Jennifer B. Thomson

Instructional treatment associated with changes in brain activation in children with dyslexia

Objective: To assess the effects of reading instruction on fMRI brain activation in children with dyslexia. Background: fMRI differences between dyslexic and control subjects have most often involved phonologic processing tasks. However, a growing body of research documents the role of morphologic awareness in reading and reading disability. Methods: The authors developed tasks to probe brain activation during phoneme mapping (assigning sounds to letters) and morpheme mapping (understanding the relationship of suffixed words to their roots). Ten children with dyslexia and 11 normal readers performed these tasks during fMRI scanning. Children with dyslexia then completed 28 hours of comprehensive reading instruction. Scans were repeated on both dyslexic and control subjects using the same tasks. Results: Before treatment, children with dyslexia showed less activation than controls in left middle and inferior frontal gyri, right superior frontal gyrus, left middle and inferior temporal gyri, and bilateral superior parietal regions for phoneme mapping. Activation was significantly reduced for children with dyslexia on the initial morpheme mapping scan in left middle frontal gyrus, right superior parietal, and fusiform/occipital region. Treatment was associated with improved reading scores and increased brain activation during both tasks, such that quantity and pattern of activation for children with dyslexia after treatment closely resembled that of controls. The elimination of group differences at follow-up was due to both increased activation for the children with dyslexia and decreased activation for controls, presumably reflecting practice effects. Conclusion: These results suggest that behavioral gains from comprehensive reading instruction are associated with changes in brain function during performance of language tasks. Furthermore, these brain changes are specific to different language processes and closely resemble patterns of neural processing characteristic of normal readers.

Investigation of a Direct Intervention for Improving Attention in Young Children With ADHD

The efficacy of a new set of child-oriented direct intervention materials, Pay Attention! (1994), was investigated in 14 children, ages 7 to 11 years, diagnosed with attention deficit hyperactivity disorder (ADHD). Treatment and control groups were matched for age, sex, and medication status. Both groups completed pre- and posttraining assessment batteries that included psychometric measures of attention, a measure of academic efficiency, and behavioral rating scales completed by parents and teachers. Results indicate that children who received the direct intervention did significantly better on a number of nontrained measures of attention and academic efficiency. Behavioral ratings of inattention-impulsivity and hyperactivity completed by parents did not differ following treatment, although a marginally significant improvement in inattention-impulsivity was noted by school teachers. These results suggest that direct interventions aimed at improving attention may be a valuable treatment option for improvi...

Modeling Phonological Core Deficits Within a Working Memory Architecture in Children and Adults With Developmental Dyslexia

Recent theoretical advances in working memory guided analyses of cognitive measures in 122 children with dyslexia and their 200 affected biological parents in families with a multigenerational history of dyslexia. Both children and adults were most severely impaired, on average, in three working memory components— phonological word-form storage, time-sensitive phonological loop, and executive functions involving phonology. Structural equation modeling showed that, for children, first-order factors from the phonological, orthographic, and/or morphological word forms uniquely predicted 11 reading and writing outcomes but, for adults, a second-order factor (reflecting interrelationships among the three first-order word-form factors) was more likely to be significant in predicting the same reading and writing outcomes. Structural equation modeling of the three working memory component factors showed that the most consistent predictor of text-level reading and writing for both children and adults was the second-order word-form factor. Phonological loop and executive support could be modeled as separate factors in children but only as combined factors in adults. Executive support in children and combined phonological loop and executive support in adults contributed uniquely to oral reading but did not contribute uniquely to reading comprehension or written expression. For both children and adults, individual differences occurred as to which of the three working memory components or three word forms fell outside the normal range.

Language Phenotype for Reading and Writing Disability: A Family Approach.

