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Biomedical subjects

M B Denckla

Publications and source records attributed to M B Denckla.

At least 37 records · Page 2Linked to original sources
PubMed2000

Thalamic involvement in neurofibromatosis type 1: evaluation with proton magnetic resonance spectroscopic imaging.

Neurofibromatosis type 1 is a common autosomal dominant disorder associated with learning disabilities. In addition to gliomas and other tumors, T2 hyperintense lesions (unidentified bright objects or UBOs) are frequently found in the globus pallidus, cerebellum, and white matter regions. To better characterize supratentorial UBO functional significance, we studied by quantitative magnetic resonance spectroscopic imaging (MRSI) 9 male subjects with neurofibromatosis type 1 (age, 6-19 years) and 9 age-matched and sex-matched controls. Maps of the anatomical distribution of the metabolites choline (Cho), N-acetylaspartate (NAA), and creatine were calculated in four axial 15-mm slices. Absolute metabolite concentrations within UBOs, unaffected globus pallidus, and thalami demonstrated an age-related pattern, characterized by elevated Cho and relatively preserved NAA in younger subjects (<10 years) and reduced NAA and normal Cho in older subjects. These changes were found in both UBOs and thalami but were only significant for NAA, NAA/creatine, and NAA/Cho in the latter region. Decreases in NAA ratios were most severe in the thalami of subjects with UBOs in the globus pallidus, whereas UBOs showed similar but milder abnormalities than those in the thalamus. We speculate that the MRSI metabolic abnormality may represent a more generalized phenomenon, without a T2 signal counterpart in the affected brain regions. Based on the neuropathological study by DiPaolo and colleagues (1995), we postulate that Cho elevations reflect increased myelin turnover in areas of intramyelinic edema, which is followed by neuropil injury (reduced NAA). Temporal progression and behavioral correlates of these MRSI changes deserve further exploration.

Adolescent↗
PubMed1999

Corpus callosum measurements in girls with Tourette syndrome.

The objective of this study was to examine whether abnormalities in corpus callosum morphology, previously reported in boys with Tourette syndrome (TS), were also present in girls with this disorder. Among the three groups of girls-TS, TS and attention deficit hyperactivity disorder, and controls-there were no significant differences in the size of the corpus callosum or any of five individual subregions. The findings suggest that abnormalities in corpus callosum morphology in TS are a gender-related phenomenon.

Adolescent↗
PubMed1998

Premorbid prevalence of ADHD and development of secondary ADHD after closed head injury.

OBJECTIVE: To determine premorbid prevalence of attention-deficit hyperactivity disorder (ADHD) in children with moderate and severe closed head injury (CHI), to determine incidence of ADHD 1 year after injury, and to characterize children who develop ADHD by demographic, neuropsychiatric, and outcome variables. METHOD: Ninety-nine children who had severe and moderate CHI were followed up for 1 year. Premorbid and 1-year postinjury psychiatric status were ascertained by parent and child structured interviews and questionnaires measuring affective lability, aggression, apathy, and social judgment. RESULTS: Premorbid prevalence of ADHD was 0.20, significantly higher than in a reference population (0.045). Fifteen of the remaining 80 children (0.19) developed full ADHD criteria (except for age of onset) by the end of the first year. Children who developed secondary ADHD (S-ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic affective lability and aggression, posttraumatic psychiatric comorbidity, and overall disability than children who did not develop S-ADHD. CONCLUSIONS: There is an excess prevalence of premorbid ADHD among children who present with moderate and severe CHI. Children with high psychosocial adversity are more likely to develop S-ADHD after CHI. S-ADHD has criteria in common with personality change due to CHI, a deficit in behavioral inhibition being the major overlapping feature.

Adolescent↗
PubMed1998

Gender study of neuropsychological and neuromotor function in children with Tourette syndrome with and without attention-deficit hyperactivity disorder.

Neuropsychological and neuromotor functions were compared between boys and girls with Tourette syndrome (TS only), attention-deficit hyperactivity disorder (ADHD only), Tourette syndrome with ADHD (TS+ADHD), and a comparison group, in an age (mean = 10 years) and IQ (Wechsler Full-Scale mean = 111) matched sample (n = 116). There were no timed-task neuromotor differences among the groups. Analyses of variance revealed a group x gender interaction for Letter Word Fluency and the Rapid Automatized Naming test. Girls with ADHD only were faster than boys on both tasks. When data for girls only were analyzed, girls with Tourette syndrome with ADHD had the greatest variability of reaction time on the Test of Variables of Attention, and were slowest on Letter Word Fluency. Girls with TS only were slower than girls in the other three groups on Letter Word Fluency. Poor Letter Word Fluency is explained as a linguistic executive dysfunction involving speed and efficiency of memory search in this bright group of girls with Tourette syndrome, not otherwise at risk for linguistic difficulties.

