Biomedical subjects

Martha B Denckla

Publications and source records attributed to Martha B Denckla.

At least 19 recordsLinked to original sources

PubMed2006

Motor signs distinguish children with high functioning autism and Asperger's syndrome from controls.

While many studies of motor control in autism have focused on specific motor signs, there has been a lack of research examining the complete range of subtle neuromotor signs. This study compared performance on a neurologic examination standardized for children (PANESS, Physical and Neurological Exam for Subtle Signs, Denckla [1974 Developmental Medicine and Child Neurology, 16(6), 729-741]) between a group of 40 boys aged 6-17 with autism and average range IQs and a group of 55 typically developing boys. The Autism group was shown to have significant impairment on several measures of motor control compared to the Control group. Regression analyses revealed that a model including four PANESS variables offered a high level of discrimination in distinguishing boys with high-functioning autism from controls.

Adolescent↗

PubMed2006

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.

Apraxias↗

PubMed2006

Motor persistence and inhibition in autism and ADHD.

The present study compared performance of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and high functioning autism (HFA) with that of controls on 4 tasks assessing 2 components of motor control: motor response inhibition and motor persistence. A total of 136 children (52 ADHD, 24 HFA, 60 controls) ages 7 to 13 years completed 2 measures of motor inhibition (Conflicting Motor Response and Contralateral Motor Response Tasks) and 2 measures of motor persistence (Lateral Gaze Fixation and NEPSY Statue). After controlling for age, IQ, gender, and basic motor speed, children with ADHD performed significantly more poorly than controls on the Conflicting Motor Response and Contralateral Motor Response Tasks, as well as on Statue. In contrast, children with HFA achieved lower scores than controls only on measures of motor persistence, with no concomitant impairment on either motor inhibition task. These results are consistent with prior research that has demonstrated relatively spared motor inhibition in autism. The findings highlight the utility of brief assessments of motor control in delineating the unique neurobehavioral phenotypes of ADHD and HFA.

Adolescent↗

PubMed2005

Atypical motor and sensory cortex activation in attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study of simple sequential finger tapping.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been shown to be associated with anomalous motor development, including excessive overflow movements. The neurological basis of these deficits has not been established. Functional magnetic resonance imaging (fMRI) was used to determine whether differences in brain activation during sequential finger tapping are present in children with ADHD compared with typically developing control subjects. METHODS: Twenty-two right-handed children between 8 and 12 years old, 11 with ADHD and 11 typically developing control subjects closely matched for age and gender, performed self-paced sequential finger tapping during fMRI acquisition. RESULTS: There were no significant between-group differences in speed of sequential finger tapping. The between-group whole-brain comparison showed greater magnitude of activation for control subjects than children with ADHD in the right superior parietal lobe during both right-handed and left-handed finger tapping. The region-of-interest analysis within Brodmann Area 4 revealed that children with ADHD showed a significantly smaller extent of fMRI activation in the primary motor cortex contralateral to the finger-sequencing hand. CONCLUSIONS: Despite similar speed of sequential finger tapping, children with ADHD showed decreased contralateral motor cortex and right parietal cortex activation during both right-handed finger sequencing (RHFS) and left-handed finger sequencing (LHFS). The fMRI findings suggest that children with ADHD have anomalous development of cortical systems necessary for execution of patterned movements.

Analysis of Variance↗

PubMed2005

The ipsilateral silent period in boys with attention-deficit/hyperactivity disorder.