A theory-driven battery of 23 psychometric measures of reading, writing, and related language processes was administered to 102 probands (affected children in Grades 1 to 6 with documented reading problems, writing problems, or both) and both of their biological parents. Affected children and parents were compared on the structural relationships between related language processes (Verbal IQ [VIQ], orthographic, phonological, and rapid naming skills), component reading, (accuracy, rate, comprehension) and writing (handwriting, spelling, composition) skills. The orthographic factor had significant paths to all reading and writing skills, except reading comprehension, in both probands and adults. The phonological factor had significant paths to all reading and writing skills except reading rate and handwriting in probands, but in affected adults only if VIQ was removed. Rapid naming had significant paths only to reading rate in probands and adults. VIQ had significant paths to reading comprehension in probands and adults, and to reading accuracy, reading rate, spelling, and composition in affected adults, but not probands. These results are consistent with the claim of functional systems theory that the same language processes are orchestrated flexibly depending on task at hand. Results for across-age differences in the covariances among related language processes confirmed developmental predictions of connectionist theory. The number of language deficits (based on discrepancy from VIQ) uniquely predicted severity of reading and writing problems in children and spelling problems in adults.

Linkage analyses of four regions previously implicated in dyslexia: Confirmation of a locus on chromosome 15q

Dyslexia is a common, complex disorder, which is thought to have a genetic component. There have been numerous reports of linkage to several regions of the genome for dyslexia and continuous dyslexia‐related phenotypes. We attempted to confirm linkage of continuous measures of (1) accuracy and efficiency of phonological decoding; and (2) accuracy of single word reading (WID) to regions on chromosomes 2p, 6p, 15q, and 18p, using 111 families with a total of 898 members. We used both single‐marker and multipoint variance components linkage analysis and Markov Chain Monte Carlo (MCMC) joint segregation and linkage analysis for initial inspection of these regions. Positive results were followed with traditional parametric lod score analysis using a model estimated by MCMC segregation analysis. No positive linkage signals were found on chromosomes 2p, 6p, or 18p. Evidence of linkage of WID to chromosome 15q was found with both methods of analysis. The maximum single‐marker parametric lod score of 2.34 was obtained at a distance of 3 cM from D15S143. Multipoint analyses localized the putative susceptibility gene to the interval between markers GATA50C03 and D15S143, which falls between a region implicated in a recent genome screen for attention‐deficit/hyperactivity disorder, and DYX1C1, a candidate gene for dyslexia. This apparent multiplicity of linkage signals in the region for developmental disorders may be the result of errors in map and/or model specification obscuring the pleiotropic effect of a single gene on different phenotypes, or it may reflect the presence of multiple genes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148‐7299:1/suppmat/index.html.

A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency.

Dyslexia is a common and complex developmental disorder manifested by unexpected difficulty in learning to read. Multiple different measures are used for diagnosis, and may reflect different biological pathways related to the disorder. Impaired phonological decoding (translation of written words without meaning cues into spoken words) is thought to be a core deficit. We present a genome scan of two continuous measures of phonological decoding ability: phonemic decoding efficiency (PDE) and word attack (WA). PDE measures both accuracy and speed of phonological decoding, whereas WA measures accuracy alone. Multipoint variance component linkage analyses (VC) and Markov chain Monte-Carlo (MCMC) multipoint joint linkage and segregation analyses were performed on 108 families. A strong signal was observed on chromosome 2 for PDE using both VC (LOD=2.65) and MCMC methods (intensity ratio (IR)=32.1). The IR is an estimate of the ratio of the posterior to prior probability of linkage in MCMC analysis. The chromosome 2 signal was not seen for WA. More detailed mapping with additional markers provided statistically significant evidence for linkage of PDE to chromosome 2, with VC-LOD=3.0 and IR=59.6 at D2S1399. Parametric analyses of PDE, using a model obtained by complex segregation analysis, provided a multipoint maximum LOD=2.89. The consistency of results from three analytic approaches provides strong evidence for a locus on chromosome 2 that influences speed but not accuracy of phonological decoding.

