Retrospective assessment of ICD-10/DSM-5 criteria of childhood ADHD from descriptions of academic and social behaviors in German primary school reports.

BACKGROUND: The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adolescence and adulthood is particularly challenging because retrospective confirmation of previous childhood ADHD is mandatory. Therefore, collecting valid diagnostic information about behavior at school is important. Primary school reports often contain descriptions of academic performance and social behaviors associated with ADHD criteria. Yet, there is no systematic approach available how to assess such reports quantitatively, and therefore, there is also no study on how valid such an approach could predict an ADHD diagnosis. METHODS: We examined primary school reports from Germany (ADHD: n = 1197, typically developing controls: n = 656) for semantic references to ICD-10/DSM-5 main and sub-criteria of ADHD. Descriptions were assessed on a quantitative scale (blinded clinical expert rating) for disorder-associated behaviors (symptoms scale) as well as for desired, adaptive behaviors (competencies scale) according to these criteria. The scores of these developed scales have been summarized to summary scores. Scores were analyzed using linear mixed models, and sensitivity and specificity were estimated using receiver operating characteristics (ROC). RESULTS: Ratings showed highly significant differences between school reports of children with and without ADHD. For the summary scores, both symptoms and competencies scales showed high diagnostic accuracy (ROC area under the curve at least 0.96) with best discrimination when combining both into an integrated index (sensitivity and specificity > 0.97). CONCLUSIONS: Our findings suggest that systematic quantitative analysis of primary school reports should be further explored to construct a valid instrument for retrospective assessment of childhood ADHD criteria to aid the diagnostic process in adolescents and adults.

Using machine learning to improve diagnostic assessment of ASD in the light of specific differential and co-occurring diagnoses.

BACKGROUND: Diagnostic assessment of ASD requires substantial clinical experience and is particularly difficult in the context of other disorders with behavioral symptoms in the domain of social interaction and communication. Observation measures such as the Autism Diagnostic Observation Schedule (ADOS) do not take into account such co-occurring disorders. METHOD: We used a well-characterized clinical sample of individuals (n = 1,251) that had received detailed outpatient evaluation for the presence of an ASD diagnosis (n = 481) and covered a range of additional overlapping diagnoses, including anxiety-related disorders (ANX, n = 122), ADHD (n = 439), and conduct disorder (CD, n = 194). We focused on ADOS module 3, covering the age range with particular high prevalence of such differential diagnoses. We used machine learning (ML) and trained random forest models on ADOS single item scores to predict a clinical best-estimate diagnosis of ASD in the context of these differential diagnoses (ASD vs. ANX, ASD vs. ADHD, ASD vs. CD), in the context of co-occurring ADHD, and an unspecific model using all available data. We employed nested cross-validation for an unbiased estimate of classification performance and made available a Webapp to showcase the results and feasibility for translation into clinical practice. RESULTS: We obtained very good overall sensitivity (0.89-0.94) and specificity (0.87-0.89). In particular for individuals with less severe symptoms, our models showed increases of up to 35% in sensitivity or specificity. Furthermore, we analyzed item importance profiles of the ANX, ADHD, and CD models in comparison with the unspecific model revealing distinct patterns of importance for specific ADOS items with respect to differential diagnoses. CONCLUSIONS: ML-based diagnostic classification may improve clinical decisions by utilizing the full range of information from detailed diagnostic observation instruments such as the ADOS. Importantly, this strategy might be of particular relevance for older children with less severe symptoms for whom the diagnostic decision is often particularly difficult.

Neural mechanisms underlying social recognition and theory of mind in adolescent patients with bulimia nervosa and transdiagnostic comparison with anorexia nervosa.

INTRODUCTION: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking. METHODS: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]). RESULTS: Compared to HCBN , patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency. DISCUSSION: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.

Group-based cognitive behavioural psychotherapy for children and adolescents with ASD: the randomized, multicentre, controlled SOSTA-net trial.

