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Background: Youth with attention-deficit/hyperactivity disorder (ADHD) exhibit increased effort aversion, likely due to deficits in anticipatory dopamine firing. Previous research has shown that transcranial direct current stimulation (tDCS) targeting the right prefrontal cortex can enhance activity in dopaminergic meso-striatal regions. However, the extent to which this specific tDCS configuration effectively modulates effort behavior in anticipation of rewards in ADHD remains uncertain. Hypothesis: We expected an increase of effort maintenance and invigoration during and following our tDCS set-up compared to sham in subjects with ADHD. Methods: Twenty-four children and adolescents with ADHD (mean age: 11.6 years; 95 % CI [10.7, 12.4]) received 2 mA and sham tDCS for 20 min each. The anode was positioned over the ventromedial prefrontal cortex (PFC), while the cathode was placed over the right dorsolateral PFC, generating an electrical field with maximal strength in the right PFC. During and after the tDCS sessions, participants performed a button-pressing task aimed at earning delayed monetary rewards. Primary outcomes were effort maintenance (frequency of button presses) and invigoration (slopes of button presses), measuring motor task performance. Results: We observed a significant increase in effort maintenance both during (b = 2.66; p < 0.001) and after tDCS (b = 2.04; p= .007) compared to sham. No significant difference was found for invigoration during stimulation, while after bonferroni correction (p = 0.025) a non-significant decrease was found after tDCS compared to sham (b = −5.18; p = 0.041). Conclusion: tDCS targeting the ventromedial PFC (anodal) and right dorsolateral PFC (cathodal) increases effort maintenance in children and adolescents with ADHD.

Background Public health measures during the COVID-19 pandemic had dramatic consequences for children and adolescents. However, policy-makers and healthcare researchers did not give sufficient weight to children’s perspectives. One common public health measure was mandatory SARS-CoV-2 tests in schools. This study examines the evaluation of such mandatory testing.Methods We investigated the effects of test type (pooled PCR tests vs antigen rapid tests) and demographic and psychological factors on evaluations of the experience of being tested. A total of 569 children (8–17 years) in two major German cities completed online questionnaires between October and December 2021. Participants answered questions addressing test evaluation, vaccination status, pandemic-related stress, mental health difficulties and health-related quality of life.Results Our results showed that overall test ratings were better for pooled PCR tests (p

Introduction: The motor system undergoes significant development throughout childhood and adolescence. The contingent negative variation (CNV), a brain response reflecting preparation for upcoming actions, offers valuable insights into these changes. However, previous CNV studies of motor preparation have primarily focused on adults, leaving a gap in our understanding of how cortical activity related to motor planning and execution matures in children and adolescents. Methods: The study addresses this gap by investigating the maturation of motor preparation, pre-activation, and post-processing in 46 healthy, right-handed children and adolescents aged 5–16 years. To overcome the resolution limitations of previous studies, we combined 64-electrode high-density Electroencephalography (EEG) and advanced analysis techniques, such as event-related potentials (ERPs), mu-rhythm desynchronization as well as source localization approaches. The combined analyses provided an in-depth understanding of cortical activity during motor control. Results: Our data showed that children exhibited prolonged reaction times, increased errors, and a distinct pattern of cortical activation compared to adolescents. The findings suggest that the supplementary motor area (SMA) plays a progressively stronger role in motor planning and response evaluation as children age. Additionally, we observe a decrease in sensory processing and post-movement activity with development, potentially reflecting increased efficiency. Interestingly, adolescent subjects, unlike young adults in previous studies, did not yet show contralateral activation of motor areas during the motor preparation phase (late CNV). Conclusion: The progressive increase in SMA activation and distinct cortical activation patterns in younger participants suggest immature motor areas. These immature regions might be a primary cause underlying the age-related increase in motor action control efficiency. Additionally, the study demonstrates a prolonged maturation of cortical motor areas, extending well into early adulthood, challenging the assumption that motor control is fully developed by late adolescence. This research, extending fundamental knowledge of motor control development, offers valuable insights that lay the foundation for understanding and treating motor control difficulties.

