Determining the Correct Resection Level in Patients with Hirschsprung Disease Using Contrast Enema and Full Thickness Biopsies: Can the Diagnostic Accuracy be Improved by Examining Submucosal Nerve Fiber Thickness?

BACKGROUND: Intraoperative resection level in patients with Hirschsprung disease (HD) is determined by contrast enema, surgeon's intraoperative judgement and full thickness biopsy (FTB) identifying ganglia. This study aims to evaluate diagnostic accuracy of contrast enema and FTB in determination of resection level and whether this can be improved by measuring submucosal nerve fiber diameter. METHODS: We retrospectively analyzed contrast enema and intraoperative FTBs obtained in our center, determining diagnostic accuracy for level of resection. Gold standard was pathological examination of resection specimen. Secondly, we matched transition zone pull-through (TZPT) patients with non-TZPT patients, based on age and length of resected bowel, to blindly compare nerve fibers diameters between two groups using group comparison. RESULTS: From 2000-2021, 209 patients underwent HD surgery of whom 180 patients (138 males; median age at surgery: 13 weeks) with 18 TZPTs (10%) were included. Positive predictive value of contrast enema was 65.1%. No caliber change was found in patients with total colon aganglionosis (TCA). Negative predictive value of surgeon's intraoperative judgement and FTB in determining resection level was 79.0% and 90.0% (91.2% single-stage, 84.4% two-stage surgery) respectively. Mean nerve fiber diameter in TZPT was 25.01 µm (SD= 5.63) and in non-TZPT 24.35 µm (SD= 6.75) (p = 0.813). CONCLUSION: Determination of resection level with combination of contrast enema, surgeon's intraoperative judgement and FTB results in sufficient diagnostic accuracy in patients with HD. If no caliber change is seen with contrast enema, TCA should be considered. Resection level or transition zone cannot be determined by assessment of submucosal nerve fiber diameter in FTB. TYPE OF STUDY: clinical research paper.

Anxiety modulates the relation between attention-deficit/hyperactivity disorder severity and working memory-related brain activity.

OBJECTIVES: Individuals with attention-deficit/hyperactivity disorder (ADHD) often have heightened levels of anxiety, which has been associated with worse performance on working memory tasks. Knowledge of the neural pathways underlying the combined presence of ADHD and anxiety may aid in a better understanding of their co-occurrence. Therefore, we investigated how anxiety modulates the effect of ADHD severity on neural activity during a visuospatial working memory (VSWM) task. METHODS: Neuroimaging data were available for 371 adolescents and young adults participating in the multicentre cohort study NeuroIMAGE (average age 17.1 years). We analysed the effects of ADHD severity, anxiety severity and their interaction on-task accuracy, and on neural activity associated with working memory (VSWM trials minus baseline), and memory load (high memory load trials minus low load trials). RESULTS: Anxiety significantly modulated the relation between ADHD severity and neural activity in the cerebellum for the working memory contrast, and bilaterally in the striatum and thalamus for the memory load contrast. CONCLUSIONS: We found that ADHD with co-occurring anxiety is associated with lowered neural activity during a VSWM task in regions important for information gating. This fits well with previous theorising on ADHD with co-occurring anxiety, and illustrates the neurobiological heterogeneity of ADHD.

A randomised trial of enteral glutamine supplementation for very preterm children showed no beneficial or adverse long-term neurodevelopmental outcomes.

AIM: This study evaluated the long-term effects of enteral glutamine supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm children at 13 years of age. METHODS: The cohort was enrolled in a randomised placebo-controlled trial between 2001 and 2003 in which infants received glutamine- or alanine-supplemented enteral nutrition during the first month of life. Participants were invited for follow-up at a mean age of 13.30 years. Motor, neurocognitive, academic and behavioural outcomes were assessed in 61 children. RESULTS: No differences were found between the groups regarding motor, intellectual, academic and behavioural functioning. Forward span visuospatial working memory performance was better in the controls (crude/adjusted model: d = 0.67/0.64, p = 0.02/0.02), but no difference was found for backward span. After the data were adjusted for confounders, the groups differed regarding parent-rated attention (crude/adjusted model: d = 0.47/0.73, p = 0.07/0.003), but both groups scored within the normal range. CONCLUSION: This was the first study on the long-term effects of enteral glutamine supplementation on the neurodevelopmental outcomes of very preterm children. Our study provided no evidence that enteral glutamine supplementation had any beneficial or adverse effects on the children's motor, neurocognitive, academic and behavioural outcomes at 13 years of age.

