Fumiko Hoeft - US grants

Abstract Not Provided.

Beuren syndrome; Brain region; CRISP; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Contiguous Gene Syndrome, Williams; Control Groups; Data; Diffusion MRI; Diffusion Magnetic Resonance Imaging; Diffusion Weighted MRI; Dorsal; Elfin Facies Syndrome; Face; Fanconi Schlesinger syndrome; Fanconi-Schlesinger syndrome; Fiber; Funding; Genetic; Grant; Individual; Institution; Investigators; Link; Methods; NIH; National Institutes of Health; National Institutes of Health (U.S.); Process; Relative; Relative (related person); Research; Research Personnel; Research Resources; Researchers; Resources; Source; Stream; United States National Institutes of Health; Visuospatial; Williams Barratt syndrome; Williams Syndrome; Williams syndrome (WMS, WS); Williams-Barratt syndrome; Williams-Beuren Syndrome; Williams-Beuren syndrome (WBS); diffusion tensor imaging; elfin-facies hypercalcemia syndrome; facial; hypercalcemia-peculiar facies-supravalvular aortic stenosis syndrome; hypercalcemia/Williams-Beuren syndrome; idiopathic hypercalcemia-supravalvular aortic stenosis syndrome; interest; mental retardation-typical facies-aortic stenosis syndrome; neuroimaging; substantia alba; visual spatial; white matter

Brain; CRISP; Computer Retrieval of Information on Scientific Projects Database; Corpus Striatum; Corpus striatum structure; Dysfunction; Encephalon; Encephalons; Escalante syndrome; Fragile X; Fragile X Syndrome; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Grant; Individual; Institution; Investigators; MRI, Functional; Magnetic Resonance Imaging, Functional; Male Adolescents; Martin-Bell Syndrome; Martin-Bell-Renpenning syndrome; Methods; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nature; Nervous; Nervous System, Brain; Pattern; Physiopathology; Process; Renpenning syndrome 2; Research; Research Personnel; Research Resources; Researchers; Resources; Source; Striate Body; Striatum; United States National Institutes of Health; X-linked mental deficiency-megalotestes syndrome; X-linked mental retardation with fragile X syndrome; X-linked mental retardation-fragile site 1 syndrome; adolescent boy; autism-fragile X (AFRAX) syndrome; autism-fragile X syndrome; executive control; executive function; fMRI; fra(X) syndrome; fra(X)(28) syndrome; fra(X)(q27) syndrome; fra(X)(q27-28) syndrome; fragile X-mental retardation syndrome; fragile Xq syndrome; fragile site mental retardation 1; fragile x [{C0016667}]; fragile x syndromes; macro-orchidism-marker X (MOMX) syndrome; macro-orchidism-marker X syndrome; mar(X) syndrome; marker X syndrome; mental retardation-macroorchidism syndrome; neural; pathophysiology; relating to nervous system; striatal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Little is known about the underlying neural processes of playing computer / video games, despite the high prevalence of its gaming behavior, especially in males. Specific Aims:To investigate the neural correlates of gender difference in video-game play. Methods: A functional magnetic resonance imaging study contrasting a space-infringement game with a control task.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. About one-fifth of individuals with developmental dyslexia develop compensatory skills for reading by the time they reach adulthood but the mechanisms remain unknown. Specific Aims: Investigation of brain activation patterns that predict future reading gains in dyslexic children. Methods: We studied 45 children with and without dyslexia with a baseline fMRI and behavioral testing, and followed them up for an average of 2.5 years.