IntroductionRapid testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections was an essential step in reducing the spread of the virus and monitoring pandemic development. Most mandatory standard pandemic testing in Germany has been performed in schools and daycare facilities. We investigated the influence of behavioral and attitudinal characteristics of children and caregivers on their acceptance of (i) antigen-based nasal swab rapid and (ii) oral saliva-based pooled Polymerase Chain Reaction (PCR) tests.MethodsConducted through a cross-sectional survey between November and December 2021, with 1962 caregivers and 581 children/adolescents participating, the study evaluated the acceptability of each testing method on a six-point scale. Participants scored one test method conducted on their child at one of six levels with 1 and 6 denoting “excellent” (1) and “inadequate” (6), respectively. We considered demographic variables, vaccination status, child mental health (measured by the SDQ-questionnaire), and facility type (kindergarten, primary school, secondary school) as covariates.ResultsResults reveal a preference for saliva-based PCR tests over nasal swabs by about one grade, particularly among parents of unvaccinated children, especially if their child expressed future vaccination reluctance. Testing acceptance was lower among children with mental health issues, primary school-aged, and those with less-educated parents. Perception of test accuracy and convenience influenced attitudes, favoring saliva-based PCR tests. Moreover, children with mental health issues felt less secure during testing.DiscussionTo our knowledge, this is the first study to investigate the influence of different testing methods on testing acceptance for SARS-CoV-2 in children and caregivers. Our study identifies predictors of lower acceptance of public health surveillance measures and enables the development of educational programs on testing and vaccination tailored to the needs of specific target groups. Moreover, we demonstrate that test acceptance in vulnerable groups can be enhanced by careful choice of an appropriate testing method.

Magnetic resonance imaging (MRI) is essential for studying brain development and psychiatric disorders in adolescents. However, the imaging consistency remains challenging, highlighting the need for advanced methodologies to improve the diagnostic and research reliability in this unique developmental period. Adolescence is marked by significant neuroanatomical changes, distinguishing adolescent brains from those of adults and making age-specific imaging research crucial for understanding the neuropsychiatric conditions in youth. This study examines the test–retest reliability of anatomical brain MRI scans in adolescents diagnosed with depressive disorders, emphasizing a developmental perspective on neuropsychiatric disorders. Using a sample of 42 adolescents, we assessed the consistency of structural imaging metrics across 95 brain regions with deep learning-based neuroimaging analysis pipelines. The results demonstrated moderate to excellent reliability, with the intraclass correlation coefficients (ICC) ranging from 0.57 to 0.99 across regions. Notably, regions such as the pallidum, amygdala, entorhinal cortex, and white matter hypointensities showed moderate reliability, likely reflecting the challenges in the segmentation or inherent anatomical variability unique to this age group. This study highlights the necessity of integrating advanced imaging technologies to enhance the accuracy and reliability of the neuroimaging data specific to adolescents. Addressing the regional variability and strengthening the methodological rigor are essential for advancing the understanding of brain development and psychiatric disorders in this distinct developmental stage. Future research should focus on larger, more diverse samples, multi-site studies, and emerging imaging techniques to further validate the neuroimaging biomarkers. Such advancements could improve the clinical outcomes and deepen our understanding of the neuropsychiatric conditions unique to adolescence.

