Martha B. Denckla

Cognitive Profiles of Difficult-to-Remediate and Readily Remediated Poor Readers: Early Intervention as a Vehicle for Distinguishing between Cognitive and Experiential Deficits as Basic Causes of Specific Reading Disability.

Reading impaired first graders were given daily tutoring as a first cut diagnostic to aid in distinguishing between reading difficulties caused by basic cognitive deficits and those caused by experiential deficits. Reading achievement in most of these children was found to be within or above the average range after one semester of remediation. Children who were difficult to remediate performed below both children who were readily remediated and normal readers on kindergarten and first-grade tests evaluating phonological skills, but not on tests evaluating visual, semantic and syntactic skills. The results are consistent with convergent findings from previous research suggesting that reading problems in some poor readers may be caused primarily by phonological deficits.

Volumetric MRI changes in basal ganglia of children with Tourette's syndrome

To define the site of pathology in Tourettes syndrome (TS), we performed a volumetric MRI study of basal ganglia structures and lateral ventricles on 37 children with this disorder and 18 controls. There were no statistically significant differences in the size of the right or left caudate, putamen, globus pallidus, or ventricles in these populations. In contrast, there were significant differences for measures of symmetry in the putamen and the lenticular region. Virtually all controls (17 right- and one left-handed) had a left-sided predominance of the putamen, whereas in 13 of 37 TS subjects, a right predominance exceeded that of any control. Statistical comparisons among TS patients, with (n = 18) or without (n = 19) attention-deficit hyperactivity disorder (ADHD), and controls showed significant differences for the volume of the left globus pallidus and for lenticular asymmetry. Post hoc evaluations showed that in the TS + ADHD group, the volume of the left globus pallidus was significantly smaller than the volume of the right and that lenticular asymmetry was due to a greater right-sided predominance in the TS + ADHD group. This study lends further support to proposals that claim the basal ganglia is involved in the pathogenesis of TS and also suggests that the comorbid problem of ADHD is related to regional changes that differ from those primarily associated with tics.

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. (J Child Neurol 1998; 13:434-439).

Dyspraxia in Autism: Association with Motor, Social, and Communicative Deficits.

Impaired performance of skilled gestures, referred to as dyspraxia, is consistently reported in children with autism; however, its neurological basis is not well understood. Basic motor skill deficits are also observed in children with autism and it is unclear whether dyspraxia observed in children with autism can be accounted for by problems with motor skills. Forty‐seven high‐functioning children with an autism spectrum disorder (ASD), autism, or Asperger syndrome (43 males, four females; mean age 10y 7m [SD 1y 10m], mean Full‐scale IQ (FSIQ) 99.4 [SD 15.9]), and 47 typically developing (TD) controls (41 males, six females; mean age 10y 6m [SD 1y 5m], mean FSIQ 113.8 [SD 12.3], age range 8–4y) completed: (1) the Physical and Neurological Assessment of Subtle Signs, an examination of basic motor skills standardized for children, and (2) a praxis examination that included gestures to command, to imitation, and with tool‐use. Hierarchical regression was used to examine the association between basic motor skill performance (i.e. times to complete repetitive limb movements) and praxis performance (total praxis errors). After controlling for age and IQ, basic motor skill was a significant predictor of performance on praxis examination. Nevertheless, the ASD group continued to show significantly poorer praxis than controls after accounting for basic motor skill. Furthermore, praxis performance was a strong predictor of the defining features of autism, measured using the Autism Diagnostic Observation Schedule, and this correlation remained significant after accounting for basic motor skill. Results indicate that dyspraxia in autism cannot be entirely accounted for by impairments in basic motor skills, suggesting the presence of additional contributory factors. Furthermore, praxis in children with autism is strongly correlated with the social, communicative, and behavioral impairments that define the disorder, suggesting that dyspraxia may be a core feature of autism or a marker of the neurological abnormalities underlying the disorder.