Adolescent↗
PubMed1998

Evaluation of cerebellar size in attention-deficit hyperactivity disorder.

Evidence from animal and human research suggests that the cerebellum may play a role in cognition. This includes domains of executive function that are normally attributed to the prefrontal cortex and are typically deficient in individuals with attention-deficit hyperactivity disorder (ADHD). To investigate cerebellar structure in ADHD, magnetic resonance imaging morphometry was used to measure the area of the cerebellar vermis in 12 males with ADHD and 23 male controls matched for age and Wechsler Full-Scale IQ. Analyses were conducted to evaluate group differences, as well as differences between matched pairs of subjects with ADHD and those without ADHD. All measurements were corrected for overall brain size. Both analyses revealed that the size of the posterior vermis was significantly decreased in males with ADHD (P < .05 in both analyses), and that within the posterior vermis, the inferior posterior lobe (lobules VIII-X) was involved in this reduction (P < .05 for group analysis, P < .005 for matched pair analysis), while the superior posterior lobe (lobules VI/VII) was not involved in the reduction. The finding of abnormal inferior posterior vermal size suggests that dysfunction within this region of the cerebellum may underlie clinical deficits seen in individuals with ADHD.

Adolescent↗
PubMed1998

Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance.

We examined whether posterior vermis size is smaller in individuals with fragile X syndrome (fra X) than in control subjects and whether this decreased size is associated with cognitive performance. Cognitive and behavioral dysfunctions have been identified in fra X; however, underlying neuropathogenic mechanisms remain unclear. MRI was used to investigate the posterior fossa in 32 males with fra X, 28 males with other causes of cognitive disability (CD), and 38 males with normal development (ND) as well as and in 37 females with fra X and 53 female control subjects. Among females with fra X, neurocognitive correlates of posterior vermis size were examined. Posterior vermis size (cross-sectional area) in males with fra X was significantly smaller compared with CD and ND groups, particularly when corrected for intracranial area. Posterior vermis size corrected for intracranial area was significantly smaller in females with fra X compared with control subjects. Compared with males with fra X and non-fra X control subjects, posterior vermis size in females with fra X was intermediate. After statistically removing the effect of mean parental IQ, posterior vermis size predicted a significant proportion of the variance (10 to 23%) of performance on full-scale, verbal, and performance IQ; block design; categories achieved on the Wisconsin Card Sorting Test; and the Rey inventory score. The size of the posterior vermis is significantly decreased in fra X, more so in males than in females. In females with fra X, posterior vermis size predicts performance on selected cognitive measures.

Adolescent↗
PubMed1997

Neuromotor functioning in children with Tourette syndrome with and without attention deficit hyperactivity disorder.

Neuromotor function was assessed in 94 children of normal intelligence with Tourette syndrome, Tourette syndrome and attention-deficit hyperactivity disorder (ADHD), or ADHD only, using the Physical and Neurological Examination of Subtle Signs (PANESS). Time to complete six motor movements was analyzed separately by side (left and right) and complexity (simple and patterned). All groups performed faster on their preferred, dominant side. Although all groups took longer to complete patterned versus simple movements, the group with ADHD had a larger discrepancy for complexity than the other two groups. The speed for simple and patterned tasks was at or faster than age expectations for 54% of tasks in the group with Tourette syndrome but only 15% of tasks in the other two groups. More children in the group with Tourette syndrome (76%) than the groups with Tourette syndrome with ADHD (54%) or ADHD (54%) or ADHD only (65%) performed movements within normal time limits for age. Findings suggest that Tourette syndrome is not associated with motor slowing.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

The Children's Affective Lability Scale: a psychometric evaluation of reliability.

The Children's Affective Lability Scale (CALS) is a 20-item parent report measure developed to assess affect regulation in children aged 6-16. It was normed with school children in regular education classrooms and with children hospitalized in a psychiatric facility. Internal-consistency reliability, split-half reliability, and two-week test-retest reliability were excellent. Staff interrater reliability in the psychiatric sample was acceptable. Higher CALS scores were observed in an in-patient psychiatric sample than in either an out-patient or a normative sample. A principal components factor analysis yielded two components for the normative sample.