IntroductionThe SARS-CoV-2 pandemic has significantly impacted children and adolescents, leading to mental health challenges. Knowledge on their resources and difficulties is crucial and there is a need for valid instruments to assess their psychosocial condition especially in this exceptional situation. We assessed psychopathological symptoms using the SDQ during the pandemic, comparing to pre-pandemic data. Our study aims to understand adolescents’ strengths and difficulties amidst COVID-19, evaluating the SDQ’s utility in crisis settings.MethodsWithin the German school-based surveillance study (“B-Fast”), we assessed behavioral strengths and difficulties in 664 adolescents aged 11–17 years during the peak of the German COVID-19 pandemic using the validated Strengths and Difficulties Questionnaire (SDQ) for both external and self-assessed data collection. Data were collected between November 2020 and April 2021. We compared self-assessed SDQ-scores to pre-pandemic data from a comparable sample and examined adolescent classification as “normal” or “borderline/abnormal” based on both external and self-assessed SDQ subscale scores using established cut-off values. Additionally, we conducted sex and rater-based score comparisons.ResultsIn our study, we observed a significant worsening of “Emotional Symptoms” compared to pre-pandemic levels, while “Conduct Problems” and “Prosocial Behavior” showed improvement. Variations in classification to “normal” and “abnormal” emerged when applying German versus British cut-off values. Females scored higher on “Emotional Symptoms” while males scored higher on “Hyperactivity Symptoms.” Correlations between external and self-assessed SDQ ratings ranged from 0.43 (p

BackgroundThe COVID-19 pandemic has significantly impacted the mental health of children and families, i.e., due to measures like social distancing and remote schooling. While previous research has shown negative effects on mental health and health-related quality of life (HRQoL), most studies have focused on pre-post comparisons in the early pandemic stages. This systematic review aims to examine longitudinal studies to understand the long-term impacts of the pandemic on children and adolescents.MethodsThis systematic review adhered to the PRISMA guidelines and was preregistered in the international prospective register of systematic reviews (Record ID: CRD42022336930). We systematically searched PubMed/MEDLINE, Web of Science, PsycINFO, PSYNDEX, and the WHO-COVID-19 database and included studies published up to August 30, 2022. Based on pre-defined eligibility criteria, longitudinal and prospective studies that assessed the mental health or quality of life of children or adolescents (0–19 years) in the general population over a longer time span (at two or more measurement points) during the COVID-19 pandemic were included in the review. The methodological quality of the included studies was assessed using an adapted version of the Effective Public Health Practice Project (EPHPP) checklist. Narrative data synthesis was used to summarize the findings.ResultsA total of 5,099 results were obtained from literature searches, with 4,935 excluded during title/abstract screening. After reviewing 163 full-text articles, 24 publications were included in the review. Sample sizes ranged between n = 86 and n = 34,038. The length of the investigated time periods and the number of assessment points, as well as outcomes, varied. The majority of studies were of moderate methodological quality. Mental health outcomes were more frequently studied compared to measures of HRQoL. The findings from these studies mostly suggest that children and adolescents experienced heightened mental health problems, specifically internalizing symptoms like anxiety and depression. Further, there was a decline in their overall HRQoL over the course of the COVID-19 pandemic that did not necessarily subside when lockdowns ended.ConclusionIt is crucial to continue monitoring the mental health and well-being of children and adolescents following the pandemic to identify groups at risks and plan interventions. This should ideally be conducted by large systematic studies, using validated instruments, and encompassing representative samples to obtain reliable and comprehensive insights with the aim of improving youth mental health care.

ObjectiveThis study tested the reactivity of motor cortex inhibition to different intensities of external stimulation by transcranial magnetic stimulation (TMS) and its internal modulation during different motor states in children and adolescents with Tourette syndrome.MethodsTMS-evoked N100 served as an indirect measure of GABAB receptor function which is related to cortical inhibition. Combined TMS/EEG was used to analyze the TMS-evoked N100 component evoked by different stimulation intensities as well as during resting condition, movement preparation (contingent negative variation task) and movement execution. The study included 18 early adolescents with Tourette syndrome and 15 typically developing control subjects.ResultsTMS-evoked N100 showed a less steep increase with increasing TMS intensity in Tourette syndrome together with less modulation (disinhibition) over the primary motor cortex during the motor states movement preparation and movement execution. Children with Tourette syndrome showed equally high N100 amplitudes at 110% resting motor threshold (RMT) intensity during resting condition and a parallel decline of RMT and N100 amplitude with increasing age as control subjects.ConclusionOur study yields preliminary evidence that modulation of motor cortical inhibitory circuits, during external direct stimulation by different TMS intensities and during volitional movement preparation and execution is different in children and adolescents with Tourette syndrome compared to controls. These results suggest that a reduced resting motor cortical inhibitory “reserve” could contribute to the production of unwanted movements. Our findings are compatible with increased regulation of motor cortex excitability by perception-action binding in Tourette syndrome instead of top-down / motor regulation and need to be replicated in further studies.

