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PubMed2006

Age-related changes in duration reproduction: involvement of working memory processes.

The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered working memory tests to measure storage and central executive functions. Findings indicated a differential involvement of working memory storage and central executive functions in age-related differences in temporal tasks. The limited storage capacities explained age-related changes in the simple task of duration reproduction, and the dysfunctioning of central executive functions accounted for age-related changes in duration reproduction performed in a concurrent task condition, which involves greater attentional resources.

Adult↗

PubMed2006

Factors mediating cognitive deficits and psychopathology among siblings of individuals with schizophrenia.

Schizotypal traits and cognitive disturbances are known to be present in first-degree relatives of people with schizophrenia. However, there is little understanding of how these endophenotypes are related to each other. We explored the nature of this relationship in individuals with schizophrenia, their full siblings, community controls, and their siblings. All participants were assessed in the domains of working memory, attention, episodic memory, and executive function, as well as in their level of positive, negative, and disorganization symptoms. Schizophrenia probands were significantly impaired on all cognitive domains, as compared with the other 3 groups, and displayed the highest levels of positive, negative, and disorganization symptoms. Proband siblings performed significantly worse than controls on tasks of working memory, episodic memory, and executive function, and they displayed significantly more positive and negative symptoms as compared with controls. Poorer task performance across all 4 cognitive domains was most strongly correlated with increased negative symptoms. Mediation analyses revealed that working memory, episodic memory, and executive function deficits partially mediated increases in negative symptoms among proband siblings. Negative symptoms fully mediated deficits in working memory and episodic memory but only partially mediated deficits in executive function. Results suggest that there is a complex relationship between cognitive and clinical factors in this high-risk population.

Adult↗

PubMed1998

Spectral analysis of wakefulness and REM sleep EEG in patients with sleep apnoea syndrome.

Neuropsychological investigations of patients with obstructive sleep apnoea syndrome (OSAS) have shown impairments in such basic functions as memory, attention and executive control. Since executive functions are known to be dependent on the integrity of the frontal lobe, it was hypothesized that OSAS may be associated with hypoxaemic frontal lobe dysfunction. To test this hypothesis, 21 apnoeic patients and 10 normal controls were studied with quantitative electroencephalographic (EEG) methods during rapid eye movement (REM) sleep, when most apnoeic events occur and during wakefulness. In apnoeic patients, EEG slowing in REM sleep was observed over frontal, central and parietal regions, while EEG slowing during wakefulness was observed over all cortical regions examined. A positive correlation was found between EEG slowing during wakefulness and oxygen desaturation during the night. Contrary to the hypothesis, these electroencephalographic changes were not localized only to the frontal region. This result may explain the wide range of neuropsychological deficits noted in patients with obstructive sleep apnoea syndrome, in addition to their poor performance in tasks of executive functioning.

Adult↗

PubMed2000

Neurobehavioral characteristics of adolescents with behavioral dysregulation disorder.

BACKGROUND: There is growing recognition that violence and other forms of conduct problems increase during adolescence. The exact relationship between biological, psychological, and social variables has not been defined yet. OBJECTIVES: To analyze whether Intelligence Quotients (IQS), neurological history, child behavioral problems, executive functions, and soft neurological signs (SNS) can differentiate between undisciplined and unreliable adolescents (Behavioral Dysregulation Disorder subjects, BDD) and normal controls. METHOD: Twenty-five 13 to 16-year-olds, adolescents with BDD and 25 matched controls were used in this study. WISC-R, executive function assessment, neurological history, child behavioral problems, and SNS scores were analyzed using a Multivariate Analysis of Variance (MANOVA). A Multiple Regression Stepwise with Criteria Probability of F Analysis was used for predicting criteria variable variance. RESULTS: WISC-R Verbal IQ (VIQ), Information, Similarities, and Vocabulary subtests presented statistically significant differences between BDD and controls (p < .001). No Performance IQ (PIQ) variables established significant differences between both groups. Executive function scores did not detect significant differences between groups either. Prenatal, neonatal, and neurological history scores were similar between both groups. Two child behavioral problem variables were significantly different, with higher scores in BDD group: use of weapons and drug-use (p < .05). A Multiple Regression Stepwise (Criteria Probability of F < .05) model, entering the predictive variables in each domain (intelligence, executive function, neurological antecedents, child behavioral problems, and SNS), and using the score on the criteria variable as dependent variable, found two predictive models: (1) WISC-R Information (Ad-R-SQ = 0.172 F-Ch. = 11.176, p < .01); and (2) WISC-R Information and drug-use (R-SQ: 0.26; F-Ch = 9.605 p < .001). CONCLUSIONS: A verbal factor and drug-use predicted fairly 30% of the variance of the criteria variable used for classifying adolescents with BDD. These results would mean that a language underlying factor and an environmental drug-use factor would be related to the BDD in adolescents.

