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Timing is everything: executive functions in children exposed to elevated levels of phenylalanine.

This study addresses how the timing of a known biological insult affects the developmental progression of executive functions. The sample consisted of children exposed to elevated levels of phenylalanine, either postnatally, as in phenylketonuria (PKU; n = 46), or prenatally, as in maternal PKU (n = 15). Nonhyperphenylanemic siblings of children with PKU (n = 18) served as controls. Results indicated that elevated levels of phenylalanine are toxic to the neurological systems that manage executive functions and cognitive tempo. This toxicity is dose dependent, with higher levels of phenylalanine being more detrimental. Executive function difficulties noted in PKU are consistent with attention deficit hyperactivity disorder (ADHD)-inattentive type, whereas maternal PKU offspring had executive function difficulties consistent with ADHD-combined type.

Adolescent↗

Familial clustering of executive functioning in affected sibling pair families with ADHD.

OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the Stroop test, go/no-go task, two different fine visuomotor tracking tasks, and a sustained-, divided-, and focused attention task. RESULTS: Significant correlations (r = 0.4) were found between siblings for response inhibition and attentional control and for fine visuomotor skills that made high demands on executive functioning. CONCLUSIONS: Response inhibition, higher order controlled fine visuomotor functioning, and attentional control seem to cluster in ADHD-affected siblings. This suggests that these aspects of executive dysfunctioning may reflect an endophenotype of ADHD. Measurement of these executive functions may facilitate the identification of genes involved in ADHD by forming more homogeneous subgroups.

Adolescent↗

Modafinil improves alertness, vigilance, and executive function during simulated night shifts.

STUDY OBJECTIVES: To assess the effect of 200 mg of modafinil compared to placebo on alertness, neurobehavioral performance, and executive function during 4 consecutive simulated night shifts. DESIGN: Double-blind, randomized, parallel groups. SETTING: Sleep research facility. PARTICIPANTS: 32 male and female volunteers between the ages of 18 and 55 years. INTERVENTIONS: 200 mg of modafinil or placebo given nightly on the 4 consecutive simulated night shifts. MEASUREMENTS AND RESULTS: Subjects were randomly assigned to 1 of the 2 treatment conditions, following medical, psychiatric, and polysomnographic screening. On 4 consecutive nights, subjects took study drug at 2200, and then from about 2300 to 0730 participated in a simulated night shift that included the Maintenance of Wakefulness Test, Psychomotor Vigilance Test, Digit Symbol Substitution Test, measures of subjective alertness, and multiple executive-function measures. At 0800, daytime sleep periods were recorded polysomnographically for 6 to 8 hours. Alertness--as measured by the MWT, vigilance and reaction time as indexed by Psychomotor Vigilance Test lapses, and slowest 10% of reaction times--and 3 executive-function tasks showed significant enhancement with modafinil versus placebo. Subjective sleepiness at night and some performance measures did not show consistent treatment differences. Daytime sleep showed minimal differences between conditions. CONCLUSIONS: The physiologic sleepiness and neurobehavioral deficits that occurred during the hours of a typical night shift were clearly attenuated by modafinil. Modafinil also had beneficial effects on some measures of executive function.

Adolescent↗

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20&#xa0;mg/day over 6&#xa0;weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n&#xa0;=&#xa0;31; placebo, n&#xa0;=&#xa0;32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P&#xa0;<&#xa0;0.001), but improvement was greater with memantine for global cognition at week 6 (MD&#xa0;=&#xa0;9.32; 95% CI, 4.84-13.81; P&#xa0;<&#xa0;0.001) and week 18 (MD&#xa0;=&#xa0;12.69; 95% CI, 8.67-16.71; P&#xa0;<&#xa0;0.001). FAB total scores favored memantine at week 18 (MD&#xa0;=&#xa0;2.68; 95% CI, 1.76-3.61; P&#xa0;<&#xa0;0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

Executive functioning predicts social skills following prenatal alcohol exposure.

Adverse sequelae of prenatal alcohol exposure include executive function and social skills impairments, although these two domains have not been empirically linked in alcohol-exposed individuals. This study investigated this relationship using the BRIEF and the SSRS in 98 children aged 6 to 11 years. Executive functions explained a significant percentage of variance in parent and teacher rated social skills. No differences were found among children with diagnoses of FAS, partial FAS, or alcohol-related neurodevelopmental disorder. It may be helpful to consider executive functioning in designing social skills interventions for alcohol-exposed children whether or not they have full FAS.

Age Factors↗

Executive functions in becoming writing readers and reading writers: note taking and report writing in third and fifth graders.

