Jack McFarlin Fletcher - US grants

This proposal addresses the neurobehavioral development of hydrocephalic children in relation to neuropathology, cognitive development, school achievement, and behavioral adjustment. Study I provides two additional two year follow-ups of a cohort of 125 children with 3 etiologies of hydrocephalus (spina bifida, aqueductal stenosis, intraventricular hemorrhage) and comparison groups (unshunted spina bifida, normals, premature-no IVH) followed yearly over 3 years. Study 2 is an expanded cross-sectional study of MRI and cognitive development in the 3 hydrocephalus etiologies and 3 comparison groups (N=160). Six specific aims will be addressed. Aim 1 (neuropathological correlates of hydrocephalus) expands our ongoing MRI research on neuro- pathological lesions associated with hydrocephalus. Aim 2 (nature of impaired abilities) expands on research showing poorer development of nonverbal skills than verbal skills in hydrocephalic children into cognitive domains involving problem solving and attention. Aim 3 (CNS lesions and cognitive development) addresses relationships of neuro- pathology and variations in cognitive skills. Aim 4 (change over time) addresses the modeling of change on an individual basis and testing of hypotheses concerning determinants of change. Aim 5 (academic achievement) addresses possible dissociations in the school-related abilities of hydrocephalic children. aim 6 (behavioral adjustment) proposes that the effects of hydrocephalus on behavioral adjustment are cumulative, emerging, and related to problems with academic achievement, behavioral disorders, and problem solving deficits. Comprehensive multivariate analyses are proposed. This study is unique because of (a) large, carefully selected cohorts; (b) concurrent longitudinal and cross-sectional designs; (c) simultaneous collection of behavioral and neuroimaging data; (d) multidisciplinary team; and (e) comprehensive multivariate approach to analysis. To study promises to enhance scientific understanding of the influence of hydrocephalus on development and the more general issue of the effect of early brain injury on development.

The goal of the proposed research is to continue a series of studies of the long-term effects of chronic cannabis use in Costa Rican males. We have a unique sample of very chronic users who have consumed marihuana on a habitual basis for about 30 years. This sample is working class largely literate urban, and does not use other drugs except for alcohol and tobacco. A sample of non-users comparable in age, education, and alcohol and tobacco use is also available. Although the initial Costa Rican study (1973-1975) yielded little evidence of adverse effects, our recent follow- up (1985-1986) found that users performed more poorly than non-users on cognitive measures involving attention, short-term memory, and mental effort. These findings correspond to studies of work in which users were found to engage in employment requiring less mental effort. Despite these differences, there was little evidence for deterioration in cognitive skills in the users over the 12 year time interval separating the two studies. Consequently, the degree of chronicity required to establish these adverse effects is not clear. Similarly, more information is needed concerning the nature of the cognitive deficits and the influence of cannabinoid levels in the body on cognitive performance. The specific aims of the proposed research are a) to replicate the results; b) recruit a younger, less chronic cohort; c) administer new tasks that measure more precisely cognitive skills that may be impaired in chronic users; and d) complete assay studies to determine cannabinoid levels in the body. Since the second study is the only well-controlled demonstration of adverse cognitive effects in non-intoxicated cannabis users who don't use other drugs, additional research is clearly indicated. If the hypotheses of this study are confirmed, the results may indicate even more adverse effects for habitual North American users of cannabis in whom greater demands are made for effortful mental processing. Such a study can only be completed in a cross-cultural setting because the degree of chronicity and absence of polydrug use does not exist in North American users. The proposed research provides a unique opportunity to explore cognitive changes in chronic marihuana users.

DESCRIPTION: (Adapted from the applicant's abstract) The objective of this proposal is to continue longitudinal, neuro-behavioral follow-up studies of children (N=171) who sustained mild, moderate, and severe closed head injuries (CHI) at 0-15 years of age. These studies, which began in 1984, represent one of only a few prospective follow-up studies in which the child is evaluated at the time of injury and followed at 6, 12, 24, 36, 48, and 60 months post-injury. At this point, follow-up studies have been virtually completed through 24 months. Because of clear evidence for persistent neuro-behavioral sequelae in severely injured children after the first year post-injury, it is proposed to a) obtain 36, 48, and 60 month longitudinal neuro-behavioral follow-up data on CHI children followed since their initial injury and classified according to age and severity; b) expand assessment of behavioral change at 60 months to include additional child, family, and environmental variables, and add additional assessments of academic achievement and problem-solving skills; c) apply multi-level models for growth curve analysis to these longitudinal data. When completed, this study will address hypotheses concerning relationships of pediatric CHI with a) age of onset; b) nature of impaired skill; c) rate of skill development; d) behavioral adjustment and academic skill development. In addition, the application of the growth curve analyses will permit evaluation of medical and demographic factors explanatory of outcomes in individual cases. As such, these techniques promise to revitalize studies of recovery from brain injury by focusing on the analysis of change in individual cases. This study will represent the only long-term prospective outcome data on pediatric CHI, offering new data on neuro-behavioral sequelae after CHI and the development of children who sustain diffuse brain injury at different stages of CNS maturation.

