Heidi M. Feldman - US grants

[unreadable] DESCRIPTION (provided by applicant): Children born prematurely are at risk for Periventricular Hemorrhage (PVH) and Periventricular Leukomalacia (PVL), lesions which lead to unilateral and multi-focal white matter damage, respectively. Children with PVH and PVL are at risk for neurodevelopmental disabilities. The goal of this study is to relate the degree and patterns of white matter damage from PVH and PVL to linguistic and cognitive outcomes. Two sophisticated MRI procedures will complement behavioral testing. Diffusion Tensor Imaging (DTI) provides detailed voxel-based quantitative information on the integrity of white matter microstructure; functional Magnetic Resonance Imaging (fMRI) characterizes the patterns of neural activity underlying cognitive skills. fMRI tasks will assess domains known to be supported in mature functioning by widely distributed brain circuitry that may be impaired after white matter injury-comprehension of syntactically complex sentences, which relies on interhemispheric integration, and oculomotor response inhibition and spatial working memory, which rely on occipital-frontal and cortical-subcortical integration. The combination of methods will allow us to link brain structure, brain functioning, and behavioral outcomes. Participants will be 40 adolescents, 9 to 14 years old, with PVH or PVL from preterm delivery. Two control groups (children born prematurely and children born at term) matched for age, gender and socioeconomic status (SES) will clarify the contribution of white matter damage versus other influences, such as age and premature delivery, on outcomes. Regression analyses will evaluate the associations of global and track-specific white matter damage and behavioral outcomes. Models will also consider the contributions of age, gender, SES, and extent of gray matter injury to white matter integrity and outcomes. Patterns of activation on fMRI will be evaluated in relation to the extent and pattern of white matter damage and to scores on the behavioral measures. We will identify cases that reveal important relations between neural structure and function. This study will contribute to understanding the outcomes of PVH and PVL, an important issue because of the large number of affected infants. It will contribute to understanding the importance of white matter connections in the normal development of cognitive processes. It will also contribute to understanding the impact of white matter injury and the development of cortical plasticity after early brain injuries. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Children born prematurely are at risk for Periventricular Hemorrhage (PVH) and Periventricular Leukomalacia (PVL), lesions which lead to unilateral and multi-focal white matter damage, respectively. Children with PVH and PVL are at risk for neurodevelopmental disabilities. The goal of this study is to relate the degree and patterns of white matter damage from PVH and PVL to linguistic and cognitive outcomes. Two sophisticated MRI procedures will complement behavioral testing. Diffusion Tensor Imaging (DTI) provides detailed voxel-based quantitative information on the integrity of white matter microstructure; functional Magnetic Resonance Imaging (fMRI) characterizes the patterns of neural activity underlying cognitive skills. fMRI tasks will assess domains known to be supported in mature functioning by widely distributed brain circuitry that may be impaired after white matter injury-comprehension of syntactically complex sentences, which relies on interhemispheric integration, and oculomotor response inhibition and spatial working memory, which rely on occipital-frontal and cortical-subcortical integration. The combination of methods will allow us to link brain structure, brain functioning, and behavioral outcomes. Participants will be 40 adolescents, 9 to 14 years old, with PVH or PVL from preterm delivery. Two control groups (children born prematurely and children born at term) matched for age, gender and socioeconomic status (SES) will clarify the contribution of white matter damage versus other influences, such as age and premature delivery, on outcomes. Regression analyses will evaluate the associations of global and track-specific white matter damage and behavioral outcomes. Models will also consider the contributions of age, gender, SES, and extent of gray matter injury to white matter integrity and outcomes. Patterns of activation on fMRI will be evaluated in relation to the extent and pattern of white matter damage and to scores on the behavioral measures. We will identify cases that reveal important relations between neural structure and function. This study will contribute to understanding the outcomes of PVH and PVL, an important issue because of the large number of affected infants. It will contribute to understanding the importance of white matter connections in the normal development of cognitive processes. It will also contribute to understanding the impact of white matter injury and the development of cortical plasticity after early brain injuries. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Each year in the U.S., one in 8 children is born prematurely and the rate of preterm birth continues to rise. Children born preterm are at substantial risk for language-based learning disabilities that may not be identified until the child enters kindergarten, a delay that precludes opportunities for early intervention. Early behavioral indicators of adverse language and cognitive outcomes are urgently needed, particularly methods that identify underlying deficits amenable to effective interventions. To meet these pressing needs, we have forged an experienced interdisciplinary team with complementary expertise in pediatrics and developmental psycho-linguistics. Our mutual long-term goals are to develop reliable and robust predictors of later outcomes for children born preterm (PT) that allow us to design effective early interventions and to elucidate the neural basis of disorders associated with prematurity and with atypical language development. Recent longitudinal studies of typically-developing infants from the Fernald laboratory have found that online measures of linguistic processing efficiency in very young children predict individual differences in language outcomes several years later. Preliminary results from a joint Feldman-Fernald effort found that 18 to 30 month old PT children had no difficulties participating in the online procedures but that PT children were slower to initiate a response and less successful at maintaining their attention compared to age-matched controls. Therefore, we propose to use these sensitive online measures in a longitudinal study of the development of language processing efficiency in PT children from 18 to 48 mos (n = 70) relative to two SES- and gender-matched comparison groups: (1) full term age-matched children (FT-AM, n = 70) with the full range of language abilities, and (2) full term language- matched children (FT-LM, n = 70) who are matched individually to the PT children on age and language level. Children will be tested longitudinally at 18, 24, 30, and 36 mos on a series of increasingly challenging, but developmentally appropriate, assessments of online language comprehension and on standardized offline tests of cognition and language. We hypothesize that PT children will perform more poorly than both groups of FT peers, and that individual differences in online processing efficiency will differentiate those children with good outcomes from those who demonstrate persistent language or associated difficulties in late preschool. We also hypothesize that clinical and/or neurological factors, such as severity of white matter injury, will correlate with language and cognitive outcomes. However, those relations will be reduced after controlling for linguistic processing efficiency, suggesting that speed and accuracy of language processing mediate the link between the neuropathology of prematurity and poor language functioning in PT children. This innovative translational project adopts a developmental psycholinguistic approach to explain individual variation in outcomes in a clinical population at high risk for language disorders, and is poised to inform future theory- and empirically-driven intervention research as well as studies of the neural basis of language disorders. PUBLIC HEALTH RELEVANCE: Children born prematurely are at substantial risk of language-based learning disabilities that may not be detected until school age, but there are considerable individual differences in outcomes. Our previous research shows that measures of speech processing efficiency in typically developing toddlers predict later success on cognitive and language tasks in childhood. In this longitudinal study from 18 to 48 mos, we examine the clinical utility of these processing measures for early identification in preterm toddlers at risk for language disorders.

DESCRIPTION (provided by applicant): Prematurity affects about 13% of the US births and its public health consequences extend far beyond the newborn period. About half of children born preterm develop cognitive, language and learning problems that adversely impact their long-term outcomes. Once these children reach school age, educational programs are dictated by their level of function in academic domains, irrespective of the underlying pathogenesis of any learning difficulties. To improve outcomes, we must ascertain whether the learning problems of children born preterm (PT) have a similar cognitive profile, neural basis, and/or developmental course as learning problems in children born full term (FT). We must also investigate if PT children respond favorably to the same interventions known to be effective in educating FT children with learning disorders. We have forged an accomplished interdisciplinary team to focus on reading skills in PT children because of the pivotal role reading plays in education and long term outcomes. The specific aims of this study are to (1) compare the cognitive profiles and neural basis of reading skills in PT and FT children using behavioral measures and diffusion tensor imaging (DTI), an magnetic resonance imaging technique that evaluates cerebral white matter microstructure, (2) determine which behavioral or neural features predict persistent good or poor reading skills in both groups and (3) pilot test an intervention to improve reading skills n PT poor readers. We will enroll 6-year old kindergarten students (PT n=50 and FT n=50), test them on a battery of reading and cognitive measures, obtain DTIs, and follow them until age 8 years when we repeat an expanded battery and DTI. We hypothesize that the PT group will perform