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Biomedical subjects

S E Shaywitz

Publications and source records attributed to S E Shaywitz.

At least 37 records · Page 2Linked to original sources

Attention-deficit/hyperactivity disorder.

In this chapter we have reviewed the diagnosis and management of attention deficit disorder, focusing particularly on the role of stimulant therapy in ADHD. Hisorical review suggests that ADHD has roots that extend back almost a century. The definition of ADHD is based on inclusion and exclusion criteria that are established by history and reflect behavioral concerns. Attention-deficit/hyperactivity disorder is a chronic disorder affecting the child's home, school, and community life. The primary symptoms of the disorder manifest a developmental pattern: activity diminishes while attentional deficits persist. Major sources of concern are the secondary and often more resistant problems of learning difficulties, behavioral problems, lack of peer acceptance, and low self-esteem. An often frustrating and perplexing characteristic of the disorder is its marked variability-over time, across situations, and within the same child and similar situations. Educational management represents an important priority and often forms the cornerstone of all other therapies, nonpharmacologic or pharmacologic. Cognitive-behavioral therapies represent the most widely used alternative to pharmacotherapy. Although the effects of CBT alone are disappointing, recent studies suggest that such therapies may provide a useful adjunct to pharmacotherapy and may be helpful when children are tapered off medication. Psychotherapy, or a combination of psychotherapy and medication (termed multimodality therapy), may also be useful. Pharmacotherapy for ADHD originated almost 60 years ago, and at this time the ameliorative effects of medications in ADHD are well established. The general skepticism of experienced clinicians, coupled with a climate where parents are reluctant to medicare children, serves to limit their use except where indicated. Although the effects of stimulants on attention and activity seem well established, effects on cognition, conduct, and social behavior are more controversial. Within recent years, a great deal has been learned about the pharmacokinetics of stimulants in children with ADHD, providing a rational basis for administration. It is also clear that side effects are minimal, the most serious being the possibility of the emergence of tics. Whereas stimulants are clearly the most effective agents, other agents, including antidepressants, may also be effective. Recent advances may now provide an opportunity to better understand the neural and molecular basis for ADHD. Recent advances in imaging technology, particularly fMRI, offer an opportunity to examine the neural basis of ADHD, and advances in genetics may provide clues to its etiology.

Attention Deficit Disorder with Hyperactivity↗

Auditory selective attention: an fMRI investigation.

In the present experiment, 25 adult subjects discriminated speech tokens ([ba]/[da]) or made pitch judgments on tone stimuli (rising/falling) under both binaural and dichotic listening conditions. We observed that when listeners performed tasks under the dichotic conditions, during which greater demands are made on auditory selective attention, activation within the posterior (parietal) attention system and at primary processing sites in the superior temporal and inferior frontal regions was increased. The cingulate gyrus within the anterior attention system was not influenced by this manipulation. Hemispheric differences between speech and nonspeech tasks were also observed, both at Broca's Area within the inferior frontal gyrus and in the middle temporal gyrus.

Adult↗

Dyslexia.

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Adolescent↗

Cerebral organization of component processes in reading.

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.

Adult↗

Sex differences in the functional organization of the brain for language.

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.

Adult↗

Defining and classifying learning disabilities and attention-deficit/hyperactivity disorder.

This paper provides an overview of current conceptualizations of learning disabilities and ADHD, a conceptual framework critical for defining and classifying each disorder and for distinguishing each disorder from the other and from other, less common problems of childhood. At a most basic level, reading disability or dyslexia (the most common and best defined of the learning disabilities) and ADHD represent two distinct disorders that may frequently cooccur in the same unfortunate child but that can be clearly distinguished from one another. Reading disability represents a disorder of cognitive functioning. In contrast, ADHD is defined by the child's behavior as perceived by the child's parents and teachers; ADHD thus refers to a disorder affecting primarily the behavioral domain. Within the last decade, considerable progress has been made in our understanding of reading and reading disability. Converging evidence from several lines of investigation now indicates that reading ability conforms to a normal distribution model, so that there is a continuum of reading ability and reading disability. Children along this continuum differ by degree but not in kind. Cutoff points may be instituted to segment this continuous distribution, but these will be arbitrary and will not reflect any natural joints in nature; there is no second mode or "hump" in the distribution of reading ability. The normal model of reading and reading disability indicates that reading disability is related to normal reading ability, that there is a seamless transition from good to poor reading ability. Awareness of this relationship is critical to our approach to understanding the basis of reading disability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Blunted catecholamine responses after glucose ingestion in children with attention deficit disorder.

Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children with attention deficit disorder (ADD), but a physiologic mechanism has not been established. To address this issue, metabolic, hormonal, and cognitive responses to a standard oral glucose load (1.75 g/kg) were compared in 17 children with ADD and 11 control children. Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3-5 h after oral glucose (3.5 +/- 0.2 mmol/L in ADD and 3.3 +/- 0.2 mmol/L in control children). The late glucose fall stimulated a rise in plasma epinephrine that was nearly 50% lower in ADD than in control children (1212 +/- 202 pmol/L versus 2228 +/- 436 pmol/L, p < 0.02). Plasma norepinephrine levels were also lower in ADD than in control children, whereas growth hormone and glucagon concentrations did not differ between the groups. Matching test scores were lower and reaction times faster in ADD than in control children before and after oral glucose, and both groups showed a deterioration on the continuous performance test in association with the late fall in glucose and rise in epinephrine. These data suggest that children with ADD have a general impairment of sympathetic activation involving adrenomedullary as well as well as central catecholamine regulation.

Adolescent↗

Brain morphology in normal and dyslexic children: the influence of sex and age.

Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5-9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia.

Age Factors↗

Aspartame, behavior, and cognitive function in children with attention deficit disorder.

OBJECTIVE: To determine the effects of large doses of aspartame on behavior, cognition, and monoamine metabolism in children with attention deficit disorder. DESIGN: A randomized, double-blind, placebo-controlled crossover study of unmedicated children meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed) criteria for attention deficit disorder. SETTING: Behavioral assessments were performed in the child's home by their parents and in the classroom by a teacher. Cognitive tests were administered and blood drawing was performed during a 2-day inpatient admission to our Children's Study Center. INTERVENTIONS: Administration of aspartame (single morning dose, 34 mg/kg) or placebo for alternate 2-week periods. MAIN OUTCOME MEASURES: Behavioral and cognitive tests included the Matching Familiar Figures Test (MFFT), Children's Checking Task (CCT), the Airplane Test, the Wisconsin Card Sorting Test (WCST), the Subjects Treatment Emergent Symptom Scale (STESS), the Multigrade Inventory for Teachers (MIT), and the Conners Behavior Rating Scale. Blood was drawn for complete blood cell count and liver function tests, as well as amino acid, methanol, formate, serotonin, and monoamine metabolite analyses, and urine was collected for measurement of catecholamine and monoamine metabolite excretion. RESULTS: No clinically significant differences between aspartame and placebo were found for the STESS, MIT, or Conners ratings, or for the MFFT, CCT, WCST, or Airplane cognition tests. Also, no differences were noted for any of the biochemical measures, except for the expected increase in plasma phenylalanine and tyrosine following aspartame. CONCLUSIONS: The findings indicate that aspartame at greater than 10 times usual consumption has no effect on the cognitive and behavioral status of children with attention deficit disorder. In addition, aspartame does not appear to affect urinary excretion rates of monoamines and metabolites.

Adolescent↗

Evidence that dyslexia may represent the lower tail of a normal distribution of reading ability.

BACKGROUND: Dyslexia is now widely believed to be a biologically based disorder that is distinct from other, less specific reading problems. According to this view, reading ability is considered to follow a bimodal distribution, with dyslexia as the lower mode. We hypothesized that, instead, reading ability follows a normal distribution, with dyslexia at the lower end of the continuum. METHODS AND RESULTS: We used data from the Connecticut Longitudinal Study, a sample survey of 414 Connecticut children who entered kindergarten in 1983 and were followed as a longitudinal cohort. Dyslexia was defined in terms of a discrepancy score, which represents the difference between actual reading achievement and achievement predicted on the basis of measures of intelligence. Data were available from intelligence tests administered in grades 1, 3, and 5 and achievement tests administered yearly in grades 1 through 6. For each child there were 108 possible discrepancy scores ([3 x 3 years] x [2 x 6 years]) based on combinations of the ability scores (full-scale, verbal, and performance IQ) in each of three years and two achievement scores (reading and mathematics) in each of six years. We demonstrated that each of the discrepancy scores followed a univariate normal distribution and that the interrelation of two different discrepancy scores followed a bivariate normal distribution. At most, only 9 of 108 discrepancy scores (8.3 percent) and 171 of 3402 pairs of discrepancy scores (5.0 percent) were significantly different (at the 5 percent level) from the expected scores--well within the expected values for data with univariate and bivariate normal distributions, respectively. We also examined the stability of dyslexia over time. The normal-distribution model predicted (and the data indicated) that only 7 of the 25 children (28 percent) classified as having dyslexia in grade 1 would also be classified as having dyslexia in grade 3. CONCLUSIONS: Reading difficulties, including dyslexia, occur as part of a continuum that also includes normal reading ability. Dyslexia is not an all-or-none phenomenon, but like hypertension, occurs in degrees. The variability inherent in the diagnosis of dyslexia can be both quantified and predicted with use of the normal-distribution model.

Child↗

The validity of discrepancy-based definitions of reading disabilities.