The methodology section describes a plan for the application of a classification model to the investigation and development of a subtyping nosology for reading disorders (dyslexia). The Methodology Core constitutes one section of a larger proposal designed to: 1) identify subtypes of reading performance within a broad population of children with learning difficulty whose deficient test performance is below expectation in reading and/or math, or who meet accepted criteria of attention disorder; 2) address the neuroanatomical correlates of reading disabilities through state-of-the-art magnetic resonance imaging of the brain; 3) provide a quantitative index of shared electrophysiological activity that assesses communication across brain areas through the use of EEG coherence analysis; 4) examine the emergence of subtypes of reading disability in an epidemiological sample and within a longitudinal framework; and 5) investigate individuals within reading disability subtypes who have affected family members in order to clarify possible genetic influences on reading disability.

Spina bifida meningomyelocele is the major severely disabling birth defect in North America, but our knowledge of the factors responsible for neurobehavioral outcome is fragmentary. The program project aims to make these fragments coherent. The overall objective of this program project is to identify sources of variability-genetic, environmental, and CNS-that explain variations in the neurobehavioral outcomes of children with spina bifida meningomyelocele and hydrocephalus (SBH). To accomplish this objective, we propose to evaluate 583 children with spina bifida and 159 controls in five projects and three cores at two primary data collection sites: the University of Texas-Houston Medical School and the Hospital for Sick Children, Toronto. Project 1 (Genetics; Northrup, P.I.) evaluates genetic factors associated with spina bifida and related neural tube defects in Hispanic and Caucasian cohorts. Approximately 100 candidate genes will be tested and a genome-wide search will be initiated that permits testing of 150 of 330 possible markers. Projects 2 (Early Learning; Landry, P.I.) is a longitudinal study of infants with SBH from 7-36 months of age. This study addresses the relationship of core neurobiological deficits and the environment in producing early learning deficits in children with SBH. Project 3 (Cerebellum; Dennis, P.I.) evaluates the role of cerebellum/midbrain dysmorphology in producing the motor, spatial, and attentional deficits associated with SBH. Project 4 (Corpus Callosum; Hannay, P.I.) examines the corpus callosum anomalies characteristic of SBH in relationship to interhemispheric transmission and hemispheric specialization. Project 5 (Discourse and Academic Skills; Barnes, P.I. evaluates factors producing deficits in discourse, reading comprehension, and math in children with SBH. These 5 projects are supported by an Administrative Services Core (A; Fletcher, P.I.), Subject Recruitment and Evaluation Core (B; Fletcher, P.I.), and Database, Computer, and Statistics Core (C; Francis, P.I.) Core B provides for comprehensive medical, neuroimaging and psychometric evaluations of each child. Core C provides databases, project-specific data analyses, and overall data analyses. Altogether, this comprehensive program project should facilitate an integrated, multi-disciplinary understanding of spina bifida, a common and significantly handicapping disability.

psychometrics; patient /disease registry; biomedical facility; spina bifida; interdisciplinary collaboration; medical outreach /case finding; human data; middle childhood (6-11); adolescence (12-20); vision tests; intelligence tests; psychological tests; magnetic resonance imaging; human subject;

This research project uses an interdisciplinary approach to large-scale educational interventions that provides for the integration of research and education around issues involving the cognitive development of beginning reading skills. Three projects are centered around a large suburban school district in Houston, TX. The participants are children who receive two types of classroom instruction (N=384) and their teachers (N=40). Within each type of classroom instruction, children are assigned to one of 4 groups (N=48) as part of a 2 (Classroom Instruction) X 4 (Group) design. The 4 groups include a no-risk group and 3 groups of children at risk for reading problems. Children in these 3 groups receive only classroom instruction or classroom instruction that matches or doesn't match the type of classroom reading instruction. All children will receive longitudinal assessments of growth in reading and reading-related skills, yearly norm-referenced achievement measures, and assessment of behaviour and the home/school environment. The intervention study (project 1) involves: a) identification of children at risk for reading problems in kindergarten; b) providing a controlled study of the efficacy of a first grade educational intervention designed to prevent reading problems in multiple high-risk schools; and c) evaluation of the use of information and computing technologies (ICT) to provide professional development of teachers on the translation of research on reading development into practice. The second project explores neural changes representing reading development using magnetoencephalography (MEG) to evaluate a) functional neural changes that occur as reading develops; and b) changes in the neural representation of reading skills as an indicator of response to intervention. The second study involves 120 children from the overall sample assigned to 3 groups (N=40 each): no risk, at-risk interventions; and at-risk classroom instruction. These children receive MEG evaluations before and after grade 1 and after grade 2. The final project addresses decodability skills and evaluates: a) how lexical and text characteristics of the basal reading programs used in archival intervention studies relate to student outcomes; b) psycholinguistic factors that moderate the impact of decodability; and c) the relationships of reading instruction in project 1 at classroom and intervention levels to the child's ability to read texts with pre-specified lexical and text characteristics. This study uses both archival data and will also collect monthly prospective data involving preconstructed textual material on the entire sample of 384 children.

