The burden of parenting children with frontal lobe epilepsy.

OBJECTIVE: Caring for a child with a chronic illness adds stress to the typical parenting stress in healthy developing children. This stress can place a heavy burden on parents and may increase when a child displays problem behavior. In general, parenting and child's behavior problems are associated. Furthermore, externalizing (more outgoing) behavior is reported frequently in children with frontal lobe epilepsy (FLE). Therefore, in this study, we first investigated the burden of parents of children with FLE, and second, we investigated the relation between the experienced burden and reported behavioral problems. The validity of parents' reports on proxy measures as well as duration of epilepsy is taken into account. METHODS: Thirty-one parents of children with FLE completed validated questionnaires about behavioral problems and burden of parenting. To examine if parents tend to be inconsistent or unusually negative, we used the two validity scales of the Behavioral Rating Inventory of Executive Function (BRIEF) (Negativity and Inconsistency). RESULTS: Only parents of children with FLE who have had epilepsy for 5 years or longer report more problems on the Nijmeegse Vragenlijst voor de Opvoedingssituatie (NVOS) subscales 'Able to manage', 'Child is a burden', and 'Good Interaction' compared with the healthy controls. The subscale 'Child is a burden' significantly predicts scores in about 20% to 49% on the main scales of the Child Behavior Checklist (CBCL), the Global Executive Composite (GEC), and Behavioral Regulation Index (BRI) of the BRIEF. Only 6% of parents scored in the clinical range of the negativity scale of the BRIEF. For the inconsistency scale, this was 45%. CONCLUSION: Parents of children with FLE do not report excessive parental burden. Longer duration of epilepsy might be a risk factor in experiencing burden. The findings suggest a link between parental burden and behavioral problems in children with FLE. Externalizing behavioral problems are the most marked behavioral problems, which relate to the parental burden. Parents tend to be inconsistent in their ratings.

Genetic analysis of reaction time variability: room for improvement?

BACKGROUND: Increased reaction time variability (RTV) on cognitive tasks requiring a speeded response is characteristic of several psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), the association with RTV is strong phenotypically and genetically, yet high RTV is not a stable impairment but shows ADHD-sensitive improvement under certain conditions, such as those with rewards. The state regulation theory proposed that the RTV difference score, which captures change from baseline to a rewarded or fast condition, specifically measures 'state regulation'. By contrast, the interpretation of RTV baseline (slow, unrewarded) scores is debated. We aimed to investigate directly the degree of phenotypic and etiological overlap between RTV baseline and RTV difference scores. Method We conducted genetic model fitting analyses on go/no-go and fast task RTV data, across task conditions manipulating rewards and event rate, from a population-based twin sample (n=1314) and an ADHD and control sibling-pair sample (n=1265). RESULTS: Phenotypic and genetic/familial correlations were consistently high (0.72-0.98) between RTV baseline and difference scores, across tasks, manipulations and samples. By contrast, correlations were low between RTV in the manipulated condition and difference scores. A comparison across two different go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high phenotypic and genetic/familial overlap (r = 0.75-0.83). CONCLUSIONS: Our finding that RTV difference scores measure largely the same etiological process as RTV under baseline condition supports theories emphasizing the malleability of the observed high RTV. Given the statistical shortcomings of difference scores, we recommend the use of RTV baseline scores for most analyses, including genetic analyses.

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ.

BACKGROUND: Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. METHOD: Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). RESULTS: Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=-0.25 to -0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. CONCLUSIONS: The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Separation of genetic influences on attention deficit hyperactivity disorder symptoms and reaction time performance from those on IQ.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) shows a strong phenotypic and genetic association with reaction time (RT) variability, considered to reflect lapses in attention. Yet we know little about whether this aetiological pathway is shared with other affected cognitive processes in ADHD, such as lower IQs or the generally slower responses (mean RTs). We aimed to address the question of whether a shared set of genes exist that influence RT variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of separate aetiological pathways. METHOD: Multivariate structural equation modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by parents and teachers collected on general population sample of 1314 twins, at ages 7-10 years. RESULTS: Multivariate structural equation models indicated that the shared genetic influences underlying both ADHD symptom scores and RT variability are also shared with those underlying mean RT, with both types of RT data largely indexing the same underlying liability. By contrast, the shared genetic influences on ADHD symptom scores and RT variability (or mean RT) are largely independent of the genetic influences that ADHD symptom scores share with IQ. CONCLUSIONS: The finding of unique aetiological pathways between IQ and RT data, but shared components between mean RT, RT variability and ADHD symptom scores, illustrates key influences in the genetic architecture of the cognitive and energetic processes that underlie the behavioural symptoms of ADHD. In addition, the multivariate genetic model fitting findings provide valuable information for future molecular genetic analyses.

