 09/17/2019 - 07/31/2024
Sponsor: National Institute of Health
Dept. Investigator(s): Jane Simoni
Abstract: Click to expand...
In 2017, UNAIDS estimated that 23% of diagnosed persons living with HIV (PLWH) were not accessing antiretroviral therapy (ART), and 18% of PLWH taking ART had unsuppressed viral loads. The development of sustained-release or long-acting injectable antiretroviral therapy (LAI ART) is an important technological advance that could increase ART uptake and adherence by providing new options to support viral load suppression. Research is urgently needed to understand factors that will drive end-user acceptability, so that developers can iteratively formulate more desirable products and funders can identify and prioritize the products most likely to have high uptake and sustained use. This proposal has the following aims: (1) To design and pilot test a discrete choice experiment (DCE) to identify product and delivery attributes related to LAI ART acceptability among patients in the United States (US), based on our prior work and key informant interviews; (2) To recruit 200 ART naïve-individuals and 500 ART-experienced individuals in Seattle and Atlanta for a DCE to estimate LAI ART product preferences and identify patient characteristics associated with acceptability among these two key potential end-user groups; and (3) To design and pilot test a similar DCE instrument for use in Kenya, then recruit 200 ART naïve-individuals and 500 ART-experienced individuals in Nairobi to learn about patient preferences in the region most impacted by the HIV epidemic. Innovations in the proposed research include a focus on novel LAI ART products in development, inclusion of two patient perspectives (i.e., those just starting treatment and those considering a switch), and exploration of how individual characteristics including prior ART adherence and treatment outcomes influence patient preferences. Our multidisciplinary team includes clinical researchers, behavioral scientists, and health economists with expertise in DCE design and modeling from the University of Washington (UW), RTI International, and Emory University in the US, and from Kenyatta National Hospital in Kenya. The proposed work will take place at two AIDS Clinical Trials Group clinical research sites in the US (i.e., the UW AIDS Clinical Trials Unit in Seattle and the Ponce de Leon Center in Atlanta), and at two HIV clinics within Kenyatta National Hospital in Nairobi, which has been a site for collaborative research with the UW’s Kenya Research and Training Program for over 25 years. Supported by preliminary studies conducted as part of an ongoing UM1 project to develop LAI ART (AI120176, Ho/Collier, NIAID Targeted Long-Acting Combination Antiretroviral Therapy), the proposed work will advance LAI ART product development efforts by providing key estimates of acceptability and patient preferences, enabling funders, product developers, and policy makers to optimize products for the greatest likelihood of uptake, adherence, and long-term viral suppression.

Testing a computational model of neural responses in autism

Project Duration: 08/01/2019 - 05/31/2024
Sponsor: National Institute of Mental Health
Dept. Investigator(s): Scott Murray
Abstract: Click to expand...
This proposal will test a novel, computationally-motivated hypothesis about neural dysfunction in autism spectrum disorder (ASD). ASD is a heterogeneous neurodevelopmental disorder of unknown etiology. However, a unifying theme of numerous proposals is that there is a pervasive disruption of neural excitatory/inhibitory (E/I) balance. A major limitation of the E/I hypothesis is that it describes a property of individual neurons; how that property scales up to neural circuits and how it relates to behavior – the level at which ASD is described – is not well specified. Neural computational models offer a way to bridge the divide between single-unit properties and behavior, and bring the necessary specificity to test possible changes in E/I in ASD. One well-established neural computation that directly relates to E/I is “divisive normalization”, a computational framework that characterizes neural responses as the ratio of net excitatory relative to net suppressive input. Here we aim to test the hypothesis that ASD involves disrupted divisive normalization using vision as a model system. We will test two possible mechanisms of weakened divisive normalization. The first is the traditionally posited disruption of local, within-area circuits that mediate suppressive drive. The second is a novel hypothesis based on recent empirical findings in our lab. We have shown enhanced suppressive feedback of responses from higher stages to lower stages of visual processing in individuals with ASD. We suggest this enhanced suppressive feedback reduces responses of neurons that would otherwise participate in divisive normalization. This hypothesis makes specific predictions about the conditions under which disrupted divisive normalization will be observed in ASD. We will test these predictions using a combination of functional MRI, ERP, and diffusion MRI.