Adolescent↗

PubMed2006

Norwegian norms and factor-structure of phonemic and semantic word list generation.

Word list generation (WLG) tasks are used world wide as measures of executive function, although the tests are sensitive also to deficits in other cognitive functions. Norms derived from English-speaking samples are often used in Norway, even though the consequences of language differences are not yet been assessed. The reliability of WLG testing in Norway is increased by the norms presented in the first part of the study. The validity of WLG tests as measures of executive function is addressed in the second part, by performing a factor-analysis of neuropsychological performance in a mixed psychiatric sample. Education contributed most to performance. There were no sex-differences in overall performance. Factor analysis indicated that phonemic WLG is a more specific measure of executive function than semantic WLG. Semantic WLG correlated higher with basal processing speed, thus being more sensitive to aging. In conclusion the clinical neuropsychologist is advised to control for reduction in basal processing speed before interpreting WLG scores as specific deficits in executive function. The Norwegian norms correspond well with most comparable studies in other languages, thus failing to show any language specific effects.

Adolescent↗

PubMed2003

Acute cardiovascular exercise and executive control function.

Acute cardiovascular exercise effects on cognitive function were examined using an executive control task by comparing neuroelectric and behavioral performance at baseline with post-exercise in 20 undergraduates. A within-subjects design was used to assess the P3 component of an event-related brain potential (ERP) and behavioral performance using a task that varied the amount of executive control required. The baseline session involved participation on the Eriksen flankers task followed by a graded maximal exercise test to measure cardiovascular fitness. The exercise session consisted of a 30-min acute bout of exercise on a treadmill followed by the Eriksen flankers task after heart rate returned to within 10% of pre-exercise levels. Across midline recordings sites, results indicated larger P3 amplitude following acute exercise compared to baseline. Shorter P3 latency was observed during the baseline Eriksen flankers task for the neutral compared to the incompatible condition; an effect not found following the acute bout of exercise. These findings suggest that acute bouts of cardiovascular exercise affect neuroelectric processes underlying executive control through the increased allocation of neuroelectric resources and through changes in cognitive processing and stimulus classification speed.

Adult↗

PubMed2000

Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer's disease.

OBJECTIVE/BACKGROUND: To determine whether difficulty in the early differentiation between frontotemporal dementia (FTD) and AD may arise from a failure to discriminate between the temporal and frontal variants of FTD. METHODS: Neuropsychological profiles of patients with early dementia of Alzheimer type (DAT; n = 10), the temporal variant of FTD (tv-FTD or semantic dementia; n = 5), and the frontal variant of FTD (fv-FTD; n = 10) were compared to each other and normal controls (n = 10). Structural MRI demonstrated temporal lobe atrophy in the tv-FTD patients and frontal lobe atrophy in the fv-FTD group. RESULTS: Subjects with tv-FTD showed severe deficits in semantic memory with preservation of attention and executive function. Subjects with fv-FTD showed the reverse pattern. Attention and executive function impairment separated the fv-FTD patients from the early DAT subjects, who were densely amnesic. CONCLUSION: The double dissociation in performance on semantic memory and attention/executive function clearly separated the temporal and frontal variants of FTD and aids the early differentiation of FTD from AD. The characteristic cognitive profiles reflect the distribution of pathology within each syndrome and support the putative role of the inferolateral temporal neocortex in semantic memory, the medial temporal lobe structures of the hippocampal complex in episodic memory, and the frontal lobes in executive function.

