Converging evidence from a number of lines of investigation indicates that dyslexia represents a disorder within the language system and more specifically within a particular subcomponent of that ...system, phonological processing. Recent advances in imaging technology, particularly the development of functional magnetic resonance imaging, provide evidence of a neurobiological signature for dyslexia, specifically a disruption of two left hemisphere posterior brain systems, one parieto-temporal, the other occipito-temporal, with compensatory engagement of anterior systems around the inferior frontal gyrus and a posterior (right occipito-temporal) system. Furthermore, good evidence indicates a computational role for the left occipito-temporal system: the development of fluent (automatic) reading. The brain systems for reading are malleable and their disruption in dyslexic children may be remediated by provision of an evidence-based, effective reading intervention. In addition, functional magnetic resonance imaging studies of young adults with reading difficulties followed prospectively and longitudinally from age 5 through their mid twenties suggests that there may be two types of reading difficulties, one primarily on a genetic basis, the other, and far more common, reflecting environmental influences. These studies offer the promise for more precise identification and effective management of dyslexia in children, adolescents and adults.
Summary The cerebral organization of word identification processes in reading was examined using functional magnetic resonance imaging (fMRI). Changes in fMRI signal intensities were measured in 38 ...subjects (19 males and 19 females) during visual (line judgement), orthographic (letter case judgement), phonological (nonword rhyme judgement) and semantic (semantic category judgement) tasks. A strategy of multiple subtractions was employed in order to validate relationships between structure and function. Orthographic processing made maximum demands on extrastriate sites, phonological processing on a number of frontal and temporal sites, and lexical-semantic processing was most strongly associated with middle and superior temporal sites. Significant sex differences in the cerebral organization of reading-related processes were also observed.
The outcome in adolescence of children diagnosed as dyslexic during the early years of school was examined in children prospectively identified in childhood and continuously followed to young ...adulthood. This sample offers a unique opportunity to investigate a prospectively identified sample of adolescents for whom there is no question of the childhood diagnosis and in whom highly analytic measures of reading and language can be administered in adolescence.
Children were recruited from the Connecticut Longitudinal Study, a cohort of 445 children representative of those children entering public kindergarten in Connecticut in 1983. Two groups were selected when the children were in grade 9: children who met criteria for persistent reading disability in grades 2 through 6 (persistently poor readers PPR; n = 21) and a comparison group of nondisabled children, subdivided into average readers (n = 35) and superior readers (n = 39). In grade 9, each child received a comprehensive assessment of academic, language, and other cognitive skills.
Measures of phonological awareness (but not orthographic awareness) were most significant in differentiating the 3 reading groups, with smaller contributions from measures of word finding and digit-span. Academic measures that best separated good from poor readers were decoding and spelling, whereas measures of math and reading comprehension did not. Measures of phonological awareness, followed next by teacher rating of academic skills were the best predictors of decoding, reading rate, and reading accuracy. In contrast, the best predictor of reading comprehension was word finding, with digit span and socioeconomic status also contributing significantly. Using a growth curve model (quadratic model of growth to a plateau) all 3 groups demonstrated similar patterns of growth over time, with the superior group outperforming the average group, and the average group outperforming the PPR group. There was no evidence that the children in the PPR group catch up in their reading skills.
Deficits in phonological coding continue to characterize dyslexic readers even in adolescence; performance on phonological processing measures contributes most to discriminating dyslexic and average readers, and average and superior readers as well. These data support and extend the findings of previous investigators indicating the continuing contribution of phonological processing to decoding words, reading rate, and accuracy and spelling. Children with dyslexia neither spontaneously remit nor do they demonstrate a lag mechanism for catching up in the development of reading skills. In adolescents, the rate of reading as well as facility with spelling may be most useful clinically in differentiating average from poor readers.
Learning to read requires an awareness that spoken words can be decomposed into the phonologic constituents that the alphabetic characters represent. Such phonologic awareness is characteristically ...lacking in dyslexic readers who, therefore, have difficulty mapping the alphabetic characters onto the spoken word. To find the location and extent of the functional disruption in neural systems that underlies this impairment, we used functional magnetic resonance imaging to compare brain activation patterns in dyslexic and nonimpaired subjects as they performed tasks that made progressively greater demands on phonologic analysis. Brain activation patterns differed significantly between the groups with dyslexic readers showing relative underactivation in posterior regions (Wernicke's area, the angular gyrus, and striate cortex) and relative overactivation in an anterior region (inferior frontal gyrus). These results support a conclusion that the impairment in dyslexia is phonologic in nature and that these brain activation patterns may provide a neural signature for this impairment.
Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of ...estrogen on verbal memory in postmenopausal women.
To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks.
Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998.
Community volunteers tested in a hospital setting.
Forty-six postmenopausal women aged 33 to 61 years (mean SD age, 50.8 4.7 years).
Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments.
Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory.
Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks.
Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.
A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such ...evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading.
Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1–9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (
n = 37), community intervention (
n = 12), and community control subjects (
n = 28).
Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions.
These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.
Two coordinated experiments using functional Magnetic Resonance Imaging (fMRI) investigated whether the brain represents language form (grammatical structure) separately from its meaning content ...(semantics). While in the scanner, 14 young, unimpaired adults listened to simple sentences that were either nonanomalous or contained a grammatical error (for example, *Trees can grew.), or a semantic anomaly (for example, *Trees can eat.). A same/different tone pitch judgment task provided a baseline that isolated brain activity associated with linguistic processing from background activity generated by attention to the task and analysis of the auditory input. Sites selectively activated by sentence processing were found in both hemispheres in inferior frontal, middle, and superior frontal, superior temporal, and temporo-parietal regions. Effects of syntactic and semantic anomalies were differentiated by some nonoverlapping areas of activation: Syntactic anomaly triggered significantly increased activity in and around Broca's area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernicke's area. These dissociations occurred when listeners were not required to attend to the anomaly. The results confirm that linguistic operations in sentence processing can be isolated from nonlinguistic operations and support the hypothesis of a specialization for syntactic processing.
DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large ...polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.
A much debated question is whether sex differences exist in the functional organization of the brain for language. A long-held hypothesis posits that language functions are more likely to be highly ...lateralized in males and to be represented in both cerebral hemispheres in females, but attempts to demonstrate this have been inconclusive. Here we use echo-planar functional magnetic resonance imaging to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.
To evaluate deficits of executive functions in children with attention-deficit/hyperactivity disorder (ADHD) classified by type (combined CT or predominantly inattentive IT) and comorbidity with ...oppositional defiant disorder (ODD) and reading disorder (RD).
The Wisconsin Card Sorting Test (WCST) and Tower of Hanoi (TOH) were administered to 28 community volunteers and 359 children (7.5-13.5 years old) divided into ADHD types, RD, and ODD.
ADHD/CT children solved fewer puzzles and violated more rules on the TOH than ADHD/IT or non-ADHD subjects. On the WCST there were no differences between diagnostic samples in perseverativeness, but ADHD/CT patients made more nonperseverative errors than ADHD/IT children. ODD was associated with moderately better TOH performance and RD with excessive rule breaks.
Executive functioning deficits were found for only ADHD/CT children and were independent of comorbidity with RD or ODD.
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