Prototypes and Perceptions of Sexual Harassment

Project Duration: 08/01/2019 - 07/31/2022
Sponsor: National Science Foundation
Dept. Investigator(s): Cheryl Kaiser
Abstract: Click to expand...
Sexual harassment is widespread, and has deleterious effects on its targets, including disengagement and withdrawal from work and school, decreased performance, anxiety, depression, and physical symptoms that adversely affect health. Despite it prevalence, sexual harassment is notoriously under-reported by both its targets and others in society. This proposal describes four sets of experiments that draw upon theoretical perspectives on prototypes to explore how a narrow prototype of women (as White, straight, traditionally feminine) prevents the recognition of sexual harassment when it targets women who do not fit the prototype, such as those who are not traditionally feminine on characteristics and attributes and those who possess intersectional identities that overlap less fully with the prototype of women (e.g., Black women). The A-Series studies investigate whether sexual harassment targets are viewed as overlapping with the prototype of women, such as feminine, White, and straight. The B-series studies explore how the prototype of women hinders perceiving sexual harassment when it targets women who do not fit with the prototype. The C-Series studies extend this reasoning to self-perceptions and explore how women's own prototypicality shapes their perceptions of sexual harassment when they are the targets of this behavior. The D-Series studies experimentally broaden the representation of women who experience sexual harassment to test whether this increases perceptions of sexual harassment targeting nonprototypical women and alters the prototype of women so it is more inclusive. Perceptions of sexual harassment are critical; these perceptions serve as the catalyst to remedying sexual harassment and realizing the protections offered by federal civil rights laws. It is thus important to understand the barriers that prevent both targets and observers from perceiving sexual harassment. This research will be of interest to scholars and practitioners who address civil rights law, as well as to organizations seeking to address sexual harassment. #Metoo is likely to put pressure on organizations to get sexual harassment training right, and evidence concerning best practices will be important in the development of more effective approaches to sexual harassment. This can in turn improve workforce diversity and mitigate the deleterious effects of sexual harassment on its targets.

Assessing the Effectiveness of a Low-Cost, Evidence-Based Naturalistic Developmental Behavioral Intervention (NDBI) in IDEA Part C Early Intervention Settings