OBJECTIVE: Characterize maturation of transcallosal inhibition (ipsilateral silent period [iSP]) in attention deficit/hyperactivity disorder (ADHD) using transcranial magnetic stimulation (TMS). BACKGROUND: Maturation of the iSP is related to acquisition of fine motor skills in typically developing children suggesting that dexterous fine motor skills depend upon mature interhemispheric interactions. Since neuromotor maturation is abnormal in boys with ADHD we hypothesized that iSP maturation in these children would be abnormal. We studied iSP maturation in 12 boys with ADHD and 12 age-matched, typically developing boys, 7-13 years of age. METHODS: Surface electromyographic activity was recorded from right first dorsal interosseus (FDI). During background activation, focal TMS was delivered at maximal stimulator output over the ipsilateral motor cortex. RESULTS: Maturation of finger speed in boys with ADHD was significantly slower than that in the control group. The iSP latency decreased with age in the control group but not in the ADHD group. CONCLUSIONS: These findings suggest the presence of a complex relationship between abnormalities of certain interhemispheric interactions (as represented by iSP latency) and delayed maturation of neuromotor skills in boys with ADHD. SIGNIFICANCE: These data provide preliminary physiologic evidence supporting delayed or abnormal development of interhemispheric interactions in boys with ADHD.

Adolescent↗

PubMed2005

Construct validity of the auditory continuous performance test for preschoolers.

Development of diagnostic instruments directed toward neuropsychological assessment of preschoolers lags significantly behind those available for school-age children (DeWolfe, Byrne, & Bawden, 2000). This is particularly true for measures of executive function (EF). The Auditory Continuous Performance Test for Preschoolers (ACPT-P; Mahone, Pillion, & Hiemenz, 2001) is a computerized, Go-No-go test developed to measure selected EF skills in preschoolers. First, to determine whether performance on the ACPT-P is associated with hearing impairment, we compared performance of children with mild hearing loss (MHL) to controls on the ACPT-P, and measures of spatial working memory (SWM) and motor persistence (MP). There were no differences between performance of the MHL group and controls on any of these measures. Second, to examine the construct validity of the ACPT-P, we compared performance of 40 preschoolers with ADHD to 40 age- and sex-matched controls, using the ACPT-P to measure response preparation, sustained attention, and inhibitory control. We also compared these groups on measures of SWM and MP. The group with attention deficit hyperactivity disorder (ADHD) performed significantly worse than controls on the ACPT-P (omissions, mean response time, variability) and MP. The ACPT-P was correlated with the MP, but not with the SWM measure. Both the ACPT-P and the MP measures showed low to moderate correlations with parent ratings of behavior associated with ADHD. These findings support the use of performance-based assessment of executive control skills in preschoolers suspected of having ADHD. In this age group, the ACPT-P may be particularly useful in assessing sustained attention and response preparation and may complement behavior rating scales.

Acoustic Stimulation↗

PubMed2004

Longitudinal evolution of unidentified bright objects in children with neurofibromatosis-1.

Neurofibromatosis type-1 (NF-1) is the most common autosomal dominant disorder affecting the central nervous system. Magnetic resonance imaging (MRI) has revealed distinctive T2-weighted hyperintense foci (termed unidentified bright objects, UBOs) which appear to represent spongiform changes in the white matter. Cross-sectional and longitudinal analyses suggest that UBOs disappear over time; however, none of these studies have examined comprehensively these foci. We conducted a quantitative MRI longitudinal study of number of affected regions, number of UBOs per region, and UBO volume per region, in a sample of 12 children with NF-1. We applied semi-automatic morphometric methods and comprehensive statistical approaches, within a detailed anatomical parcellation framework. Our data demonstrate that, despite a similar UBO regional distribution (e.g., prevalent globus pallidus/internal capsule (GP/IC) location), UBO evolution was more complex than previously reported. In some subjects, the total number of UBO-occupied locations demonstrated a decrease between approximately ages 7 and 12 years, followed by a progressive increase during adolescence. This pattern was also found for UBO number and/or volume for all regions, with the exception of the cerebellar hemispheres. This REGIONAL distinction may reflect differences in white matter structure between affected long tract fiber bundles and that of cerebral and cerebellar myelinated fibers. The findings are also discussed in the context of previous MR and behavioral studies. We conclude that studies like the present one, in association with other MR modalities, are necessary to characterize more completely the nature and evolution of UBOs and their role in the cognitive phenotype of NF-1.