Objective: Biological motion perception (BMP) correlating with a mirror neuron system (MNS) is attenuated in underage individuals with autism spectrum disorder (ASD). While BMP in typically-developing controls (TDCs) encompasses interconnected MNS structures, ASD data hint at segregated form and motion processing. This coincides with less fewer long-range connections in ASD than TDC. Using BMP and electroencephalography (EEG) in ASD, we characterized directionality and coherence (mu and beta frequencies). Deficient BMP may stem from desynchronization thereof in MNS and may predict social-communicative deficits in ASD. Clinical considerations thus profit from brain–behavior associations. Methods: Point-like walkers elicited BMP using 15 white dots (walker vs. scramble in 21 ASD (mean: 11.3 ± 2.3 years) vs. 23 TDC (mean: 11.9 ± 2.5 years). Dynamic Imaging of Coherent Sources (DICS) characterized the underlying EEG time-frequency causality through time-resolved Partial Directed Coherence (tPDC). Support Vector Machine (SVM) classification validated the group effects (ASD vs. TDC). Results: TDC showed MNS sources and long-distance paths (both feedback and bidirectional); ASD demonstrated distinct from and motion sources, predominantly local feedforward connectivity, and weaker coherence. Brain–behavior correlations point towards dysfunctional networks. SVM successfully classified ASD regarding EEG and performance. Conclusion: ASD participants showed segregated local networks for BMP potentially underlying thwarted complex social interactions. Alternative explanations include selective attention and global–local processing deficits. Significance: This is the first study applying source-based connectivity to reveal segregated BMP networks in ASD regarding structure, cognition, frequencies, and temporal dynamics that may explain socio-communicative aberrancies.

Somatosensory short-term memory is essential for object recognition, sensorimotor learning, and, especially, Braille reading for people who are blind. This study examined how visual sensory deprivation and a compensatory focus on somatosensory information influences memory processes in this domain. We measured slow cortical negativity developing during short-term tactile memory maintenance (tactile contralateral delay activity, tCDA) in frontal and somatosensory areas while a sample of 24 sighted participants and 22 participants who are blind completed a tactile change-detection task where varying loads of Braille pin patterns served as stimuli. Auditory cues, appearing at varying latencies between sample arrays, could be used to reduce memory demands during maintenance. Participants who are blind (trained Braille readers) outperformed sighted participants behaviorally. In addition, while task-related frontal activation featured in both groups, participants who are blind uniquely showed higher tCDA amplitudes specifically over somatosensory areas. The site specificity of this component's functional relevance in short-term memory maintenance was further supported by somatosensory tCDA amplitudes first correlating across the whole sample with behavioral performance, and secondly showing sensitivity to varying memory load. The results substantiate sensory recruitment models and provide new insights into the effects of visual sensory deprivation on tactile processing. Between-group differences in the interplay between frontal and somatosensory areas during somatosensory maintenance also suggest that efficient maintenance of complex tactile stimuli in short-term memory is primarily facilitated by lateralized activity in somatosensory cortex.

While Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD) and Schizophrenia (SCZ) differ in many clinically relevant features such as symptomatology and course, they may also share genetic underpinnings, affective problems, deviancies in social interactions, and are all characterized by some kind of cognitive impairment. This situation calls for a joint investigation of the specifics of cognitive (dys-)functions of the three disorders. Such endeavor should focus, among other domains, on the inter-section of processing cognitive, affective and social information that is crucial in effective real-life interactions and can be accomplished when attentional preferences for human facial expressions of emotions is studied. To that end, attention to facial expressions of basic emotions was examined in young adults with ASD, ADHD, or SCZ in the present study. The three clinical groups were compared with an age-matched group of typically-developing participants (TD) during the free contemplation of five different facial emotions presented simultaneously, by varying identities, through the registration of eye movements. We showed, that dwell times and fixation counts differed for the different emotions in TD and in a highly similar way in ADHD. Patients with ASD differed from TD by showing a stronger differentiation between emotions and partially different attentional preferences. In contrast, the SCZ group showed an overall more restricted scanning behavior and a lack of differentiation between emotions. The ADHD group, showed an emotion-specific gazing pattern that was highly similar to that of controls. Thus, by analyzing eye movements, we were able to differentiate three different viewing patterns that allowed us to distinguish between the three clinical groups. This outcome suggests that attention for emotion may not tap into common pathophysiological processes and argues for a multi-dimensional approach to the grouping of disorders with neurodevelopmental etiology.

IntroductionTranscranial magnetic stimulation (TMS)–evoked potentials (TEPs) allow for probing cortical functions in health and pathology. However, there is uncertainty whether long-latency TMS-evoked potentials reflect functioning of the targeted cortical area. It has been suggested that components such as the TMS-evoked N100 are stereotypical and related to nonspecific sensory processes rather than transcranial effects of the changing magnetic field. In contrast, TEPs that vary according to the targeted brain region and are systematically lateralized toward the stimulated hemisphere can be considered to reflect activity in the stimulated brain region resulting from transcranial electromagnetic induction.MethodsTMS with concurrent 64-channel electroencephalography (EEG) was sequentially performed in homologous areas of both hemispheres. One sample of healthy adults received TMS to the dorsolateral prefrontal cortex; another sample received TMS to the temporo-occipital cortex. We analyzed late negative TEP deflections corresponding to the N100 component in motor cortex stimulation.ResultsTEP topography varied according to the stimulation target site. Long-latency negative TEP deflections were systematically lateralized (higher in ipsilateral compared to contralateral electrodes) in electrodes over the stimulated brain region. A calculation that removes evoked components that are not systematically lateralized relative to the stimulated hemisphere revealed negative maxima located around the respective target sites.ConclusionTEPs contain long-latency negative components that are lateralized toward the stimulated hemisphere and have their topographic maxima at the respective stimulation sites. They can be differentiated from co-occurring components that are invariable across different stimulation sites (probably reflecting coactivation of peripheral sensory afferences) according to their spatiotemporal patterns. Lateralized long-latency TEP components located at the stimulation site likely reflect activity evoked in the targeted cortex region by direct transcranial effects and are therefore suitable for assessing cortical functions.

Transcranial magnetic stimulation (TMS) with simultaneous electroencephalography applied to the primary motor cortex provides two parameters for cortical excitability: motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). This study aimed to evaluate the effects of systematic coil shifts on both the TEP N100 component and MEPs in addition to the relationship between both parameters. In 12 healthy adults, the center of a standardized grid was fixed above the hot spot of the target muscle of the left primary motor cortex. Twelve additional positions were arranged in a quadratic grid with positions between 5 and 10 mm from the hot spot. At each of the 13 positions, TMS single pulses were applied. The topographical maximum of the resulting N100 was located ipsilateral and slightly posterior to the stimulation site. A source analysis revealed an equivalent dipole localized more deeply than standard motor cortex coordinates that could not be explained by a single seeded primary motor cortex dipole. The N100 topography might not only reflect primary motor cortex activation, but also sum activation of the surrounding cortex. N100 amplitude and latency decreased significantly during stimulation anterior-medial to the hot spot although MEP amplitudes were smaller at all other stimulation sites. Therefore, N100 amplitudes might be suitable for detecting differences in local cortical excitability. The N100 topography, with its maximum located posterior to the stimulation site, possibly depends on both anatomical characteristics of the stimulated cortex and differences in local excitability of surrounding cortical areas. The less excitable anterior cortex might contribute to a more posterior maximum. There was no correlation between N100 and MEP amplitudes, but a single-trial analysis revealed a trend toward larger N100 amplitudes in trials with larger MEPs. Thus, functionally efficient cortical excitation might increase the probability of higher N100 amplitudes, but TEPs are also generated in the absence of MEPs.

