Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with Dravet syndrome: A critical period for early neurodevelopment.

OBJECTIVE: To evaluate whether fenfluramine (FFA) is associated with improvement in everyday executive function (EF)-self-regulation-in preschool-aged children with Dravet syndrome (DS). METHODS: Children with DS received placebo or FFA in one of two phase III studies (first study: placebo, FFA 0.2 mg/kg/day, or FFA 0.7 mg/kg/day added to stiripentol-free standard-of-care regimens; second study: placebo or FFA 0.4 mg/kg/day added to stiripentol-inclusive regimens). Everyday EF was evaluated at baseline and Week 14-15 for children aged 2-4 years with parent ratings on the Behavior Rating Inventory of Executive Function®-Preschool (BRIEF®-P); raw scores were transformed to T-scores and summarized in Inhibitory Self-Control Index (ISCI), Flexibility Index (FI), Emergent Metacognition Index (EMI), and Global Executive Composite (GEC). Clinically meaningful improvement and worsening were defined using RCI ≥ 90% and RCI ≥ 80% certainty, respectively. The associations between placebo vs FFA combined (0.2, 0.4, and 0.7 mg/kg/day) or individual treatment groups and the likelihood of clinically meaningful change in BRIEF®-P indexes/composite T-scores were evaluated using Somers'd; pairwise comparisons were calculated by 2-sided Fisher's Exact tests (p ≤ 0.05) and Cramér's V. RESULTS: Data were analyzed for 61 evaluable children of median age 3 years (placebo, n = 22; FFA 0.2 mg/kg/day, n = 15; 0.4 mg/kg/day [with stiripentol], n = 10; 0.7 mg/kg/day, n = 14 [total FFA, n = 39]). Elevated or problematic T-scores (T ≥ 65) were reported in 55% to 86% of patients at baseline for ISCI, EMI, and GEC, and in ∼33% for FI. Seventeen of the 61 children (28%) showed reliable, clinically meaningful improvement (RCI ≥ 90% certainty) in at least one BRIEF®-P index/composite, including a majority of the children in the FFA 0.7 mg/kg/day group (9/14, 64%). Only 53% of these children (9/17) also experienced clinically meaningful reduction (≥50%) in monthly convulsive seizure frequency, including 6/14 patients in the FFA 0.7 mg/kg/day group. Overall, there were positive associations between the four individual treatment groups and the likelihood of reliable, clinically meaningful improvement in all BRIEF®-P indexes/composite (ISCI, p = 0.001; FI, p = 0.005; EMI, p = 0.040; GEC, p = 0.002). The FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than placebo in ISCI (50% vs 5%; p = 0.003), FI (36% vs 0%; p = 0.005), and GEC (36% vs 0%; p = 0.005). For EMI, the FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than the FFA 0.2 mg/kg/day group (29% vs 0%; p = 0.040), but did not meet the significance threshold compared with placebo (29% vs 5%; p = 0.064). There were no significant associations between treatment and the likelihood of reliable, clinically meaningful worsening (p > 0.05). SIGNIFICANCE: In this preschool-aged DS population with high baseline everyday EF impairment, FFA treatment for 14-15 weeks was associated with dose-dependent, clinically meaningful improvements in regulating behavior, emotion, cognition, and overall everyday EF. These clinically meaningful improvements in everyday EF were not entirely due to seizure frequency reduction, suggesting that FFA may have direct effects on everyday EF during the early formative years of neurodevelopment.

Executive function in individuals who are compliant and non-compliant with the conditions of a community-based sentence.

Executive function encompasses multiple processes (e.g. regulating emotions, managing behaviours, problem-solving) essential in daily living. A growing body of neuropsychological research shows a relationship between executive dysfunction and criminal behaviour. However, is executive functioning relevant to sentence management? We examined relationships between self-reported executive functioning and community supervision sentence compliance. Sixty-four individuals serving community-based supervision sentences completed the Behavior Rating Inventory of Executive Function-Adult Version, and their compliance data for six months were collected from probation officer notes. The sample's mean scores were significantly higher (i.e. poorer executive functioning) than those for the normative sample. Those who complied with sentence conditions had higher mean scores than those who were non-compliant. Subsequent exploratory analyses showed that those with poorer executive functioning received more probation officer support to comply with sentence conditions. Attention to responsivity issues like executive function problems may help avoid entrapping people in the criminal justice system.