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of this K23 Award is to help establish the candidate's independent research career in the field of educational neuroscience and learning disabilities. The candidate has completed clinical training in psychiatry. She also has research experience in neuroimaging and developing 'simple' models to predict reading success using functional and structural neuroimaging. The candidate's training will take place at interdisciplinary research centers/labs directed by international leaders in developmental disorders and clinical neuroscience (Allan Reiss), in neuroimaging methodology (Gary Glover), and in education and reading acquisition (Connie Juel). The mentoring team will be complemented by consultants who are experts in reading and dyslexia (Bruce McCandliss, Heikki Lyytinen and John Gabrieli) and statistics (Booil Jo). The [unreadable] specific aim of the project is to develop models using a combination of behavioral and neuroimaging [unreadable] measures to predict reading success. Learning to read is important for the well-being of individuals, and [unreadable] inadequate reading skill leads to a higher probability of early school drop-out and a greater likelihood of [unreadable] having a lower paying job. The development of better and novel methods for identifying children's future [unreadable] reading success is an essential step for the development of effective approaches to prevention and early intervention of reading disabilities. The proposed research project is therefore greatly compatible with the mission of the NICHD and is highly relevant to public health. To develop prediction models, initial neuropsychological evaluation, functional and structural neuroimaging, followed by longitudinal [unreadable] neuropsychological evaluations will be performed in kindergarten children with high risk for reading [unreadable] disorders. Models will be created and validated using advanced statistical analyses. The main hypotheses, based on preliminary data, are that 1) there will be abnormal brain patterns associated with reading in high risk children, 2) specific, a priori hypothesized profiles of brain function and morphology will predict reading outcome, and 3) combining neuroimaging and behavior will predict reading outcome significantly better than using a behavioral model alone - the current standard in educational practice. The candidate will pursue formal coursework in literacy, education and statistics that will make substantive contributions to her development as an independent clinical investigator focused on reading research. [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: In functional neuroimaging studies, individuals with dyslexia often exhibit both hypoactivation, often in left parieto-temporal cortex, and hyperactivation, often in left inferior frontal cortex. Specific Aims: To perform fMRI and VBM analyses to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. Methods: We measured brain activation and grey matter morphology in dyslexic adolescents.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies of genetic disorders such as fragile X syndrome (FXS) which is a disorder caused by a single gene mutation resulting in abnormal dendritic and synaptic pruning, together with healthy individuals may provide valuable information to study gene, brain-behavior relationship. Specific Aims: To examine morphometric spatial patterns that differentiate between FXS from controls in early childhood. Methods: Voxel-based morphometry was examined in a total of 101 children of ages 1 to 3;51 boys with FXS, 32 typically developing (TD) boys and 18 boys with idiopathic developmental delay (DD).

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies of genetic disorders such as fragile X syndrome (FXS) which is a disorder caused a single gene mutation resulting in abnormal dendritic and synaptic pruning, together with healthy individuals may provide valuable information to study gene, brain-behavior relationship. Specific Aims: To examine morphometric spatial patterns that differentiate between FXS from controls in early childhood. Methods: Voxel-based morphometry was examined in a total of 101 children of ages 1 to 3;51 boys with FXS, 32 typically developing (TD) boys and 18 boys with idiopathic developmental delay (DD).

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies of genetic disorders such as fragile X syndrome (FXS) which is a disorder caused a single gene mutation resulting in abnormal dendritic and synaptic pruning, together with healthy individuals may provide valuable information to study gene, brain-behavior relationship. Specific Aims: To examine morphometric spatial patterns that differentiate between FXS from controls in early childhood. Methods: Voxel-based morphometry was examined in a total of 101 children of ages 1 to 3;51 boys with FXS, 32 typically developing (TD) boys and 18 boys with idiopathic developmental delay (DD).

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Introduction: Morphologic brain differences have been identified between children with autism and typically-developing children, though findings have been inconsistent across studies. One potential cause is the variability in brain morphology resulting from the influence of multiple genetic and environmental factors on brain development. A strategy to control for such factors is to compare brain structure between siblings discordant for autism. Specific Aim: To assess the relationship between brain morphology and autism using voxel-based morphometry to examine siblings discordant for autism. Methods: To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)

Understanding how the brain of a student learns new information and flexibly applies that information in real-world settings is critical for guiding efforts to improve the U.S. education system. How a student learns is fundamentally related to core aspects of cognition, termed executive functions (EFs). EFs are known predictors of academic achievement across multiple content areas (e.g., math and reading); however, there remain many unanswered questions regarding exactly how EFs contribute to academic performance and whether weak EFs can be enhanced with cognitive training. It is important to build a precise understanding of how these abilities develop over childhood and how they can be improved in order to supply educators with precise tools and insights about whether, when, and how to intervene when a student is struggling.