Spina bifida meningomyelocele is the major severely disabling birth defect in North America, but our knowledge of the factors responsible for neurobehavioral outcome is fragmentary. The program project aims to make these fragments coherent. The overall objective of this program project is to identify sources of variability-genetic, environmental, and CNS-that explain variations in the neurobehavioral outcomes of children with spina bifida meningomyelocele and hydrocephalus (SBH). To accomplish this objective, we propose to evaluate 583 children with spina bifida and 159 controls in five projects and three cores at two primary data collection sites: the University of Texas-Houston Medical School and the Hospital for Sick Children, Toronto. Project 1 (Genetics; Northrup, P.I.) evaluates genetic factors associated with spina bifida and related neural tube defects in Hispanic and Caucasian cohorts. Approximately 100 candidate genes will be tested and a genome-wide search will be initiated that permits testing of 150 of 330 possible markers. Projects 2 (Early Learning; Landry, P.I.) is a longitudinal study of infants with SBH from 7-36 months of age. This study addresses the relationship of core neurobiological deficits and the environment in producing early learning deficits in children with SBH. Project 3 (Cerebellum; Dennis, P.I.) evaluates the role of cerebellum/midbrain dysmorphology in producing the motor, spatial, and attentional deficits associated with SBH. Project 4 (Corpus Callosum; Hannay, P.I.) examines the corpus callosum anomalies characteristic of SBH in relationship to interhemispheric transmission and hemispheric specialization. Project 5 (Discourse and Academic Skills; Barnes, P.I. evaluates factors producing deficits in discourse, reading comprehension, and math in children with SBH. These 5 projects are supported by an Administrative Services Core (A; Fletcher, P.I.), Subject Recruitment and Evaluation Core (B; Fletcher, P.I.), and Database, Computer, and Statistics Core (C; Francis, P.I.) Core B provides for comprehensive medical, neuroimaging and psychometric evaluations of each child. Core C provides databases, project-specific data analyses, and overall data analyses. Altogether, this comprehensive program project should facilitate an integrated, multi-disciplinary understanding of spina bifida, a common and significantly handicapping disability.

The objective of Project II is to evaluate the growth and development of skills related to oral language proficiency, literacy, and literacy-related skills in children who spear Spanish as their initial and primary language. We propose a 4-year longitudinal investigation of a large sample (n=1,440) of English-language learners from 144 classrooms enrolled in kindergarten and followed through grade 3. These children will be sampled from 3 geographic units (urban Texas, border Texas, urban California) and will be obtained from classrooms representative of 4 types of bilingual instruction programs: (1) English language immersion, in which predominantly English instruction begins in Grade 1; 92) early exit, in which English-language instruction begins after Grade 1, but before Grade 4; (3) late exit, in which instruction is done predominantly in English after Grade 3; and (4) dual language, in which a balance of English and Spanish language instruction is maintained beyond Grade 3. Three Specific Aims will be addressed: (1) reading precursors addresses the development of precursor skills to literacy skills, including oral language proficiency and specific literacy-related skills (e.g., phonological awareness); (2) growth and development addresses the developmental trajectories and co-development of oral language proficiency, literacy, and literacy-related skills; and (3) early identification uses assessments of precursor cells in kindergarten to identify English-language learners who are at risk for problems in literacy development as a basis for early intervention programs. Altogether, Project II addresses the need identified in the RFA for programmatic research efforts addressing the normative language, reading, and writing development among English-language learners. It will address important gaps in the knowledge base concerning the development of oracy and literacy in English-language learners and ultimately help provide the basis for prevention and early prevention efforts in this rapidly growing population.