Executive function as measured by the Behavior Rating Inventory of Executive Function-2: children and adolescents with Williams syndrome.

BACKGROUND: Difficulties with executive functions (EF) are very common among individuals with Williams syndrome (WS). To characterise the pattern of relative strengths and weaknesses in EF for children and adolescents with WS, we considered the performance of a large sample on the parent version of the Behavior Rating Inventory of Executive Function-2 (BRIEF-2). Associations between distinct components of EF and adaptive behaviour, behaviour problems and intellectual ability were investigated. The concurrent effects of components of behaviour regulation and emotion regulation on attention problems and anxiety problems also were evaluated. METHODS: Participants were 308 6-17-year-olds with genetically confirmed classic WS deletions. Parent report of EF was measured by the BRIEF-2 questionnaire. Most participants (223/308) completed the Differential Ability Scales-II as a measure of intellectual ability. The parents of these individuals also completed the Child Behavior Checklist and the interview form of the Scales of Independent Behavior-Revised. RESULTS: As a group, the participants evidenced considerable parent-reported EF difficulty. A profile of relative strength and weakness was found at the index level, with performance on both the Behavior Regulation Index and the Emotion Regulation Index significantly better than performance on the Cognitive Regulation Index. Within each index, a statistically significant pattern of relative strength and weakness also was identified. Difficulties with behaviour regulation and emotion regulation were related to both behaviour problems and adaptive behaviour limitations. Higher inflexibility and more difficulty with self-monitoring were associated with lower overall intellectual ability. Difficulty with inhibition was uniquely associated with attention problems, and inflexibility was uniquely associated with anxiety problems. CONCLUSIONS: Executive function difficulties are highly prevalent among children and adolescents with WS and are associated with adaptive behaviour limitations, both internalising and externalising behaviour problems and more limited intellectual ability. These results highlight the importance of designing and delivering research-based interventions to improve the EF of children and adolescents with WS.

Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: Analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome.

OBJECTIVE: Individuals with Dravet syndrome (DS) experience frequent pharmacoresistant seizures beginning in infancy. Most exhibit poor neurodevelopmental outcomes including motor function difficulties, behavior problems, and cognitive impairment. Cognitive deficits in children with DS have been associated with seizure frequency and antiseizure medication (ASM) use. Recent research in children and young adults with DS has begun to examine the role of executive functions (EFs), as these include higher-order cognitive functions and may mediate the relationship between risk factors and cognitive impairment. Current conceptualizations, however, of EFs involve the broader self-regulation of cognitive, behavioral, and emotional domains. We explored relationships between reduction in convulsive seizure frequency and everyday EFs in a subset of children and young adults with DS treated with adjunctive fenfluramine for 1 year. METHODS: This is a post-hoc analysis of data from children and young adults with Dravet syndrome aged 5-18 years who participated in a phase 3 randomized, placebo-controlled clinical trial (core study) followed by completion of at least 1 year of fenfluramine treatment in an open-label extension (OLE) study. Eligible children and young adults started the OLE study at 0.2 mg/kg/day fenfluramine and were titrated to optimal seizure control and tolerability (maximum daily dose: 26 mg/day). Parents/caregivers documented convulsive seizure frequency per 28 days (i.e., monthly convulsive seizure frequency [MCSF]) by electronic diary. A parent/caregiver for each child also completed the Behavior Rating Inventory of Executive Function (BRIEF®) parent form, a questionnaire capturing parents'/caregivers' perceptions of everyday EF that was included as a safety measure to assess treatment-related adverse effects on EF during the trial. Ratings on BRIEF® were mapped to the current edition, the BRIEF®2 parent form, and were used to calculate T-scores for the Behavior Regulation Index (BRI), Emotion Regulation Index (ERI), Cognitive Regulation Index (CRI), and Global Executive Composite (GEC). Change in BRIEF®2 T-scores from baseline in the core study to Year 1 of the OLE study was calculated. Spearman's rho correlation coefficients assessed associations between change in BRIEF®2 indexes/composite T-scores and percentage change in MCSF. Children and young adults were divided into 2 groups based on percentage of MCSF reduction achieved from pre-randomization baseline in the core study to Year 1 of the OLE study: <50% and ≥50% MCSF reduction. Changes in the distribution of BRIEF®2 indexes/composite T-scores were compared between MCSF reduction groups using Mann-Whitney U tests. The proportions of children and young adults in these groups who showed clinically meaningful improvement in everyday EF, defined as Reliable Change Index (RCI) values ≥95% certainty relative to a reference population of neurotypically developing healthy volunteers, were then assessed by cross-tabulations and Somers' D tests (p ≤ 0.05). When there was a significant meaningful improvement in an index score, post-hoc analyses using the same statistical methods were conducted to evaluate the individual BRIEF®2 scales composing that index. Supplemental analyses examined the proportions of patients in MCSF reduction groups <25% and ≥75% who achieved clinically meaningful improvement or worsening in everyday EF using RCI values ≥95% certainty and ≥80% certainty, respectively, relative to the reference population. RESULTS: At the time of analysis, 58 children and young adults (mean age: 11 ±â€¯4 years) had reached OLE Year 1 of fenfluramine treatment with a 75% median percentage reduction in seizure frequency from pre-randomization baseline. Overall, there was a significant correlation between change in MCSF and change in BRIEF®2 T-scores for ERI (p = 0.008), but not for BRI, CRI, or GEC (p > 0.05). At OLE Year 1, 78% (n = 45) of total children/young adults had ≥50% MCSF reduction (50% [n = 29] achieved ≥75% MCSF reduction) and 22% (n = 13) of total children/young adults had <50% MCSF reduction (12% [n = 7] showed <25% MCSF reduction). The ≥50% MCSF reduction group was significantly more likely to achieve clinically meaningful improvement (RCI ≥ 95% certainty) in ERI (p = 0.002) and in CRI (p = 0.001) than the <50% MCSF reduction group. There were no significant differences in the proportions of children and young adults in the 2 MCSF reduction groups showing clinically meaningful worsening (RCI ≥ 80% certainty) on the BRIEF®2 indexes/composite. SIGNIFICANCE: In children and young adults with DS, the magnitude of reduction in MCSF after long-term treatment with adjunctive fenfluramine was associated with clinically meaningful levels of improvement in everyday EF. Seventy-eight percent (78%) of children and young adults treated with adjunctive fenfluramine for 1 year in the OLE study achieved ≥50% reduction in MCSF, for a magnitude of efficacy associated with a significantly greater likelihood of experiencing clinically meaningful improvement in emotion regulation and cognitive regulation.