Adolescent↗

PubMed2004

Impaired habituation in children with attention deficit hyperactivity disorder.

OBJECTIVE: To investigate whether children with attention deficit hyperactivity disorder show impaired habituation to peripheral stimuli. METHOD: We compared the Troxler effect (the ability to habituate to a peripheral visual stimulus when presented with a competing central visual stimulus) in groups of 23 children with attention deficit hyperactivity disorder and 15 controls matched for age, gender, and IQ. RESULTS: Regression analyses revealed a statistically significant effect of diagnosis on fading (P = 0.03), with attention deficit hyperactivity disorder subjects taking longer to fade to a peripheral stimulus than controls. Additional analyses revealed a significant interaction between diagnosis and visual field; control subjects showed similar fading times to stimuli presented in the right and left visual fields (13.25 vs. 12.96 seconds), while the attention deficit hyperactivity disorder group showed much slower fading in the right than in the left visual field (18.64 vs. 15.00 seconds). CONCLUSIONS: Our results suggest that children with attention deficit hyperactivity disorder have impaired visual habituation. The findings provide evidence of frontal dysfunction in attention deficit hyperactivity disorder and suggest that impaired habituation contributes to off-task behavior in children with the disorder.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry.

OBJECTIVE: Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. METHODS: The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured. RESULTS: Chelation therapy with succimer lowered average blood lead levels for approximately 6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints. CONCLUSION: These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL (0.96-2.17 micromol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L).

Chelating Agents↗

PubMed2003

fMRI evidence that the neural basis of response inhibition is task-dependent.

Event-related fMRI was used to investigate the hypothesis that neural activity involved in response inhibition depends upon the nature of the response being inhibited. Two different Go/No-go tasks were compared-one with a high working memory load and one with low. The 'simple' Go/No-go task with low working memory load required subjects to push a button in response to green spaceships but not red spaceships. A 'counting' Go/No-go task (high working memory load) required subjects to respond to green spaceships as well as to those red spaceships preceded by an even number of green spaceships. In both tasks, stimuli were presented every 1.5 s with a 5:1 ratio of green-to-red spaceships. fMRI group data for each task were analyzed using random effects models to determine signal change patterns associated with Go events and No-go events (corrected P< or =0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded 'counting' task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load.

Adult↗

PubMed2003

Ocular motor behavior of children with neurofibromatosis 1.

Patients with neurofibromatosis 1 show neurocognitive deficits including abnormal visuospatial performance, but oculomotor behavior has not been studied. We recorded saccades in neurofibromatosis 1 and normal children, ages 6 to 12 years. Patients showed increased latency and diminished amplitude to more eccentric targets for both visually guided and memory-guided saccades. Subtracting the latencies of visually guided saccades from memory-guided saccades produced no differences between groups. For predictive saccades (0.5 Hz), patients with neurofibromatosis 1 generated fewer anticipatory saccades than normal subjects, but patients with neurofibromatosis 1 made more direction errors in an antisaccade task. Patients with neurofibromatosis 1 show saccade abnormalities that are not easily ascribed to dysfunction within single cortical areas. Rather, the findings likely reflect (1) partial involvement of different components of a widely distributed cerebral network that controls saccades, (2) impaired visuomotor maturation in a brain abnormal early in development, and (3) excessive gamma-aminobutyric acid-mediated inhibition, which could influence basal ganglia pathways that modulate superior colliculus activity.

Basal Ganglia↗

PubMed2003

Overflow movements predict impaired response inhibition in children with ADHD.