Acoustic Stimulation↗

PubMed2002

Brain metabolic effects of Neotrofin in patients with Alzheimer's disease.

Neotrofin, a reported inducer of CNS neurotrophic factor synthesis and release, with memory-enhancing activity and demonstrated restoration of age-induced memory deficits in animals, was tested in patients with mild to moderate Alzheimer's disease. Nineteen subjects were treated with 1 week of low-dose (150 mg per day) and 1 week of high-dose (500 or 1000 mg per day) Neotrofin. Cognitive composite scores demonstrated improvement in memory (F=9.6, P=0.0004), executive functioning (P=0.004), and attention (P=0.004). PET scanning was obtained before, after low, and after high dosing. The brain areas most affected were the cerebellum, and sensory and prefrontal cortices, where increases in GMR (Glucose Metabolic Rate) were observed. Increases and decreases were observed in the posterior superior temporal (BA 22), parahippocampal, inferior temporal (BA 37, 20), and fusiform gyri as well as the superior parietal lobule and postcentral gyrus. There were strong hemispheric differences, producing opposite metabolic effects in homologous brain regions. Subcortically, the posterior thalamic region, meso-pontine tegmentum, and tectum had increases in GMR on the left side. At the low dose, GMR was generally increased, but to a lesser degree. The brain areas subserving memory, attention and executive functions were significantly altered in GMR by Neotrofin; however, the directions of these changes were complex. There were significant correlations between improvement in memory and executive function in brain areas involved in circuits subserving these functions. Thus, Neotrofin appears to induce metabolic changes in brain regions involved in circuits underlying memory, attention, and executive functioning.

Aged↗

PubMed2006

Effect of age and education on the Trail Making Test and determination of normative data for Japanese elderly people: the Tajiri Project.

The Trail Making Test (TMT) is a common two-part neuropsychological test, in which visuospatial ability (TMT-A) and executive function (TMT-B) are evaluated. Normative data for this test have not been reported for Japanese subjects; therefore, the purpose of the present paper was to investigate the effect of age and education on the TMT in 155 healthy elderly adults with clinical dementia rating 0 (healthy). The participants were classified into three groups based on age (70-74 years, 75-84 years and >or=85 years), and also into three groups based on educational level (6 years, 8 years and >or=10 years). The time to complete TMT-A and TMT-B were measured, and the difference in score between TMT-A and TMT-B (B-A) and the ratio of the score (B/A) were calculated as indices of executive function. The time for completion of both parts of the TMT increased markedly in the >or=85-years group. For TMT-A, there was a significant difference between the 6-years and 8-years groups, and between the 6-years and >or=10-years groups, and for TMT-B, there was a significant difference between the 6-years and >or=10-years groups, and between the 8-years and >or=10-years groups. The difference and ratio scores increased in the >or=85-years group, but the educational level did not significantly influence these scores. Our data suggest that cognitive functions evaluated by TMT-A and TMT-B are not affected by aging until the subjects are >or=85 years old. For TMT-A, an educational effect becomes apparent when the population includes poorly educated subjects, but this part of the test is not affected by educational level provided that the subjects have some education (>6 years). The time to complete TMT-B is affected by educational level, consistent with previous reports. However, when adjusted using the results for TMT-A [(B-A) or (B/A)], the educational effect on executive function disappeared. Thus, the effect of educational level on executive function was unclear in normal elderly subjects.

Aged↗

PubMed1999

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.

Antipsychotic Agents↗

PubMed2006

Neurocognitive influences on health behavior in a community sample.

CONTEXT: Dominant models of individual health behavior omit biological variables entirely and are composed almost exclusively of social-cognitive and conative variables. Research from the neurosciences suggests a role for brain function in explaining behaviors that require active self-regulation for consistent performance. However, the association between brain function and health behavior is underexplored. OBJECTIVE: To examine the predictive power of executive function for 2 health risk behaviors and 2 health protective behaviors in healthy adults. DESIGN: A cross-sectional community sample (N = 216) of adults 20-100 years of age were administered a battery of neuropsychological tests and completed self-report questionnaires regarding their health practices. It was hypothesized that poor performance on neuropsychological tests tapping executive function would be associated with poor health behavior tendencies. RESULTS: Errors on the Stroop task were positively associated with health risk behavior and negatively associated with health protective behavior after controlling for demographics, education, and IQ. CONCLUSION: Executive function is associated with health behavior tendencies. If the association is causal, explanatory models of individual health behavior should be revised to account for individual differences in biologically imbued self-regulatory abilities.

Adult↗

PubMed2006

Cognitive function, habitual gait speed, and late-life disability in the National Health and Nutrition Examination Survey (NHANES) 1999-2002.

BACKGROUND: Both cognitive function and gait speed are important correlates of disability. However, little is known about the combined effect of cognitive function and gait speed on multiple domains of disability as well as about the role of gait speed in the association between cognitive function and late-life disability. OBJECTIVE: To investigate (1) how cognition and habitual gait speed are related to late-life disability; (2) the role of habitual gait speed in the cognitiondisability association; and (3) the combined effect of cognitive function and habitual gait speed on late-life disability. METHOD: Participants (>60 years, n = 2,481) were from the National Health and Nutrition Examination Survey 1999-2002. Disability in activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), and lower extremity mobility (LEM) was obtained by self-report. Cognitive function was measured by a 2-min timed Digit Symbol Substitution Test (DSST), an executive function measure from the Wechsler Adult Intelligence Test. Habitual gait speed was obtained from a 20-foot timed walk. Multiple logistic regression was used to assess the association between cognitive function and disability. RESULTS: Cognitive function was associated with decreased likelihood for disability in each domain. The odds ratios (ORs) for disability in ADL, IADL, LSA, and LEM for each standard deviation (SD) increase in the DSST score were 0.47 (95% confidence interval [CI] = 0.34-0.64), 0.53 (95% CI = 0.42-0.67), 0.61 (95% CI = 0.47-0.79), and 0.73 (95% CI = 0.61-0.86), respectively, in the multi-variable models. After additional adjustment for habitual gait speed in the cognition-disability relationship, DSST score was no longer a significant correlate for LSA and LEM disability. The strength of the association between DSST score and disability in ADL/IADL was also diminished. The attenuated association between cognition and disability implies that limitation in gait speed likely mediates the association between cognitive function and disability. We found additive effects of cognition and habitual gait speed on late-life disability. The OR of disability in respective domains were lowest among participants with high-DSST score (high executive function) and with high gait speed. In contrast, the OR tended to be highest among participants with low-DSST score (low executive function) and low gait speed. CONCLUSION: Cognitive function was associated with multiple domains of disability. There was a joint effect of cognitive function and gait speed on late-life disability. This study also suggested that habitual gait speed partially mediated the inverse association between cognitive function and late-life disability, providing a mechanistic explanation in the context of disablement process.

Activities of Daily Living↗

PubMed2005

Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation.

Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with dextroamphetamine on others. At the doses tested, caffeine, dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear.

Adult↗

PubMed1996

Executive cognitive functioning predicts reactive aggression in boys at high risk for substance abuse: a prospective study.

This study assessed the ability of executive cognitive functioning (ECF) to predict reactive aggression in boys at high and low risk for substance abuse using a 2-year prospective design. ECF is defined as the self-regulation of goal-directed behavior. Reactive aggression involves impulsive hostile reactions committed with little forethought. ECF was measured using five neuropsychological tests in 198 10- to 12-year-old boys with (SA+) and without (SA-) a paternal history of substance abuse/dependence. Reactive aggression was measured, 2 years later, using a composite index of items derived from two self-report measures. It was hypothesized that ECF would predict reactive aggression, and that this relation would be stronger for the SA+ compared with the SA- boys. SA+ subjects demonstrated lower ECF scores and higher reactive aggression scores, compared with SA- controls. ECF predicted reactive aggression in the SA+ group (beta = 0.37, p = 0.001), but not in the SA- group (beta = 0.09, p = NS). This suggests that compromised ECF may be a risk factor for reactive aggression in SA+ youth. The hypothesis that the relation between ECF and reactive aggression is a manifestation of a mild dysfunction of the prefrontal cortex is discussed.