Vitamin D status in early childhood is not associated with cognitive development and linear growth at 6-9 years of age in North Indian children: a cohort study.

BACKGROUND: Vitamin D is important for brain function and linear growth. Vitamin D deficiency during pregnancy has been linked with impaired neurodevelopment during early childhood. However, there is limited evidence from population-based studies on the long-term impact of vitamin D deficiency on cognitive development and linear growth. The objective of the current analysis is to examine whether vitamin D deficiency during infancy and early childhood is associated with cognitive development and linear growth measured in school age. METHODS: This is a follow-up study of a placebo-controlled trial among 1000 North Indian children 6-30 months of age. We measured growth and neurodevelopment in 791 of these children when they were 6-9 years old. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children, 4th edition INDIA, the Crichton Verbal Scale, NEPSY-II subtests, and the BRIEF 2. We categorized vitamin D concentrations during infancy and early childhood according to the US Institute of Medicine's recommendations; serum 25(OH)D < 12 ng/ml as deficient; 12-20 ng/ml as inadequate; > 20 ng/ml as sufficient. In multivariable regression models, adjusting for relevant confounders, we estimated the association between vitamin D status, growth and neurodevelopmental outcomes. RESULTS: Among the 791 children, baseline vitamin D status was available for 716. Of these, 45.8% were vitamin D deficient, 32.7% were inadequate, and 21.5% were sufficient. Vitamin D status was not associated with any of the cognitive outcomes or linear growth [Adjusted ß coefficient for height for age z-score between deficient and sufficient children was - 0.06 (95% CI - 0.24 to 0.11)] at follow up. CONCLUSION: Our findings do not support the notion that poor vitamin D status in early childhood is an important limitation for cognitive development and linear growth. TRIAL REGISTRATION: The trial was first registered at www.clinicaltrials.gov as NCT00717730 in July, 2008, and at CTRI/2010/091/001090 in August, 2010 and then as CTRI/2016/11/007494 in November 2016.

Assessment of everyday executive functioning using the BRIEF in children and adolescents treated for brain tumor.