Increased Intra-Subject Variability (ISV) is a candidate endophenotype of ADHD. ISV’s relationship with response speed is highly relevant for ADHD as patients are highly variable but typically no slower than controls. This brief report addresses the relationship between variability and speed by employing dimensional analyses for differentiated performance measures, with a particular focus on the ex-Gaussian measures, across relevant ADHD studies and in young healthy adults (N = 70). For both patients with ADHD and healthy adults, we found that reaction time standard deviation and mean reaction time were strongly correlated, thus failing to dissociate, but ex-Gaussian tau (τ) shared only little variance with Gaussian mu (μ), thus dissociating slow responses (τ) from response speed or—if given—slow responding (μ). Our results highlight the utility of employing the ex-Gaussian measures to disentangle ISV and speed, particularly for ADHD data as patients make more slow responses but are not overall slower than typical controls.

Background: A noticeable proportion of adolescents with depression do not respond to guideline recommended treatment options. This systematic review and meta-analysis investigated the effectiveness of physical activity interventions as an alternative or complementary treatment for adolescents (12–18 years) with depression. The characteristics of the physical activity treatment that were most effective in reducing symptoms in adolescents with depression and the impact of methodological shortcomings in the existing research were also examined.Methods: Medline, PsycINFO, SPORTDiscus, ProQuest, and CENTRAL were searched for eligible records. Effect size estimates were pooled based on the application of a random-effects model. Potential moderation by physical activity characteristics (i.e., intensity, type, context, and time frame) and methodological features (i.e., type of control group and diagnostic tool to identify depression at baseline) was investigated by means of subgroup analyses and meta-regressions. The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was the antidepressant effect of physical activity at postintervention measurement time point. As secondary outcomes, the sustainability of effects after the end of physical activity treatment and the acceptability of physical activity treatments were assessed. Overall, 10 studies were included in the qualitative synthesis and 9 studies involving 431 patients were included in the quantitative synthesis.Results: A moderate, significant antidepressant effect of physical activity was found (Hedges' g = −0.47, 95% CI = −0.71 to −0.24). Heterogeneity was small (T2 = 0.0313, I2 = 27%, p = 0.18). However, the certainty of evidence was downgraded to low because the included studies contained serious methodological limitations. Moderator analyses revealed that session intensity significantly moderated the antidepressant effect of physical activity. Moreover, noticeably smaller effect sizes were found in studies that used non-physical activity sham treatments as control treatments (e.g., playing board games), compared to studies that used no control group treatments. Only three studies assessed the sustainability of effects after the end of physical activity treatment. The results suggest that the antidepressant effects further increase after the end of physical activity interventions. There was no significant difference in dropout risk between the physical activity and control groups.Conclusions: This review suggests that physical activity is effective in treating depression in adolescents. Physical activity sessions should be at least moderately intense [rate of perceived exertion (RPE) between 11 and 13] to be effective. Furthermore, our results suggest that physical activity treatments are well accepted. However, the low methodological quality in included studies might have led to effect overestimation. Therefore, more studies with higher methodological quality are needed to confirm the recommendation for physical activity treatments in adolescents with depression.