Project Duration: 07/15/2019 - 07/14/2023
Sponsor: US Department of Defense
Dept. Investigator(s): Wendy Stone
Abstract: Click to expand...
Young children with autism spectrum disorder (ASD) face a unique set of challenges in several key areas of development: their ability to interact socially with others, to communicate their needs and desires effectively, and to respond flexibly to events and changes in their environment. Research has indicated that these challenges are best addressed by providing ASD-specialized interventions, and by starting these interventions within the first 3 years of life. Several different interventions have led to improvements in social, communication, and behavioral functioning, and have accumulated enough research evidence to support their use with young children with ASD. In addition, some of these interventions have been found to reduce parents’ stress and to increase their feelings of competence as a parent, perhaps by improving their child’s social responsiveness. Most of these evidence-based interventions have been implemented successfully by clinicians or by parents, but have not yet been adapted for use community-based early intervention (EI) programs, where they may reach a broader segment of the population. The purpose of this project is to identify whether a specific ASD-focused intervention, Reciprocal Imitation Training (RIT), can be used by community-based EI providers to improve ASD symptoms in children and to improve stress levels in their parents. RIT is a short-term, focused intervention that teaches the spontaneous imitation of object use and gestures to children with ASD during ongoing play interactions. In addition to improving imitation skills, RIT has also led to improvements in children’s play, language, and social attention. This project will provide training in RIT to community providers working in publicly funded (IDEA Part C) EI programs serving children from birth to 3 years. These programs are available in every state, at no cost to families, and often serve as the first line of treatment for children with ASD. RIT is ideally suited for EI settings because it is inexpensive, play-based, easy to learn and implement, and can be taught to parents (as well as siblings). This project aligns with three goals listed in the FY18 ARP Clinical Trial Award Areas of Interest: (1) Behavioral, cognitive, and other non-pharmacological therapies; (2) Dissemination/implementation of clinically validated interventions; and (3) Healthcare provider-focused training or tools to improve healthcare delivery for individuals with ASD. We have learned from our preliminary studies and current work that most EI providers have children with ASD in their caseloads, yet they are not satisfied with the interventions they are using, and many do not feel comfortable identifying treatment goals, providing intervention to children, or coaching parents of children with ASD. We also know that they report enjoying the RIT training activities and indicate that the training leads to increased comfort and skills in working with the families they serve. The proposed study will help us identify the extent to which RIT impacts important family and child outcomes, as well as whether certain characteristics of children or families, or aspects in the way RIT is used by providers, may impact its effectiveness. This information will lead to a more refined approach to training EI providers in RIT as well as tailoring the intervention to better match the needs of different families. This project has the potential to enable more children with ASD to receive evidence-based, specialized intervention during the birth-to-three years, when it is likely to have the greatest impact. We expect that the receipt of early, ASD-specialized intervention will improve children’s social communication and ability to interact with their families as well as other children, and that these improvements will have positive effects over the long term. We also expect that caregivers who use RIT will experience increased confidence in their ability to parent their child, as well as decreased parenting stress, as their ability to engage and interact with their child improves. In addition, we believe that EI providers will feel more confident and capable in working with children with ASD and their parents. Importantly, if RIT is found to be effective for use by EI providers, we have the potential to disseminate this intervention within the existing infrastructure of the EI system. In this way, RIT could have a major impact on the treatment and course of ASD, as it would give toddlers and families an early start in receiving ASD-specialized treatment through the Part C EI system that is available to all families across the U.S.

Ecological Momentary Assessment of Negative Urgency’s Effects on Alcohol and Marijuana Misuse

Project Duration: 07/15/2019 - 04/30/2024
Sponsor: National Institute on Drug Abuse
Dept. Investigator(s): Kevin King
Abstract: Click to expand...
Negative urgency, a tendency to rash action in the face of negative emotions, is one of the strongest personality predictors of alcohol and marijuana misuse (heavy use, intoxication, and the experience of consequences). In the face of strong negative emotions, people high on negative urgency are theorized to engage in impulsive behavior that is hyper-focused on relieving negative affect despite the long-term consequences, negatively reinforcing impulsive behavior. However, no research has tested whether individuals high on urgency actually behave more impulsively in the face of negative emotions, what situations might enhance or buffer this effect, or what role affect-driven impulsivity plays in the development of alcohol and marijuana misuse during young adulthood. The goal of the current study is to (Aim 1) characterize the within-person process of negative urgency (Aim 2) identify between and within person moderators of that process, such as alcohol-promoting situations and emotion regulation, and (Aim 3) test the role of EMA-assessed urgency in the development of alcohol and marijuana misuse over two years of young adulthood. Using a large (n = 500) sample of young adults (age 18 – 22) who regularly use alcohol or marijuana recruited from the community, the proposed study will critically test this theory of urgency using an ecological momentary assessment design matched with longitudinal follow-ups, allowing us to characterize between individual differences in the within-person process of impulsive responses to negative emotions, and the situations and behaviors that may exacerbate or attenuate this link. Understanding the mechanisms by which personality may lead to substance misuse will provide novel targets of research as well as spur the development of more focused personality targeted interventions.