Objective: Childhood brain tumors (BTs) and their treatment often negatively affect development of executive functions. Previous studies have reported executive functions deficits, particularly through questionnaires of daily life. This study aimed to assess executive functioning in everyday life following pediatric BT, in a larger and more histologically diverse sample than previously, and to study clinical and demographic factors influencing outcome.Methods: Assessment of executive functioning using parent ratings of the Behavior Rating Inventory of Executive Function (BRIEF), in a large sample of children treated for various BT (n = 153). Clinical and demographic factors were: age at diagnostic, age at assessment, parental education level, radiation therapy.Results: Significant difficulties were found in the 3 composite indices and in the majority of the BRIEF subscales. The highest level of difficulties was observed in the Working Memory subscale. Older age at assessment and younger age at diagnosis were significantly associated with higher levels of parent-reported difficulties, particularly for metacognition.Conclusions: Parents of children treated for BT report widespread and persistent deficits in executive functions that negatively affect their everyday functioning. Including analysis of all clinical scales and composite indices allows a more comprehensive approach and enables to specify the patients' executive profile.

Long-term neurofunctional outcome, executive functioning, and behavioral adaptive skills following fetal myelomeningocele surgery.

BACKGROUND: Myelomeningocele (MMC) represents the first nonlethal anomaly to be treated by prenatal intervention. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks' gestation may preserve neurological function. Long-term follow-up is a fundamental component to evaluate the overall efficacy of any new medical or surgical procedure. To further delineate the long-term impact of fMMC surgery, we continued to follow children treated in our institution before the Management of Myelomeningocele Study trial by the means of parental questionnaires to assess changes in functional, developmental, and cognitive status as these unique patients grow older. OBJECTIVE: The objective of the study was to evaluate the long-term neurological outcome, executive functioning (EF), and behavioral adaptive skills (BAS) following fetal myelomeningocele (fMMC) surgery. STUDY DESIGN: Prior to the Management of Myelomeningocele Study trial, 54 patients underwent fMMC surgery at our institution. Parents of 42 children (78%) participated in structured questionnaires focusing on neurofunctional outcome. EF and BAS were measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Adaptive Behavioral Assessment System II. The BRIEF is organized into 3 primary indices including the following: Global Executive Composite, Metacognition Index, and Behavioral Regulation Index. The Adaptive Behavioral Assessment System II results in a general adaptive composite score. Based on SD intervals, EF and BAS were categorized as being average, borderline, or impaired. RESULTS: At a median follow-up age of 10 years (range, 8-14 years), 33 (79%) are community ambulators, 3 (9%) are household ambulators, and 6 (14%) are wheelchair dependent. Preschool ambulation was predictive of long-term ambulation (P < .01), whereas the need for tethered cord surgery was associated with persistent deterioration of ambulatory status (P = .007). Normal bladder function was found in 26%. Although the majority scored within the average range for the Behavioral Regulation Index, Metacognition Index, and Global Executive Composite indices, significantly more children who had fMMC surgery had deficits in EF in all 3 BRIEF indices compared with the population norms. The general adaptive composite scores were also more likely to fall below average following fMMC surgery. Normal early neurodevelopmental outcomes were predictive of normal EF and BAS (P < .01). Need for shunting was associated with a significant impairment of BAS (P = .02). CONCLUSION: The present study suggests that fMMC surgery improves long-term functional outcome. The majority of fMMC children can successfully complete everyday tasks at home and at school. Abnormalities of BAS appear to be more common than impairments in EF and therefore offer an area for early screening and interventional therapy for these at-risk children. Non-shunted fMMC children with normal early neurodevelopmental outcome are less likely to experience problems with EF and BAS. fMMC surgery improves long-term ambulatory status. Symptomatic spinal cord tethering with or without intradural inclusion cyst is associated with functional loss. More than expected fMMC children are continent, but bowel and bladder control continue to be an ongoing challenge for the fMMC children.

Executive Function in Children and Adolescents with Critical Cyanotic Congenital Heart Disease.

