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BACKGROUND Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. METHODS For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. RESULTS Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2 = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2 = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp = -.642, p = .120) and cumulative (HCC: rp = -.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. CONCLUSIONS The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.

Zusammenfassung. Schlafstörungen sind im Erwachsenen- wie auch im Kindes- und Jugendalter weit verbreitet. Kinder und Jugendliche in kinder- und jugendpsychiatrischer (KJP) Behandlung sind insbesondere davon betroffen. Die kognitive Verhaltenstherapie ist die Behandlung der ersten Wahl bei Schlafstörungen, der eine standardisierte Schlafdiagnostik vorangehen sollte. Im deutschsprachigen Raum fehlen bislang systematische Untersuchungen zur Schlafdiagnostik im teilstationären (TK) KJP-Setting. Für N = 46 Kinder/Jugendliche in TK-KJP-Behandlung wurde ein Schlafprotokoll (7 Tage), ein Schlafanamneseschema (Eltern & Kind/Jugendlicher) sowie ein klinisches Urteil zum Schlafverhalten (Diagnostiker_in) erhoben. Zudem wurde die Eltern-, Selbst- und klinische Beurteilung der psychischen Störung erfasst. Bei 52 % der Kinder/Jugendlichen wurden Schlafauffälligkeiten (= Schlafstörungssymptome im Rahmen komorbider Störungen) oder Schlafstörungen festgestellt, insbesondere Einschlafstörungen oder Ein- und Durchschlafstörungen (26 %). Zudem berichteten 33 % Albträume. Das Schlafverhalten korrelierte signifikant mit externalen Auffälligkeiten (r = .38 bis .61, p = 02 bis .04), auch beeinflussten Geschlecht (weiblich: p = .01 bis ≤ .001, |d| = 1.57 bis 2.50) und Alter (Ältere: p = .05, |d| = 0.78) das Schlafverhalten signifikant. Es scheinen insbesondere externale Auffälligkeiten einen Zusammenhang zu Schlafstörungen in der teilstationären Population aufzuweisen. Für die systematische Diagnostik der im TK-KJP-Setting vielfach vorliegenden Schlafauffälligkeiten, empfiehlt sich zusammenfassend ein Multi-Informant-Multi-Method-Vorgehen mit einer anschließenden individualisierten kognitiven Verhaltenstherapie der Schlafstörungen – gehäuft bei externalen Auffälligkeiten. Abstract. Sleep disorders are common in adults as well as children and adolescents. Children and adolescents in psychiatric treatment (CAP) are especially affected by sleep problems. Cognitive behavioral therapy represents the first-line treatment, preceded by a standardized procedure for sleep diagnostics. To date, no study has investigated sleep behavior in CAP day clinics in Germany. In this study, N = 46 children/adolescents receiving CAP treatment in a day clinic completed a sleep diary (7 days) and a sleep anamnesis scheme with the help of their parents, and their sleep behavior was assessed by a clinician. Furthermore, a parent- and a self-report questionnaire plus a clinical assessment of the mental disorders in the children/adolescents were collected. 52 % of the children/ adolescents exhibited sleep disorders or sleep abnormalities (= sleep disorder symptoms in the context of comorbid disorders), in particular problems falling asleep or to falling asleep and sleeping through the night (26 %). In addition, 33 % reported having nightmares. Their sleep behavior correlated significantly with their external behavior problems (r = .38 .61, p = .02-.04); their sex (female: p = .01–≤ .001, |d| = 1.57–2.50) and their age (older: p = .05, |d| = .78) also significantly influenced sleep behavior. Particularly external behavior problems were associated with sleep problems in this day-care population. In summary, a multi-method-multi-informant procedure should be established for the systematic diagnostics of sleep abnormalities, together with individualized cognitive-behavioral therapy of sleep problems, especially in patients with external behavior problems.

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.

Differential effects of blue- and red-enriched light on attention and sleep have been primarily described in adults. In our cross-over study in typically developing adolescents (11-17 years old), we found attention enhancing effects of blue- compared to red-enriched light in the morning (high intensity of ca. 1000 lx, short duration:1 h) in two of three attention tasks: e.g. better performance in math tests and reduced reaction time variability in a computerized attention test. In our pilot study, actigraphy measures of sleep indicated slight benefits for red- compared to blue-enriched light in the evening: tendencies toward a lower number of phases with movement activity after sleep onset in the complete sample and shorter sleep onset latency in a subgroup with later evening exposure times. These findings point to the relevance of light concepts regarding attention and sleep in typically developing adolescents. Such concepts should be developed and tested further in attention demanding contexts (at school) and for therapeutic purposes in adolescents with impaired attention or impaired circadian rhythms.

Background Dipeptidyl peptidase 4 (DPP4, CD26) is a moonlighting enzyme responsible for the proteolytic inactivation of neuropeptide Y (NPY), a peptide known for its anxiolytic effect in the central nervous system. Our previous work revealed a stress-resilient phenotype and a potentiation of short-term fear extinction in a congenic rat model deficient for DPP4 activity (DPP4mut). Here, we investigated neuroendocrine mechanisms underlying the phenotype of the DPP4mut animals. We studied the function of the hypothalamus–pituitary–adrenal (HPA) axis including the expression levels of its key genes and explored the possibility of structural NPY system changes. Methods and results We find decreased expression of Nr3c1 (glucocorticoid receptor - GR) and Fkbp5 (FK506 binding protein 5) in the amygdala and the hypothalamus of the DPP4mut rats, as well as the lower stress-induced peripheral corticosterone (CORT) levels. We detect no significant alterations in basal and DEX-induced CORT levels in the DPP4mut animals. The abundance of NPY-ergic neurons in the basolateral amygdala, dentate gyrus and hippocampus did not differ between the DPP4mut and their wild type littermates. Conclusion DPP4mut rats show blunted CORT response in line with their lower behavioral stress-response profile. These results are consistent with the hypothesis that increased central NPY levels elevate the threshold of stress response. We suggest that changes in the expression levels of key HPA axis genes (Nr3c1 and Fkbp5) are a consequence of the altered stress-perception of DPP4mut animals, thus further contributing to the stress-resilient phenotype.