Methylphenidate, interstimulus interval, and reaction time performance of children with attention deficit/hyperactivity disorder: a pilot study.

Thirteen children with attention deficit/hyperactivity disorder (ADHD: DSM-IV-TR) participated in the pilot study. They carried out a Go/No-Go test with a short (2 seconds) and long (6 seconds) interstimulus interval (ISI) when on placebo and a therapeutic dose of methylphenidate (MPH). For the long-ISI placebo condition the responses were slow and inaccurate. This pattern of response may be due to underactivation of the readiness-to-respond state that is not fully controlled by effort allocation. Speed of response and accuracy were enhanced during the short-ISI placebo condition and the long-ISI MPH condition. However, the combined effect (short ISI and MPH) resulted in a fast but inaccurate response style. This pattern of response may be due to overactivation of the readiness-to-respond state. The data of the pilot study support the stimulus shift hypothesis: MPH administration result in deterioration on tests on which children had previously done well (short ISI plus placebo versus short ISI plus MPH). In addition, the data support the idea that ADHD is associated with poor state regulation rather than motivational (delay aversion) theories or temporal-processing/time-estimation theories of ADHD. The pilot study defined empirically an issue for further study with the larger controlled sample.

ERP correlates of error monitoring in adult ADHD.

The purpose of the current study was to evaluate whether error monitoring difficulties persist in adults with attention deficit hyperactivity disorder (ADHD) using the event-related potential (ERP) methodology. Adults with ADHD and age-matched healthy controls executed a visual Go/No-Go task with 25% No-Go trials. Performance and ERP correlates of error monitoring were compared between groups. At the performance level no difference was noted between groups. However, exploring the error-related potentials revealed that the error-related negativity (ERN) was the same for both groups, but that adults with ADHD showed a smaller error positivity (Pe). Based on these findings, we conclude that adults with ADHD are normal in early automatic error detection, but are deviant in later conscious evaluation of the error. The findings add to the increasing evidence supporting disturbances in error monitoring in ADHD and show that these problems may persist in adulthood ADHD.

HFA and ADHD: a direct comparison on state regulation and response inhibition.

This study examined whether children with high-functioning autism (HFA) are easily overaroused/activated and whether children with attention-deficit/hyperactivity disorder (ADHD) are easily underaroused/activated. This double dissociation was tested using a go/no-go paradigm with computer-paced fast and slow conditions and a self-paced condition. In the HFA group, a performance decline in the fast condition and slow performance in the self-paced condition were expected. In the ADHD group, a performance decline in the slow condition and fast performance in the self-paced condition were expected. No difference was found between groups for state regulation and response inhibition. Findings are discussed in the light of development, comorbidity, and subtypes.

ERP correlates of impaired error monitoring in children with ADHD.

OBJECTIVE: The purpose of the current study was to elaborate on error monitoring in children with Attention Deficit Hyperactivity Disorder (ADHD) using the ERP methodology. METHOD: Children with ADHD executed a visual Go/No-Go task with 25 percent No-Go trials; and a two stimulus reaction time task wherein a neutral warning signal (S1) was presented to inform the child to prepare for an imperative stimulus (S2). RESULTS: In both tasks, children with ADHD responded as fast as controls but made twice as many errors. In addition, they failed to adjust their speed of responding after making an error. Exploring the error-related potentials revealed that the error-related negativity (ERN) was the same for the two groups, but that children with ADHD showed a diminished error positivity (Pe). CONCLUSIONS: Based on these findings, we conclude that children with ADHD are normal in early error monitoring processes related to error detection, but show abnormal response strategy adjustments and are deviant in later error monitoring processes associated with the subjective/emotional, conscious evaluation of the error.