A 6-month follow-up of an RCT on behavioral and neurocognitive effects of neurofeedback in children with ADHD.

To assess the long-term effects of neurofeedback (NFB) in children with attention deficit hyperactivity disorder (ADHD), we compared behavioral and neurocognitive outcomes at a 6-month naturalistic follow-up of a randomized controlled trial on NFB, methylphenidate (MPH), and physical activity (PA). Ninety-two children with a DSM-IV-TR ADHD diagnosis, aged 7-13, receiving NFB (n = 33), MPH (n = 28), or PA (n = 31), were re-assessed 6-months after the interventions. NFB comprised theta/beta training on the vertex (cortical zero). PA comprised moderate to vigorous intensity exercises. Outcome measures included parent and teacher behavioral reports, and neurocognitive measures (auditory oddball, stop-signal, and visual spatial working memory tasks). At follow-up, longitudinal hierarchical multilevel model analyses revealed no significant group differences for parent reports and neurocognitive measures (p = .058-.997), except for improved inhibition in MPH compared to NFB (p = .040) and faster response speed in NFB compared to PA (p = .012) during the stop-signal task. These effects, however, disappeared after controlling for medication use at follow-up. Interestingly, teacher reports showed less inattention and hyperactivity/impulsivity at follow-up for NFB than PA (p = .004-.010), even after controlling for medication use (p = .013-.036). Our findings indicate that the superior results previously found for parent reports and neurocognitive outcome measures obtained with MPH compared to NFB and PA post intervention became smaller or non-significant at follow-up. Teacher reports suggested superior effects of NFB over PA; however, some children had different teachers at follow-up. Therefore, this finding should be interpreted with caution. Clinical trial registration Train your brain and exercise your heart? Advancing the treatment for Attention Deficit Hyperactivity Disorder (ADHD), Ref. no. NCT01363544, https://clinicaltrials.gov/show/NCT01363544 .

Learning curves of theta/beta neurofeedback in children with ADHD.

Neurofeedback is widely applied as non-pharmacological intervention aimed at reducing symptoms of ADHD, even though efficacy has not been unequivocally established. Neuronal changes during the neurofeedback intervention that resemble learning can provide crucial evidence for the feasibility and specificity of this intervention. A total of 38 children (aged between 7 and 13 years) with a DSM-IV-TR diagnosis of ADHD, completed on average 29 sessions of theta (4-8 Hz)/beta (13-20 Hz) neurofeedback training. Dependent variables included training-related measures as well as theta and beta power during baseline and training runs for each session. Learning effects were analyzed both within and between sessions. To further specify findings, individual learning curves were explored and correlated with behavioral changes in ADHD symptoms. Over the course of the training, there was a linear increase in participants' mean training level, highest obtained training level and the number of earned credits (range b = 0.059, -0.750, p < 0.001). Theta remained unchanged over the course of the training, while beta activity increased linearly within training sessions (b = 0.004, 95% CI = [0.0013-0.0067], p = 0.005) and over the course of the intervention (b = 0.0052, 95% CI = [0.0039-0.0065], p < 0.001). In contrast to the group analyses, significant individual learning curves were found for both theta and beta over the course of the intervention in 39 and 53%, respectively. Individual learning curves were not significantly correlated with behavioral changes. This study shows that children with ADHD can gain control over EEG states during neurofeedback, although a lack of behavioral correlates may indicate insufficient transfer to daily functioning, or to confounding reinforcement of electromyographic activity. CLINICAL TRIALS REGISTRATION: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov, ref. no: NCT01363544); https://clinicaltrials.gov/show/NCT01363544 .

An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD.

Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [η p2  = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range η p2  = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (η p2  = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD.

Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

OBJECTIVE: The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally titrated methylphenidate and (2) a semi-active control intervention, physical activity, to account for nonspecific effects. METHODS: A multicenter 3-way parallel-group study with balanced randomization was conducted. Children with a DSM-IV-TR diagnosis of ADHD, aged 7-13 years, were randomly allocated to receive neurofeedback (n = 39), methylphenidate (n = 36), or physical activity (n = 37) over a period of 10-12 weeks. Neurofeedback comprised theta/beta training on the vertex (Cz). Physical activity consisted of moderate to vigorous intensity exercises. Neurofeedback and physical activity were balanced in terms of number (~30) and duration of sessions. A double-blind pseudorandomized placebo-controlled crossover titration procedure was used to determine an optimal dose in the methylphenidate intervention. Parent and teacher ratings on the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) were used to assess intervention outcomes. Data collection took place between September 2010 and March 2014. RESULTS: Intention-to-treat analyses revealed an improvement in parent-reported behavior on the SDQ and the SWAN Hyperactivity/Impulsivity scale, irrespective of received intervention (ηp² = 0.21-0.22, P ≤ .001), whereas the SWAN Inattention scale revealed more improvement in children who received methylphenidate than neurofeedback and physical activity (ηp² = 0.13, P ≤ .001). Teachers reported a decrease of ADHD symptoms on all measures for methylphenidate, but not for neurofeedback or physical activity (range of ηp² = 0.14-0.29, P < .001). CONCLUSIONS: The current study found that optimally titrated methylphenidate is superior to neurofeedback and physical activity in decreasing ADHD symptoms in children with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01363544.

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

BACKGROUND: Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). METHODS: Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. RESULTS: A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). CONCLUSION: Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS.

No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: The aim of the current study was to explore the role of aromatic amino acids (AAAs) in blood in relation to attention-deficit/hyperactivity disorder (ADHD). Given their impact on the synthesis of serotonin and dopamine, decreased concentrations of the AAAs tryptophan, tyrosine and phenylalanine in blood may contribute to the expression of ADHD symptoms. Decreased AAA blood concentrations, in turn, may be related to lowered dietary protein intake or to abnormal AAA catabolism, as evidenced by increased urinary AAA concentrations. METHODS: Eighty-three children with ADHD (75% males) and 72 typically developing (TD) children (51% males), aged 6 to 13 years, participated in the study. AAA concentrations were assessed in blood spots and an 18-hour urinary sample. A nutritional diary was filled out by parents to calculate dietary protein intake. Parent and teacher questionnaires assessed symptoms of ADHD, oppositional defiant disorder, conduct disorder, and autism spectrum disorder. RESULTS: Children with ADHD showed normal AAA concentrations in blood spots and urine, as well as normal protein intake compared to controls. No associations between AAA concentrations and symptoms of ADHD or comorbid psychiatric disorders were found. CONCLUSIONS: This study is the first to explore AAA metabolism in children with ADHD using a well-defined and relatively large sample. We found that AAA deficiencies are not related to ADHD. The results do not support treatment with AAA supplements in children with ADHD. Future studies regarding the cause of serotonin and dopamine alterations in ADHD should focus on other explanations, such as effects of altered transport of AAAs.

A randomized controlled trial into the effects of neurofeedback, methylphenidate, and physical activity on EEG power spectra in children with ADHD.

BACKGROUND: The clinical and neurophysiological effects of neurofeedback (NF) as treatment for children with ADHD are still unclear. This randomized controlled trial (RCT) examined electroencephalogram (EEG) power spectra before and after NF compared to methylphenidate (MPH) treatment and physical activity (PA) - as semi-active control group - during resting and active (effortful) task conditions to determine whether NF can induce sustained alterations in brain function. METHODS: Using a multicentre three-way parallel group RCT design, 112 children with a DSM-IV diagnosis of ADHD, aged between 7 and 13 years, were initially included. NF training consisted of 30 sessions of theta/beta training at Cz over a 10-week period. PA training was a semi-active control group, matched in frequency and duration. Methylphenidate was titrated using a double-blind placebo controlled procedure in 6 weeks, followed by a stable dose for 4 weeks. EEG power spectra measures during eyes open (EO), eyes closed (EC) and task (effortful) conditions were available for 81 children at pre- and postintervention (n = 29 NF, n = 25 MPH, n = 27 PA). CLINICAL TRIALS REGISTRATION: Train Your Brain? Exercise and Neurofeedback Intervention for ADHD, https://clinicaltrials.gov/show/;NCT01363544, Ref. No. NCT01363544. RESULTS: Both NF and MPH resulted in comparable reductions in theta power from pre- to postintervention during the EO condition compared to PA (ηp (2)  = .08 and .12). For NF, greater reductions in theta were related to greater reductions in ADHD symptoms. During the task condition, only MPH showed reductions in theta and alpha power compared to PA (ηp (2)  = .10 and .12). CONCLUSIONS: This study provides evidence for specific neurophysiological effects after theta/beta NF and MPH treatment in children with ADHD. However, for NF these effects did not generalize to an active task condition, potentially explaining reduced behavioural effects of NF in the classroom.