Unfavourable intrauterine environmental factors increase the risk of delivery complications as well as postpartum developmental and behavioural problems in children and adolescents with ongoing effects into older age. Biomarker studies show that maternal stress and the use of alcohol and tobacco during pregnancy are associated with a higher intrauterine testosterone exposure of the child. The antenatal testosterone load, in turn, is a risk factor for lasting adverse health effects which extend into adulthood. A 15-week, mindfulness-oriented, app-based programme for the reduction of stress as well as for the reduction of alcohol and tobacco use in pregnant women is established. In the monocentre, prospective, controlled, and investigator-blinded MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention) study, pregnant women carry out the programme. Its effect on antenatal testosterone exposure of the child is examined by assessing the index/ring finger length ratio and other biomarkers in the 1-year-old children. In addition, the programme's effects on self-regulation, the developmental status and the mental health of the children at the age of one year will be investigated. Additional aspects of the course of the pregnancy and delivery represent exploratory study objectives. This longitudinal study project is intended to improve the understanding of the impact of intrauterine environmental factors on early childhood development and health. Maternal stress as well as alcohol and tobacco use during pregnancy are modifiable factors and represent potential preventive targets.Ungünstige intrauterine Umweltfaktoren erhöhen das Risiko für Geburtskomplikationen sowie postpartale Entwicklungs- und Verhaltensauffälligkeiten bei den Kindern und Jugendlichen mit permanenten Auswirkungen bis ins höhere Alter. Biomarkerstudien zeigen, dass mütterlicher Stress und Konsum von Alkohol und Tabak während der Schwangerschaft mit höherer intrauteriner Testosteronexposition des Kindes assoziiert sind. Die pränatale Testosteronlast ist wiederum ein Risikofaktor für anhaltende und bis ins Erwachsenenalter reichende Gesundheitsbeeinträchtigungen. Es wird ein 15-wöchiges, achtsamkeitsorientiertes, App-basiertes Programm zur Reduktion von Stress sowie zur Verminderung von Alkohol- und Tabakkonsum bei schwangeren Frauen etabliert. In der monozentrischen, prospektiven, kontrollierten und untersucherverblindeten MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention)-Studie führen schwangere Frauen das Programm durch. Dabei wird der Effekt auf die pränatale Testosteronexposition des Kindes untersucht, die mit dem Zeige-/Ringfingerlängenverhältnis und weiteren Biomarkern bei den 1-jährigen Kindern erhoben wird. Außerdem soll beforscht werden, wie sich das Programm auf die Selbstregulation, den Entwicklungstand und die psychische Gesundheit der Kinder im Alter von einem Jahr auswirkt. Weitere Aspekte des Schwangerschafts- und Geburtsverlaufs stellen explorative Studienziele dar. Dieses longitudinale Studienprojekt soll das Verständnis der Bedeutung intrauteriner Umweltfaktoren für die frühe kindliche Entwicklung und Gesundheit verbessern. Mütterlicher Stress sowie Alkohol- und Tabakkonsum während der Schwangerschaft sind modifizierbare Faktoren und stellen potenzielle präventive Ansatzpunkte dar.

ObjectiveDifferent components of body image processing seem to be reflected by different neural mechanisms. A core symptom of Anorexia nervosa (AN) is a disturbance of body image with correlates found on a neural level. The present study focusses at the neural processing of visual body stimuli of different weight categories in adolescent and adult AN patients.Method33 adolescents aged 12–18 years (15 AN patients, 18 control participants) and 36 adult women (19 AN patients, 17 control participants) underwent functional magnetic resonance imaging (fMRI) while performing a perceptive and an affective body image task involving photographic stimuli of women belonging to different BMI categories.ResultsDifferential effects on activation depending on the BMI of the women shown in the pictures were found in frontal brain regions, the thalamus, caudate and the fusiform gyrus. Group effects differentiating between AN patients and control participants were seen mainly in the caudate and insula.DiscussionDuring a perceptive task, diminished activation of regions involved in perceptive and evaluative functions as well as emotional reasoning was seen in AN. During evaluation of the neural processing in an affective task there was a tendency towards activation differences reflecting reduced ability of size estimation and impaired integration of visual and body perception with emotions.

ObjectiveTo elucidate the mechanisms of how snack foods may induce non-homeostatic food intake, we used resting state functional magnetic resonance imaging (fMRI), as resting state networks can individually adapt to experience after short time exposures. In addition, we used graph theoretical analysis together with machine learning techniques (support vector machine) to identifying biomarkers that can categorize between high-caloric (potato chips) vs. low-caloric (zucchini) food stimulation.MethodsSeventeen healthy human subjects with body mass index (BMI) 19 to 27 underwent 2 different fMRI sessions where an initial resting state scan was acquired, followed by visual presentation of different images of potato chips and zucchini. There was then a 5-minute pause to ingest food (day 1=potato chips, day 3=zucchini), followed by a second resting state scan. fMRI data were further analyzed using graph theory analysis and support vector machine techniques.ResultsPotato chips vs. zucchini stimulation led to significant connectivity changes. The support vector machine was able to accurately categorize the 2 types of food stimuli with 100% accuracy. Visual, auditory, and somatosensory structures, as well as thalamus, insula, and basal ganglia were found to be important for food classification. After potato chips consumption, the BMI was associated with the path length and degree in nucleus accumbens, middle temporal gyrus, and thalamus.ConclusionThe results suggest that high vs. low caloric food stimulation in healthy individuals can induce significant changes in resting state networks. These changes can be detected using graph theory measures in conjunction with support vector machine. Additionally, we found that the BMI affects the response of the nucleus accumbens when high caloric food is consumed.