State regulation and response inhibition in children with ADHD and children with early- and continuously treated phenylketonuria: an event-related potential comparison.

BACKGROUND: The presentation rate of stimuli plays an important role in explaining the performance inefficiency in children with ADHD. In general, children with ADHD have been found to perform more poorly in conditions of relatively slow event rates as compared with fast and moderate event rates. The state regulation hypothesis states that these children have problems in correcting their energetic state necessary to counteract a performance decrement, which requires extra effort allocation. In this study, we investigated state regulation in children with ADHD and used children with early- and continuously treated phenylketonuria (PKU) as a clinical contrast group. METHOD: We measured the parietal P3 during a Go/No-Go task that incorporated a condition with a fast and a slow presentation rate. RESULTS: We were able to show that children with ADHD, relative to controls, responded more slowly and more variably in the slow condition only, which was accompanied by a smaller P3, suggesting less effort allocation. In contrast, the children with PKU did not show a state regulation deficit. The PKU group showed prolonged stimulus evaluation processing, as indexed by P3 latency, compared to controls and children with ADHD. In addition, they made more errors of commission than the controls and the ADHD group. CONCLUSIONS: Our electrophysiological data support the state regulation hypothesis of ADHD. Only the children with PKU had more problems in inhibiting pre-potent responding than controls, which is in accord with the prefrontal dysfunction hypothesis of PKU.

Behavioural correlates of early-treated congenital hypothyroidism.

UNLABELLED: Parents' and teachers' ratings were used to evaluate the behavioural characteristics of children with early-treated congenital hypothyroidism (CH). Comparisons were made between 63 children with early-treated CH and 34 healthy controls at the ages of 7.5 and 9.5 y. Additional comparisons were made between the two largest CH subgroups (thyroid agenesis, thyroid dysgenesis) and controls. The most marked differences were found on the introversion cluster and the motor clumsiness scale within it. Children with CH, particularly those with thyroid agenesis, showed introversion and motor clumsiness rather than social negativity and inattention. It is suggested that this behavioural profile may well have its origins in the often-reported inefficient motor behaviour of these children. Results are discussed in the light of recent findings suggesting an association between thyroid hormone problems and attention deficit hyperactivity disorder. CONCLUSION: Early-treated CH is associated with introversion rather than with social negativity.

Behaviour and school achievement in patients with early and continuously treated phenylketonuria.

Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a group, demonstrated more problems in task-oriented behaviour and average academic performance than did matched controls. Interestingly, whereas male PKU patients were rated significantly lower on introversion by their teachers, female patients were rated significantly higher on introversion and lower on extraversion than matched controls. This sex difference was also reflected in the relationship between measures of dietary control and the behaviour clusters, suggesting that male and female patients respond differently to elevated Phe levels or the stress associated with PKU. The teacher rating on average academic performance of the PKU patients was associated with recent level of dietary control, which suggests that it might be improved by more strict adherence to the diet. In addition, academic performance correlated negatively with the behaviour cluster negative task orientation. Further studies are recommended to obtain a more complete evaluation of this relationship and to replicate the current findings on larger samples. Over the years a number of studies have examined behaviour and school achievement in patients with early treated phenylketonuria (PKU; McKusick 261600). In general, these studies have found that despite early treatment with a phenylalanine (Phe)-restricted diet, PKU patients demonstrate more behavioural and school problems than do healthy controls. The behaviour problems include both internalizing symptoms (e.g. solitary, unresponsive, anxious, depressed mood: Pietz et al 1997; Smith et al 1988; Weglage et al 1992) and externalizing symptoms (e.g. hyperactive, talkative, impulsive, restless: Hendrikx et al 1994; Kalverboer et al 1994; Realmuto et al 1986; Smith et al 1988), but not antisocial or socially negative symptoms (e.g. lying, teasing, disobedience: Kalverboer et al 1994; Pietz et al 1997; Smith et al 1988). With respect to school achievement, studies have shown that patients with early treated PKU more often repeat classes or need special tutoring (Berry et al 1979; Brunner et al 1983; Koch et al 1987; Rey et al 1996; Verkerk 1995), have to work harder than healthy controls to achieve the same results (Weglage et al 1993), or have specific deficits in arithmetic achievement scores (Azen et al 1991; Berry et al 1979; Fishler et al 1987; Koch et al 1987; Weglage et al 1993). Nevertheless, many questions regarding the behavioural and school problems of patients with early treated PKU remain unanswered. For instance, the relationship between behavioural and school problems on the one hand and levels of dietary control on the other is still relatively unclear. The few studies that examined this relationship, have focused primarily on children in primary school (Azen et al 1991; Koch et al 1987; Smith et al 1988). Furthermore, although several psychological studies have shown that the pattern of behavioural problems varies by sex (see Prior et al 1999a for a discussion), so far very few studies have examined this issue in PKU patients and results are contradictory (Kalverboer et al 1994; Pietz et al 1997; Smith et al 1988; Weglage et al 1992). In addition, so far no study has actually examined whether there is a relationship between the behavioural problems and school difficulties of PKU patients, even though this relationship has been well documented in the psychological literature (Prior et al 1999b; Richards et al 1995). The aim of the present study is therefore to examine these issues in patients with early and continuously treated PKU over a wide age range and in relation to dietary control. More specifically, school achievement as well as social and task-oriented behaviour (at home