This grant supports the acquisition of a multi-channel biomagnetometer system for Magnetic Source Imaging (MSI). This system will be used for non-invasive recording of magnetic signals emitted naturally by the human brain during performance of sensory-motor, cognitive and linguistic tasks, and for constructing functional images of brain activation. These images reflect the spatio-temporal patterns of brain activity mediating the psychological and behavioral functions required by the experimental tasks. During the past three years, we have used MSI to establish (i) the reliability and validity of functional maps of the brain mechanisms underlying cognitive functions, including motor, somatosensory, and receptive language (Breier et al., 1999a,b; Breier et al., 2000, in press; Papanicolaou et al., 1999; Simos, 1998a,b; 1999a,b; 2000a). These maps have proven so accurate that MSI is routinely used in our institution for outlining the borders of language-specific cortex in neurosurgical candidates in order to avoid damage to normally functioning neural mechanisms during resection of brain lesions lying close to these areas of the brain, thus reducing post-operative morbidity. (ii) We have accumulated sufficient data for constructing reliable maps of brain mechanisms associated with reading and phonological decoding in adults (Breier et al., 1998, 1999c, Simos et al., 1998a, 2000a, in press) and in school-age children (Simos et al., 2000b,c, in press) as well as kindergarten children learning to read. (iii) We have identified brain activation maps specific to children with identified reading difficulties and children at-risk for developing reading difficulties. We are following these children as they learn to read through different instructional methods to determine how these maps change with improved reading proficiency (Simos et al., 2000b,c,d).

These discoveries led us to consider a host of experimental questions ranging from the layout of the mechanisms of oral and written language in the brains of bilingual and polyglot children and adults to questions regarding the formation of such mechanisms in the course of brain maturation and development, and to questions relating to specific spatio-temporal activation patterns underlying component cognitive and linguistic functions. We have begun addressing these questions with the support of several NSF and NIH grants (NSF grant #9979968; NIH grants RO1 NS37941 and RO1 HD38346) using a 148-channel biomagnetometer acquired for clinical studies belonging to Hermann Hospital. Not surprisingly, the use of that system for the conduct of basic research involving normal volunteers and children has become problematic. The system we will purchase will be located on the U of Texas- Houston campus, outside Hermann Hospital, and will be exclusively used for basic research involving children and adults.

Our group has advanced MSI technology, especially in areas involving higher cortical functions. We have developed specific applications to education, literally bringing neuroscience into public schools. In order to continue to advance the technology and expand educational and training applications, a MSI laboratory dedicated to research is needed, leading to this grant under the Major Research Instrumentation Program.

Description: (Adapted from applicant's description) The Methodology Core has been designed to provide support in three broadly defined areas: Data Acquisition, Data Management and Communications, and Data Analysis. The specific objectives of the Methodology Core are to (a) facilitate acquisition of data; (b) develop tools and procedures for ensuring and monitoring the accuracy and confidentiality of all collected data; (c) develop databases for all behavioral and cognitive data; (d) facilitate communication and sharing of data among investigators through state-of-the-art computer networking; and (e) provide statistical support to investigators in the evaluation of hypotheses.

Cognitive, Instructional, & Neuroimaging Factors in Math. The objective of this program project in respond to RFA HD-02-031 is to integrate investigations of the cognitive, instructional, and neurobiological factors that account for individual differences in the development of mathematical proficiencies in children with different types of learning disabilities in math. The central theme is that children vary in the degree to which they learn mathematical proficiencies and that these individual differences manifest themselves in different subtypes of math disability. To understand the sources of variability, the types must be defined and evaluated against cognitive, instructional, and neurobiological measures, and in relation to other learning and attention difficulties. The proposed program project includes four projects and three cores. Project I (Cognition) proposes to evaluate mathematical and cognitive processes that underlie the difficulties experienced by children with specific math disabilities as well as comorbid math and reading disabilities. Project II (Instruction) provides randomized controlled studies of children with only reading and comorbid reading and math disabilities, including interventions addressing of fact retrieval, procedural knowledge, and arithmetic word problems. Project III (MRI) proposes functional and structural neuroimaging studies of the subtypes of math disability evaluated in Projects I and II, specifically examining the neural correlates of these subtypes and response to intervention. Project IV (MSI) proposes magnetic source imaging studies of the subtypes evaluated in Projects I and II, also identifying the neural correlates and response to intervention with a different, but complementary functional neuroimaging modality. The cores include the Administrative Services Core (A), the Recruitment and Evaluation Core (B), and the Database and Statistics Core (C). This research program will lead to a more comprehensive classification of learning disabilities in general, a more integrated understanding of how children develop mathematical proficiencies and why some struggle, provide specific evaluations of remedial interventions, and provide important cross-discipline insights into the nature of math disabilities in children.