The second-to-forth digit length ratio (2D:4D) is considered to be a biomarker for intrauterine androgen levels. It is associated with adult and child mental health problems, primarily with behavioral symptoms and predominantly in males. Using a cross-sectional design, we examined whether 2D:4D was associated with conduct disorder (CD) symptoms in 138 primary-school aged children (54% boys, Mage = 7.70 years) and considered child sex as a moderating factor. Children's digit lengths were measured from hand scans and mothers rated the behavioral/emotional symptoms of their child. The regression analyses revealed that 2D:4D ratios were associated with behavioral symptoms in boys (β = −0.260, p = 0.026), but not in girls (β = −0.040, p = 0.762). Child emotional symptoms, analyzed as a control, were not significantly correlated with 2D:4D. In conclusion, prenatal brain hyperandrogenization - operationalized by the 2D:4D biomarker - could result in behavioral symptoms in boys at early school age, reflecting one predictor for early onset CD. Our data support the use of 2D:4D as a marker of prenatal androgen exposure.

(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring’s low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: n = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: n = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: n = 35). Fifteen years later, 122 adolescents (M = 13.32 years, 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP, M = 0.91, SD = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents (p = 0.036, ηp2 = 0.04) and an inverse non-significant dose–response relation with hsCRP (r = −0.35, p = 0.113). For maternal self-reported prenatal alcohol consumption (p = 0.780, ηp2 = 0.00) and prenatal depressive symptoms (p = 0.360, ηp2 = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.

Background Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. Methods Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. Results Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. Conclusions Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.

Studies have shown that child development is negatively affected by prenatal depression. A dysregulated hypothalamic-pituitary-adrenal axis in the pregnant woman, passed to the fetus, is one discussed key mechanism. Studies, investigating primary-school age children, have found effects on antisocial behavior. Effects on internalizing symptoms were not found, but the analysis did not distinguish between anxiety and depression symptoms. Additionally, until now, no objective test data operationalizing social-emotional competencies have been included. The present study examined: 1.Whether the effects on child externalizing symptoms could be replicated; 2. If there are specific effects on child internalizing symptoms, separated for anxiety and depression; and 3. Are child clinical symptoms reflected in reductions in social-emotional competencies. A sample of 61 prenatally depressed and 143 prenatally not-depressed women and their 6–9 year old children were compared, controlling for key confounders in both the perinatal period and in middle childhood. Children of prenatally depressed mothers had more antisocial behavior and depression symptoms reported by their mothers. The prediction of antisocial behavior scores tended to be more significant for boys than for girls. Child anxiety symptoms were primarily explained by current maternal depressive symptoms. Children of prenatally depressed mothers also showed a reduction in social-emotional competencies, specifically regarding the ability to interpret complex social situations. This study showed that, even in a non-clinical sample, there are distinct effects of prenatal depression on child externalizing and internalizing symptoms which are accompanied by reductions in specific social-emotional competencies. These results emphasize that treatment for depressed pregnant women and/or early support for affected families is worthwhile. Additional work is required to identify the underlying biological mechanisms.

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016.

Aim This case-control study examined the long-term consequences of surgical correction for ventricular septal defect (VSD; the most common congenital heart defect) in infancy. It assessed children who had undergone VSD surgery and the factors related to maternal conditions, surgery, and hospital stay. Method Thirty-nine children (23 females, 16 males; age range 6y 1mo-9y 7mo [mean 7y 4mo, SD 1y]) with repaired isolated, non-syndromic, non-genetic VSD were compared with 39 typically developing children (22 females, 17 males; age range 6y-9y 2mo [mean 7y 3mo, SD 10mo]). The children completed behavioural tests of neurodevelopment and a quality of life (QoL) questionnaire. Mothers rated children's emotional/behavioural symptoms and QoL. Measures of maternal parenting behaviour and psychopathology were treated as moderators. Results Affected children showed reduced language skills (p=0.002) unless mothers reported high parenting behaviour subscale scores (p=0.04). Children's anxiety symptoms were elevated when mothers had anxiety symptoms (p=0.01). Longer hospital stay was associated with lower intelligence (p=0.003) and psychomotor scores (p=0.006). Longer scars predicted elevated child anxiety (p=0.008), and age at surgery and QoL were inversely related (p=0.01). Interpretation Impairments could be mitigated if VSD repair was performed early in life with a relatively small scar and uncomplicated hospital stay. This outcome depends on maternal parenting behaviour and anxiety symptoms. What this paper adds Children's cognitive and psychomotor development after surgical ventricular septal defect repair was unimpaired. Children showed no mental health restrictions when their mothers reported few anxiety symptoms themselves. Language impairments might be preventable by pro-active parenting. The outcome also depends on variables related to surgery and hospital stay.

Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD.