The study of how EFs contribute to academic achievement has advanced rapidly in recent years, but has not typically included the investigation of EFs in middle childhood. Because middle childhood is a period of high neural plasticity, it promises great opportunity to intervene when EFs are weak. This research program develops an innovative approach that improves both diagnostic and intervention methodology for detecting and remediating EF weaknesses in educational settings. The program leverages a novel, precision EF assessment tool in order to rapidly assess and longitudinally track the multidimensional profile of EFs in children over time. The critical advancement is the adaptive nature of the assessment tool, which increases in difficulty as the learner improves. This adaptivity allows multiple, precise assessments over time and thus enables unprecedented understanding of how different EF profiles develop across middle childhood and, critically, how these profiles contribute to math and reading achievement. Additionally, by utilizing a novel intervention that uses each student's multidimensional EF profile to selectively challenge subdomains of EF during physical fitness training, the research will inform us if personalized, multi-factor EF training can improve math and reading outcomes. Specifically, the research will: (1) fill gaps in existing knowledge about the relationship between EF profiles and academic skills beyond early childhood, (2) characterize how these relationships evolve across age, (3) determine whether EFs are more critical to certain content areas (subdomains of math and reading), and (4) advance the field's understanding of the feasibility and timeline of personalized EF interventions. Importantly, this research will serve to lay a definitive foundation for future science of learning research to build upon. In particular, the proposed investigations of the typically developing mind will inform efforts to understand disorders of development such as ADHD and autism. Finally, the EFs assessment tool will be made publicly available, to promote widescale investigations of EFs across the diverse range of student learners. A precise understanding of how the multidimensional profile of EFs contributes to academic achievement promises tremendous societal impact by guiding efforts to intervene when students are struggling academically.

DESCRIPTION (provided by applicant): This proposal is an experiment of nature that examines the profound effect of contrasting environment on neuroplasticity. Most current views of reading posit that the development, involvement and interaction of ortho-phonological and ortho-semantic systems depend on the statistical properties of languages. The overarching goal of this study is to take advantage of these differences, and perform a comprehensive neurocognitive investigation of how the complex process of learning to read in English (Eng.) is shaped online during the critical period of reading acquisition. This will be achieved by prolonged and intensive exposure to contrasting languages (Spanish, SP; Cantonese, Cn) that differentially stress these ortho-phonological and ortho-semantic systems. Sp has the same Roman alphabet as Eng., but with a different and more regular spelling-to-sound mapping that emphasizes phonological recoding. Cn uses the Chinese morphosyllabic writing system that is opaque and has weak character-to-sound mapping, presumably leading to greater reliance on ortho-semantic processes. Specifically, we will launch a prospective, longitudinal, and bidirectional examination of reading acquisition from kindergarten (K) to end of 2nd grade in 5 groups that is manipulated based on Eng. being their first or second language (L1 vs. L2) and the immersed language (Sp vs. Cn vs. none): native Eng. (L1) emerging readers in the U.S. starting Sp and Cn immersion programs initially learning primarily their L2 (L1Eng/L2Sp, L1Eng/L2Cn), L1 Sp and Cn speakers in the U.S. starting the same two-way immersion programs initially learning primarily their L1 (L1Sp/L2Eng, L1Cn/L2Eng), and Eng. monolinguals attending the same schools but not in the immersion programs (L1Eng). The main aims of the study are to investigate: 1) individual differences in the development of reading-related processes and brain circuitries in Eng., 2) how learning to read in Sp and Cn influence Eng. reading development given variant linguistic properties, 3) factors that affect interlinguistic/interliteracy influence (or transfer) , and 4) how these processes are shaped by early linguistic environment (e.g. early exposure to Eng., Cn versus Sp as their L1) and neurocognitive capacities (e.g. phonological awareness and related brain circuits, a significant risk factor of future reading impairment). The findings from this last exploratory aim will provide important initial insight into the influence of second language learning on children at-risk for developing reading disabilities, a population that is often discouraged from learning a foreign language. Children will be recruited from a local school district with which we have a collaborative relationship. The district is well-known for its extensive two-way immersion programs. This large-scale effort will advance theories of the neurocognitive processes underlying literacy development in Eng. by perturbing the system with languages of variant linguistic properties, advance understanding of the neurocognitive processes underlying multilingualism, and how minority students learn to read Eng. in the U.S.