A Randomized Controlled Trial Investigating the Effects of Neurofeedback, Methylphenidate, and Physical Activity on Event-Related Potentials in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Electroencephalographic (EEG) neurofeedback (NF) is considered a nonpharmacological alternative for medication in attention-deficit/hyperactivity disorder (ADHD). Comparisons of the behavioral efficacy of NF and medication have produced inconsistent results. EEG measures can provide insight into treatment mechanisms, but have received little consideration. In this randomized controlled trial (RCT), effects of NF were compared with methylphenidate (MPH), and physical activity (PA) in children with ADHD on event-related potential (ERP) indices of response inhibition, which are involved in ADHD psychopathology. METHODS: Using a multicenter three way parallel group RCT design, 112 children with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) (American Psychiatric Association 1994 ) diagnosis of ADHD, between 7 and 13 years of age, were initially included. NF training consisted of 30 sessions of theta/beta training at Cz over a 10 week period. PA training was a semiactive control group, matched in frequency and duration. MPH was titrated using a double-blind placebo controlled procedure in 6 weeks, followed by a stable dose for 4 weeks. ERP measures of response inhibition, N2 and P3, were available for 81 children at pre- and postintervention (n = 32 NF, n = 25 MPH, n = 24 PA). RESULTS: Only the medication group showed a specific increase in P3 amplitude compared with NF (partial eta-squared [ηp(2) ] = 0.121) and PA (ηp(2) = 0.283), which was related to improved response inhibition. Source localization of medication effects on P3 amplitude indicated increased activation primarily in thalamic and striatal nuclei. CONCLUSIONS: This is the first study that simultaneously compared NF with stimulant treatment and a semiactive control group. Only stimulant treatment demonstrated specific improvements in brain function related to response inhibition. These results are in line with recent doubts on the efficacy and specificity of NF as treatment for ADHD. CLINICAL TRIALS REGISTRATION: Train Your Brain? Exercise and Neurofeedback Intervention for ADHD, https://clinicaltrials.gov/show/NCT01363544 , Ref. No. NCT01363544.

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. OBJECTIVE: To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). MAIN OUTCOMES AND MEASURES: Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. RESULTS: Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (ß = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (ß = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (ß = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P < .001) and putamen (P = .01) volumes (both corrected for total brain volume) in control individuals, whereas age was unrelated to these volumes in participants with ADHD and their unaffected siblings. Attention-deficit/hyperactivity disorder was not significantly related to the other subcortical volumes. CONCLUSIONS AND RELEVANCE: Global differences in gray matter volume may be due to alterations in the general mechanisms underlying normal brain development in ADHD. The age-by-diagnosis interaction in the caudate and putamen supports the relevance of different brain developmental trajectories in participants with ADHD vs control individuals and supports the role of subcortical basal ganglia alterations in the pathophysiology of ADHD. Alterations in total gray matter and caudate and putamen volumes in unaffected siblings suggest that these volumes are linked to familial risk for ADHD.

Glutamine effects on brain growth in very preterm children in the first year of life.