Results are reported for a study of 2 separate processes of report writing-taking notes while reading source material and composing a report from those notes-and related individual differences in executive functions involved in integrating reading and writing during these writing activities. Third graders (n = 122) and 5th graders (n = 106; overall, 127 girls and 114 boys) completed two reading-writing tasks-read paragraph (mock science text)-write notes and use notes to generate written report, a reading comprehension test, a written expression test, four tests of executive functions (inhibition, verbal fluency, planning, switching attention), and a working memory test. For the read-take notes task, the same combination of variables was best (explained the most variance and each variable added unique variance) for 3rd graders and 5th graders: Wechsler Individual Achievement Test-Second Edition (WIAT-II) Reading Comprehension, Process Assessment of the Learner Test for Reading and Writing (PAL) Copy Task B, WIAT-II Written Expression, and Delis-Kaplan Executive Function System (D-KEFS) Inhibition. For the use notes to write report task, the best combinations of variables depended on grade level: For 3rd graders, WIAT-II Reading Comprehension, WIAT-II Written Expression, D-KEFS Verbal Fluency, and Tower of Hanoi; for 5th graders, WIAT-II Reading Comprehension, D-KEFS Verbal Fluency, WIAT-II Written Expression, and PAL Alphabet Task. These results add to prior research findings that executive functions contribute to the writing development of elementary-grade students and additionally support the hypothesis that executive functions play a role in developing reading-writing connections.

Analysis of Variance↗

Executive function as a predictor of inattentive behavior after traumatic brain injury.

Emerging evidence from recent studies using laboratory and naturalistic attention tasks suggests that individuals with traumatic brain injury (TBI) may have a deficit mainly in strategic control of attention. In the present study, we tested the hypothesis that inattentive behavior after TBI could be predicted by performance on psychometric measures of executive function. A group of 37 individuals with moderate to severe TBI were assessed with previously validated naturalistic measures of attention. A battery of neuropsychological tests was also administered to assess various aspects of executive function. Seven measures of executive function and 10 variables reflecting inattentive behavior were combined to form 1 executive and 3 inattentive behavior (IB) composite scores. Three predictors (executive composite, current disability scores, and age) were associated, at the univariate level, with one of the IB composites reflecting frequency and duration of off-task episodes. A stepwise multiple regression procedure indicated that the executive composite was the only significant predictor of the IB composite. Additional post-hoc regression analyses suggested that the relationship was not likely to be mediated by processing speed. The current study supports the hypothesis that executive function, measured by commonly used neuropsychological tests, significantly predicts certain aspects of inattentive behavior in real-world tasks after TBI.

Adolescent↗

Assessing executive functions in children: biological, psychological, and developmental considerationst.

Executive functions may be defined as those skills necessary for purposeful, goal-directed activity, and are generally considered to be largely mediated by the frontal and prefrontal cortices of the brain. These cerebral regions are relatively immature during childhood, with development thought to be a protracted process which continues into early adolescence. While early theorists suggested that executive skills were not functional until cerebral maturity, recent research provides evidence that such skills can be elicited in early childhood. The aim of this paper is to review current theories of development of executive functions throughout childhood. In keeping with contemporary approaches to child neuropsychology, three critical dimensions will be evaluated; biological factors, psychological dimensions, and developmental trajectories. In addition, the literature which addresses assessment of these functions will be examined, with reference to developmental trajectories observed in normal populations, and in brain-damaged samples, where there may be disruption to the underlying neural substrates thought to be subsuming these functions.

Adolescent↗

Executive functions and the natural habitat behaviors of children with autism.

Research suggests that impairments in executive functions play a role in the cognitive deficit in autism. Possible autism-specific impairments include an inability to engage in goal-directed behaviors and adjust behaviors given environmental demands. What has been described as executive functions is based largely on observations of performance in the laboratory rather than in natural settings. An ecological method first described by Barker and Wright and adapted by Scott was used to assess the patterns of goal-directed behaviors of eight children with autism and eight chronological and mental age comparable children with Down syndrome. Quantitative and qualitative features of naturalistic behaviors were collected, and coded using previously described categories of children's behavior. Results indicated that children with autism exhibited shorter and less overlapping goal-directed behaviors. These data suggest a cognitive difference rather than developmental delay, and lend support for impaired executive functions in autism. Practical implications for educators and caregivers are discussed.

Autistic Disorder↗

Measures of executive functioning as predictors of functional ability and social integration in a rehabilitation sample.