Testing a Common Model for Human and Human-Like Intelligence

Project Duration: 07/01/2019 - 06/30/2021
Sponsor: Air Force Office of Scientific Research (AFOSR)
Dept. Investigator(s): Andrea Stocco
Abstract: Click to expand...
Cognitive architectures are general computational modeling tools that lie at the intersection of cognitive, neuroscientific, and Artificial Intelligence research. In the cognitive neurosciences, they have been recently surged in interests as a way to frame and understand large-scale brain activity. In Artificial Intelligence, they have been proposed as the next step in machine intelligence. However, despite their importance, development of cognitive architectures has so far progressed in a cumulative but a-systematic and haphazard way. Inspirations for architectures are often left to the preferences of individual researchers, while empirical tests have been few and limited, and do not take advantage of contemporary neuroscientific tools that integrate both regional activity and network dynamics and rely on modern Bayesian assessment methods. This proposal aims to put the architectural approach on a solid ground by developing a methodology to systematically test theoretical architectures against large-scale human neurophysiological data, using measures of both regional fit and connectivity. The methodology includes procedures to describe architectures in a common language, translate such descriptions int dynamic models of brain activity, finally compare the architecture predictions against large datasets, and identify missing components and functionalities based on the examination of brain data. This methodology will then be applied to the Human Connectome Project dataset, the largest repository of high-quality fMRI data, including data from 1,200 healthy young adults. In this large-scale test, alternative interpretations of the brain architecture that have previously suggested and published will be compared against the Common Model of Cognition, a consensus architecture specification that has been developed by integrating the lessons learned from multiple previous computational architectures, and covers both human and human-like intelligent system. A strict comparison with human data would examine the feasibility of the CMC, and eventually suggest modification and further specification.

Two Axes of Subordination: Disaggregating Racial Groups to Understand the Contexts that Shape Discrimination

Project Duration: 07/01/2019 - 06/30/2022
Sponsor: National Science Foundation (NSF)
Dept. Investigator(s): Sapna Cheryan
Abstract: Click to expand...
Racial minority groups have been Othered in U.S. society, but not in uniform ways. This proposal draws on our model of racial stereotyping (Zou & Cheryan, 2017)—integrating a dimension of cultural foreignness along with the more commonly studied dimension of perceived inferiority—to suggest that different racial and ethnic groups face qualitatively different experiences of discrimination. Using a combination of large-scale audit studies and controlled laboratory experiments, we investigate 1) whether racial and ethnic minority groups face different forms of discrimination, 2) the implications of these different forms of discrimination for the likelihood of reporting it, and 3) the strategies that are required to ameliorate discrimination based on which racial and ethnic group is targeted. Systematically integrating two dimensions of perceived inferiority and cultural foreignness gives us insight into forms of discrimination faced by groups less frequently studied in social psychology, such as Latinos, Asian Americans, and Arab Americans. Knowledge about how perceived cultural foreignness and inferiority contribute to discrimination is important so that these forms of discrimination can be recognized, attended to, and eventually eliminated. For instance, knowledge of which groups are most susceptible and when could be used to inform policies and strategies that bring racial and ethnic minority groups together to fight against discrimination. This work would further demonstrate that laws, policies, and community and individual efforts to reduce racial discrimination may benefit from paying attention to discrimination based on perceived cultural foreignness because perceivers and targets may be particularly unaware or less likely to report these forms of discrimination when they occur. In recent decades, the U.S. has seen unprecedented growth in its Latino and Asian American populations (Colby & Ortman, 2014). The rising population of Arab Americans has also drawn much political attention (Asi & Beaulieu, 2013). Such contemporary demographic changes, along with the longtime presence of many racial and ethnic groups in the U.S., underscore the importance of incorporating multiple groups into our research and studying the distinct ways in which they are perceived and treated.