Neurologic models proposed to explain mechanisms underlying ADHD have emphasized deficits in response inhibition. Age-inappropriate overflow movements, e.g., mirror movements, are motor signs thought to reflect immaturity in cortical systems involved in automatically (unconsciously, without explicit effort) inhibiting extraneous movement. We investigated the hypothesis that the presence of excessive overflow movements would predict measures of conscious, effortful response inhibition (conflicting and contralateral motor response tests) in children with ADHD. 42 children with ADHD and 30 controls, ages 8 through 12 years, participated. Children with ADHD showed significantly more overflow movements than did controls and made more errors on the conflicting and contralateral motor response tests. Multiple linear regression analysis indicated that overflow movements predicted performance on measures of motor response inhibition. For one of those measures, the contralateral motor response test, there was a significant interaction with diagnosis, such that overflow predicted response inhibition in ADHD but not in controls. The findings suggest that overflow movements, which can be readily observed as part of clinical examination, are more evident in children with ADHD. Positive correlations between measures of overflow movements and measures of response inhibition suggest that closely associated neural mechanisms underlie these deficits and support hypotheses that age-inappropriate overflow reflects immaturity of cortical systems involved in automatic inhibition.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

MRI parcellation of the frontal lobe in boys with attention deficit hyperactivity disorder or Tourette syndrome.

Dysfunction of frontal-striatal-thalamic-frontal circuitry has been hypothesized to underlie both attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS). Several research groups have therefore used anatomic magnetic resonance imaging (aMRI) to obtain volumetric measurements of subregions of the frontal lobe in these disorders. Most previous studies have relied on subparcellation methods that utilize callosal landmarks to derive subregions of the frontal lobe. In contrast, we present here an investigation of frontal lobe morphometry in ADHD and TS based on a reliable frontal subparcellation protocol that combines contiguous sulcal/gyral boundaries to derive frontal lobe modules based on prior functional studies. This highly reliable procedure subdivides the frontal lobe into five major modules: prefrontal, premotor, motor (precentral gyrus), anterior cingulate, and deep white matter. The first four modules are also segmented into gray and gyral white matter compartments. The protocol was applied to T1-weighted, SPGR coronal MRI images of 13 school-aged boys with ADHD, 13 boys with TS, and 13 age- and gender-matched controls. In ADHD, we found volumetric reductions in both the gray and white matter of the prefrontal cortex. These findings, in conjunction with previous reports on basal ganglia abnormalities, suggest that prefrontal-striatal pathways may be anomalous in ADHD. In TS, we found volumetric decreases in the left deep frontal white matter. Decreases in deep white matter suggest the presence of abnormalities in long associational and projection fiber bundles in TS. The findings of this study both confirm and extend our knowledge of the neurobiology of ADHD and TS, indicating that the reliable parcellation method presented has the potential of increasing our understanding of the role of the frontal lobe in developmental and psychiatric disorders.

Adult↗

PubMed2002

Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit/hyperactivity disorder (ADHD) have been limited by use of callosal rather than sulcal/gyral landmarks in defining cerebral lobes and functionally relevant sublobar regions (e.g., prefrontal cortex). We present an investigation of cerebral volumes in ADHD using a Talairach-based approach that uses cortical landmarks to define functionally relevant regions. METHODS: Volumes were compared between groups of 12 boys with ADHD and 12 age- and gender-matched control subjects, using a series of multiple analyses of variance. RESULTS: Boys with ADHD had (on average) 8.3% smaller total cerebral volumes. Significant reductions in lobar volumes were seen only for the frontal lobes. Within the frontal lobes, a reduction was seen in both gray and white matter volumes, with some evidence suggesting lateralization of these findings: reduction in frontal white matter volume was specific to the left hemisphere; there was a bilateral reduction in frontal gray matter volume but more so in the right hemisphere. Subparcellation of the frontal lobe revealed smaller prefrontal, premotor, and deep white matter volumes. CONCLUSIONS: Findings suggest that ADHD is associated with decreased frontal lobe gray and white matter volumes. More than one subdivision of the frontal lobes appears to be reduced in volume, suggesting that the clinical picture of ADHD encompasses dysfunctions attributable to anomalous development of both premotor and prefrontal cortices.