OBJECTIVE: To examine the utility of executive function tests in predicting rehabilitation outcome. DESIGN: A prospective, descriptive study of the value of neuropsychologic and motor functioning measures in the prediction of functional outcome 6 months after acute rehabilitation. SETTING: A Midwestern, urban, university-affiliated rehabilitation hospital. PATIENTS: Ninety consecutive admissions to traumatic brain injury, orthopedic, and spinal cord injury units. Age of the participants ranged from 17 to 73. MAIN OUTCOME MEASURES: Community Integration Questionnaire (CIQ), Disability Rating Scale (DRS), SF-36 Health Survey. RESULTS: Canonical correlation analyses indicated that measures of executive functioning and verbal memory were strongly related to measures of functional outcome 6 months after rehabilitation, as measured by the DRS and the CIQ. In contrast, perceived health status as measured by the SF-36 was highly related to estimated premorbid IQ and modestly related to visuospatial impairment. CONCLUSIONS: Executive functioning, verbal memory, and estimated premorbid intelligence predict functional dependence after discharge from rehabilitation beyond information regarding basic sensory and motor skills. Moreover, there is a dissociation between measures of functional outcome, such that objective and behaviorally oriented measures of disability (CIQ and DRS) are strongly related to each other; however, they are not related to perceptions of general health status (SF-36).

Adolescent↗

Age differences in executive functioning across the lifespan: the role of verbalization in task preparation.

Age-related changes in executive functioning across the lifespan were assessed in children (mean age=9.4 years), younger adults (mean age=21.5 years), and older adults (mean age=65.3 years). Executive functioning was investigated with a task-switching paradigm that permits the separation of two control components: to select and to switch between task sets. The specific aims of this study were (a) to determine developmental functions in both control components across the lifespan; and (b) to examine whether age-related changes in these components are influenced by verbal prompts during task preparation. The results revealed an inverted u-shaped developmental function for the ability to select between task sets but not for the ability to switch between task sets. In contrast to younger adults and children, older adults generally benefited from verbalizations during task preparation. Children, but not older adults, showed a facilitation of task execution when verbal prompts were task-compatible. Conversely, older adults, but not children, showed stronger interference when verbal prompts are task-incompatible. Our findings suggest that inner speech in an important modulator of developmental changes in executive functioning across the lifespan.

Adult↗

Effects of acute tryptophan depletion on executive function in healthy male volunteers.

BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.

Adolescent↗

The development of executive function in early childhood.

According to the Cognitive Complexity and Control (CCC) theory, the development of executive function can be understood in terms of age-related increases in the maximum complexity of the rules children can formulate and use when solving problems. This Monograph describes four studies (9 experiments) designed to test hypotheses derived from the CCC theory and from alternative theoretical perspectives on the development of executive function (memory accounts, inhibition accounts, and redescription accounts). Each study employed a version of the Dimensional Change Card Sort (DCCS), in which children are required first to sort cards by one pair of rules (e.g., color rules: "If red then here, if blue then there"), and then sort the same cards by another, incompatible pair of rules (e.g., shape rules). Study 1 found that although most 3- to 4-year-olds failed the standard version of this task (i.e., they perseverated on the preswitch rules during the postswitch phase), they usually performed well when they were required to use four rules (including bidimensional rules) and those rules were not in conflict (i.e., they did not require children to respond in two different ways to the same test card). These findings indicate that children's perseveration cannot be attributed in a straightforward fashion to limitations in children's memory capacity. Study 2 examined the circumstances in which children can use conflicting rules. Three experiments demonstrated effects of rule dimensionality (uni- vs. bidimensional rules) but no effects of stimulus characteristics (1 vs. 2 test cards; spatially integrated vs. separated stimuli). Taken together, these studies suggest that conflict among rules is a key determinant of difficulty, but that conflict interacts with dimensionality. Study 3 examined what types of conflict pose problems for 3- to 4-year-olds by comparing performance on standard, Partial Change, and Total Change versions of the DCCS. Results revealed effects of conflict at the level of specific rules (e.g., "If red, then there"), rather than specific stimulus configurations or dimensions per se, indicating that activation of the preswitch rules persists into the postswitch phase. Study 4 examined whether negative priming also contributes to difficulty on the DCCS. Two experiments suggested that the active selection of preswitch rules against a competing alternative results in the lasting suppression of the alternative. Taken together, the results of these studies provide the basis for a revision of the CCC theory (CCC-r) that specifies more clearly the circumstances in which children will have difficulty using rules at various levels of complexity, provides a more detailed account of how to determine the complexity of rules required in a task, takes account of both the activation and inhibition of rules as a function of experience, and highlights the importance of taking intentionality seriously in the study of executive function.

Attention↗

Parental alcohol use disorders and child delinquency: the mediating effects of executive functioning and chronic family stress.