This study addressed the validity of distinguishing children with reading disabilities according to the presence or absence of discrepancies between intelligence test scores and academic achievement. Three definitions of reading disability were used to provide criteria for five groups of children who (a) met a discrepancy-based definition uncorrected for the correlation of IQ and achievement; (b) met a discrepancy-based definition correcting for the correlation of IQ and achievement; (c) met a low achievement definition with no IQ discrepancy; (d) met criteria a and b; and (e) met none of the criteria and had no reading disability. Comparison of these five groups on a set of 10 neuropsychological tests corrected for correlations with IQ showed that group differences were small and accounted for little of the variability among groups. These results question the validity of segregating children with reading deficiencies according to discrepancies with IQ scores.

Achievement↗

Discrepancy compared to low achievement definitions of reading disability: results from the Connecticut Longitudinal Study.

We used data derived from a survey sample, the Connecticut Longitudinal Study (CLS), to compare two commonly employed definitions of reading disability: a discrepancy-based model (D) and a low reading achievement model (L). We identified children satisfying each definition in second grade and compared the groups retrospectively in kindergarten and prospectively in fifth grade using parent-based, teacher-based, and child-based measures. Our findings suggest more similarities than differences between the reading disabled groups. The most salient differences were those related to ability and seem inherent in the definitions of the groups: Children identified as D have significantly higher verbal, performance, and full scale IQ scores than those identified as L. These findings suggest that both groups of children with reading disability, that is, those defined by either D or L, should be considered eligible for special education services.

Achievement↗

The boundaries of attention deficit disorder.

This report examines distinctions and interrelationships among attention deficit disorder (ADD) and two closely related conditions: learning disability (LD) and oppositional/conduct (O/C) disorder. To evaluate our hypothesis that some of the difficulty in resolving the relationship between ADD and, particularly, O/C may reflect the consequences of selective referral patterns, we studied groups of children diagnosed as ADD from different referral sources. Results suggest that referral bias does exist and that children referred to mental health settings differ from those referred to pediatricians, child neurologists, or psychologists. Because of the nature of the subjects referred to mental health services, nonrepresentative associations may emerge. Rather than being considered as prototypical of all children with attention disorder, children referred to mental health facilities may represent simply an extreme of the continuum of ADD. Evidence suggests that many children with ADD will be represented by those referred primarily for attentional deficits and learning problems, rather than those with inattention, hyperactivity, or aggression referred for child psychiatric evaluation.

Adolescent↗

Comorbidity: a critical issue in attention deficit disorder.

In this report, we examine the interrelationships between attention deficit disorder (ADD), learning disabilities (LD), and conduct and oppositional disorders (COD). We indicate that it is reasonable to consider ADD as a distinct entity, frequently co-occurring with LD on the one hand, and COD on the other. The first section reviews the interrelationships between ADD and LD. Here we focus on definitional issues, trace the historical antecedents of ADD and LD, examine the prevalence of ADD and LD, and review studies designed to differentiate cognitive from attentional mechanisms in children with ADD, LD, or both. In the next section, we review the evidence linking ADD with COD, a distinction blurred in earlier investigations by problems with referral bias. More recent studies suggest that the antecedents, clinical characteristics, and prognosis may differ in children with ADD alone compared to those with ADD in association with COD.

Attention Deficit Disorder with Hyperactivity↗

Growth hormone and prolactin response to methylphenidate in children with attention deficit disorder.

Utilizing a double-blind, drug-placebo design, we examined growth hormone (GH) and prolactin (Pro) response to oral administration of methylphenidate (MPH) in 14 boys (ages 7.0-12.4 years) with Attention Deficit Disorder (ADD). Four conditions representing three different MPH doses (0.3 mg/kg O.D., 0.3 mg/kg B.I.D., 0.6 mg/kg O.D.) and Placebo were compared in each subject, each condition lasting for a period of 3 weeks. GH and Pro response were measured both as maximum peak GH (DGH) or nadir of Pro (DPro) as well as area under the curve for the first four hours after MPH administration (AUCGH, AUCPro). Behavioral measures included parent ratings on the Yale Children's Inventory and teacher ratings on the Yale and Conners Behavior Rating Scales and Kagan's Matching Familiar Figures Test (MFFT). Prolactin response as measured by AUCPro was significantly increased after MPH compared to placebo (t = 2.04, p less than 0.05, placebo vs all doses MPH). This difference observed for AUCPro between placebo and MPH was evident as well when we considered the number of times AUCPro declined after MPH as compared to placebo (p = .018, Fisher's exact test). Within-subjects analysis of covariance demonstrated significant correlations between the improvement in reaction time on the MFFT and 1) GH response (AUCGH, r = .58, p less than .001) and 2) prolactin response (AUCPro, r = .40, p less than .05) and between improvement in attention as measured on the Yale BRS and GH response (AUCGH, r = .57, p less than .05). Our findings suggest that measures other than GH and prolactin may be more desirable measures of brain catecholaminergic functioning.

Attention Deficit Disorder with Hyperactivity↗