Adolescent↗
PubMed1996

Psychometric characteristics of the Children's Motivation Scale.

A 16-item Children's Motivation Scale (CMS) was developed to evaluate level of motivation in children and adolescents. The study population consisted of a normative sample of 290 school children and a clinical sample of 165 child and adolescent psychiatric patients. Test-retest, internal consistency, and interrater reliability were fair to good for both samples. Validity of the CMS was demonstrated by its ability to differentiate clinical from normative samples according to the level of motivation, by a significant correlation of the CMS with an independent measure of withdrawal, and by its lack of correlation with an independent measure of depression. Principal components analysis identified a three-component structure. These findings support the conclusion that the CMS accesses a clinically important but often overlooked psychiatric construct.

Adolescent↗
PubMed1996

Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1.

To address the controversy regarding the relationship between cognitive impairment (lowering of IQ) and magnetic resonance imaging (MRI) characteristics (T2-weighted hyperintensities or unidentified bright objects [UBOs]) in children with neurofibromatosis-1 (NF-1), we used a pairwise NF-1/ sibling design; we set out to predict the lowering of IQ in each child with NF-1 as a discrepancy from the IQ of an unaffected sibling (D-SIQ). Our multiple regression model included the age of the child with NF-1, familial or sporadic nature of the NF-1, number of locations in the child's brain occupied by T2-weighted hyperintensities (UBOs), and the volumetric percentage of brain tissue occupied by T2-weighted hyperintensities (UBOs). Only the number of locations occupied by UBOs accounted for IQ lowering (D-SIQ) in children with NF-1 (42% of the variance in D-SIQ). This is the first report to confirm that a continuum of lowered IQs in NF-1-affected children exists in relation to the distribution of UBOs (range 0-7), not just presence (vs. absence) of any UBOs.

Adolescent↗
PubMed1996

Brain development, gender and IQ in children. A volumetric imaging study.

Normal brain development during childhood is a complex and dynamic process for which detailed scientific information is lacking. MRI techniques, combined with methods for advanced image analysis, offer the potential to begin to construct a quantitative map of normal paediatric brain development in vivo. In this study we utilize volumetric analysis of high resolution brain images obtained from MRI to describe cerebral development and morphology in 85 normal children and adolescents ranging in age from 5 to 17 years. The results show that total cerebral volume is 10% larger in boys compared with girls. However, both boys and girls show little change in total cerebral volume after the age of 5 years. Increased cortical grey matter is the primary contributor to larger brain volume in boys, thus supporting the hypothesis that gender associated differences in brain size are related to differences in cortical neuronal density. Prominent, age-related changes in grey matter, white matter and CSF volumes are evident during childhood and appear to reflect ongoing maturation and remodelling of the CNS. Both boys and girls show a similar pattern of cerebral asymmetry; a rightward prominence of cortical and subcortical grey matter and a leftward prominence of CSF is observed. IQ is positively correlated with total cerebral volume in children, in particular, with the volume of cortical grey matter in the prefrontal region of the brain. Subcortical grey matter also contributes to the variance in IQ, although to a lesser extent than cortical grey volume. Quantitative knowledge of the developing human brain will play an increasingly greater role in improving sensitivity and specificity in the interpretation of brain abnormalities in patients within the clinical environment, as well as in groups of children with suspected brain dysfunction in the research setting.

Adolescent↗
PubMed1996

Basal ganglia volumes in children with attention-deficit hyperactivity disorder.

Previous research has demonstrated volume reduction of the left globus pallidus in children with the codiagnoses of Tourette syndrome and attention-deficit hyperactivity disorder (ADHD), in comparison with children who have Tourette syndrome alone and with normal controls. The purpose of this study was to determine whether children with ADHD alone also had volume reduction of the globus pallidus or other basal ganglia structures. Subjects were 10 boys with ADHD, 16 boys with Tourette syndrome and ADHD, and 11 normal control boys. Groups were matched for age. Boys with ADHD were individually matched for age, handedness, and IQ to 10 of the 16 boys with Tourette syndrome and ADHD. Volumes of caudate, putamen, and globus pallidus were measured and corrected for brain volume. The boys with ADHD had significantly smaller left globus pallidus volume and total globus pallidus volume (corrected for brain volume) than the normal controls. The Tourette syndrome plus ADHD group did not differ from the ADHD group on any of the measures. We conclude that small globus pallidus volume, particularly on the left side, is associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Neuropsychological status of children with Tourette's syndrome with and without attention deficit hyperactivity disorder.