Adolescent↗

PubMed2002

Effects of IQ on executive function measures in children with ADHD.

The present study compared children with Attention-Deficit Hyperactivity Disorder (ADHD) and controls on a selected set of clinical measures of executive function (EF). A total of 92 children (51 ADHD, 41 control), ages 6-16, completed measures chosen from a larger neuropsychological battery to illustrate diverse components of the EF construct (planning, inhibitory control, response preparation, memory search). The selected measures were moderately correlated with one another, and moderately correlated with IQ. After controlling for age, sex, presence of learning disability (LD), ADHD, and IQ test version, Full Scale IQ was significantly related to four of the five selected EF measures. A second analysis showed group differences on the EF measures at different IQ levels. After covarying for age, there was a significant multivariate effect for IQ level (average, high average, superior) and a significant multivariate interaction between group (ADHD vs. control) and IQ level. Three of the five selected EF measures showed significant univariate group effects (controls performing better than ADHD) at the average IQ level; however, there were no significant group differences between children with ADHD and controls at high average or superior IQ levels. These results suggest that clinical measures of EF may differ among children with ADHD and controls at average IQ levels, but there is poorer discriminatory power for these measures among children with above average IQ.

Adolescent↗

PubMed2002

Anxiety after severe pediatric closed head injury.

OBJECTIVE: To assess the frequency of anxiety symptoms and disorders 1 year after severe pediatric closed head injury (CHI) and to determine the risk factors associated with these postinjury outcomes. METHOD: Ninety-seven subjects were prospectively followed for 1 year after severe CHI (Glasgow Coma Scale Score = 3-8). Assessments of preinjury and 1-year postinjury psychiatric status and psychosocial adversity were conducted. Frequency of anxiety symptoms and disorders 1 year after injury were the outcome measures. Data collection occurred between 1992 and 1996. RESULTS: There was a significant increase in the total number of anxiety symptoms after injury compared with before injury. The most frequent symptoms were overanxious symptoms, followed by obsessive-compulsive symptoms, separation anxiety symptoms, and simple phobia symptoms. There was a trend toward an increase in the frequency of overanxious disorder after injury. Preinjury anxiety symptoms correlated positively with postinjury anxiety symptoms and disorders. Younger age at injury correlated positively with postinjury anxiety symptoms. CONCLUSIONS: One year after severe CHI, children are at risk for a variety of anxiety symptoms and, possibly, overanxious disorder. Preinjury anxiety and younger age at injury are risk factors for these disturbances.

Adolescent↗

PubMed2002

Clinical predictors of posttraumatic stress disorder after closed head injury in children.

OBJECTIVE: To describe injury, demographic, and neuropsychiatric characteristics of children who develop posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) after closed head injury (CHI). METHOD: Ninety-five children with severe CHI and amnesia for the event were prospectively followed for 1 year. Structured interviews were administered twice to the parents: shortly after injury to cover the child's premorbid status, and 1 year after injury. The child was also interviewed twice: shortly after injury to cover current status, and 1 year after injury. Outcome measures were diagnostic status (PTSD by parent or child) and symptom severity (PTSS by parent or child). RESULTS: Twelve children developed PTSD by 1 year after injury, 5 according to parent report, 5 according to child report, and 2 according to both parent and child report. Predictors of PTSD at 1 year post-CHI included female gender and early post-CHI anxiety symptoms. Predictors of PTSS at 1 year post-CHI were (1) premorbid psychosocial adversity, premorbid anxiety symptoms, and injury severity; and (2) early post-CHI depression symptoms and nonanxiety psychiatric diagnoses. CONCLUSIONS: PTSD developed in 13% of children with severe CHI accompanied by traumatic amnesia. Predictors of PTSD and PTSS after CHI, according to parent and child report, are consistent with predictors of PTSD and PTSS that develop after non-head injury trauma.

Adolescent↗

PubMed2002

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.

Journal Article↗