more poorly than the FT group. We will assess if the PT group has distinctive profiles of test performance or patterns of white matter microstructure compared to FT children equated for single word reading level. We will determine which behavioral and/or neural features are associated with persistent reading difficulties two years later. In Years 4 and 5 we will recruit another sample of PT children with reading scores below the 25th percentile for age. We will pilot test a 6-week summer tutoring program using two evidence-based curricula, one focused narrowly on phonemic awareness and one focused more broadly on other aspects, including reading comprehension. We will establish the feasibility and acceptability of the intervention for families and assess if the preterm children have the attentional capacity and endurance to work in small groups of 3 for 90 minutes 5 days/week for 6 weeks. This innovative study will make a sustained impact on understanding (1) reading outcomes in PT children, (2) the neural basis of normal and abnormal reading in both PT and FT children, and (3) neural plasticity, the ability of white matter to change over time and with educational interventions. It will position us to conduct a randomized clinical trial on reading intervention in children born preterm in the subsequent phase. PUBLIC HEALTH RELEVANCE: This research program is designed to improve academic outcomes for children born preterm, a large and growing population of children at high risk for significant learning disorders. The study will determine whether poor reading skills in children born preterm have distinctive cognitive and academic profiles and different neural characteristics than poor reading skills in full-term children. We will also determine which factor at kindergarten predict those children who are likely to have long-term reading problems in each group so that the appropriate group can be targeted for early intensive reading interventions. In preparation for a randomized clinical trial of treatments, the studies will also pilot-test two interventions currently used for full term poor readers in terms of feasibility, acceptability for families, and appropriateness for the preterm poor readers.

Each year in the U.S., more than one in 10 children are born preterm (PT). Approximately half of very preterm survivors, born at < 32 weeks? gestation, develop language-based learning impairments that may be discovered late and put children at substantial risk for poor outcomes throughout their lives. Our previous grant (HD069150) convincingly demonstrated that language processing efficiency, assessed at 18 months in an eye- tracking paradigm, called looking-while-listening (LWL), was more predictive of long-term outcomes than standardized tests and parent reports. PT children who were faster at language processing at 18 months showed advantages in both verbal and non-verbal skills at 54 months. Our next step is to understand early predictors of language processing efficiency in PT children. In this renewal, we enroll PT neonates (n = 140) from two language groups, primarily English- and primarily Spanish families, to increase the diversity of our sample and to improve generalizability. We assess social-environmental predictors at 12 months (infant environment) and 18 months (toddler environment) using day-long audio recordings of the child?s language environment and naturalistic laboratory observations of caregiver-child interactions. We assess neurobiological predictors, focusing on white matter microstructure, in the neonatal period (neonatal scans) and at 12 months (infant scans). We use two complementary types of MRI scans to assess white matter axonal properties and myelin content. At 18 months, the primary outcome measure is language processing speed in the LWL task, the time it takes the child to shift eye gaze to the picture of an object that was just named. Parent reports of vocabulary and scores on a standardized test of language development are secondary measures. Our aims are to: (1) determine if properties of the infant and/or toddler environments predict language processing speed and secondary outcomes in PT children from the two language-groups; (2) determine if properties of white matter pathways, assessed from neonatal and/or infant MRI scans, predict language processing speed and secondary outcomes, after consideration of language group, clinical variables, and other covariates; and (3) investigate the contributions of social-environmental factors and white matter development on language processing speed in this diverse sample of children born PT. Our main hypothesis is that relations between language learning environments and language processing speed are mediated by changes in white matter development, suggesting that supportive learning environments impact language outcomes because learning environments advance the development of white matter microstructure. The demonstration that white matter change mediates the association of social-environmental factors on language outcomes provides a clear example of experience-dependent plasticity in the human brain. This finding would represent a theoretical contribution to models of learning and development in PT children across language groups and would inform clinical practice and early intervention for PT children who are at high risk for poor language outcomes.