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. NEUROLOGY 1996;47: 477-482

Validity of the behavior rating inventory of executive function in children with ADHD and/or Tourette syndrome

The dynamic, multidimensional nature of executive function (EF), thought to be characteristically impaired in those with attention deficit hyperactivity disorder (ADHD), has been challenging to operationalize and assess in a clinical setting [Barkley, R. A. (1997). ADHD and the nature of self-control. New York: Guilford Press.]. Gioia, Isquith, Guy, and Kenworthy [Gioia, G. A., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000) Behavior Rating Inventory of Executive Function. Odessa, FL: Psychological Assessment Resources.] developed the Behavior Rating Inventory of Executive Function (BRIEF) to address these concerns. In order to provide concurrent validity information on the BRIEF, parents of 76 children (ADHD=18; Tourette syndrome (TS)=21; TS+ADHD=17; controls=20) completed the BRIEF, additional behavior rating scales and interviews, measures of psychoeducational (PE) competence, and performance-based measures of EF. Both ADHD and TS+ADHD groups were rated as more impaired (P<.0001) than the other groups on the five primary BRIEF indices. BRIEF index scores showed no significant correlation with performance-based EF or PE measures, with the exception of math achievement; however, the BRIEF showed a strong relationship with interviews and other parent rating measures of behaviors seen in ADHD. Future attempts to validate the BRIEF should focus on differences within subtypes of ADHD (e.g., inattentive, combined subtypes), and separating ADHD from other clinical groups in which EF is reported to be a problem.

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. (J Child Neurol 1996; 11: 112-115).

Cognitive function and academic performance in neurofibromatosis. 1: consensus statement from the NF1 Cognitive Disorders Task Force.

Neurofibromatosis type 1 (NF1) is the most common single gene disorder to affect the human nervous system; it is inherited in an autosomal dominant manner with an estimated incidence of 1 in 3,500.l The physical features of NF1 are well characterized and include multiple cafe-au-lait spots, skinfold freckling, iris hamartomas (Lisch nodules), and benign and malignant neural tumors (e.g., neurofibromas, pheochromocytomas, and neurofibrosarcomas).’X2 CNS lesions include optic pathway gliomas, dural ectasia, and aqueduct stenosis. In addition to these specific pathologic lesions, cognitive impairment is common. Learning disabilities occur in at least 30 to 45% of children with NF1 and can be responsible for significant lifetime m~rb id i ty .~ ,~ The NF1 gene on human chromosome 17 has been ~ l o n e d ~ ~ and its protein product neurofibromin identified.*b9 The NF1 gene is usually classified as a tumor suppressor gene, as mutations in both NF1 alleles are detectable in malignant tumors associated with NF1lOJ1 and in benign tumors such as neurofibromas.12 The effects of the disorder on higher cortical function and the relationship between NF1 gene mutations, cognitive deficits, and intracranial pathology are less well understood. This consensus statement summarizes our current understanding of the frequency and nature of cognitive deficits and learning disability in children with NF1, provides recommendations for assessment and management, and examines the putative relationship between cognitive deficits and MRI signal abnormalities. We review possible pathogenetic mechanisms and future directions for research.

Neurodevelopmental effects of the FMR-1 full mutation in humans

Brain dysfunction is the most important sequelae of the fragile X (FMR-1) mutation, the most common heritable cause of developmental disability. Using magnetic resonance imaging (MRI) and quantitative morphometry, we have compared the neuroanatomy of 51 individuals with an FMR-1 mutation with matched controls and showed that subjects with an FMR-1 mutation have increased volume of the caudate nucleus and, in males, the lateral ventricle. Both caudate and lateral ventricular volumes are correlated with IQ. Caudate volume is also correlated with the methylation status of the FMR-1 gene. Neuroanatom-ical differences between two monozygotic twins with an FMR-1 mutation who are discordant for mental retardation are localized to the cerebellum, lateral ventricles and subcortical nuclei. These findings suggest that the FMR-1 mutation causing the fragile X syndrome leads to observable changes in neuroanatomy that may be relevant to the neurodevelopmental disability and behavioural problems observed in affected individuals.

Developmental dyspraxia is not limited to imitation in children with autism spectrum disorders

Impaired imitation of skilled gestures is commonly reported in autism. Questions, however, remain as to whether impaired imitation is associated with a more generalized deficit in performance of gestures consistent with a dyspraxia and whether the pattern of errors differs from that observed in typically developing children. To address these questions, praxis in 21 high-functioning children with autism spectrum disorders (ASD) was compared with 24 typically developing controls using a traditional approach in which performance was evaluated through detailed examination of error types. Children with ASD produced significantly fewer correct responses not only during Gesture to Imitation, but also during Gesture to Command and with Tool Use. The pattern of errors in ASD was similar to that of controls with spatial errors being most common in both groups; however, body-part-for-tool errors were more common in children with ASD, suggesting dyspraxia is not entirely attributable to motor deficits. The findings suggest that autism is associated with a generalized praxis deficit, rather than a deficit specific to imitation. In a developmental disorder such as autism, the findings may reflect abnormalities in frontal/parietal-subcortical circuits important for acquisition (i.e., learning) of sensory representations of movement and/or the motor sequence programs necessary to execute them.