Aggression↗

PubMed2006

[Ecologic evaluation in the cognitive assessment of brain injury patients: generation and execution of script].

OBJECTIVE: Assessment of executive functions in an everyday life activity, evaluating brain injury subjects with script generation and execution tasks. MATERIALS AND METHODS: We compared a script generation task to a script execution task, whereby subjects had to make a cooked dish. Two grids were used for the quotation, qualitative and quantitative, as well as the calculation of an anosognosis score. We checked whether the execution task was more sensitive to a dysexecutive disorder than the script generation task and compared the scores obtained in this evaluation with those from classical frontal tests. Twelve subjects with brain injury 6 years+/-4.79 ago and 12 healthy control subjects were tested. The subjects carried out a script generation task whereby they had to explain the necessary stages to make a chocolate cake. They also had to do a script execution task corresponding to the cake making. RESULTS: The 2 quotation grids were operational and complementary. The quantitative grid is more sensitive to a dysexecutive disorder. The brain injury subjects made more errors in the execution task. CONCLUSION: It is important to evaluate the executive functions of subjects with brain injury in everyday life tasks, not just in psychometric or script-generation tests. Indeed the ecological realization of a very simple task can reveal executive function difficulties such as the planning or the sequencing of actions, which are under-evaluated in laboratory tests.

Adult↗

PubMed1996

Relation between executive cognitive functioning and the adverse consequences of alcohol use in social drinkers.

The purpose of this study was to assess the relation between Executive Cognitive Functioning (ECF) and the adverse consequences of alcohol consumption. ECF encompasses "higher order" cognitive abilities involved in goal-directed behavior, such as attentional control, mental flexibility, planning, and self-monitoring. Impaired ECF has been shown to result in a variety of negative consequences, including excessive drug and alcohol use. Subjects were 79 nonalcoholic male social drinkers between 17 to 30 years of age. ECF was measured using three neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Conditional Associative Learning Test (CAT), and the Sequential Matching Memory Test (SMMT). Adverse drinking consequences were measured using the Drinker Inventory of Consequences (DrInC). The DrInC assesses drinking consequences in five domains: Physical, Intrapersonal, Interpersonal, Social Responsibility, and Impulse Control. Scores from the neuropsychological tests were reduced into two latent variables: one representing the WCST and the other representing the CAT and SMMT. The results indicated that errors on the CAT/SMMT variable were positively related to adverse consequences in each domain, except for physical consequences. A similar association was found between the WCST variable and impulse control consequences. These findings indicate that performance on tests measuring ECF is related to the severity of drinking consequences. Therefore, prevention and treatment outcomes may be improved by incorporating cognitive habilitation into current interventions.

Adolescent↗

PubMed2003

Neuropsychological deficits associated with Alzheimer's disease in the very-old: discrepancies in raw vs. standardized scores.

The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age and 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; Very-Old: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions. Young-Old AD and Very-Old AD groups were comparable in education, gender, dementia severity, and disease duration. Results showed that both AD groups achieved comparable raw scores on all the neuropsychological measures. However, when scores were standardized on the basis of performance of their respective NC groups (i.e., age-corrected z scores), Very-Old AD patients significantly outperformed Young-Old AD patients on tests of executive functions, visuospatial skills, and delayed memory. Furthermore, the relationship between age and memory and executive function deficits in AD was modified by APOE genotype. These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old.

Aged↗

PubMed1992

CNV evidence for the distinctiveness of frontal and posterior neural processes in a traumatic brain-injured population.

The association between certain behavioral tests of executive functions in humans and the integrity of the prefrontal lobes has rested primarily on studies comparing subjects with frontal versus other loci of damage. Another approach is to compare the within-group variation on a physiological index of frontal functioning with the behavioral tests of interest. In the present study, subjects with traumatic brain injury (TBI) were given four behavioural measures of executive function, two measures of posterior nonexecutive function, and a Contingent Negative Variation (CNV) task, a proposed electrophysiological index of frontal-lobe functioning. We found that three of the four executive function tests were significantly related to the CNV, accounting for 23-52% of the variance, while the CNV did not correlate at all with the posterior tasks.

Adolescent↗