Consuming alcohol during pregnancy is one of the most verified prenatal risk factors for impaired child development. Information about the amount of alcohol consumed prenatally is needed to anticipate negative effects and to offer timely support. Women's self-reports are not reliable, often influenced by social stigmas and retrospective recall bias, causing biomarkers of intrauterine ethanol exposure to become more and more relevant. The present study compares both women's gestational and retrospective self-reports of prenatal alcohol consumption with levels of ethyl glucuronide (EtG) in meconium. Women (n = 180) gave self-reports of prenatal alcohol consumption both during their 3rd trimester (gestational self-report) and when their children were 6–8 years old (retrospective self-report). Child meconium was collected after birth and analyzed for EtG. No individual feedback of children's EtG level was given to the women. All analyses were run separately for two cut-offs: 10 ng/g (limit of detection) and 120 ng/g (established by Goecke et al., 2014). Mothers of children with EtG values above 10 ng/g (n = 42) tended to report prenatal alcohol consumption more frequently. There was no trend or significance for the EtG cut-off of 120 ng/g (n = 26) or for retrospective self-report. When focusing on women who retrospectively reported alcohol consumption during pregnancy, a claim to five or more consumed glasses per month made an EtG over the 10 ng/g and the 120 ng/g cut-off more probable. Women whose children were over the 10 ng/g EtG cut-off were the most inconsistent in their self-report behavior, whereas the consistency in the above 120 ng/g EtG group was higher than in any other group. The next step to establish EtG as a biomarker for intrauterine alcohol exposure is to correlate EtG values in meconium with child developmental impairments.

Neurofeedback stellt ein computergestütztes Verhaltenstraining dar, das in der Behandlung von Kindern mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) zunehmend Beachtung findet. Der vorliegende Beitrag geht auf den aktuellen Stand der Forschung ein, insbesondere die methodischen Grundlagen und Aspekte der Evaluation. In den bislang durchgeführten Evaluationsstudien konnte die klinische Wirksamkeit nachgewiesen werden. So zeigte sich ein Neurofeedback-Training z. B. in einer randomisierten kontrollierten Studie einem herkömmlichen Computer-Aufmerksamkeitstraining überlegen (mittlere Effektstärke). Die Trainingseffekte erweisen sich auch längerfristig als stabil, wie Follow-up Untersuchungen (z. B. nach sechs Monaten) belegen. Auf klinischer Ebene scheinen mit den Neurofeedback-Protokollen Theta/Beta-Training und Training langsamer kortikaler Potentiale vergleichbare Effekte erzielt werden zu können. Untersuchungen auf neurophysiologischer Ebene weisen allerdings auf unterschiedliche Wirkmechanismen dieser Neurofeedback-Protokolle hin. Künftige Studien sollten die Spezifität der Trainingseffekte weiter beleuchten und sich der Optimierung und Individualisierung des Trainings widmen. Schlagwörter Neurofeedback – Verhaltenstherapie – ADHS – Evaluation – EEG Neurofeedback is a computer-based behavior training, which is gaining increasing interest in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This article gives an introduction to neurofeedback and summarizes the state of research, discussing inter alia methodical aspects (e. g., requirements to a control training). Evaluation studies conducted so far indicate clinical efficacy. For example, neurofeedback training was superior to a computerized attention training in a randomized controlled trial (medium effect size). Follow-up investigations suggest that treatment effects remain stable (at least six months). At the clinical level, comparable improvements could be obtained for the neurofeedback protocols theta/beta training and training of slow cortical potentials. Neurophysiological findings document different mechanisms of theta/beta training and slow cortical potential training. Future studies should further elucidate the specificity of training effects related to the kind of training and certain disorders and address how to optimize and individualize neurofeedback training. Keywords neurofeedback – behavior therapy – ADHD – evaluation – EEG

The neuronal processes underlying response inhibition are often studied using either event-related potentials (ERPs) or by applying transcranial magnetic stimulation (TMS) to investigate excitatory and inhibitory processes in the motor system. We performed a more refined analysis of response inhibition by combining both approaches with the aim of identifying an interplay between ERPs and TMS parameters. During a go/nogo task, motor system excitability was measured using TMS single and double pulses and brain electrical activity was recorded in healthy adults (n=14). Each participant completed two testing sessions, once on placebo and once on methylphenidate (double-blind, crossover design). Studying the effects of methylphenidate served as an example application for this combined approach. Developing regression models, inhibition-related TMS measures (e.g., short intracortical inhibition) and the contingent negative variation explained about 85% of the variance of the nogo-P3 under both MPH and placebo medication. The smaller the inhibitory effect in the motor system, the more terminal response control was required and the more resources were allocated for the evaluation of the inhibitory process, respectively, as indicated by a larger P3. Thus, an interplay between processes in the motor system (cortex) and control processes with sources in the prefrontal cortex and the anterior cingulate cortex (ACC) may take place, acting complementarily to facilitate a correct nogo-response. While ERPs rather represent initiation and monitoring of inhibitory processes and response control, motor inhibition may be best analyzed using TMS. A combined ERP/TMS analysis may allow for the development of distinct models concerning the interplay of processes involved in response inhibition.

Im Rahmen einer multizentrischen, randomisierten, kontrollierten Studie evaluierten wir die klinische Wirksamkeit eines Neurofeedback-Trainings (NF) bei Kindern mit einer Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) und untersuchten die einem erfolgreichen Training zugrunde liegenden neurophysiologischen Wirkmechanismen. Als Vergleichstraining diente ein computergestütztes Aufmerksamkeitstraining, das dem Setting des Neurofeedback-Trainings in den wesentlichen Anforderungen und Rahmenbedingungen angeglichen war. Auf Verhaltensebene (Eltern- und Lehrerbeurteilung) zeigte sich das NF-Training nach Trainingsende dem Kontrolltraining sowohl hinsichtlich der ADHS-Kernsymptomatik als auch in assoziierten Bereichen überlegen. Für das Hauptzielkriterium (Verbesserung im FBB-HKS Gesamtwert) ergab sich eine mittlere Effektstärke (von 0.6). Sechs Monate nach Trainingsende (follow-up) konnte das gleiche Ergebnismuster gefunden werden. Die Ergebnisse legen somit den Schluss nahe, dass NF einen klinisch wirksamen Therapiebaustein zur Behandlung von Kindern mit ADHS darstellt. Auf neurophysiologischer Ebene (EEG; ereignisbezogene Potentiale, EPs) konnten für die beiden Neurofeedback-Protokolle Theta/Beta-Training und Training langsamer kortikaler Potentiale spezifische Effekte aufgezeigt werden. So war für das Theta/Beta-Training beispielsweise die Abnahme der Theta-Aktivität mit einer Reduzierung der ADHS-Symptomatik assoziiert. Für das SCP-Training wurde u. a. im Attention Network Test eine Erhöhung der kontingenten negativen Variation beobachtet, die die mobilisierten Ressourcen bei Vorbereitungsprozessen widerspiegelt. EEG- und EP-basierte Prädiktorvariablen konnten ermittelt werden. Der vorliegende Artikel bietet einen Gesamtüberblick über die in verschiedenen Publikationen unserer Arbeitsgruppe beschriebenen Ergebnisse der Studie und zeigt zukünftige Fragestellungen auf.