BACKGROUND & AIMS: Glutamine supplementation in the neonatal period has been associated with increased brain structure volumes at school-age in very preterm children. The aim of this study was to clarify the emergence and specificity of differences in brain structure volumes, using growth trajectories of head circumference, weight, and length. METHODS: Sixty-five very preterm (<32 weeks gestation) children, who originally took part in a randomized controlled trial on glutamine supplementation, participated. Head circumference, weight, and length, were measured at the neonatal intensive care unit, and at routine follow-up assessments at the outpatient clinic and well baby clinics. Magnetic Resonance Imaging was used to determine brain structure volumes at school-age. Growth trajectories were investigated using multilevel modeling analyses. RESULTS: Head circumference in the first year of life was positively associated with white matter volume and grey matter volume (range r = 0.55-0.81, all p < 0.002) at school-age. Furthermore, neonatal glutamine supplementation was associated with increased head circumference growth (p = 0.008) in the first year of life, but not with increased growth in weight (p = 0.44) and length (p = 0.73). CONCLUSIONS: This study indicates a specific increase in head circumference growth in very preterm children that received neonatal glutamine supplementation, and suggests that group differences in brain structure volumes at school-age may have emerged during the first year of life.

Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial.

BACKGROUND: Neurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. METHODS/DESIGN: Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. DISCUSSION: If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT00961922.

Effects of glutamine on brain development in very preterm children at school age.

OBJECTIVES: The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections. METHODS: Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts. RESULTS: Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group. CONCLUSIONS: Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.

Effects of neonatal enteral glutamine supplementation on cognitive, motor and behavioural outcomes in very preterm and/or very low birth weight children at school age.

In very preterm ( < 32 weeks of gestation) and/or very low birth weight (VLBW, < 1500 g birth weight) children, serious neonatal infections are among the main causes of poor developmental outcomes later in childhood. The amino acid glutamine has been shown to reduce the incidence of serious neonatal infections in very preterm and/or VLBW children, while developmental effects beyond 24 months are unknown. We determined the cognitive, motor and behavioural outcomes at school age of a cohort of sixty-four very preterm and/or VLBW children (aged 7·5 (sd 0·4) years) who participated in a randomised placebo-controlled trial using enteral glutamine between day 3 and day 30 of life. Cognitive and motor outcomes were studied using the Wechsler Intelligence Scale for Children-III, the Movement Assessment Battery for Children (MABC), the Attention Network Test and a visual working memory task. Behavioural outcomes were evaluated using parent- and teacher-rated questionnaires. Intelligence quotient, processing speed, attentional functioning, working memory and parent- and teacher-rated behavioural outcomes were not different between children treated with glutamine or placebo; only visuomotor abilities as measured by the Ball Skills scale of the MABC (P = 0·002; d = 0·67) were poorer in the glutamine group. This effect persisted after taking into account the beneficial effects of lower serious neonatal infections rates in children treated with glutamine (P = 0·005). In conclusion, glutamine supplementation between day 3 and day 30 of life had neither beneficial nor detrimental effects on long-term cognitive, motor and behavioural outcomes of very preterm and/or VLBW children at school age, although visuomotor abilities were poorer in children that received glutamine.

When distraction is not distracting: a behavioral and ERP study on distraction in 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.

Psychophysiological determinants and concomitants of deficient decision making in pathological gamblers.

Psychophysiological responses are considered to be a mediating factor in the development of pathological gambling (PG) and PG has been associated with differential arousal levels during gambling. Yet little is known about the specific psychophysiological responses to wins and losses in PG. This study investigated heart rate (HR) and skin conductance responses (SCRs) during the Iowa Gambling Task (IGT) in an adult PG group (n=46) and a normal control (NC) group (n=47). Anticipatory psychophysiological reactions to disadvantageous and advantageous choices during the IGT and psychophysiological responses to wins and losses were measured. The PG group performed worse than the NC group on the IGT and exhibited lower anticipatory SCRs and HR decreases when pondering choices of disadvantageous card decks during the IGT. The PG group showed a decrease in HR after losses and wins, whereas the NC group showed a decrease in HR after losses, but an increase in HR after wins. Reward and punishment sensitivity as measured by the self-report BIS/BAS scale influenced IGT performance and psychophysiological responses, but in general these effects were similar for the PG group and the NC group. Lower anticipatory psychophysiological responses to disadvantageous choices in PG suggest impaired risk assessment in this group. Absence of a HR increase after wins possibly implies that reward sensitivity is decreased in PG. Because levels of reward and punishment sensitivity were associated with differential anticipatory HR responses to advantageous and disadvantageous decks, it would be advisable to include this taxonomy in studies on psychophysiological responses to rewards and losses.