Neurobehavioral Profiles in Individuals with Hyperimmunoglobulin E Syndrome (HIES) and Brain White Matter Hyperintensities

Purpose

Individuals with hyperimmunoglobulin E Syndrome (HIES) have central nervous system abnormalities, including focal white matter hyperintensities (WMH), or unidentified bright objects. This cross-sectional study aimed to describe the cognitive and emotional functioning and quality of life of people with HIES. We also sought to explore the relationship between cognitive functioning and WMHs in this population.

Methods

Twenty-nine individuals (13 males) with autosomal-dominant HIES (mean age?=?35.1 years, range 16–55) were administered a comprehensive psychological assessment as part of a natural history protocol. The assessment included measures of global cognitive functioning (Wechsler Adult Intelligence Scale-III), memory (California Verbal Learning Test-II, Wechsler Memory Scale-III), executive skills (Delis Kaplan Executive Function System), and attention (Test of Everyday Attention). Emotional symptoms and quality of life also were assessed.

Results

All mean cognitive scores were within normal limits. Mean scores on memory and executive functioning measures were significantly lower than Full Scale IQ scores (ps?<?.05). Substantial percentages of patients self-reported executive skills to be in the clinical range. Patients with fewer (1–20) versus more (21+) WMHs scored significantly better on measures of global cognitive skills, visual-perceptual skills, and working memory. Mean scores on emotional symptom and quality of life measures were in the average range and unrelated to WMHs.

Conclusions

Global cognitive functioning was average to high average in our sample of individuals with HIES. However, focal brain lesions were associated with lower scores in specific domains. Emotional functioning and quality of life are within normal limits in this sample.     

Electrocortical indices of selective attention predict adolescent executive functioning

Executive functioning is considered a powerful predictor of behavioral and mental health outcomes during adolescence. Our question was whether executive functioning skills, normally considered “top-down” processes, are related to automatic aspects of selective attention. Event-related potentials (ERPs) were recorded from typically-developing 12–14-year-old adolescents as they responded to tones presented in attended and unattended channels in an auditory selective attention task. Examining these ERPs in relation to parental reports on the Behavior Rating Inventory of Executive Function (BRIEF) revealed that an early frontal positivity (EFP) elicited by to-be-ignored/unattended tones was larger in those with poorer executive functions, driven by scores on the BRIEF Metacognition Index. As is traditionally found, N1 amplitudes were more negative for the to-be-attended rather than unattended tones. Additionally, N1 latencies to unattended tones correlated with parent-ratings on the BRIEF Behavior Regulation Index, where shorter latencies predicted better executive functions. Results suggest that the ability to disengage attention from distractor information in the early stages of stimulus processing is associated with adolescent executive functioning skills.     

Neurobehavioral correlates of sleep-disordered breathing in children

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.     

Age effects on executive ability

Heterogeneity of executive tasks has made it difficult to determine whether there are age-related declines in executive functioning. To address this issue, 112 individuals, 20-79 years old, took the California Trail Making Test (CTMT) and the California Stroop Test (CST), subtests of the Delis-Kaplan Executive Function Scale (D. C. Delis, E. Kaplan, & J. H. Kramer, in press) that include measurement of component skills embedded in the executive function tasks. Multiple regression analyses revealed that after controlling for component skills, age had a significant effect on the executive requirement of the CST, namely speed on the interference condition. Age did not affect switching performance on the letter-number condition of the CTMT. Additional analyses revealed that age was significantly associated with commission of certain types of errors. This study confirms the importance of partialing out components in the assessment of multidimensional cognitive tasks, particularly when making age comparisons. It also emphasizes specificity over generalizability when examining the impact of age on cognition.     