OBJECTIVE: This study examines the relationship between parental alcohol use disorders (AUDs) and child violent and nonviolent delinquency. It also explores the mediating effects of executive functioning and chronic family stress on the parental AUD/child delinquency relationship. METHOD: Participants were 816 families with children (414 boys and 402 girls) born between 1981 and 1984 at Mater Misericordiae Mother's Hospital in Brisbane, Australia. Parents and children completed semistructured interviews, questionnaires and neuropsychological tests that assessed parental alcohol use, family psychiatric history, chronic family stress, child delinquency and child executive functioning. RESULTS: Paternal (but not maternal) AUDs predicted child violent and nonviolent delinquency. Executive functioning mediated the relationship between paternal AUDs and violent delinquency, whereas family stress mediated the relationship between paternal AUDs and both violent and nonviolent delinquency. CONCLUSIONS: Results support a biosocial conceptualization of the paternal AUD/delinquency relationship. They suggest that paternal AUDs may be associated with child executive functioning and family stress, which may in turn lead to child delinquency.

Adolescent↗

Memory and executive function in sporadic and familial Parkinson's disease.

Some studies have demonstrated that the motor symptomatology in sporadic and familial Parkinson's disease was identical. From a physiopathological point of view, and perhaps in the future from a therapeutic point of view, it seems important to determine whether sporadic and familial Parkinson's disease are also similar with regard to cognitive impairment. The aim of the present study was to assess cognitive functions in patients suffering from sporadic and familial Parkinson's disease. Executive functions and memory were investigated in particular. Two groups of 12 patients with Parkinson's disease (sporadic and familial) and 12 healthy controls performed a set of tasks known to evaluate different aspects of executive function and memory. One-way analysis of variance tested for significant group effects, and when justified, post hoc analysis was performed. Cognitive impairment was different in sporadic and familial forms of Parkinson's disease. Indeed, although executive function was impaired in both groups of patients, deficits in tests of explicit memory recall were only observed in patients with sporadic Parkinson's disease. Although the impairment observed in both groups of patients suggests a disruption of the striatoprefrontal circuits, this disruption seems to be quantitatively more important and more widespread in the sporadic patients than in the familial ones. In both patient groups, the deficits probably result from dopaminergic and nondopaminergic deprivation and a greater participation of nondopaminergic factors in patients with sporadic Parkinson's disease could be suggested. In this group, a xenobiotic could be responsible for an acquired metabolic defect involving more widespread structures of the striatoprefrontal circuits, leading to disruption of nondopaminergic loops. Cholinergic deprivation is considered in particular.

Adult↗

Executive function and social communication deficits in young autistic children.

Preschool-aged, autistic children were compared with both developmentally delayed children of similar non-verbal mental age and normally developing children of similar verbal skill on measures of executive function and social communication skills. Autistic children exhibited significantly more perseverative responses on a test of executive function when compared to both comparison groups. Autistic children also exhibited significantly fewer joint attention and social interaction behaviors. Moreover, a significant relationship was found between executive function skill and the two social communication skills, which was independent of group membership or verbal ability. Competing hypotheses to account for the relationship between executive function deficits and social communication deficits in autism are discussed.

Attention↗

Theory of mind, humour processing and executive functioning in alcoholism.

AIMS: Alcoholism is associated with cognitive deficits, which have been interpreted in terms of a specific vulnerability of the frontal lobes to the toxic effects of alcohol. While executive functions in alcoholism have been investigated extensively, only little work has been carried out on social cognition. The aim of the present study was to investigate the association between executive functions, theory of mind and humour processing in alcoholism. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A comprehensive neuropsychological test battery was administered to 29 alcoholic patients (Alc) and 29 healthy controls (HC). The test battery included measurements of affect, general intellectual abilities, executive functions, humour processing and theory of mind. The two groups were comparable with respect to affective variables, IQ, gender and age. FINDINGS AND CONCLUSIONS: Group comparisons revealed cognitive as well as affective humour processing deficits of alcoholics in comparison with HC. The observed impairments were related to theory of mind and executive functions. The deficits may contribute to interpersonal problems and are thus of relevance to rehabilitation.

Adult↗

The relationship of behavioral inhibition to executive functions in young adults.

Barkley's hybrid model of executive functions (EFs) predicts that individuals with deficient inhibitory control should show impairment of EFs. Thirty-eight nonreferred young adults were administered tests of EFs and four laboratory measures of inhibitory control: Stop Signal (SS), Go No-Go, Competing Motor Program (CMP), and Stroop Color-Word tests. Behavioral ratings of impulsivity were collected using the Barratt Impulsivity Scale-11 (BIS-11). CMP and SS accounted for a significant proportion of variance in measures of EFs beyond that accounted for by IQ. Additionally, increased impulsivity, as measured by the BIS-11, was associated with poorer performance on some tests of EFs. These findings provide partial support for Barkley's theory in that effective executive functioning is associated with sufficient inhibitory control.

Adolescent↗