BACKGROUND: Group-based psychotherapy in Autism Spectrum Disorder (ASD) has predominantly been studied in the United States by small studies in school-aged children without long-term follow-up. We report results of a large, confirmatory, multicentre randomized-controlled phase-III trial in children and adolescents studying the ASD specific, manualized group-based cognitive behavioural SOSTA-FRA approach. METHODS: High-functioning ASD individuals aged 8-19 years old were randomized to 12 sessions SOSTA-FRA or treatment as usual. Primary outcomes were change in total raw score of the parent-rated Social Responsiveness Scale (pSRS) between baseline (T2) and end of intervention (T4), and between T2 and 3 months after end of intervention (T5). TRIAL REGISTRATION: ISRCTN94863788. RESULTS: Between 20/5/2010 and 14/2/2013, n = 320 ASD patients were screened, n = 228 patients were randomized, and N = 209 analysed. Mean pSRS difference between groups at T4 was -6.5 (95% CI -11.6 to - 1.4; p = .013), and at T5 -6.4 (-11.5 to -1.3, p = .015). Pre-treatment SRS and IQ were positively associated with stronger improvement at T4 and T5. CONCLUSIONS: Short-term ASD-specific add-on group-based psychotherapy has shown postintervention efficacy with regard to parent-rated social responsiveness predominantly in male high-functioning children and adolescents with ASD. Future studies should implement blinded standardized observational measures of peer-related social interaction.

Impairment in face processing in autism spectrum disorder: a developmental perspective.

Findings on face identity and facial emotion recognition in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about the developmental trajectory of face processing skills in ASD. Taking a developmental perspective, the aim of this study was to extend previous findings on face processing skills in a sample of adolescents and adults with ASD. N = 38 adolescents and adults (13-49 years) with high-functioning ASD and n = 37 typically developing (TD) control subjects matched for age and IQ participated in the study. Moreover, n = 18 TD children between the ages of 8 and 12 were included to address the question whether face processing skills in ASD follow a delayed developmental pattern. Face processing skills were assessed using computerized tasks of face identity recognition (FR) and identification of facial emotions (IFE). ASD subjects showed impaired performance on several parameters of the FR and IFE task compared to TD control adolescents and adults. Whereas TD adolescents and adults outperformed TD children in both tasks, performance in ASD adolescents and adults was similar to the group of TD children. Within the groups of ASD and control adolescents and adults, no age-related changes in performance were found. Our findings corroborate and extend previous studies showing that ASD is characterised by broad impairments in the ability to process faces. These impairments seem to reflect a developmentally delayed pattern that remains stable throughout adolescence and adulthood.

Impaired recognition of interactive intentions in adults with autism spectrum disorder not attributable to differences in visual attention or coordination via eye contact and joint attention.

Altered nonverbal communication patterns especially with regard to gaze interactions are commonly reported for persons with autism spectrum disorder (ASD). In this study we investigate and differentiate for the first time the interplay of attention allocation, the establishment of shared focus (eye contact and joint attention) and the recognition of intentions in gaze interactions in adults with ASD compared to control persons. Participants interacted via gaze with a virtual character (VC), who they believed was controlled by another person. Participants were instructed to ascertain whether their partner was trying to interact with them. In fact, the VC was fully algorithm-controlled and showed either interactive or non-interactive gaze behavior. Participants with ASD were specifically impaired in ascertaining whether their partner was trying to interact with them or not as compared to participants without ASD whereas neither the allocation of attention nor the ability to establish a shared focus were affected. Thus, perception and production of gaze cues seem preserved while the evaluation of gaze cues appeared to be impaired. An additional exploratory analysis suggests that especially the interpretation of contingencies between the interactants' actions are altered in ASD and should be investigated more closely.

Revealing the neurobiology underlying interpersonal neural synchronization with multimodal data fusion.

Humans synchronize with one another to foster successful interactions. Here, we use a multimodal data fusion approach with the aim of elucidating the neurobiological mechanisms by which interpersonal neural synchronization (INS) occurs. Our meta-analysis of 22 functional magnetic resonance imaging and 69 near-infrared spectroscopy hyperscanning experiments (740 and 3721 subjects) revealed robust brain regional correlates of INS in the right temporoparietal junction and left ventral prefrontal cortex. Integrating this meta-analytic information with public databases, biobehavioral and brain-functional association analyses suggested that INS involves sensory-integrative hubs with functional connections to mentalizing and attention networks. On the molecular and genetic levels, we found INS to be associated with GABAergic neurotransmission and layer IV/V neuronal circuits, protracted developmental gene expression patterns, and disorders of neurodevelopment. Although limited by the indirect nature of phenotypic-molecular association analyses, our findings generate new testable hypotheses on the neurobiological basis of INS.