Visual behaviour of ADHD children during an attention test: an almost forgotten variable. Attention-Deficit Hyperactivity Disorder.

The goal of this study was to examine whether looking away behaviour of ADHD children interferes with their test performance. ADHD and normal children carried out two continuous performance tests (CPTs): one with a regular interstimulus interval (ISI), and the other with an irregular ISI. Children were instructed to push a response button when a target stimulus was presented on the monitor. The children's visual behaviour was recorded and scored offline. A micro-analysis of the visual behaviour indicated that ADHD children timed their looking away behaviour in the regular CPT: i.e. they looked away from the monitor and back in the interval between two succeeding stimuli. As a result they did not miss stimuli. Timing of looking away was less possible in the CPT with the irregular ISI. In this condition, looking away interfered with the ADHD children's task accuracy. In sum, looking away behaviour had a negative effect on the accuracy of test performance of ADHD children when stimuli were unpredictable. Looking away behaviour was not associated with the slower reaction times of the ADHD children. Hence, the often reported slowness of ADHD children is not to be explained by their visual behaviour.

Motor control and state regulation in children with ADHD: a cardiac response study.

The goal of the current study was to investigate whether poor motor control in children with Attention-Deficit Hyperactivity Disorder (ADHD) was associated with a state regulation deficit. For this purpose, 28 ADHD and 22 healthy children carried out two Go No-Go tests: one with a fast stimulus presentation rate, and the other with a slow stimulus presentation rate. Groups were compared on RT performance and on specific cardiac measures, reflecting arousal, motor activation/inhibition, and effort allocation. No group difference in the arousal measure (mean heart rate) was found. Further, groups did not differ with respect to response inhibition: in both the fast and slow condition, ADHD children made comparable numbers of errors of commission to the control group, and the groups did not differ with respect to the heart rate deceleration after the onset of the No-Go signal, reflecting motor inhibition. Group differences were found with respect to motor activation and effort allocation in the condition with a slow presentation rate. In this condition: (1) ADHD children reacted more slowly to Go signals than control children, suggesting poor motor activation; (2) the heart rate deceleration before the onset of Go signals, which is believed to reflect motor preparation, was less pronounced in the ADHD children; (3) after Go signals, where a response was given, the cardiac shift from deceleration to acceleration, indicating response initiation, was delayed in ADHD children; and (4) ADHD children had greater heart rate variability (0.10 Hz component) than the control group, indicating that less effort was allocated. No group differences in motor activation and effort allocation were found in the condition with a fast presentation rate of stimuli. We conclude, therefore, that a slow presentation rate of stimuli brings the ADHD child in a non-optimal activation state.

Attention-deficit hyperactivity disorder and developmental right-hemisphere syndrome: congruence and incongruence of cognitive and behavioral aspects of attention.

We studied clinical aspects of attention in three groups: children with developmental right-hemisphere syndrome and attention-deficit hyperactivity disorder (ADHD), children with ADHD only, and normal controls. The three groups (N = 54) were case-matched for age, sex, IQ, hand dominance, and socioeconomic status. ADHD was diagnosed clinically using the Diagnostic and Statistical Manual of Mental Disorders-III-Revised criteria and the Conners' Abbreviated Teacher Questionnaire. Additional aspects of attention and behavior were measured by the Child Behavior Checklist, a low-cognitive-load continuous performance task, and the visual target cancellation test (paper and pencil). Although the Child Behavior Checklist profile of attentional deficits in the two clinical groups was similar, we found that the developmental right-hemisphere syndrome group was more severely impaired on parameters of attention measured by the continuous performance task and visual target cancellation test than the children with ADHD. We conclude that the profile of attentional deficits in developmental right-hemisphere syndrome is different than that seen in children with ADHD only, possibly reflecting disparate neurologic underpinnings for the two syndromes.

Heart rate variability and sustained attention in ADHD children.

The major goal of the current study was to investigate the association between continuous performance tests (CPTs) and the heart rate variability (HRV) of attention deficit hyperactivity disorder (ADHD) children. The HRV, specifically the 0.10-Hz component, may be considered to be a psychophysiological index of effort allocation (motivation): The less effort the subject allocates, the greater the 0.10-Hz component. Results indicated that, compared to controls, ADHD subjects had a greater 0.10-Hz component, which was associated with poor test performance over time. Thus, using a psychophysiological measure, we were able to confirm the clinical concept of ADHD from a motivational perspective.

The effect of methylphenidate and clonidine on response inhibition and state regulation in children with ADHD.

The goal of this study was to evaluate the effect of methylphenidate (MPH) and clonidine in comparison with placebo on response inhibition and state regulation in children with Attention Deficit Hyperactivity Disorder (ADHD). The study utilised a double-blind cross-over design in which children were randomly assigned without replacement to placebo, MPH, and clonidine following baseline assessment. The primary dependent measures were derived from children's performance (reaction time and errors) on a GO-NO GO task under three conditions that altered the inter-stimulus interval (ISI) for presented GO-NO GO stimuli: ISI of 1 sec (fast condition), 4 sec (medium condition), and 8 sec (slow condition). Findings indicated no difference in task performance between groups treated for 7 weeks with placebo, MPH, and clonidine. We concluded that the state regulation problem in ADHD is resistant to MPH and clonidine.

Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?

OBJECTIVE: To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. RESULTS: None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. CONCLUSION: Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.

Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?

OBJECTIVE: To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. RESULTS: None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. CONCLUSION: Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.

Changing a response set in normal development and in ADHD children with and without tics.

The current study was designed to provide a rigorous investigation of the locus of task-inappropriate (impulsive) responding in ADHD children with and without tics. For this purpose we used a variant of Sternberg's (1969) response bias task. The task measures a set of mental operations, namely, preparing a planned response, carrying out or stopping a planned response, and preparing to execute an alternative response. In the first study, we determined the effect of age in a normal sample. As expected, task performance improved as a function of age. Younger children had problems changing a response set. In the second experiment, we compared ADHD children with and without tics with normal children. Unexpectedly, the noticeable task inefficiency of the patient groups was not related to (a) a hasty scan of the display, (b) an inability to change response set, or (c) a speed-accuracy trade-off. Implications for and a discussion about the response inhibition hypothesis in ADHD are discussed.

Sustained attention problems in children with early treated congenital hypothyroidism.

Sustained attention was studied in 48 children with early treated congenital hypothyroidism and 35 healthy controls, using a computer-paced and a self-paced continuous performance task. The performance of the patients, particularly those in the low T4 group (38 patients with T4 levels < 50 nmol/l at neonatal screening), declined in the final stage of the computer-paced task, suggesting a problem in remaining attentive over time. The performance of all children declined in the first and improved in the final stage of the self-paced task. This pattern was most pronounced in the low T4 group, reflecting greater variability in their task performance over time, again indicating a problem in sustaining attention. No correlation was found between onset of treatment and sustained attention. The small size of the intermediate T4 group (10 patients with T4 levels > or = 50 nmol/l at neonatal screening) made the results more difficult to interpret and may have concealed a problem with sustained attention in this group.