Social modifiers of the pace of aging across multiple domains

Project Duration: 07/01/2019 - 01/31/2024
Sponsor: National Institute on Aging
Dept. Investigator(s): Noah Snyder-Mackler
Abstract: Click to expand...
With a rapidly growing aging population comes a correspondingly rapid increase in the incidence of aging-related diseases. However, not everyone falls victim to aging-related diseases at the same time – there is substantial variability in the age at onset and progression of diseases of aging. Evidence suggests that part of this variation is associated with social adversity, such as low socioeconomic status and social isolation. But precisely how social adversity “gets under the skin” to alter the pace of aging remains elusive. Progress on this front lags because comprehensive portraits of individuals’ realized biological age are required across the lifespan in multiple domains and organ systems, a feat largely unfeasible in humans. A suitable animal model, such a non-human primate, is needed where natural variation in both social behavior and aging are homologous to that in humans, and can be tracked across the lifespan in different tissues and domains of aging. The objective of this proposal is to develop a biological model of the social contributions to aging in a natural population of nonhuman primates. To do so, it draws on a long-term study of a free-living population of rhesus macaques. These animals present an unparalleled opportunity to probe aging and its social determinants in a large population living in naturalistic circumstances because of their phylogenetic proximity to humans, homologous natural markers of social adversity, including social isolation and low social status represented by low dominance rank, and considerably shorter (3-4x) lifespans. This project tests the hypothesis that social adversity accelerates biological aging across multiple tissue types and in three central aging domains: (i) molecular (e.g., DNA methylation and telomere attrition), (ii) immunological (e.g., inflammation and leukocyte composition), and (iii) physical (e.g., frailty, including joint mobility and body condition). Aim 1 of this project aims to generate comprehensive aging profiles across domains and systems by taking an approach that is: (a) cross-sectional across tissue types and (b) longitudinal over individuals’ lifespans. By tracking aging across tissue types and the lifespan, we will pinpoint modifiable sources of aging variation, as well as establish the timing and sex-specificity of modifiable aging domains. Aim 2 draws on detailed social phenotypes to test how, and in what domains, social adversity accelerates aging. This project will lend transformative insights into two major issues in the biology of aging. First, it will generate valuable data on molecular, immunological and physical signatures of aging using a naturalistic primate model for human aging. Second, it will reveal how the social environment alters the pace of aging, which will inform the targeted development of social and physiological interventions that could reduce the burden of aging-related disease in our aging population.

The neural basis of individual differences in amblyopia: Neural assessment as a route to individualized treatment

Project Duration: 06/01/2019 - 05/31/2020
Sponsor: Research to Prevent Blindness (RPB)
Dept. Investigator(s): Ione Fine
Abstract: Click to expand...
Amblyopia arises after clear vision in one eye is impaired for a prolonged period during early development, e.g. from defocus (anisometropia) or cataract, or the two eyes are misaligned in early development (strabismus). Amblyopia is a brain-based, rather than ocular, disorder: it persists even after the defocus, cataract or strabismus is corrected, because during development the neural connections of the brain develop abnormally - discounting information from one eye. It is clinically defined as a Snellen chart acuity difference of 2 lines after correction of any focusing errors or cataracts. Amblyopia treatment continues to frustrate patients and clinicians alike. Historically, amblyopia treatment has consisted of crudely depriving the dominant eye, in the hope that two wrongs make a right; but even when patients are compliant many individuals have deficits that are refractory to treatment or recur following treatment cessation. There is currently a great deal of interest in using perceptual learning to improve function in amblyopia. Examples include direct targeting of acuity using training with a monocular position discrimination task, or targeting of unequal contrast response functions across the two eyes by lowering the contrast or brightness of the fellow eye so the stimuli are equally visible. Such treatments show great promise, but effectiveness varies widely across individuals across all these treatments. We believe this is because patients vary in their deficits, and so not all patients will benefit from all treatments. A patient whose primary deficit lies in their acuity loss may not be helped by treatments aimed at reducing suppression. Alternatively, in a different patient, constant strong binocular suppression may undermine the benefits of monocular acuity training. We will use advanced neuroimaging techniques in conjunction with psychophysics to accurately measure population receptive field sizes (thought to be related to the size of the underlying neural receptive fields), monocular contrast responses, and binocular suppression in amblyopes and neurotypicals, across the entire visual field. We will use these neural responses to develop behavioral tests that can be applied in the clinic.