In a randomized controlled trial, neurofeedback (NF) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology (Gevensleben et al., 2009). The aims of this investigation were to assess the impact of different NF protocols (theta/beta training and training of slow cortical potentials, SCPs) on the resting EEG and the association between distinct EEG measures and behavioral improvements. In 72 (of initially 102) children with ADHD, aged 8-12, EEG changes after either a NF training (n=46) or the control training (n=26) could be studied. The combined NF training consisted of one block of theta/beta training and one block of SCP training, each block comprising 18 units of 50 minutes (balanced order). Spontaneous EEG was recorded in a two-minute resting condition before the start of the training, between the two training blocks and after the end of the training. Activity in the different EEG frequency bands was analyzed. In contrast to the control condition, the combined NF training was accompanied by a reduction of theta activity. Protocol-specific EEG changes (theta/beta training: decrease of posterior-midline theta activity; SCP training: increase of central-midline alpha activity) were associated with improvements in the German ADHD rating scale. Related EEG-based predictors were obtained. Thus, differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD.

Background: For children with attention deficit/hyperactivity disorder (ADHD), a reduction of inattention, impulsivity and hyperactivity by neurofeedback (NF) has been reported in several studies. But so far, unspecific training effects have not been adequately controlled for and/or studies do not provide sufficient statistical power. To overcome these methodological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite randomised controlled study using a computerised attention skills training as a control condition. Methods: 102 children with ADHD, aged 8 to 12 years, participated in the study. Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each (randomised group assignment). The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training. Pre-training, intermediate and post-training assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents and teachers. Evaluation (‘placebo’) scales were applied to control for parental expectations and satisfaction with the treatment. Results: For parent and teacher ratings, improvements in the NF group were superior to those of the control group. For the parent-rated FBB-HKS total score (primary outcome measure), the effect size was .60. Comparable effects were obtained for the two NF protocols (theta/beta training, SCP training). Parental attitude towards the treatment did not differ between NF and control group. Conclusions: Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD. Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD. Keywords: Neurofeedback, attention deficit/hyperactivity disorder (ADHD), slow cortical potentials (SCPs), theta/beta training, randomised controlled trial (RCT), EEG.

Deficient inhibitory processes within the sensorimotor circuit, reflected by a shortened cortical silent period (CSP), have previously been described in both children and adults with tic disorders (TD) using transcranial magnetic stimulation (TMS). In contrast to adults, tic distribution (presence or absence of distal tics) did not affect CSP duration in children. The aim of this developmental TMS study was to clarify this striking difference. 127 children with TD were stratified into three age-groups (8-11.5, 11.5-15, 15-19 years) with and without distal tics. CSP was recorded from the abductor digiti minimi. Statistics revealed a significant tic distributionxage interaction effect. Only in the 15-19 years subgroup, CSP was shorter in patients with distal tics in comparison to patients without distal tics (94.1+/-54.1 ms versus 135.2+/-36.8 ms at a stimulus intensity of active motor threshold plus 30%). Inhibitory processes in the sensorimotor circuit could reflect developmental aspects of tic phenomenology, particularly tic distribution during adolescence.

Interactions of the serotonergic and noradrenergic system at different sites of the brain may be important for efficacy and side effects of antidepressant drugs. Further, serotonin and noradrenaline play a critical role in the development of neurons during brain maturation. To gain further insight how brain maturation and the two monoaminergic systems are influenced by drug treatment during early postnatal development, this animal study investigated possible effects on the noradrenaline and serotonin transporter density of the frontal cortex very early in postnatal life. Rats were treated from postnatal day 2 to 5 either with fluoxetine (5 mg/kg per day s.c.) or with reboxetine (10 mg/kg per day s.c.). At day 90 the serotonin and noradrenaline transporter density in the frontal cortex was measured by ligand binding assay. Fluoxetine treatment led to a significant long-lasting increase of serotonin (not noradrenaline) transporter density (Bmax = 1231 +/- 34) in the frontal cortex (compared with saline-treated controls (Bmax = 1112 +/- 58)). Reboxetine treatment (surprisingly) led to an even more enhanced serotonin transporter density (Bmax = 1322 +/- 46), while noradrenaline transporter density seemed to be unaffected. There were no significant differences for KD values. The results support the idea that serotonin seems to play an important role during early brain development. Moreover, drug-related modulation of the noradrenergic system during brain maturation seems to cross-influence the serotonergic system.