Children and adolescents with critical cyanotic congenital heart disease (CHD) are at risk for deficits in aspects of executive function (EF). The primary aim of this investigation was to compare EF outcomes in three groups of children/adolescents with severe CHD and controls (ages 10-19 years). Participants included 463 children/adolescents with CHD [dextro-transposition of the great arteries (TGA), n=139; tetralogy of Fallot (TOF), n=68; and, single-ventricle anatomy requiring Fontan procedure (SVF), n=145] and 111 controls, who underwent laboratory and informant-based evaluation of EF skills. Rates of EF impairment on D-KEFS measures were nearly twice as high for CHD groups (75-81%) than controls (43%). Distinct EF profiles were documented between CHD groups on D-KEFS tasks. Deficits in flexibility/problem-solving and verbally mediated EF skills were documented in all three CHD groups; visuo-spatially mediated EF abilities were impaired in TOF and SVF groups, but preserved in TGA. Parent, teacher, and self-report ratings on the BRIEF highlighted unique patterns of metacognitive and self-regulatory concerns across informants. CHD poses a serious threat to EF development. Greater severity of CHD is associated with worse EF outcomes. With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment.

Predictors of executive complaints and executive deficits in multiple sclerosis.

OBJECTIVES: To investigate executive complaints and objective executive deficits and their relations to both depression and neurological function in multiple sclerosis (MS). MATERIALS AND METHODS: One hundred and twenty MS patients participating in multidisciplinary rehabilitation underwent assessment with the Expanded Disability Status Scale (EDSS), neuropsychological tests of executive function, self-report measures of executive function (BRIEF-A), and depression (BDI-II). RESULTS: Multivariate regression analysis showed that moderate depression and above (BDI-II > 20) significantly predicted a high degree of subjective executive complaints. Multivariate regression analysis showed that EDSS scores above 4.3 significantly predicted executive cognitive deficit, measured by neuropsychological tests. CONCLUSION: Among the study variables, depression was the strongest predictor of executive complaints. A high degree of neurological disability was the strongest predictor for executive deficit, measured by neuropsychological tests.

Assessment of everyday executive functioning in children with frontal or temporal epilepsies.

Executive functions are particularly vulnerable in case of brain disruption during childhood, when the brain is not fully mature. Some studies showed impairments of executive functions in children with epilepsy, but only a few of them investigated the impact of executive dysfunctions on daily life. The aim of this study was to understand the everyday executive functioning of children with epilepsy both at home and in school. We administered the Behavior Rating Inventory of Executive Function to parents and teachers of 53 children (7-16 years of age) with structural epilepsies or epilepsies of unknown cause of temporal lobe (n=25) or frontal lobe (n=28). The results indicated a global executive impairment in the whole group of patients, compared with normative data, with no difference between the group with temporal lobe epilepsy (TLE) and that with frontal lobe epilepsy (FLE), except for monitor domain, which seemed more frequently impaired in the group with FLE. Congruence between parent and teacher ratings was found. The frequency of seizures was not related to executive dysfunction, whereas the number of antiepileptic drugs tended to positively correlate with working memory impairment. Onset of epilepsy at a younger age was also related to more executive difficulties but only according to teacher ratings. Lastly, duration of epilepsy was strongly associated with executive deficits reported in the context of school. Our results support the executive dysfunction hypothesis in daily life of children with structural focal epilepsy or focal epilepsy of unknown cause and are consistent with the early brain vulnerability hypothesis currently prevalent in the context of child neuropsychology. The BRIEF appears to be a clinically useful tool for assessing executive function impairment in this clinical population.

Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4-5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4-5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up.

Differences between parent- and teacher-reported executive functioning behaviors after traumatic injuries.

Deficits in executive functioning (EF) behaviors are very common following pediatric traumatic brain injury (TBI) and can linger well after acute injury recovery. Raters from multiple settings provide information that may not be appreciated otherwise. We examined differences between parent and teacher ratings of EF using data examining longitudinal outcomes following pediatric TBI in comparison to orthopedic injury (OI). We used linear mixed models to determine the association of rater type and injury type with scores on the Behavior Rating Inventory of Executive Functioning (BRIEF). After controlling for demographic variables, rater type and injury type accounted for a small but significant proportion of the variance in EF. Teachers' ratings on the BRIEF were significantly higher than parent ratings for global EF and metacognition, but not for behavior regulation, regardless of injury type, indicating greater EF concerns. All BRIEF ratings, whether from teachers or parents, were higher for children with TBI than for those with OI. Results suggest that parents and teachers provide unique information regarding EF following traumatic injuries and that obtaining ratings from persons who observe children at school as well as at home can result in a better understanding of situation-specific variability in outcomes.

Tick-borne encephalitis carries a high risk of incomplete recovery in children.