Executive function in XXY: Comparison of performance‐based measures and rating scales

Few studies have systematically assessed executive functioning (EF) skills in boys with XXY, and these are limited by small samples and restricted EF assessment. This study used a broader battery of performance‐based measures as well as parent‐rating scales of EF in 77 boys and adolescents with XXY (mean age = 12.5 years), recruited from a clinical trial and an outpatient clinic. Exploratory factor analyses were used to create EF domains from performance‐based measures, and similar domains were measured using the Behavior Rating Inventory of Executive Function and Conners Parent‐Rating Scales. The boys with XXY showed a distinct EF profile, with the greatest deficit in attention and more moderate deficits in working memory, switching, and planning/problem solving. Parent ratings showed similar challenges, as well as impaired inhibition. Independent sample t‐tests showed no difference on performance measures between boys diagnosed or not diagnosed with attention‐deficit/hyperactivity disorder (ADHD), although parents of boys diagnosed with ADHD reported more difficulties. There were no differences on performance‐based tests between those diagnosed pre‐ and postnatally, although parents of postnatally diagnosed boys reported more metacognitive problems. Language deficits, cognition, and socio‐economic status did not account for EF deficits.     

Ecological Assessment of Executive Function in Traumatic Brain Injury

Executive dysfunction is a common outcome in children who have sustained traumatic brain injury (TBI). Appropriate assessment of these complex interrelated regulatory functions is critical to plan for the necessary interventions yet present a challenge to our traditional methodologies. Ecological validity has become an increasingly important focus in neuropsychological assessment with particular relevance for the executive functions, which coordinate one's cognitive and behavioral capacities with real-world demand situations. The Behavior Rating Inventory of Executive Function (BRIEF) was developed to capture the real-world behavioral manifestations of executive dysfunction. Its development and various forms of validity, including ecological validity, are described. Application of the BRIEF's methodology to the assessment of executive dysfunction in TBI is provided. We advocate a multilevel approach to understanding executive function outcome in TBI, including traditional test-based measures of executive function, real-world behavioral manifestation of executive dysfunction, and the environmental system factors that impact the child. In this model, ecologically valid assessment of executive dysfunction provides an important bridge toward understanding the impact of component-level (i.e., test-based) deficits on the child's everyday adaptive functioning, which can assist the definition of targets for intervention.     

The Tower of London and neuropsychological assessment of ADHD in adults.

Executive function refers to a variety of behaviors and abilities related to planning and strategy use, as well as the maintenance of attention and behavior in the pursuit of some goal; these behaviors are generally deficient in individuals with Attention Deficit Hyperactivity Disorder (ADHD). The Tower of London (TOL) is one task used in the assessment of executive function. For adults with ADHD, there is minimal research on the extent to which they demonstrate impaired performance on tower tasks. With a sample of 102 individuals between the ages of 16 and 33 years, the extent to which performance on the TOL-Drexel Edition (TOL(DX)) was related to performance on other measures of executive function and diagnostic grouping was investigated. Results indicated that TOL(DX) variables are not correlated significantly with age or Global Assessment of Functioning (GAF). Of the TOL(DX) variables, only Rule Violations correlated with multiple other executive function variables. Rule Violations correlated minimally, but significantly, with cognitive ability, perceptual skills, Matrix Reasoning, Processing Speed, and immediate memory. As might be expected, Processing Speed also significantly correlated with Total Time and Time Violations. Notably, scores on the TOL(DX) did not correlate significantly with behavioral self-report; no between-group (ADHD, Clinical Control, No Diagnosis) differences emerged for any of the TOL(DX) variables. Further, with this sample, mean scores across the TOL(DX) variables were well within the average range. Taken together, these results suggest that while the TOL(DX) measures aspects of ability not tapped by other measures, and may therefore provide additional information on individual functioning, results should not be interpreted as indicative of the presence or absence of a disorder.     