Background: The benzamide tiapride, a selective dopamine D2/ D3-receptor antagonist, can be used effectively in children to treat tic disorders and stuttering. Tiapride is a clinically safe substance (even during long-term treatment and when given to young children). Unfortunately, its probable effects on general brain development and the maturation of the dopaminergic system have not been investigated. Thus, important information for drug treatment in children is missing. Therefore, this study in rats describes tiapride's effects on several parameters of dopaminergic activity (dopamine transporter, D2 receptor, dopamine, DOPAC, and homovanillic acid in the striatum) seen after tiapride administration (30 mg/kg/day) to prepubertal (from day 25-39) and postpubertal (from day 50-64) rats. Methods: Three groups of rats (n = 6) received tiapride within their drinking water for 14 days. Two groups were treated before puberty; one of those was killed at day 50, the other at day 90. The group treated after puberty was measured at day 90. A fourth group (n = 6) was treated from day 50 to day 53 and measured under tiapride at day 53. Changes were measured by ligand-binding assays (K D and B m a x values of dopamine transporter by [ 3 H]-GBR binding and D2 receptor by [ 3 H]- spiperone binding) and by HPLC (concentrations of dopamine, DOPAC, and homovanillic acid). Results: The density of dopamine transporters and D2 receptors remained unaffected after early (day 25) and late (day 50) tiapride administration. Only during the treatment period could a significant reduction of D2-receptor binding (displacement of spiperone) and of dopamine and DOPAC levels be stated. Conclusions: These data suggest that tiapride treatment during postnatal brain development causes no long-lasting changes in the development of the central dopaminergic system and is in line with clinical experience in children.

Background Learned self-control of slow cortical potentials (SCPs) may lead to behavioral improvement in attention-deficit/hyperactivity disorder (ADHD). Hence, training effects should also be reflected at the neurophysiological level. Methods Thirteen children with ADHD, aged 7–13 years, performed 25 SCP training sessions within 3 weeks. Before and after training, the German ADHD rating scale was completed by parents, and event-related potentials were recorded in a cued continuous performance test (CPT). For a waiting-list group of nine children with ADHD, the same testing was applied. Results ADHD symptomatology was reduced by approximately 25% after SCP training. Moreover, a decrease of impulsivity errors and an increase of the contingent negative variation were observed in the CPT task. Conclusions This study provides first evidence for both positive behavioral and specific neurophysiological effects of SCP training in children with ADHD.

Objective: To test the effects of a standard dosage of the psychostimulant methylphenidate (MPH) – which significantly enhances intracortical inhibition but had no effects on intracortical facilitation in children with attention-deficit hyperactivity disorder (ADHD) – on intracortical excitability in healthy subjects. Method: In 12 healthy subjects, aged 20–40 years, intracortical inhibition and facilitation were investigated before and 70 min after the intake of 10 mg MPH using the technique of transcranial magnetic stimulation (TMS) with the paired-stimulus paradigm. Results: In comparison of the two TMS measurements, a significant enhancement in intracortical facilitation but no effects on intracortical inhibition could be stated under MPH administration. Conclusion: This study provides first evidence for opposite effects of MPH on intracortical excitability in healthy adult subjects showing enhanced intracortical facilitation in contrast to ADHD children in whom enhanced intracortical inhibition has recently been shown.

Normal development and dysfunctions of motor system excitability can be investigated in vivo by means of single- and paired-pulse transcranial magnetic stimulation (TMS). While different TMS-parameters show different developmental time courses between 8 and 16 years of age, distinct dysfunctional patterns of motor system excitability can be demonstrated in child psychiatric disorders with hypermotoric behavior: in tic disorder, a shortened cortical silent period can be stated providing evidence for deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. In attention deficit hyperactivity disorder (ADHD), a decreased intracortical inhibition indicates deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In children with comorbid ADHD and tic disorder, the findings of a reduced intracortical inhibition as well as a shortened cortical silent period provide evidence for additive effects at the level of motor system excitability. Thus, TMS allows us to obtain substantial insight into both the normal development and the neurobiological basis of hypermotoric syndromes in child psychiatry.

Zusammenfassung: Mit der transkraniellen Magnetstimulation (TMS) kann die Exzitabilität des motorischen Systems direkt in vivo untersucht werden. Diese Methode wurde deshalb bei Kindern mit solchen Störungsbildern angewandt, bei denen sich eine unzureichende Steuerung, Kontrolle und/oder Regulation motorischer Abläufe feststellen lässt: Eine “musterbezogene” Überaktivität bei Tic-Störungen, eine “allgemeine” motorische Überaktivität bei Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen (ADHS). Im Vergleich zu gesunden Kindern waren bei Kindern mit diesen hypermotorischen Störungsbildern unterschiedliche Auffälligkeiten festzustellen: (1) Eine verkürzte Kortikale Silent Period und damit ein Hinweis auf defizitäre inhibitorische Prozesse wahrscheinlich auf Ebene der Basalganglien bei Kindern mit Tic-Störungen (offenbar kein Einfluss klinisch wirksamer Medikamente), (2) eine verminderte intrakortikale Inhibition und damit ein Hinweis auf defizitäre inhibitorische Prozesse eher im Bereich des Motorkortex bei Kindern mit ADHS (Zunahme der intrakortikalen Inhibition unter Methylphenidatgabe). (3) Bei Kindern mit komorbider ADHS und Tic-Störung waren beide neurophysiologischen Veränderungen i.S. eines “additiven” Inhibitionsdefizites im motorischen System aufzeigbar. Mit diesen TMS-Untersuchungen konnten bei Kindern mit den hypermotorischen Störungsbildern Tic-Störungen und ADHS neue Befunde zur Darstellung neurobiologischer Grundlagen (“Inhibitionsdefizite im motorischen System”), zur Frage der Komorbidität (“additiver Effekt im motorischen System”) sowie zum Wirkmechanismus entsprechender Psychopharmaka (“Verbesserung des Inhibitionsvermögens im motorischen System bei ADHS unter Methylphenidat”) erarbeitet werden.