Abstract Background Moderate to vigorous endurance and strength-training exercise was suggested as a treatment option for major depression. However, there is little evidence to support this suggestion in adolescent patients. The present study investigates the effects of a whole-body vibration strength-training intervention on symptoms in medication-naïve adolescent inpatients experiencing a major depressive episode. Potential underlying endocrinological and neurobiological mechanisms are explored. Methods/design A double-blinded randomized controlled trial is conducted at the University Hospital of Cologne in Germany, comparing a 6-week, whole-body vibration strength-training with a 6-week placebo-intervention, as add-on therapy to inpatient treatment as usual. Forty-one subjects (13–18 years of age) will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients’ change in the Children’s Depression Rating Scale raw-score, from baseline until the end of the intervention. As secondary endpoints, the effects of exercise treatment on patients’ cortisol awakening response as well as on brain-derived neurotrophic factor, insulin-like growth factor 1 and inflammatory markers (tumor necrosis factor-alpha, interleukin-6 and C-reactive protein) serum levels will be assessed. Discussion This study will provide evidence on the effectiveness of whole-body vibration strength-training as an add-on therapy in adolescent inpatients experiencing a major depressive episode. After completion of data collection, the present study will be the largest randomized controlled trial so far to investigate the effectiveness of an exercise intervention in inpatient adolescents suffering from a major depressive episode. Moreover, the present study may help to determine the underlying mechanisms of potential anti-depressant effects of exercise in depressed adolescent inpatients. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00011772. Registered on 20 March 2017.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by problems in social behaviour, which are sometimes similar to some symptoms of autism-spectrum disorders (ASD). However, neuronal mechanisms of ASD-like deficits in ADHD have rarely been studied. The processing of biological motion-recently discussed as a marker of social cognition-was found to be disrupted in ASD in several studies. Thus in the present study we tested if biological motion processing is disrupted in ADHD. We used 64-channel EEG and spatio-temporal source analysis to assess event-related potentials associated with human motion processing in 21 children and adolescents with ADHD and 21 matched typically developing controls. On the behavioural level, all subjects were able to differentiate between human and scrambled motion. But in response to both scrambled and biological motion, the N200 amplitude was decreased in subjects with ADHD. After a spatio-temporal dipole analysis, a human motion specific activation was observable in occipital-temporal regions with a reduced and more diffuse activation in ADHD subjects. These results point towards neuronal determined alterations in the processing of biological motion in ADHD.

Increased intra-subject variability of reaction times (ISV-RT) is one of the most consistent findings in attention-deficit/hyperactivity disorder (ADHD). Although the nature of this phenomenon is still unclear, it has been hypothesised to reflect interference from the Default Mode Network (DMN). So far, ISV-RT has been operationally defined either as a frequency spectrum of the underlying RT time series, or as a measure of dispersion of the RT scores distribution. Here, we use a novel RT analysis framework to link these hitherto unconnected facets of ISV-RT by determining the sensitivity of different measures of RT dispersion to the frequency content of the underlying RT time series. N=27 patients with ADHD and N=26 healthy controls performed several visual N-back tasks. Different measures of RT dispersion were repeatedly modelled after individual frequency bands of the underlying RT time series had been either extracted or suppressed using frequency-domain filtering. We found that the intra-subject standard deviation of RT preserves the "1/f noise" characteristic typical of human RT data. Furthermore and most importantly, we found that the ex-Gaussian parameter τ is rather exclusively sensitive to frequencies below 0.025 Hz in the underlying RT time series and that the particularly slow RTs, which nourish τ, occur regularly as part of an quasi-periodic, ultra-slow RT fluctuation. Overall, our results are compatible with the idea that ISV-RT is modulated by an endogenous, slowly fluctuating process that may reflect DMN interference.

BACKGROUND: Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. METHODS: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val(158)Met and two DAT1 polymorphisms (variable number tandem repeats in the 3'-untranslated region and in intron 8). RESULTS: The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500-1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. CONCLUSIONS: Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming.

BACKGROUND: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of visual processing in a contingent negative variation (CNV) task. METHODS: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as preceding visual evoked potential components were assessed. RESULTS: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced. CONCLUSIONS: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children.ObjectiveTMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available.MethodsIn a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition.ResultsTMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation.ConclusionThe TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.

BACKGROUND: Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. METHODS: We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. RESULTS: We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes. CONCLUSIONS: A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology.