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Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual's responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure.

Maternal smoking during pregnancy is a risk factor for attention-deficit/hyperactivity disorder (ADHD), but data on its adverse effects on cognitive functioning are sparse and inconsistent. Since the effect of maternal smoking during pregnancy may be due to correlated genetic risk factors rather than being a pure environmental effect, we examined the effect of prenatal exposure to smoking on attentional control, taking into account the effects of both maternal and paternal smoking, and examined whether these effects were genetically mediated by parental genotypes. We further examined whether the effect of prenatal exposure to smoking on attentional control interacted with genotypes of the child. Participants were 79 children with ADHD, ascertained for the International Multi-centre ADHD Gene project (IMAGE), and 105 normal controls. Attentional control was assessed by a visual continuous performance task. Three genetic risk factors for ADHD (DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3' untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses. Paternal smoking had a negative effect on attentional control in children with ADHD and this effect appeared to be mediated by genetic risk factors. The prenatal smoking effect did not interact with genotypes of the child. Maternal smoking had no main effect on attentional control, which may be due to lower smoking rates. This study suggests that the effects of paternal smoking on attentional control in children with ADHD should be considered a proxy for ADHD and/or smoking risk genes. Future studies should examine if the results can be generalized to other cognitive domains.

Background: Impairments in executive functioning (EF) and intelligence quotient (IQ) are frequently observed in children with attention deficit hyperactivity disorder (ADHD). The aim of this paper was twofold: first, to examine whether both domains are viable endophenotypic candidates for ADHD and second to investigate whether deficits in both domains tend to co-segregate within families., Method: A large family-based design was used, including 238 ADHD families (545 children) and 147 control families (271 children). Inhibition, visuospatial and verbal working memory, and performance and verbal IQ were analysed., Results: Children with ADHD, and their affected and non-affected siblings were all impaired on the EF measures and verbal IQ (though unimpaired on performance IQ) and all measures correlated between siblings. Correlations and sibling cross-correlations were not significant between EF and IQ, though they were significant between the measures of one domain. Group differences on EF were not explained by group differences on IQ and vice versa. The discrepancy score between EF and IQ correlated between siblings, indicating that siblings resembled each other in their EF-IQ discrepancy instead of having generalized impairments across both domains. Siblings of probands who had an EF but not IQ impairment, showed a comparable disproportionate lower EF score in relation to IQ score. The opposite pattern was not significant., Conclusions: The results supported the viability of EF and IQ as endophenotypic candidates for ADHD. Most findings support an independent familial segregation of both domains. Within EF, similar familial factors influenced inhibition and working memory. Within IQ, similar familial factors influenced verbal and performance IQ.

The question whether executive function (EF) deficits in children are associated with conduct problems remains controversial. Although the origins of aggressive behavior are to be found in early childhood, findings from EF studies in preschool children with aggressive behavior are inconsistent. The current study aimed to investigate whether preschool children with aggressive behavior show impairments in EF. From a population-based sample, 82 preschool children who were showing aggressive behavior as indicated by scores at or above the 93rd percentile on the Aggressive Behavior Scale of the CBCL 1 1/2-5 were selected. These children with aggressive behavior were matched on IQ to a group of typically developing control children (N = 99). Six neuropsychological tasks were administered to assess set shifting, inhibition, working memory and verbal fluency. A factor analysis was conducted which yielded one clear factor: inhibition. Aggressive preschool children showed poorer performance on this inhibition factor than control children and boys performed worse on this factor than girls. This association between aggressive behavior and inhibition deficits was maintained after controlling for attention problems. In addition, gender differences in all EFs measured were found with boys exhibiting more impairment in EF than girls. These findings demonstrate that preschool children with aggressive behavior show impairments in inhibition, irrespective of attention problems.