Decoding-based reading disorder (RD; or dyslexia) is a highly prevalent neurodevelopmental disorder that often persists into adulthood. Poor literacy in adulthood has negative impact on socioeconomic and educational outcomes, which in turn affect the outcomes of subsequent generations. Despite significant consequences, research on RD adults is severely lagging. There is also increasing interest in understanding compensatory mechanisms in RD, which are thought to develop into adulthood. Compensation in RD allows for less efficient but functional reading abilities, and is thought to be supported by alternative linguistic, cognitive and sensory processing strategies and their underlying neural pathways. This is in contrast to the more typical `reading network' found in the left posterior brain system. Neurocognitive mechanisms of compensation are however, far from understood. This in part because the operational definitions of compensation have been ambiguous, and because functional MRI approaches most often used in compensation research are inherently correlational in nature. For example, it is currently unknown whether the proposed compensatory processes are causally related to reading behaviors in compensated RD or whether they are epiphenomena. The degree to which various alternative neural pathways are recruited and contribute to individual differences in compensatory abilities is also unknown. This proposal addresses these scientific gaps by building on our past work on the neurocognitive mechanisms of adult RD and compensation using an experimental neuromodulation technique, transcranial magnetic stimulation (TMS), coupled with multimodal neuroimaging including MR Spectroscopy (MRS) of gamma-aminobutyric acid (GABA) and glutamate, and functional MRI. In this proposal, (1) We will identify neurocognitive profiles of compensated RD adults compared to persistent RD adults with continued reading difficulties as well as typical readers with no RD history. We also identify neurocognitive mechanisms and networks underlying individual differences in current reading ability (regardless of past RD diagnosis) and past RD diagnosis (regardless of current reading ability). (2) Using transcranial magnetic stimulation (TMS) within an experimental, hypothesis testing paradigm, we will discover the processes underlying short-term functional reorganization and its impact on reading in key neural nodes thought to be critical for reading, RD and compensation. Through TMS-induced neuromodulation, we systematically test hypotheses regarding causal processes thought to be involved in compensation. (3) In order to address hypotheses regarding the neurochemical mechanisms underlying compensatory processes and pathways, we will discover how regionally specific levels of GABA, important for modulation of cortical excitability, predict responses to TMS-induced (meta)plasticity. Such work will not only advance theories of RD and compensation, but ultimately may improve strategies to promote intervention models and successful compensation in RD, in both children and adults with RD.

ABSTRACT The main objective of the proposed research is to examine, for the first time, intergenerational transmission of human brain networks using a natural cross-fostering design. We take reading-related brain networks, in particular those related to phonological and orthographic processing (as well as in language- and more preliminarily in math-related processes), as model systems because of the potentially differential impact of genetic and environmental factors on these networks and corresponding behavioral phenotypes. In addition, impairment of these neurocognitive processes is associated with specific learning disorder of word reading (aka decoding-based reading disorder [RD] or developmental dyslexia) that has a lifetime prevalence of 5- 10%, and an increased risk of the offspring developing RD by 4 to 8 times the general population with an immediate family member with RD. The proposed natural cross-fostering design addresses a critical question about the mechanisms of intergenerational effects, i.e., whether they are genetic (G), prenatal (PreE) or postnatal environmental (PostE) in origin. This is only now possible with the widespread availability of in-vitro fertilization (IVF). We will obtain cognitive measures, and functional and structural MRI, in healthy families (triads) at a pace of 30 families per site per year. We will examine parent-offspring correlations, including brain- brain correlations, across four groups of IVF children that receive distinctive G/PreE/PostE contributions from their rearing parents as well as a fifth group of naturally conceived children (N=60 triads per group, with children of ages 8-11, half with daughters and the other half with sons): (1) the HOMOLOGOUS group in which offspring conceived through IVF are borne and reared by their genetic parents, thus being exposed to maternal and paternal G/PreE/PostE influences; (2) the DONOR EGG and (3) DONOR SPERM groups, in which offspring are conceived from donor eggs/sperm, and hence rearing mothers/fathers only have PreE/PostE, not G, influence on their offspring; (4) the gestational SURROGACY group in which offspring are borne through non-genetic, non-rearing mothers, and hence rearing parents only have G/PostE but no PreE influences over their offspring; and (5) the NATURAL conception group in which naturally conceived offspring are borne and reared by their genetic parents, thus being exposed to maternal and paternal G/PreE/PostE influences and without the influence of IVF. Fathers? PreE influence is typically considered minimal. The specific aims of the proposal are: to examine parent-offspring (dyad) correlations, to examine the extent to which environmental and genetic factors contribute to shared variance in reading- and language-related cognitive and neurobiological processes, to examine parent-of-origin effects, and to dissociate G, PreE and PostE influences. A successful outcome will establish a new paradigm for studying genetic and environmental influences on brain networks, and ultimately provide us with important information about risk/protective factors, windows of opportunity to intervene, and development of early intervention and preventive strategies of RD.

ABSTRACT Although the critical role of Emotional Well-Being (EWB; e.g., life satisfaction, happiness, meaning and purpose, positive emotions) in public health is increasingly acknowledged, research has lagged due to lack of consensus on essential components of EWB, valid ways to measure its components, and mechanisms to inform intervention theory. Mind-body interventions (MBIs) increasingly demonstrate effectiveness in reducing adverse mental health states, including dysfunction, depression, anxiety, and stress. Whether MBIs are also effective in promoting EWB, however, remains far less clear. Further, the mechanisms through which MBIs facilitate EWB and especially how they may work to target EWB across the life course (e.g., children, caregivers, adults with health challenges) remain largely unknown. To address this crucial gap in knowledge, we respond to RFA-AT-20-003 in proposing to lead a network to deepen our understanding of EWB measurement approaches and their role in MBIs as outcomes and as mechanisms. We capitalize on MPIs' interdisciplinary expertise in MBIs, EWB, measurement, neuroimaging, and inter-generational transmission and tap our broad network of colleagues across disciplines. To promote research linking MBIs and EWB, new avenues and resources are needed. First, we need to more fully characterize the dimensions comprising the umbrella construct of EWB. Second, we need to identify and/or create psychometrically sound instruments that fully capture these dimensions of wellbeing. Third, we need to identify the biological, psychological, and social mechanisms through which MBIs promote and maintain EWB. Inclusivity is essential; in addition to the more typical lifespan approach, we will focus on populations often excluded from this area of work by applying a developmental and inter-generational transmission lens that includes both child and caregiver populations as critical to work that moves the field vertically. Capitalizing on this critical moment in intervention science, we will establish a network that brings together a corps of researchers who can learn from one another's work to collectively establish innovative and rigorous scientific bases for a new generation of EWB research. The overarching goal of the network is to provide researchers with the conceptual and methodological resources to appropriately assess EWB and to promote interdisciplinary research that illuminates the role of EWB in MBIs as both an outcome itself and as a mechanism in improving mental and physical health outcomes. Specifically, we will create a taxonomy of components and collection of measures for EWB that spans the life course, establish a toolkit by refining measurement tools and approaches appropriate for populations across the life course, and identify potential mechanisms through which MBIs promote EWB. We will achieve these aims through a series of activities that include targeted strategies to engage a broad network of scholars including early career, focused meetings for co-learning and sharing findings, and robust multi-media dissemination.