OBJECTIVE: To examine long-term outcome after tick-borne encephalitis (TBE) in children. STUDY DESIGN: In this population-based cohort, 55 children with TBE with central nervous system involvement infected during 2004-2008 were evaluated 2-7 years later using the Rivermead post-concussion symptoms questionnaire (n = 42) and the Behavior Rating Inventory of Executive Functioning for parents and teachers (n = 32, n = 22, respectively). General cognitive ability was investigated in a subgroup (n = 20) using the Wechsler Intelligence Scale for Children, 4th edition. RESULTS: At long-term follow-up, two-thirds of the children experienced residual problems, the main complaints being cognitive problems, headache, fatigue, and irritability. More than one-third of the children were reported by parents or teachers to have problems with executive functioning on the Behavior Rating Inventory of Executive Functioning, mainly in areas involving initiating and organizing activities and working memory. Children who underwent Wechsler Intelligence Scale for Children, 4th edition testing had a significantly lower working memory index compared with reference norms. CONCLUSION: A large proportion of children experience an incomplete recovery after TBE with central nervous system involvement. Cognitive problems in areas of executive function and working memory are the most prevalent. Even if mortality and severe sequelae are low in children after TBE, all children should be followed after TBE to detect cognitive deficits.

Cognitive features that distinguish preschool-age children with neurofibromatosis type 1 from their peers: a matched case-control study.

OBJECTIVE: To examine the cognitive functioning of 40-month-old children with neurofibromatosis type 1 (NF1). STUDY DESIGN: In this case-control study, 43 children with NF1 and 43 comparison children (matched by age, sex, and maternal years of education) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Language, visual perception, preliteracy, and executive functioning were also examined. Parents completed questionnaires about their child's behavior. Group differences were examined using the paired-samples t test or the related Wilcoxon signed rank test. Conditional logistic regression was conducted to identify which cognitive variables predicted group membership (ie, NF1 or control). RESULTS: The NF1 group had significantly poorer general intelligence than matched comparisons. Preschool-age children with NF1 had significantly poorer language, visual perception, response inhibition, and preliteracy skills than comparison children. The Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Object Assembly and Information subtests were significant predictors of group membership. Parent ratings indicated no group differences in behavior. CONCLUSIONS: After accounting for potentially confounding variables of age, sex, and maternal years of education, young children with NF1 have significantly poorer intellectual functioning, expressive language, and visual perception. These cognitive features that distinguish young children with NF1 from healthy peers can be detected in the preschool age group and are likely to impact on learning and performance during early school years. These areas should be targeted for intervention to maximize the developmental outcomes of young children with NF1.

Sex as a Moderator Between Parent Ratings of Executive Dysfunction and Social Difficulties in Children and Adolescents with Autism Spectrum Disorder.

Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and autistic symptoms in 116 children and adolescents (25 girls) aged 5-19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (p < 0.001) and communication (p = 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD.

BRIEF-A: Factor structure and measurement invariance across self-report and informant forms.

OBJECTIVE: This study analyzes the psychometric properties of the two forms (self-report and informant) of the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) in a sample of healthy Portuguese adults. METHOD: The participants were 608 adults, 304 of whom answered the self-report form (ages 18-59; 137 male and 167 female) and 304 who answered the informant form (ages 18-70; 110 male and 194 female). RESULTS: The internal consistency for the indexes and the Global Executive Composite was very good (≥.90), whereas for the scales they were either acceptable (between .70 and .80) or good (≥.80), except for the Inhibit scale in both forms. Confirmatory factor analysis was used to test seven competing factor models for each of the forms. The original two-factor model (Behavioral Regulation and Metacognition Indexes) showed a slightly better model fit than the three-factor model (Behavioral Regulation, Emotional Regulation, and Metacognition Indexes) in both forms. The multiple-group analysis of the two-correlated-factor model across forms was supported (configural, metric, and partial scalar invariance). CONCLUSIONS: Overall, the BRIEF-A showed adequate psychometric properties, suggesting that it is a useful instrument to assess everyday executive functioning in healthy Portuguese adults.

Real-world executive functioning for autistic children in school and home settings.