To determine the frequency of learning disabilities (LD) and describe the neuropsychological profile of children with Tourette's syndrome (TS) with and without attention deficit hyperactivity disorder (ADHD), we analyzed psychosocial, psychoeducational, and neuropsychological data from 65 children between the ages of 6 and 14 years selected from a larger study of LD. Three groups were formed: TS only, TS+ADHD, and TS +/- ADHD. The third group was composed of children whose ADHD status was not as strongly confirmed by the three different instruments used for ADHD diagnosis. From other (non-TS) research projects in the Center, a comparison group of 27 unaffected siblings who had no diagnosis of ADHD was formed. All children were unmedicated at the time of assessment and had the full set of data available for analysis. LDs were present in 23% of the total TS sample, but LD was not present in the TS-only group. All TS groups had scores at or below 1 SD from the mean on measures of choice reaction time, but the TS-only group was significantly poorer on a measure of executive function (letter word fluency). We discuss the implication of the finding in the TS-only group in terms of a slowing of linguistic productivity.

Adolescent↗
PubMed1996

Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder.

The aim of this study was to investigate the morphology of the corpus callosum (CC) in Tourette syndrome (TS) and attention deficit hyperactivity disorder (ADHD) to determine whether these conditions affect distinct regional differences. Seventy-seven children and adolescents, aged 6 to 16 years, comprised the four research groups--16 patients with TS, 21 patients with TS plus ADHD, 13 patients with ADHD, and 27 unaffected control subjects. A semiautomated, computer-assisted procedure was used to measure the total area, five subregions, centerline length, perimeter, and bending angle of the CC. MRI data were analyzed using several statistical methods, primarily two-tailed analysis of variance to test the effects of TS and ADHD status, while controlling for the influence of age, gender, and total intracranial area (an estimate of brain size). TS was associated with significant increases in the area of four of five subdivisions, the total area, and the perimeter of the CC. ADHD was associated with a significant decrease in the area of the rostral body. There were no interactions between TS and ADHD factors. These findings suggest that the area of the CC is larger in children with TS, and that this difference is independent of age, handedness, intracranial area, and the diagnosis of ADHD. Our findings support hypotheses that the neurobiologic mechanisms in TS and ADHD involve frontal/subcortical circuits.

Adolescent↗
PubMed1996

Biological correlates of learning and attention: what is relevant to learning disability and attention-deficit hyperactivity disorder?

Advances in the related fields of cognitive neuroscience and neuropsychology offer intriguing reformulations of the clinical entities of attention-deficit hyperactivity disorder (ADHD) and learning disabilities (LD). The definition of such terms as attention and learning used in cognitive neuroscience differ from their use in clinical practice and emphasize such processes as intention, working memory, and executive function. Research suggests that neither attention nor long-term memory are the critical cognitive correlates of ADHD or LD. Rather, encoding processes, particularly working memory, are identified as deficiencies for children with these conditions. Furthermore, intention and inhibition appear to be particularly impaired in children with ADHD, who exhibit broader deficits in so-called executive function. Findings from cognitive neuroscience offer explanations of the neuroanatomical and neurophysiological underpinnings of learning problems and the frequent comorbidity of LD and ADHD.

Attention↗
PubMed1995

Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder.

Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.

Adolescent↗
PubMed1995

Contribution of the FMR1 gene mutation to human intellectual dysfunction.

The degree to which genetic factors influence human intelligence remains a matter of some controversy. However, there is little doubt that single gene mutations can significantly alter brain development and function. For example, mutations affecting the FMR1 gene cause the fragile X syndrome, the most prevalent known inherited cause of intellectual dysfunction. The most common mutation occurring in the FMR1 locus involves expansion of a trinucleotide (CGG)n repeat sequence within the promoter region of the gene. Between 6 and 54 repeats are typically observed in individuals from the general population. When > or = 200 CGG repeats are present, the expanded repeat sequence and an adjacent CpG island are usually hypermethylated, Aa phenomenon associated with transcriptional silencing of the gene and commonly referred to as the FMR1 full mutation. The intermediate range of repeats (approximately 50 to 200 CGGs), referred to as the premutation, is characterized by the absence of hypermethylation within the promoter region and normal phenotype. Some individuals have a combination of methylated and unmethylated alleles of differing size and are referred to as having mosaic status. Most males with the FMR1 full mutation function in the mentally retarded range of intelligence; in contrast, females with the FMR1 full mutation show a broader range of intelligence, from mental retardation to normal IQ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