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Bennett A Shaywitz

Publications and source records attributed to Bennett A Shaywitz.

17 recordsLinked to original sources

The role of functional magnetic resonance imaging in understanding reading and dyslexia.

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 (fMRI), provide evidence of a neurobiological signature for dyslexia, specifically a disruption of 2 left hemisphere posterior brain systems, 1 parietal-temporal, the other occipital-temporal, with compensatory engagement of anterior systems around the inferior frontal gyrus and a posterior (right occipital-temporal) system. Furthermore, good evidence indicates a computational role for the left occipital-temporal system: the development of fluent (automatic) reading. In addition, fMRI studies of young adults with reading difficulties followed prospectively and longitudinally from age 5 through their mid 20s suggests that there may be 2 types of reading difficulties, 1 primarily reflecting a genetic basis, the other, and far more common, reflecting environmental influences. The brain systems for reading are malleable and their disruption in children with dyslexia may be remediated by provision of an evidence-based, effective reading intervention. These studies offer the promise for more precise identification and effective management of dyslexia in children, adolescents, and adults.

Brain↗

DCDC2 is associated with reading disability and modulates neuronal development in the brain.

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.

Adult↗

Dyslexia (specific reading disability).

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.

Age Factors↗

A quantitative analysis of prenatal methyl mercury exposure and cognitive development.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper quantifies the impact of prenatal MeHg exposure on cognitive development. Other papers quantify the beneficial impact of prenatal intake of n-3 PUFAs on cognitive function and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This analysis aggregates results from three major prospective epidemiology studies to quantify the association between prenatal MeHg exposure and cognitive development as measured by intelligence quotient (IQ). It finds that prenatal MeHg exposure sufficient to increase the concentration of mercury in maternal hair at parturition by 1 microg/g decreases IQ by 0.7 points. This paper identifies important sources of uncertainty influencing this estimate, concluding that the plausible range of values for this loss is 0 to 1.5 IQ points.

Central Nervous System↗

A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.

Central Nervous System↗

A quantitative risk-benefit analysis of changes in population fish consumption.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.

Adolescent↗

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Child↗

The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder.

OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal cortical functioning. However, these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms. METHOD: The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a randomized, double-blind, placebo-controlled pharmacological challenge with methylphenidate in 15 adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages 12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who were scanned during both a methylphenidate and a placebo session. Fourteen healthy comparison subjects (ages 12-20) who were not given methylphenidate served as the primary comparison group. RESULTS: During the divided attention task, unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects. Methylphenidate led to an increase in activation in this region but had no effect on task performance. Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects, but methylphenidate did not have a direct effect on activation in this region. CONCLUSIONS: These results suggest that ADHD is associated with abnormal processing in attentional networks, with specific dysfunction in striatal circuitry. Methylphenidate may act to normalize activity within this network.

Adolescent↗

Neural systems for compensation and persistence: young adult outcome of childhood reading disability.

BACKGROUND: This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes. METHODS: Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27). RESULTS: Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies. CONCLUSIONS: These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Adult↗

Effects of event probability and sequence on children with attention-deficit/hyperactivity, reading, and math disorder.

BACKGROUND: We investigated the impact of stimulus probability and sequence on performance and event-related potentials of 310 children classified into 12 combinations of attention-deficit/hyperactivity disorder (Not-attention-deficit/hyperactivity disorder, Inattentive and Combined subtypes) with presence/absence of reading disorder and math disorder. METHODS: Subjects pressed buttons to displays of the letters O and X, which were presented with probabilities of either .17/.83 or .50/.50. Greater response selection was required in the .17/.83 condition. RESULTS: Stimulus probability had comparable effects on all diagnostic groups. The extent of mismatch between a stimulus and preceding events elicited less systematic increases in errors, P3b latency, and P3b amplitude among both attention-deficit/hyperactivity disorder subtypes than controls. Mismatch with preceding trials more greatly reduced math disorder and reading disorder + math disorder children's speed in the Rare task and accuracy in both conditions. Math disorder and reading disorder + math disorder subjects also registered less the effects of alternations of the infrequent O on N2 amplitude and on P3b latency. CONCLUSIONS: Math disorder and reading disorder + math disorder youngsters' lower sensitivity to sequence irregularity in their event-related potentials along with greater disruption of performance suggest working memory deficits that adversely affected response selection. Comorbidity of attention-deficit/hyperactivity disorder and reading disorder did not affect the results.

Adolescent↗

Disruption of posterior brain systems for reading in children with developmental dyslexia.

BACKGROUND: Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words). METHODS: We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words. RESULTS: Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children. CONCLUSIONS: These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults.

Adolescent↗

Aspartame: review of safety.

Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. These findings are reviewed here. The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.

Affect↗

Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen.

OBJECTIVE: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability. DESIGN: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task. RESULTS: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group. CONCLUSION: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.

Adult↗

Psychometric approaches to the identification of LD: IQ and achievement scores are not sufficient.

Simulated data were used to demonstrate that groups formed by imposing cut-points based on either discrepancy or low-achievement definitions of learning disabilities (LD) are unstable over time. Similar problems were demonstrated in longitudinal data from the Connecticut Longitudinal Study, where 39% of the children designated as having LD in Grade 3 changed group placement with repeated testing in Grade 5. These results show that the practice of subdividing a normal distribution with arbitrary cut-points leads to instability in group membership. Approaches to the identification of children as having LD based solely on individual test scores not linked to specific behavioral criteria lead to invalid decisions about individual children. Low-achievement definitions are not a viable alternative to IQ-discrepancy definitions in the absence of other criteria, such as the traditional exclusions and response to quality intervention. If we accept the premise of multiple classes of low achievers, then we must develop identification systems that are valid and abandon systems whose only merits are their historical precedence and convenience.

Child↗