LAY ABSTRACT: Executive functioning skills are important for children to be able to control thoughts, emotions, and actions, and for their ability to adapt to different settings. Previous studies have found that autistic children have difficulty with executive functioning, but most of these studies took place in the home setting. Executive functioning skills in autistic children have not yet been fully examined in the school setting. This is a knowledge gap that needs to be addressed because the school setting is potentially one of the most demanding in terms of executive functioning and is a setting where executive function interventions are already being used for autistic children. In order to learn more about executive functioning for autistic children in the school setting, this study compared ratings of executive function from autistic children's caregivers and school professionals. The study found that autistic children experience similar but not identical executive function challenges across school and home settings and that supports may differ in each setting. Having information about differences in executive functioning challenges and supports for autistic children across settings can help lead to development of supports that are tailored to each setting.

[Formula: see text]Enhanced interpretation of the BRIEF2: multivariate base rates of elevated scores in the standardization samples.

The Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) is a standardized rating (self, parent, and teacher) scale of executive functioning in children and adolescents. Here, we provide multivariate base rate (MBR) information (for the Self, Parent, and Teacher forms), which is not included in the BRIEF2 Professional Manual. Participants were children and adolescents for the BRIEF2 Self-Report (ages = 11-18; N = 803), Parent-Report (ages = 5-18; N = 1,400), and Teacher-Report (ages = 5-18; N = 1,400) standardization samples. We focused on cumulative (e.g., % of sample with oneor more elevated scores) MBRs across scales, which were examined at three elevation levels on each form: T≥ 60, ≥65, and ≥70. Across forms, MBRs predictably decreased with increasing number of elevated scores and at higher cutoffs. The cumulative MBR of having at least one score at T≥ 60 was common (37.5-42.2%), but less frequent at T≥ 70 (15.4-17.4%). The probability of having elevated scores on all scales was very low, irrespective of form, age, or elevation threshold (T≥ 60 = 2.4-4.4%; T≥ 65 = 1.0-1.4%; T≥ 70 = 0.0-0.7%). There was no clinically meaningful relation between demographic factors (age, gender, race, and parental education) and MBRs. These data provide clinicians and researchers with an enhanced way of concurrently interpreting multiple BRIEF2 scales.

Adolescents with solid organ transplant: Using the BRIEF2 parent-report and self-report to measure parent-child agreement and everyday executive function.

Agreement between parent and adolescent ratings of executive function (EF) is not known in adolescents with solid organ transplant (SOT), even though pressing concerns about EF deficits are being raised in this population. The current study investigated EF in adolescents with SOT using parent and self report. Twenty-five adolescents (M = 15.51 years) with SOT and their parent completed a behavior rating scale assessing EF within everyday context using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parents and their adolescents demonstrated moderate to excellent agreement across the BRIEF2 clinical and index scores, higher than previous research with a typical sample. Adolescent males had higher agreement with their parents than female adolescents. Both parents and adolescents reported significantly higher mean T scores on various BRIEF2 indices and domains, in addition to higher rates of clinically elevated executive dysfunction than their peers. Assessment of EF and targeting specific EF domains for intervention may be useful in this population.

Parent-Reported Perceived Cognitive Functioning Identifies Cognitive Problems in Children Who Survived Neonatal Critical Illness.

Children with congenital anatomical foregut anomalies and children treated with neonatal extracorporeal membrane oxygenation (ECMO) are at risk for neurocognitive morbidities. We evaluated the association between the parent-reported pediatric perceived cognitive functioning (PedsPCF) questionnaire and the parent-reported behavior rating inventory of executive function (BRIEF) as well as neuropsychological assessments (NPA). We included 8-, 12- and 17-year-old participants who had joined a prospective follow-up program between 2017 and 2019. Self- and parental proxy-reported PedsPCF and proxy-reported BRIEF scores and their mutual association were evaluated. In total, 168 participants were included. Self- and proxy-reported PedsPCF scores were significantly below normal (mean (SD) z-score: −0.35 (0.88), p < 0.001; −0.36 (1.06), p < 0.001, respectively). Total BRIEF scores were significantly above normal (mean (SD) z-score 0.33 (0.98), p < 0.001). Proxy-reported PedsPCF scores and the Metacognition Index subscores of the BRIEF correlated strongly (τ = 0.551, p < 0.001). Self-reported PedsPCF scores were not associated with NPA test scores. Proxy-reported PedsPCF scores were positively associated with multiple NPA test scores, especially intelligence (R2 = 0.141). The proxy-reported PedsPCF revealed cognitive problems more often than the BRIEF in school-aged children who had survived neonatal critical illness. The proxy-reported PedsPCF may support clinical decision-making regarding the need for extensive neuropsychological assessments.