MACR Fledgling Mortality Monitoring

Project Duration: 04/25/2019 - 12/31/2020
Sponsor: US Fish and Wildlife Service (FWS)
Dept. Investigator(s): Renee Ha
Abstract: Click to expand...
The Mariana Crow population on Rota has declined by 90% since the 1980s, largely due to poor first year survival. Between 2009 and 2018, the primary cause of death for juvenile crows necropsied by the USGS National Wildlife Health Center was liver and lung inflammation, with pathology suggestive of infectious disease. In order to determine the cause of this disease, sick and dying individuals must be radio-tracked to collect blood samples from sick individuals and to locate carcasses for necropsy in cases where this inflammatory disease is fatal. Due to high rates of decomposition and large numbers of scavengers, studies of cause-specific mortality in Mariana Crows requires the use of radio-telemetry and a protocol of frequent monitoring. Knowledge of causes of juvenile mortality are essential to supporting recovery efforts for the species.

Lateral Habenula and Memory Guided Response Flexibility

Project Duration: 02/15/2019 - 12/31/2020
Sponsor: NATIONAL INSTITUTE OF MENTAL HEALTH
Dept. Investigator(s): Sheri Mizumori
Abstract: Click to expand...
A significant challenge is to understand neural mechanisms that ensures rapid, dynamic and accurate switches in responses when outcomes of a prior act or choice are not optimal or as expected. The underlying mechanisms likely depend on task-dependent interactions amongst different brain regions. There are many demonstrations that neural activity becomes synchronized across distal brain areas in tasks that require flexible responding. For example, particular frequency bands of the local field potential, or LFP (e.g. theta) are observed to synchronize between hippocampus (HPC), medial prefrontal cortex (mPFC), and lateral habenula (LHb) at times when animals select actions or deliberate during task performance (52,54,56,57,58,59). While demonstration of such comodulation is intriguing and important, the informational or behavioral significance of this correlation remains unknown. The present application tests a novel theory of response flexibility that posits an integrative HPC-mPFC-LHb neural system is fundamental to an animal’s ability to adaptively respond to changing environments. Aim 1 will determine the behavioral and neural contribution of LHb on mPFC and HPC-mediated response flexibility through a series of disconnection experiments in which the HPC, mPFC, and/or the LHb are temporarily inactivated as rats perform a delayed alternation or repeated probabilistic reversal task. High density, simultaneous recording of neural activity in HPC, mPFC, and LHb will provide new insight into coordinated comodulation of neural activity across these brain areas as well as the underlying information that may be contained within comodulated LFP signals. Aim 2 will disconnect mPFC from LHb via chemical or DREADD inactivation to test the hypothesis that mPFC provides LHb with information about the current behavioral state (e.g. velocity of movement). In this Aim we will also develop a closed loop experimental model to isolate, on-line, discrete neural signals (i.e. HPC SWRs or theta) to trigger temporally precise, light-activated excitation or inhibition of a connected system (the mPFC). This should disrupt goal outcome information transfer to the LHb, which is proposed to determine whether rats appropriately switch behavioral responses. The closed loop model will allow us to test the hypothesis that known mPFC functions (working memory, action selection, and the evaluation of behavioral outcomes [18,19,20]), rely on temporally organized spatial information from the HPC to affect behavioral control systems such as the LHb. To test the hypothesis that the HPC-mPFC-LHb circuit contributes generally to an animal’s ability to flexibly switch responses regardless of the type of learning,