Objective : The aim of this event-related potential (ERP) study was to test time-on-task analysis at the level of single sweeps in a clinical trial. Since inattentiveness is one of the main symptoms of attention-deficit hyperactivity disorder (ADHD), this child psychiatric disorder was chosen as an exemplary application. Methods : Twenty-four healthy and 24 ADHD boys, aged 9–15 years, performed an auditory selective attention task for about 5 min. ERP single trials were analyzed using wavelet networks. Time-on-task analysis was applied to omission errors, reaction time and slow ERP components (frontal negativity, parietal positivity), represented by a low-frequency wavelet component. Results : Both performance and ERP measures showed distinct temporal dynamics. Time-on-task effects were not only linear, but also of higher order and started after less than 1 min. For ADHD children, earlier time-on-task effects, i.e. an earlier increase of omission errors and frontal negativity, resulted. Healthy children could allocate more attentional resources during the course of the experiment. Conclusion : Time-on-task analysis at the level of single trials revealed phenomena probably reflecting ADHD children's attentional deficits. Thus, a more differentiated ERP analysis may provide a better understanding of the pathophysiological background in neuropsychiatric disorders.

For children with attention-deficit-hyperactivity disorder (ADHD) or tic disorder (TD), we recently reported deficient inhibitory mechanisms within the motor system by using transcranial magnetic stimulation. These deficits—stated as reduced intracortical inhibition in ADHD and shortened cortical silent period in TD—could be seen as neurophysiological correlates of motor hyperactivity and tics, respectively. To investigate neurophysiological aspects of comorbidity, we measured motor system excitability for the first time also in children with combined ADHD and TD. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence for additive effects at the level of motor system excitability. Ann Neurol 2001;49:393–396

The binding parameters of highly selective ligands of serotonin (5-HT) transporters ([ 3 H ]paroxetine), noradrenaline (NE) transporters ([ 3 H ]nisoxetine), and of dopamine (DA) transporters ([ 3 H ]GBR-12935) were determined on membrane preparations from frontal cortex, striatum, midbrain and brain stem of Wistar rats on postnatal days 25, 50, 90 and 240, i.e., from the time of weaning till late adulthood. No age-dependent alterations in the affinity-parameters (KD-values) of all three monoamine transporters were observed. Age-associated changes in Bmax-values of the binding of all three specific ligands were most pronounced in the phylogenetically younger, late maturing brain regions (frontal cortex, striatum). Most likely, these changes reflect age-related changes in 5-HT, NE and DA-innervation densities. In the frontal cortex, 5-HT-transporter density increased steadily from weaning (day 25) till late adulthood, whereas the density of NE-transporters was highest at weaning, declined till puberty (day 50) and remained at this level until old age. DA-transporter density in the frontal cortex was not reliably measurable by [ 3 H ]GBR-binding assays. In the striatum, DA-transporter density increased till puberty and declined thereafter considerably and steadily to about one-fourth of the pubertal values at old age. No such age-associated changes in DA-transporter density were seen in the midbrain. Densities of 5-HT and NE remained at the level reached already at weaning until old age in the striatum, midbrain and brain stem. These findings provide the first comprehensive description of the normally occurring changes in the densities of all three presynaptically located monoamine transporters in the rat brain throughout the life span from weaning to late adulthood.

This experimental animal study was performed in order to assess possible long-term effects of the administration of the selective serotonin reuptake inhibitor fluoxetine (Prozac) during early periods of juvenile life on the developing central serotonergic and noradrenergic systems. Fluoxetine was administered via the drinking water (5 mg/kg/day) for a period of two weeks to very young (day 25) and somewhat older (day 50) rats. The effect of this treatment on the density of serotonin and noradrenaline transporters was measured by ligand-binding assays in various brain regions. The Bmax-values of [3H]-nisoxetine binding were not affected by either treatment schedule, but a significant increase of the Bmax-values of [3H]-paroxetine binding was found in the brains of early fluoxetine-treated rats. This increase was restricted to the frontal cortex and persisted long after the termination of the treatment into adulthood (day 90). The most likely explanation of this observation is a stimulatory effect of the fluoxetine treatment on the outgrowth of serotonergic projections in the frontal cortex of very young rats. This is the first empirical demonstration of long-lasting effects of the administration of a selective serotonin reuptake inhibitor during juvenile life on the maturation of the central serotonergic system.

Neurofeedback (NF), a type of neurobehavioral training, has gained increasing attention in recent years, especially concerning the treatment of children with ADHD. Promising results have emerged from recent randomized controlled studies, and thus, NF is on its way to becoming a valuable addition to the multimodal treatment of ADHD. In this review, we summarize the randomized controlled trials in children with ADHD that have been published within the last 5 years and discuss issues such as the efficacy and specificity of effects, treatment fidelity and problems inherent in placebo-controlled trials of NF. Directions for future NF research are outlined, which should further address specificity and help to determine moderators and mediators to optimize and individualize NF training. Furthermore, we describe methodological (tomographic NF) and technical ('tele-NF') developments that may also contribute to further improvements in treatment outcome.