Objective: To determine the potential of inhibitory performance, response speed, and response accuracy and variability, measures central to the conceptualization of attention-deficit/hyperactivity disorder (ADHD), in distinguishing children with ADHD from healthy controls (HCs)., Method: The stop signal paradigm was administered to 38 children with ADHD and 31 NCs. The stop signal reaction time (SSRT), mean reaction time (MRT), intraindividual coefficient of variation (ICV), and number of errors were used to predict diagnostic status., Results: Univariate tests showed that the ADHD group performed worse than NCs on all of the dependent variables. Exploratory univariate analyses showed that oppositional defiant disorder comorbidity and ADHD type did not influence results except for the ICV, the effect for this variable (more variability in the ADHD group) being less pronounced for the Predominantly Inattentive type than for the Hyperactive-Impulsive and Combined types. A logistic regression model of the MRT, ICV, and number of errors combined showed best predictive performance, with the MRT contributing the most to group classification (56% of the variance). The final model (MRT, ICV, and number of errors) predicted 87% of the sample in the correct diagnostic category. Operating characteristics showed excellent sensitivity and specificity of 89.5% and 83.9%, respectively., Conclusions: Our results contrast with theoretical accounts emphasizing inhibitory control as the pivotal measure characterizing cognitive performance in ADHD. Results are discussed in the context of a delay aversion perspective of ADHD.

Objective: Although an increased distractibility is one of the behavioral criteria of Attention Deficit Hyperactivity Disorder (ADHD), there is little empirical evidence that children with ADHD are in fact more distractible than their normal peers., Methods: We recorded event-related potentials (ERPs) to distracting novel sounds (novels) and standard sounds, (standards) while children performed a visual two-choice reaction time task. Twenty-five children with ADHD were compared with eighteen normal controls (aged 8-12 years)., Results: Children with ADHD showed a larger early P3a (150-250 ms), both in response to the standard and in response to the novel. The late phase of the P3a had a larger amplitude in the ADHD group in the 250-300 ms window compared to the control group, which was only present in response to the novel. Interestingly, the novel reduced the errors of omission in the ADHD group to a greater extent than in the normal control group., Conclusions: Although children with ADHD show an increased orienting response to novels, this distracting information can enhance their performance temporarily, possibly by increasing their arousal to an optimal level, as indicated by the reduced omission rate., Significance: These data indicate that distraction is not always distracting in children with ADHD and that distraction can also have beneficial effects.

Cognitive performance of children with attention-deficit hyperactivity disorder (ADHD) is characterized by large moment-to-moment fluctuations in cognitive control reflected by a highly inconsistent and inaccurate response style. It has been suggested that abnormal error processing underlies this failure to implement adequate control. We investigated the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) time-locked to erroneous responses in 16 rigorously screened ADHD boys aged 8-12 years and 16 age-matched normal control boys during a modified Eriksen flanker paradigm with two levels of time pressure. Children with ADHD responded as fast and regularly as controls, but committed significantly more errors, particularly when facing time pressure and response conflict. ADHD children produced shorter runs of correct responses than controls. In addition, with high time pressure, error runs were prolonged relative to control children, suggesting an increase in both frequency and magnitude of temporary lapses of control. ERP amplitude differences between correct and incorrect responses were diminished in ADHD children, whereas post-error slowing remained unaffected. This pattern of results indicates that a specific deficit in monitoring ongoing behaviour, rather than insufficient strategic adjustments, gave rise to performance limitations in ADHD. Findings are discussed in terms of anterior cingulate cortex (ACC) dysfunction, leading to a failure to predict the likelihood that an error occurs in a given context.

In Experiment 1, the effects of stop signal modality on the speed and efficiency of the inhibition process were examined. Stop signal reaction time (SSRT) and inhibition function slope in an auditory stop signal condition were compared to SSRT and inhibition function slope in a visual stop signal condition. It was found that auditory stop signals compared to visual stop signals enhanced both the speed and efficiency of stopping. The modality effects were attributed to differences in the neurophysiological processes underlying perception. However, Experiment 2 demonstrated that the modality difference was larger for 80 dB(A) auditory stop signals than 60 dB(A) auditory stop signals. This effect was reconciled with the suggestion that loud tones are more capable of eliciting immediate arousing effects on motor processes than weak tones and visual stimuli. The second purpose of the present investigation was to explore the utility (and potential advantages) of an alternative way of setting stop signal delay relative to mean reaction time (MRT). The method that was suggested compensates for inter-individual differences in primary task reaction speed by setting stop signal delays as proportions of the subjects' MRT.

This study examined hemispheric specialization for stop task performance. It was found that inhibitory performance was better for stop signals presented in the right visual field. This result provided support for the hypothesis that, during stop task performance, subjects call upon the left-lateralized neural system that is involved in active attention. It was suggested that a stop task requires such a mode of attention because subjects maintain a tonic readiness for inhibitory action while being engaged in the stop task's go routine. Subjects are continuously alert for possible stop signals while discriminating between go stimuli. The stop task may be considered a typical activation task.

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Non-selective attention (NSA) to environmental stimuli has been measured in putative animal models of Attention-Deficit Hyperactivity Disorder (ADHD), such as the Spontaneously Hypertensive (SHR) and the Naples High-Excitability (NHE) rat lines. A series of experiments has been carried out on male juvenile SHR and Wistar-Kyoto (WKY) controls (experiment 1) and on the NHE and two controls, i.e. the Naples Low-Excitability (NLE) and a random-bred (NRB) line (experiment 2). It was done under basal conditions or following a single injection of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine-methylester (L-NAME: 0.1-10 mg/kg, i.p.), or vehicle, 30 min before testing on day 1 and vehicle alone before testing on days 2 and 3 in SHR/WKY (experiment 3) and the Naples lines (experiment 4). The behavior in a Lát maze during three consecutive 10-min exposures at 24-h intervals was monitored by a CCD video camera and analyzed off-line for frequency and duration of rearings on hindlimbs per 1-min blocks. The results demonstrated that both SHR and NHE rats showed a higher frequency of rearings of shorter duration than controls. With time of testing, the duration of rearings tended to increase in the WKY but not the SHR. In the Naples lines the duration tended to increase in all but mostly in the NHE rats. The acute inhibition of NOS by L-NAME significantly increased the duration of rearing episodes both in SHR and NHE rats only at 10 mg/kg in the second part of the testing period. Therefore, NSA, as indexed by the duration of rearings, is defective in both hyperactivity models against different genetic backgrounds. In addition, this impairment is dependent upon nitric oxide (NO), which appears to play a significant role in these processes.

A total of 11 children with attention deficit disorder (ADD) and nine control children performed a continuous performance test (CPT) of the A-X type with concurrent neuroelectric brain mapping to assess preparatory processing, purportedly mediated by the frontal lobes. This cued CPT task proved to be a highly specific task. The groups could be clearly differentiated both at the behavioral and electrophysiological level. ADD children detected fewer signals and made more false alarms. There were no major group differences in topographical distribution of the event-related potential microstates, but ADD children displayed reduced global field power (GFP) in an early CNV/P3 microstate to cues. This indicated that impaired orienting to cues, rather than impaired executive target processing, determines the initial processing stages in ADD. In comparison with data from the same task run in Utrecht, the same orienting deficit in clinically diagnosed ADHD children was demonstrated. Low resolution electromagnetic tomography (LORETA) estimated posterior sources underlying these orienting processes and the orienting deficit. This argued against frontal lobe involvement at this stage and suggested involvement of a posterior attention system.

In a memory search task with context recognition, three groups of children were examined: hyperactives, somewhat hyperactives and controls. It was found that the hyperactive groups differed from controls at the intercept of reaction time and not the slope. This was interpreted as evidence against a selective attention hypothesis in hyperactivity and evidence of either an 'encoding' or a response organization deficit. The unexpected slower and less accurate performance of somewhat hyperactives than those rated as hyperactives may have been due to the higher rating of variable task application in the former than in the latter.

Three groups of children rated firstly as overactive and distractible, secondly as distractible and thirdly as low on both activity and distractibility were examined in a visual search task with three levels of display load: two, three and four items. The children were tested twice in two conditions of stimulus visibility to examine the encoding stage of the model used here. The experimental results reject the hypothesis that an encoding deficit or data limitation may explain the attentional performance of either hyperactive or somewhat hyperactive subjects. They suggest, rather, that a trade-off in speed and accuracy may be evident in (the) hyperactives.