Segregation Analysis of Phenotypic Components of Learning Disabilities. I. Nonword Memory and Digit Span

Dyslexia is a common and complex disorder with evidence for a genetic component. Multiple loci (i.e., quantitative-trait loci [QTLs]) are likely to be involved, but the number is unknown. Diagnosis is complicated by the lack of a standard protocol, and many diagnostic measures have been proposed as understanding of the component processes has evolved. One or more genes may, in turn, influence these measures. To date, little work has been done to evaluate the mode of inheritance of individual component-as opposed to composite-phenotypes, beyond family or twin correlation studies that initially demonstrate evidence for a genetic basis of such components. Here we use two approaches to segregation analysis in 102 nuclear families to estimate genetic models for component phenotypes associated with dyslexia: digit span and a nonword-repetition task. Both measures are related to phonological skills, one of the key component processes in dyslexia. We use oligogenic-trait segregation analysis to estimate the number of QTLs contributing to each phenotype, and we use complex segregation analysis to identify the most parsimonious inheritance models. We provide evidence in support of both a major-gene mode of inheritance for the nonword-repetition task, with approximately 2.4 contributing QTLs, and for a genetic basis of digit span, with approximately 1.9 contributing QTLs. Results obtained by reciprocal adjustment of measures suggest that genes contributing to digit span may contribute to the nonword-repetition score but that there are additional QTLs involved in nonword repetition. Our study adds to existing studies of the genetic basis of composite phenotypes related to dyslexia, by providing evidence for major-gene modes of inheritance of these single-measure component phenotypes.

Effects of Prior Attention Training on Child Dyslexics' Response to Composition Instruction

Twenty children (Grades 4 to 6) who met research criteria for dyslexia were randomly assigned to a treatment (attention training) or contact control (reading fluency training) group during their regular language arts block at a school that had emphasized multisensory, structured language treatment for reading disability. A university team provided either individual attention training (sustained, selective, alternating, and divided attention) or reading fluency training during the first 10 sessions and group composition instruction during the next 10 sessions. Analysis of variance evaluated the significance of Treatment × Session interactions from pretest to midtest (before composition instruction began) and midtest to posttest (when compositon instruction ends). Treatment × Time interactions were not significant between pretest and midtest, but the Treatment × Time interactions were significant from midtest to posttest for Wechsler Individual Achievement Test, Second Edition Written Composition and Delis–Kaplan Executive Function System Verbal Fluency (attention treatment group improved more over time). Individual children showed the same pattern as group results. For child dyslexics in upper elementary school, attention training did not transfer directly to improved composition but prior attention training led to faster improvement in composing and oral verbal fluency once composition instruction was introduced. Effective instruction for dyslexia may depend on the sequencing as well as the nature of instructional components and require specialized instruction for writing as well as reading.

Segregation analysis of phenotypic components of learning disabilities. II. Phonological decoding

Dyslexia is a common, complex disorder, which is thought to have a genetic component. The study of the genetics of dyslexia is complicated by a lack of consensus on diagnostic criteria, and the probability of genetic heterogeneity—it is possible that deficits in different language processes are caused by different underlying genes. In order to address these difficulties, we study continuous phenotypes that are part of the psychometric test batteries often used to diagnose dyslexia. Prior to embarking on a linkage study, it is helpful to employ segregation analysis, both to identify phenotypes that may be amenable to mapping by linkage analysis, and to determine the best models to use for model based analyses. We study 409 people in 102 nuclear families, and employ (1) oligogenic segregation analysis to estimate the number of quantitative trait loci (QTLs) contributing to each phenotype, and (2) complex segregation analysis in order to identify the most parsimonious inheritance model. In this paper, we consider two measures of phonological decoding ability—word attack and phonemic decoding efficiency. We find evidence for one or two genes of at least modest effect contributing to phonemic decoding efficiency, and the best fitting model is a dominant major gene model with residual familial correlations. For word attack, we find evidence for one or two genes of at least modest effect, and the variation in the trait is best explained by a polygenic model.

Implementation of a compensatory memory system in a school age child with severe memory impairment

Impairments in memory and new learning secondary to neurological illness or injury pose significant problems for school age children. This paper describes the development and implementation of compensatory memory aids for an adolescent girl who demonstrated significant memory impairment following irradiation for an intracranial tumour. Strategies for integrating the system with the students academic programme and school-related activities, and involvement of school personnel are emphasized, as is a theoretically and behaviourally based training programme.