Objective In a randomized controlled trial, we could demonstrate clinical efficacy of neurofeedback (NF) training for children with ADHD (Gevensleben et al., 2009a). The present investigation aimed at learning more about the neuronal mechanisms of NF training. Methods Children with ADHD either completed a NF training or a computerized attention skills training (ratio 3:2). NF training consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training, each comprising 18 training units. At three times (pre-training, between the two training blocks and at post-training), event-related potentials (ERP) were recorded during the Attention Network Test. ERP analysis focused on the P3, reflecting inter alia attentional resources for stimulus evaluation, and the contingent negative variation (CNV), primarily related to cognitive preparation. Results After NF training, an increase of the CNV in cue trials could be observed, which was specific for the SCP training. A larger pre-training CNV was associated with a larger reduction of ADHD symptomatology for SCP training. Conclusions CNV effects reflect neuronal circuits underlying resource allocation during cognitive preparation. These distinct ERP effects are closely related to a successful NF training in children with ADHD. In future studies, neurophysiological recordings could help to optimize and individualize NF training. Significance The findings contribute to a better understanding of the mechanisms underlying NF training in children with ADHD.

Methylphenidate is widely and effectively used for the treatment of attention deficit hyperactivity disorder during early childhood and adolescence, but until now possible effects of this treatment on brain development and the maturation of monoaminergic systems have not been investigated systematically. This experimental animal study describes the effects of methylphenidate administration (2 mg/kg/day) for 2 weeks to very young (prepubertal) and somewhat older (postpubertal) rats on the densities of dopamine, serotonin, and norepinephrine transporters in the striatum and in the midbrain. As shown by ligand-binding-assays, the K(D) values of all three transporters were unaffected by this treatment. No alterations were found for the Bmax values of [3H]-paroxetine and [3H]-nisoxetine binding, but the density of dopamine transporters (Bmax values of [3H]-GBR binding) in the striatum (but not in the midbrain) was significantly reduced after early methylphenidate administration (by 25% at day 45), and this decline reached almost 50% at adulthood (day 70), that is, long after termination of the treatment. This is the first empirical demonstration of long-lasting changes in the development of the central dopaminergic system caused by the administration of methylphenidate during early juvenile life.

In children with attention-deficit hyperactivity disorder (ADHD), motoric hyperactivity is one of the striking abnormalities. Because this symptom might be due to an insufficient motor control, motor system excitability in 18 drug-naive ADHD-children aged 8-12 years was compared to 18 age-matched healthy children using the technique of transcranial magnetic stimulation (TMS). Whereas motor thresholds, cortical silent period, and intracortical facilitation did not differ between the two groups, ADHD-children had significantly reduced intracortical inhibition compared to healthy controls. In all ADHD-children, a second TMS could be started after their first intake of 10 mg methylphenidate. Under this medication, a significant enhancement in intracortical inhibition could be stated. This study provides the first evidence for inhibitory deficits within the motor cortex in ADHD-children and for an enhancement of inhibitory mechanisms in this brain region by methylphenidate.

Decreased motor inhibition was reported in adult patients with tic disorder (TD) using the technique of transcranial magnetic stimulation. Since tics usually begin during childhood, motor threshold, cortical silent period (CSP) and intracortical inhibition/facilitation were measured in 21 TD children and 25 healthy children aged 10-16 years. In TD children motor threshold was normal. The CSP was significantly shortened compared to healthy controls but did not depend on tic localization. Intracortical inhibition and facilitation did not differ between the two groups. This study confirms that the finding of decreased motor control in adult patients also holds true for children wherever the tics in the latter group were located.

Trial-to-trial variabilities in event-related potentials (ERP's), which are neglected by investigating averaged ERP's, can be important to establish group-specific effects in clinical studies. Single ERP responses have to be analyzed to quantify these variations. In order to overcome the disadvantages of existing single-sweep estimators, we have developed a new procedure based on wavelet networks (WN's) and applied this novel approach in a study concerning attention deficit hyperactivity disorder (ADHD) in children.WN's represent signals as a linear combination of wavelet nodes, i.e., components characterized by time-frequency features related to the wavelet transformation. In single-sweep analysis, each wavelet node is restricted to a specific region of the time-frequency plane during the recursive WN training process. This is achieved by means of tapering and bandpass filtering with Gaussian functions which are automatically adapted and closely related to the Morlet basis wavelet. The time course of a single event-related response can be reliably estimated. Furthermore, the WN method automatically provides well-defined parameters for single event-related responses, respectively ERP trial-to-trial variabilities.In a psychophysiological study on ADHD using auditory evoked potentials (AEP's), latency and amplitude parameters extracted from averaged ERP's did not reveal any significant differences between 25 control and 25 ADHD boys. In contrast, interesting group-specific differences could be established by WN single-sweep analysis.WN single-sweep analysis can be recommended as a sensitive tool for clinical ERP studies which should be applied in addition to the investigation of averaged responses. INDEX TERMS: Attention deficit hyperactivity disorder (ADHD), event-related potentials, single-sweep estimation, single-sweep parameterization, time-frequency method, wavelet networks.

In children with attention-deficit hyperactivity disorder (ADHD) some deficits in auditory information processing seem to exist. Further, comorbidity of ADHD with conduct disorder (CD) and tic disorder (Tic) is quite common but not yet fully understood. Thus, we investigated the effects of these two disturbances, when combined with ADHD, on electrophysiological correlates of auditory information processing. An auditory selective-attention task was used, and temporal as well as frontal lobe sensitive event-related electrical brain activity indicators like mismatch negativity (MMN) and negative difference wave (Nd), as well as P300 were registered in four groups of children (healthy controls, ADHD-only, and combined ADHD + CD as well as ADHD + Tic; total number 42). Performance measures showed that ADHD + CD had a higher impact on errors and reaction times than ADHD + Tic. The MMN effect indicated that all ADHD groups showed lower MMN amplitudes compared to normals, but only the group with ADHD + CD suffered from a significant deficiency in automatic auditory information processing. Nd and P300 amplitudes showed no significant group differences. It may be assumed that neurodynamic sufficiency in ADHD-only and ADHD + Tic children seems to be similarly impaired while there might be a greater deficit in ADHD + CD.