ABSTRACT NOT PROVIDED

Core B was positively reviewed with a priority score in the Outstanding range (146). The Reviewers specifically noted that we had addressed concerns expressed in the previous review, including speech and language capabilities, need for pragmatic language assessment, and concerns about quality control. The review was also positive about the empirical contributions of the Core (see Core B Appendix), which will continue to emerge. The main concern expressed in the most recent review was the amount of data collection that was proposed, involving the Core B assessment as well as the measures associated with Projects 2, 3, and 4. To respond to these concerns, we have added a new section to Core B that provides a flow chart (Figure CB-1, p. 413) illustrating the involvement of a single participant/family. We have also been more specific about the time requirements for each of the projects, including tables CB- 5 (p. 435) and CB- 6 (p. 438). summarizing the time required for the interviews, rating scales, and psychometric assessments. However, please note that we completed Core B (n = 457) and either Project 2 (N-158) with multiple assessments, as well as up to three other projects on approximately 200 participants in the first five years of funding. Participation in these studies required about 4 hours for the Core B psychometric assessment and an hour for the MRI (5 hours), and about 3-4 hours for each of the other three school-age projects. That is a total of about 16 hours if the family and child volunteered for each component, which most who were eligible did. We did not require participation in all 3 components, but most who volunteered did complete all 3 projects. For those who did not continue, they were either not eligible, or found the Core B component all they could handle. In this revision, we have reduced the amount of time for the Core B psychometric assessment (less than 3 hours), and also reduced the time that would be required for Project 3 (2.5 hours for children;3.5 hours for adults). Project 4 is setup to require a 3-4 hour visit, but is divided by a lunch break. It only occurs in Houston, does not involve Project 2 until the end of the 9.5 year follow-up, and can be completed without participants volunteering for all experiments. Therefore, an individual who agrees to participant in Core B, Project 3, and one of the projects for experiment is making a commitment of about 9 hours, a significant reduction from the first 5 years. In addition, Project 3 does not require that the participant attend the Center. It is fully portable. The proposed participant burden is consistent with the commitment that families have made in the past. It is consistent with what we have asked of our participants in other studies. Families are very committed to these research projects. They are aware that this study is one of only a few studies oriented to spina bifida supported by NIH. We also provide benefits in the way of a written report that is highly motivating to parents, consultation about school-related issues and development, a book on education issues for children with spina bifida written specifically for this project, and a clinical interpretation of the MRI, all of which are highly motivating to parents. We provide flexible scheduling and are available on weekends and in the summers. Families are reimbursed for parking, transportation, and time The bottom line is that we were successful in collecting data that placed a greater burden on participants in the in the previous cycle and do not anticipate problems in the next cycle.

[unreadable] DESCRIPTION (provided by applicant): The purpose of this application is to respond to RFA-HD-04-027 by developing a multi-disciplinary research center on learning disabilities (LD), the Texas Center for Learning Disabilities. Consistent with the goals of the RFA, we will focus on definition and measurement issues, intervention in preventative (younger students) and remedial (older students) modes, and the neurobiological correlates of LD. The central theme is that response to instruction (RTI) operationalizes the historically prominent component of the LD construct, "unexpected underachievement." Whereas approaches to identification typically have viewed performance on cognitive tests and the application of exclusionary criteria as the primary markers for "unexpected underachievement," such approaches have not been supported by classification research over the past two decades. Rather, it has become increasingly clear that "unexpected underachievement" can only be understood in children who have received high quality instruction and respond inadequately to instruction that is effective with most students. Thus, to establish a reliable and valid classification of LD, inadequate responders should be systematically studied from instructional, neurobiological, and cognitive perspectives. To accomplish these goals, we propose a multi-disciplinary center involving researchers with backgrounds in neuropsychology, cognitive neuroscience, reading intervention, special education, and methodology to work together in a LD Center that includes four Projects and three Cores. Project 1 (Classification) evaluates definition and classification issues pertinent to RTI models of identification, including the reliability and validity of classifications based on RTI. Project 2 (Early Intervention) provides randomized controlled studies of Grade 1 children at-risk for reading difficulties, including enhanced reading instruction at a secondary level (Tier II) and more intense tertiary interventions for students who do not respond adequately to Tier II instruction. Project 3 (Remediation) involves randomized controlled trials of studies of middle schoolers with identified reading problems using a multi-tiered approach and tertiary interventions with students who do not respond to enhanced reading instruction at Tier II. Project 4 (Magnetic Source Imaging) will provide functional neuroimaging studies of reading component subtypes defined in Project 1, and the intervention outcomes in Projects 2 and 3. It specifically addresses the validity of RTI classifications, compares responders and inadequate responders, and evaluates response to tertiary interventions. The Cores include the Administrative Services Core (A), the Database and the Statistics Core (B), and the Dissemination Core (C). This research center will support research that leads to a more comprehensive classification of LD, a more integrated understanding of intervention at different levels and intensities for children with reading problems, and provide important cross-discipline insights into the nature of LD. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): We seek support to analyze existing data from the Oregon Adolescent Depression Project (OADP) to better understand the long-term course and outcome of major depressive disorder (MOD). The OADP is a multi-generational project that includes a study of prevalence and risk factors for adolescent psychopathology in a large community sample; a longitudinal follow-up of probands' diagnostic course and psychosocial outcomes through young adulthood; a family study of their 1st-degree relatives; and a longitudinal study of their children. We seek to extend prior work with this data set by addressing three broad issues that integrate these components using state of the art data analytic techniques. 1. Psychosocial Functioning and Depressive Symptoms: Growth. Predictors, and Outcomes. Little is known about distinct courses and outcomes of depressive symptoms and psychosocial functioning. We will identify distinct growth trajectories in and reciprocal relations between these areas through young adulthood, and examine prospective predictors and long-term outcomes of distinct trajectories. Identification of unique growth patterns, their risk factors, and their outcomes will have important screening, prevention, and treatment implications for reducing the long-term burden of depression. 2. MOD: Comorbidity. Growth, and Long-term Outcomes. MOD often co-occurs with other psychiatric disorders, particularly substance use disorders (SUDs) and anxiety disorders (ANX). Although MOD comorbidity is associated with elevated impairment in numerous domains, little is known about its etiology and long-term impact. We will examine MDD-SUD and MDD-ANX comorbidity models based upon patterns of risk and protective factors and long-term outcomes of pure and comorbid disorders. Identification of prospective predictors and long-term outcomes of comorbidity will improve nosology and inform screening and prevention strategies. 3. Intergenerational Outcomes: Transmission of Psvchopathology across Three Generations. Evidence indicates that MOD is familial, yet the circumstances under which and mechanisms by which MOD is transmitted across generations remain unknown. We will examine moderational and mediational models of transmission between grandparents, parents, and children, and examine the diagnostic specificity of intergenerational transmission of psychopathology. We will also examine risk and protective factor profiles according to familial MDD patterns. Uncovering the conditions, mechanisms of, and risk and protective factors for MDD transmission across generations will have important implications for identifying those at risk for the disorder and point to potential targets for intervention. [unreadable] [unreadable] [unreadable] [unreadable]

Project 2. Response to Early Reading Intervention and the Identification of Learning Disabilities The 2004 reauthorization of IDEA brings the use of student response to instruction (RTI) as an element in the identification of learning disabilities (IDs) into practice in American schools. In Project 2, we seek to address gaps in knowledge that must be filled as RTI models are implemented, particularly questions pertaining to (a) the precise nature of the instruction to which response should be measured and (b) the long-term implications of response to this instruction in terms of IDs in word-level reading, reading fluency, and comprehension. Our objective is to systematically study variables related to RTI and student outcomes in multi-tiered reading intervention provided in Grades 1-2. We propose 3 specific aims. Specific Aim 1 will determine differences in outcomes and long-range consequences of RTI within 2 competing intervention models for students in Grade 1: (a) a problem-solving model derived from behavioral consultation in which classroom teachers provide individualized prereferral interventions and (b) a standard protocol supplemental intervention provided outside the classroom and based on reading intervention research. Specific Aim 2 will determine the effectiveness of RTI in (a) individualized intervention (the standard in special education) and (b) standardized intervention with a comprehensive, sequential reading program, both provided to students with inadequate response to Grade 1 intervention. Specific Aim 3 will determine the impact of various student characteristics, teacher characteristics, and intervention implementation characteristics on student response to this intervention. To address these aims, we propose a longitudinal study (with 1-2 years of follow-up) of three Grade 1 cohorts (176 students per year, 528 total) across two sites (Houston, Austin). First graders at-risk for reading difficulty will be randomly assigned to receive 20 weeks of either problemsolving or standardized protocol intervention. Students whose RTI fails to meet multiple criteria will participate in 30 weeks of highly intensive Tier III intervention in Grade 2, comparing the effectiveness of (a) individualized and (b) standardized intensive intervention. The proposed research will enhance our understanding of the practices related to classification, definition, and treatment of reading and readingrelated IDs and enable the implementation of practical, valid RTI models in our schools. It will significantly inform both processes related to identification of IDs and instructional decisions for students with IDs identified within a RTI model.