Performance of Zambian Children on the NEPSY: A Pilot Study

Forty-five literate schoolchildren aged 9 (n = 25) and 11 (n = 20) from urban Zambia were given core and expanded tests on the NEPSY and their performance was scored according to age-equivalent norms for U.S. children. This study indicates that in urban, literate Zambian children, the NEPSY is relatively insensitive to language and cultural influences that often compromise the applicability of Western tests in the developing world. No consistent improvement in the standard scores was found as a function of educational experience. Comparison against the U.S. normative average revealed that both age groups were poorer in the domains of language and attention and executive functions, whereas their performance was better in the visuospatial processing domain. It is concluded that the NEPSY in its present form may be clinically useful, but its results should still be treated with caution, taking into account cultural, language, and personal demographic information. More studies, with divergent and larger samples of varying age ranges are required. It seems that the NEPSY could serve as the initial step in the development of neuropsychological practices in Zambia.     

High‐level language competencies and Theory of Mind in a group of children with Klinefelter syndrome

Klinefelter syndrome (KS) is a genetic anomaly involving the presence of one or more supernumerary X chromosomes in male individuals. In the cognitive profile of these individuals, strengths are found in nonverbal abilities, whereas weaknesses are observed in executive function, language, and academic performance. Our study is based on a comparison between eight children diagnosed with KS (47,XXY) (age range: 9–13 years; IQ range: 80–123), with no delay in language development, and eight typically developing (TD) controls. We explored a range of high‐level language competencies and Theory of Mind (ToM) in addition to basic language competency. High‐level language competencies were assessed by a battery that measures pragmatic language skills and a metaphor comprehension test (MCT). To assess ToM, we administered the corresponding subtest of the NEPSY II. Basic language competence was assessed by the NEPSY II Comprehension of Instructions subtest. Although basic language performance did not differentiate the individuals with KS from the TD controls, relevant differences appeared in some of the high‐level language competencies as well as in the ToM task. All tasks in which the individuals with KS performed less well were characterized by complex inferential processes. Some possible clinical and educational implications are discussed.     

Performance of Zambian children on the NEPSY: a pilot study

Forty-five literate schoolchildren aged 9 (n = 25) and 11 (n = 20) from urban Zambia were given core and expanded tests on the NEPSY and their performance was scored according to age-equivalent norms for U.S. children. This study indicates that in urban, literate Zambian children, the NEPSY is relatively insensitive to language and cultural influences that often compromise the applicability of Western tests in the developing world. No consistent improvement in the standard scores was found as a function of educational experience. Comparison against the U.S. normative average revealed that both age groups were poorer in the domains of language and attention and executive functions, whereas their performance was better in the visuospatial processing domain. It is concluded that the NEPSY in its present form may be clinically useful, but its results should still be treated with caution, taking into account cultural, language, and personal demographic information. More studies, with divergent and larger samples of varying age ranges are required. It seems that the NEPSY could serve as the initial step in the development of neuropsychological practices in Zambia.     

An empirical analysis of the BASC Frontal Lobe/Executive Control scale with a clinical sample.

Data from a clinical sample of children and adolescents were used to examine the characteristics of the Frontal Lobe/Executive Control (FLEC) scale of the Behavior Assessment System for Children Parent Rating Scales, including preliminary evidence of the scale's clinical utility and relationship to other behavioral measures of executive function and characteristics of Attention Deficit Hyperactivity Disorder (ADHD). Results indicate that participants in the ADHD and other clinical groups received very similar scores on the FLEC scale, and both groups were rated significantly higher in behaviors associated with executive dysfunction than were participants in the no diagnosis group. Correlational results indicate that scores on the FLEC scale were significantly correlated with scores on the Behavior Rating Inventory of Executive Function-Parent Form and Conners' Parent Rating Scales Revised-Short Form. Based on our results, the FLEC scale appears to be a useful behavioral rating tool in the assessment of executive function that may serve as a supplement to more traditional measures.     