Scaling Up Educational Culture Change: Culturally Inclusive Growth Mindset Teacher Training

Project Duration: 12/10/2018 - 03/29/2021
Sponsor: Bill and Melinda Gates Foundation
Dept. Investigator(s): Stephanie Fryberg
Abstract: Click to expand...
In the proposed work, we will build internal capacity and scale up our CIGM teacher training curriculum by building online modules that will help teachers in the Road Map Region (30-50 teachers in the initial pilot) learn to implement CIGM practices in their classrooms. As a result of completing these modules, teachers will better understand how culture shapes racial/ethnic minority and low-income students’ cognition, motivation, emotion, and behavior. They will also have a better understanding of how to tailor their teaching practices to engage diverse cultural perspectives and experiences in the classroom and use students’ cultural differences to enhance the learning environment. As a result, we anticipate that racial/ethnic minority and low-income students will experience a greater sense of identity safety (i.e., the belief that people from their backgrounds belong in school and can be successful) and growth mindset (i.e., the belief that intelligence can be grown through persistence and effective effort) and thus will demonstrate enhanced engagement and performance in school. By creating environments where racial/ethnic minority and low-income students feel that they belong and can succeed and are encouraged to embrace growth mindset, we anticipate that teachers can help to reduce achievement gaps while enhancing all students’ learning. This project will set the stage for larger scaling efforts aimed at reducing achievement gaps on a larger scale by training teachers across the U.S. to create CIGM classroom cultures.

MRI: Acquisition of a Siemens MAGNETOM Prisma 3-Tesla MRI

Project Duration: 09/01/2018 - 08/31/2021
Sponsor: National Science Foundation (NSF)
Dept. Investigator(s): Geoffrey Boynton
Abstract: Click to expand...
With support from a National Science Foundation Major Research Instrumentation Award, the University of Washington (UW) plans to acquire a state-of-the-art 3 Tesla (3T) scanner for structural and functional brain imaging research. This shared instrument will be the primary tool for advancing scientific research and training on topics including language, visual neuroscience, social psychology, autism, child development, cognition, brain-computer interfaces and neurological disorders.

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.

Fear and Natural Risky Decisions in Rats

Project Duration: 06/01/2018 - 02/28/2023
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.

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).

Mechanisms of adult forebrain neural circuit regeneration

Project Duration: 05/15/2018 - 02/28/2023
Sponsor: National Institute of Health
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.

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.

Effects of Blindness on Human Early Visual Pathways

Project Duration: 06/01/2017 - 06/30/2022
Sponsor: National Eye Institute
Dept. Investigator(s): Ione Fine
Abstract: Click to expand...
Early blind individuals show enhanced performance on a wide variety of auditory tasks. However, fMRI studies examining neural plasticity resulting from blindness have almost exclusively focused on techniques that pool information across voxels, making it impossible to develop models linking alterations in neural activity to behavioral performance. 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 measuring PAC size, responsiveness and frequency tuning bandwidths within early blind and sighted individuals. We will then examine whether PAC contains a map (orthogonal to frequency) that is tuned for amplitude modulation (AM), and whether AM modulation tuning is affected by blindness. Computational models will be used to link PAC 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 spectral tuning in secondary auditory areas and occipital cortex. Again, computational models will be used to link each individual’s neural responses to their 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 this cross-modal plasticity helps 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, how hMT+ frequency and motion tuned neural responses might result in enhanced behavioral performance on auditory motion tasks, and whether the auditory motion responses found in hMT+ are due to plasticity in feedforward or feedback connections.

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.

Closed loop analysis of hippocampus-prefrontal cortex during flexible navigation

Project Duration: 05/15/2017 - 01/31/2020
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

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 - 05/31/2020
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.

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

Project Duration: 08/15/2015 - 08/31/2020
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.

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.

The Effects of Attention in Human Visual Cortex

Project Duration: 09/01/2014 - 08/31/2020
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.