The objectives of Core A are to a) facilitate the conduct and productivity of the overall research center, and b) provide proper oversight of fiscal management and institutional communication to ensure timely responses to the needs of each investigator, project, and core. Dr. Jack Fletcher, University of Houston, is the core director and Principal Investigator of the Texas Center for Learning Disabilities (TCLD). The Co-PI of Core A and the TCLD is Dr, Sharon Vaughn, University of Texas-Austin. Dr. Fletcher and Vaughn are experienced investigators and administrators and have worked together for the past 14 years, including the last 5 years as PI and Co-PI of the TCLD. Decision-making and the overview of quality control occurs through monthly conference calls between the PI and members of the Executive Committee. There are meetings of the Houston and Austin groups every 6 months and monthly conference calls that are focused on Joint efforts at data collection, reviews of quality control efforts, and paper productivity. Core A works closely with Core B (Services) on dissemination and training and with Core C (Data) and Core D (assessment and Recruitment on cross-site quality control issues. There is a formal data sharing plan for each project, but we also allow other individuals outside the center to access data that does not conflict with efforts at accomplishing the primary aims of each project. Altogether, Core A has effectively managed the TCLD over the past 5 years, with a strong publication record, established mechanisms for training and dissemination, and other accomplishments.

The purpose of this proposal is to respond to RFA-HD-12-202 by continuing a multi-disciplinary research center on learning disabilities (LD), the Texas Center for Learning Disabilities. Consistent with the goals of RFA, we focus on definition and measurement issues, executive functions, interventions addressing reading comprehension, and the neurobiological correlates of LD. The central theme is that assessments of instructional response operationalize the historically prominent component of the LD construct, unexpected underachievement, which must be evaluated in children who respond inadequately to instruction, establish a reliable and valid classification of LD, inadequate responders should be systematically studied from instructional, neurobiological, and cognitive perspectives. To accomplish these goals, we propose to continue a multi-disciplinary center that includes four Projects and four Cores. Project 1 (Classification and Integration) continues to evaluate classification issues pertinent to LD through evaluation of actual data and simulated data, including the reliability and validity of classifications based on RTI. Project 1 also continues empirical syntheses involving the correlates of intervention response (including executive functions) and intervention outcomes. Project 2 (Executive Functions) provides a measurement study designed to address differences in models of executive functions from frameworks in neuropsychology, cognitive neuroscience, and education. It also introduces three design experiments on the role of executive functions in reading comprehension intervention. Project 3 (Intervention) follows up the previous 5 years of intervention research with 2 two-year randomized controlled trials of studies of Grade 4 students with identified reading comprehension problems. In Study 1, comparisons are made of Language/Knowledge or Skills/Strategies vs. Business as Usual (BAU). Study 2 compares a hybrid intervention in which the Study 1 interventions are integrated with and without executive functioning elements based in part on the design experiments in Project 2. Project 4 (Neuroimaging) will provide structural and functional neuroimaging studies of children who respond adequately and inadequately to Project 3 interventions, imaging executive function, word level, and sentence comprehension tasks. The Cores include the Administrative Services Core (A), the Service Core (B), the Data Management and Statistics Core (C), and the Assessment and Recruitment Core (D).

Core B (Engagement) Summary The specific aims for Core B (Engagement) of the Texas Center for Learning Disabilities (TCLD) are 1) Dissemination: to establish, maintain, and enhance strategic connections with researchers, clinicians and educators for the purpose of disseminating findings, informing practice and influencing policy; 2) Data Sharing: to coordinate intra- and extra-TCLD resource and data sharing; 3) Career Enhancement: to provide project-embedded, career-enhancing research opportunities to early-career scholars; and 4) Pilot Grants: to solicit, review, and select applications for pilot studies focusing on early career scholars.Dr. Greg Roberts will be the Core B Director. He will work closely with Dr. Jack Fletcher as overall PI of the TCLD and Co-PI on Core B as well as Dr. Sharon Vaughn as overall Co-PI and Co-PI of Core B to address the Core B objectives. Drs. Roberts, Fletcher, and Vaughn will coordinate with Project PIs and Core Directors (the Executive Committee) to plan, implement, and evaluate progress towards benchmarks for each of the four aims and the Core B will continue to operate a website that translates and disseminates research findings and evidence-based practices relevant to researchers and practitioners. These materials will include external resources, lesson plans from Project 3 (Intervention), research summaries under Education Research Matters, and TCLD research findings. Under Aim 2, data sharing plans will be implemented for investigators working within the center and for interested external investigators. Under Aim 3, early career researchers at the graduate student, post-doctoral fellow, and junior faculty levels will be embedded across the Center's program of research to support their developing careers as researchers in learning disabilities. Aim 3 will also provide career-enhancing opportunities to more-senior investigators interested in broadening their research to include LD-related topics. Under Aim 4, Core B will oversee and evaluate the proposed ancillary pilot projects Publication Plan. Under Aim 1, awarded to LDRC early career researchers and to more-senior investigators who are beginning programs of research into learning disabilities. Core B will also initiate and manage the required Publication Plan and facilitate the utilization of technology to foster engagement among other LDRC sites and investigators and to target dissemination activities.