Ecological Assessment of Executive Function in Traumatic Brain Injury

Executive dysfunction is a common outcome in children who have sustained traumatic brain injury (TBI). Appropriate assessment of these complex interrelated regulatory functions is critical to plan for the necessary interventions yet present a challenge to our traditional methodologies. Ecological validity has become an increasingly important focus in neuropsychological assessment with particular relevance for the executive functions, which coordinate one's cognitive and behavioral capacities with real-world demand situations. The Behavior Rating Inventory of Executive Function (BRIEF) was developed to capture the real-world behavioral manifestations of executive dysfunction. Its development and various forms of validity, including ecological validity, are described. Application of the BRIEF's methodology to the assessment of executive dysfunction in TBI is provided. We advocate a multilevel approach to understanding executive function outcome in TBI, including traditional test-based measures of executive function, real-world behavioral manifestation of executive dysfunction, and the environmental system factors that impact the child. In this model, ecologically valid assessment of executive dysfunction provides an important bridge toward understanding the impact of component-level (i.e., test-based) deficits on the child's everyday adaptive functioning, which can assist the definition of targets for intervention.     

Ecological assessment of executive function in traumatic brain injury

Executive dysfunction is a common outcome in children who have sustained traumatic brain injury (TBI). Appropriate assessment of these complex interrelated regulatory functions is critical to plan for the necessary interventions yet present a challenge to our traditional methodologies. Ecological validity has become an increasingly important focus in neuropsychological assessment with particular relevance for the executive functions, which coordinate one's cognitive and behavioral capacities with real-world demand situations. The Behavior Rating Inventory of Executive Function (BRIEF) was developed to capture the real-world behavioral manifestations of executive dysfunction. Its development and various forms of validity, including ecological validity, are described. Application of the BRIEF's methodology to the assessment of executive dysfunction in TBI is provided. We advocate a multilevel approach to understanding executive function outcome in TBI, including traditional test-based measures of executive function, real-world behavioral manifestation of executive dysfunction, and the environmental system factors that impact the child. In this model, ecologically valid assessment of executive dysfunction provides an important bridge toward understanding the impact of component-level (i.e., test-based) deficits on the child's everyday adaptive functioning, which can assist the definition of targets for intervention.     

Prediction of ADHD in boys and girls using the D-KEFS

To examine patterns of executive dysfunction associated with ADHD, 123 children (54 ADHD, 69 controls) of ages 8–16 years were administered selected subtests from the Delis–Kaplan Executive Function System (D-KEFS). Children with ADHD performed significantly worse than controls on measures of both basic (less executive demand) skills and those with more executive demand from the Color–Word Interference and Tower subtests; however, no group differences were noted on any of the D-KEFS contrast scores. Most subtype comparisons yielded no differences; however, children with the Combined subtype outperformed children with the Inattentive subtype on measures of both basic and executive skills from the Trail Making Test. Children with ADHD demonstrate executive dysfunction that is identified by D-KEFS summary, but not contrast scores. In this carefully screened sample of children with ADHD, few significant differences were found between groups suggesting limited sensitivity or specificity of the D-KEFS for classifying children with ADHD.     

注意缺陷多动障碍儿童父母的执行功能生态学特征

目的:探讨注意缺陷多动障碍(ADHD)儿童父母执行功能生态学特征。方法:选取147名符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的注意缺陷多动障碍儿童的父母亲,130名无注意缺陷多动障碍及其他神经疾患的正常儿童的年龄、受教育年限匹配的父母亲,让其分别填写执行功能行为评定量表成人问卷(自评和他评)(BRIEF-A),比较两组对象执行功能。结果:ADHD组父母BRIEF-A自评、他评量表,在执行总分、行为管理指数和元认知管理指数及其所属的抑制、转换、情绪控制、自我监控、启动、工作记忆、计划和组织因子方面,均明显低于对照组(均P<0.05);而父母自评的任务监控因子两组差异无统计学意义(P>0.05)。结论:注意缺陷多动障碍患儿父母的执行功能存在一定的缺陷。     

Executive dysfunction and its relation to language ability in verbal school-age children with autism

This study examined executive dysfunction and its relation to language ability in verbal school-age children with autism. Participants were 37 children with autism and 31 nonautistic comparison participants who were matched on age and on verbal and nonverbal IQ but not on language ability, which was lower in the autism group. Children with autism exhibited deficits compared to the comparison group across all 3 domains of executive function that were assessed including working memory (Block Span Backward; Isaacs & Vargha-Khadem, 1989), working memory and inhibitory control (NEPSY Knock-Tap; Korkman, Kirk, & Kemp, 1998), and planning (NEPSY Tower; Korkman et al., 1998). Children with autism were less developed than the comparison group in their language skills, but correlational analyses revealed no specific association between language ability and executive performance in the autism group. In contrast, executive performance was positively correlated with language ability in the comparison group. This pattern of findings suggest that executive dysfunction in autism is not directly related to language impairment per se but rather involves an executive failure to use of language for self-regulation.     

Attention problems in a representative sample of extremely preterm/extremely low birth weight children

The aim of this study was to examine attention in a large, representative, contemporary cohort of children born extremely preterm (EP) and/or extremely low birth weight (ELBW). Participants included 189 of 201 surviving children born EP (<28 weeks' gestation) or ELBW (<1,000 g) in 1997 in the state of Victoria, Australia. A comparison group of 173 of 199 children born full term and normal birth weight (FT/NBW) were randomly selected matching for birth hospital, expected due date, gender, mother's country of birth, and health insurance status. Participants were assessed at 8 years of age on subtests from the Test of Everyday Attention for Children (TEA-Ch) and the Wechsler Intelligence Scale for Children-4th Edition (WISC-IV). Measures of selective attention, sustained attention, attention encoding, and executive attention (inhibition, shifting attention, and divided attention) were administered. To assess behavioral elements of inattention, the primary caregiver completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Conners' ADHD/DSM-IV Scale (CADS-P). The EP/ELBW group performed more poorly across all cognitive and behavioral measures than the FT/NBW group, with the exception of inhibition. The EP/ELBW group also had significantly elevated rates of impairment in selective, sustained, shifting and divided attention, as well as attention deficit hyperactivity disorder (ADHD) symptoms. No significant gender or gradient effects (e.g., <26 weeks' gestation vs. ≥ 26 weeks' gestation) were identified. Neonatal medical factors were not strong predictors of attention, although necrotizing enterocolitis (NEC) and cystic periventricular leukomalacia (PVL) were independent predictors of selective attention. In conclusion, our comprehensive assessment of attention provides strong evidence that children born EP/ELBW are at increased risk for attentional impairments, and as such, this population should be monitored closely during early and middle childhood with a focus on attention functioning.     

Differentiation of executive and attention impairments in affective illness

BACKGROUND: Executive impairments have been reported in affective illness, but the influence of attention on executive performance has not been fully considered. The purpose of this study was to investigate whether executive impairments in affective illness were independent of attention impairments, and whether independent executive impairments were specific to bipolar (BP) affective illness. METHOD: Forty-two individuals with major affective disorders [20 unipolar (UP) depression and 22 BP disorder] were compared with 40 healthy controls on measures of attention and executive function. None of the patients were currently experiencing an episode of affective illness. RESULTS: As expected, both UP and BP patient groups showed significant neuropsychological impairments relative to controls. Significant differences in performance on executive function measures were also observed between UP and BP patients, even after the influence of attention had been taken into account. These impairments were not attributable to current levels of affective symptomatology or to medication. CONCLUSIONS: A single neuropsychological dissociation appears to be present between UP and BP affective illness, with BP individuals showing a specific executive deficit that is independent of attention impairment on the Hayling Sentence Completion Test (HSCT).     

Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children.

BACKGROUND: Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments. METHODS: Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naive and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls. RESULTS: The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory. CONCLUSIONS: ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.     

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.