There is insufficient research-based data on remedial interventions for children and adolescents who do not receive early interventions or receive them and show persistent reading difficulties. This is especially true for students who are English learners (Els), where there is relatively little research addressing Els in middle schools at a point when their reading problems are significantly disabling and presage adverse academic and behavioral outcomes associated with reading disabilities. Consistent with the RFA, we focus on Els as a group that is historically underserved and at a time in their development when it is possible to deliver reading comprehension interventions sufficiently intense to ameliorate a host of adverse outcomes. From a scientific perspective, the focus on persistent reading difficulties in any sociodemographic subgroup is important given the small effects associated with remedial interventions, which is compounded by the lack of research on adolescent Els. Aim 1 determines the efficacy of reading comprehension interventions integrating attention and self-regulation practices for Els in Grades 7 and 8 with persistent reading difficulties. Building on previous intervention studies we have conducted with students in Grades 4 through 8 over the past 10 years111, we propose a longitudinal, double-cohort design utilizing a randomized control trial assigning students to supplemental reading intervention or a ?business as usual? control condition (i.e., Cohort 1 ? Years 1 and 2; 205 students in treatment and 205 in control condition; Cohort 2 ? Years 3 and 4; 205 students in treatment and 205 in control condition; total 410 in each condition). Students in each cohort will be treated for 2 years (i.e., 7th and 8th grade) and then followed for one year (9th grade). Aim 2 determines the impact of co- occurring conditions such as attention problems and English language proficiency on a range of student outcomes including reading-related outcomes, math outcomes, and writing outcomes. Aim 3 examines student characteristics and contextual factors associated with response to intervention as a means of informing treatment decisions, and to determine the extent to which response to intervention can be predicted initially and longitudinally from students' characteristics (e.g., attention) and contextual factors (e.g., teachers' knowledge, school effectiveness ratings). Project 3 (Intervention) is closely tied by its longitudinal design to Projects 2-5, including the epigenetic focus of Project 5 (Epigenetics), and conceptually to Project 1 (Integration), with its focus on syntheses of intervention practices and reciprocal cross-project analyses. It is expected that this robust model of examining the efficacy of improving reading comprehension and outcomes primarily for reading and secondarily for writing for students in the middle grades will yield high impact on instructional practices for remediating reading difficulties generally, and specifically in Els.

Core A Summary The objectives of Core A (Administration) are to 1) manage the research program of the center to facilitate overall research productivity by promoting communication and interaction among the investigators, graduate students and post-doctoral fellows, cores, and the scientific advisory committee; 2) provide cost-effective oversight of financial management and institutional communication to ensure timely responses to the needs of each investigator, project, and core; and 3) leverage the resources of the center through additional support and philanthropy. For Aim 1 (Management), Dr. Jack Fletcher, University of Houston, is the Core Director and Principal Investigator of the Texas Center for Learning Disabilities (TCLD). The Co-PI of Core A and the TCLD is Dr. Sharon Vaughn, University of Texas-Austin. Dr. Fletcher and Vaughn are experienced investigators and research administrators and have worked together for the past 20 years on numerous research projects, including the last 10 years as PI and Co-PI of the TCLD. Decision-making and the overview occurs through monthly conference calls among the PI, Co-PI, and members of the Executive Committee. There are face-to- face meetings of the Houston and Austin groups every 6 months and monthly conference calls focused on joint efforts at data collection, risk mitigation, and paper productivity. We have plans in place for mitigation of issues involving execution of the research program and risks to human participants. For Aim 2 (Efficiency and Institutional Communication), we operate from our bases in the three university centers supporting the TCLD. Efficient procedures are in place for creating accounts, establishing subcontracts, and managing post award reconciliation and processing of orders and payments. Core A works closely with Core C (Data) and Core D (Assessment and Recruitment) on ensuring cross-site quality control. There are established working relations with the research divisions and IRBs at each institution. For Aim 3 (Leverage) we have secured direct subsidies from our Universities and external support for center activities through the Texas Education Agency (TEA) for our previous 10 year funding cycle and philanthropy through the Texas Consortium on High Risk Children (Texas Consortium) and anticipate future support from these groups. Core A works closely with Core B (Engagement) on dissemination and training, with an emphasis on promoting diversity and inclusion with respect to the research and the researchers. Core A has effectively managed the TCLD the past 10 years, with a strong publication record, reliable financial management, established mechanisms for publications, training and dissemination, and other accomplishments that make our Center efficient, effective, synergistic, and cohesive.