Emotion regulation training for adolescents with major depression: Results from a randomized controlled trial.

Difficulties in emotion regulation (ER) are thought to contribute to the development and maintenance of major depression (MD) in adolescents. In healthy adults, a task-based training of ER has previously proven effective to reduce stress, but no such studies are available for MD. It is also unclear whether findings can be generalized onto adolescent populations. The final sample consisted of n = 70 adolescents with MD, who were randomized to a task-based ER training (n = 36) or a control training (n = 34). Across four sessions, the ER group was trained to downregulate negative affect to negative images via reappraisal, while the control group was instructed to attend the images. Rumination, stress-, and affect-related measures were assessed as primary outcomes, behavioral and neurophysiological responses (late positive potential, LPP), as secondary outcomes. The trial was preregistered at clinicaltrials.gov (NCT03957850). While there was no significant differential effect of the ER training on primary outcomes, we found small to moderate effects on rumination in the ER group, but not the control group. During reappraisal (compared to attend), the ER group showed an unexpected increase of the LPP during the first, but not during later training sessions. Although replication in large, multicenter trials is needed, our findings on effect sizes suggest that ER training might be promising to decrease rumination in adolescent MD. The LPP increase at the first session may represent cognitive effort, which was successfully reduced over the sessions. Future studies should research whether training effects transfer to daily life and are durable over a longer time period. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mobile Solutions for Clinical Surveillance and Evaluation in Infancy-General Movement Apps.

The Prechtl General Movements Assessment (GMA) has become a clinician and researcher toolbox for evaluating neurodevelopment in early infancy. Given that it involves the observation of infant movements from video recordings, utilising smartphone applications to obtain these recordings seems like the natural progression for the field. In this review, we look back on the development of apps for acquiring general movement videos, describe the application and research studies of available apps, and discuss future directions of mobile solutions and their usability in research and clinical practice. We emphasise the importance of understanding the background that has led to these developments while introducing new technologies, including the barriers and facilitators along the pathway. The GMApp and Baby Moves apps were the first ones developed to increase accessibility of the GMA, with two further apps, NeuroMotion and InMotion, designed since. The Baby Moves app has been applied most frequently. For the mobile future of GMA, we advocate collaboration to boost the field's progression and to reduce research waste. We propose future collaborative solutions, including standardisation of cross-site data collection, adaptation to local context and privacy laws, employment of user feedback, and sustainable IT structures enabling continuous software updating.

Open video data sharing in developmental science and clinical practice.

In behavioral research and clinical practice video data has rarely been shared or pooled across sites due to ethical concerns of confidentiality, although the need of shared large-scaled datasets remains increasing. This demand is even more imperative when data-heavy computer-based approaches are involved. To share data while abiding by privacy protection rules, a critical question arises whether efforts at data de-identification reduce data utility? We addressed this question by showcasing an established and video-based diagnostic tool for detecting neurological deficits. We demonstrated for the first time that, for analyzing infant neuromotor functions, pseudonymization by face-blurring video recordings is a viable approach. The redaction did not affect classification accuracy for either human assessors or artificial intelligence methods, suggesting an adequate and easy-to-apply solution for sharing behavioral video data. Our work shall encourage more innovative solutions to share and merge stand-alone video datasets into large data pools to advance science and public health.

Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes.

OBJECTIVE: The neurobiological mechanisms of structural brain abnormalities in patients with anorexia nervosa (AN) remain poorly understood. In particular, little is known about the changes in and the recovery of gray matter (GM) volumes after weight gain and the relation to hormonal normalization in adolescent patients with AN. METHODS: Nineteen female patients aged 12 to 17 years were assessed using magnetic resonance imaging at the time of admission to the hospital (T1) and after weight recovery (T2). Patients were compared with typically developing girls matched for age and intelligence quotient. Structural brain images were analyzed using a voxel-based morphometric approach. Circulating levels of cortisol and gonadotropins were assessed in blood samples. RESULTS: Compared with controls, patients with AN showed reduced GM in several brain regions along the cortical midline, reaching from the occipital cortex to the medial frontal areas. These GM reductions were mostly reversible at T1. Patients showed a GM increase from T1 to T2 along the cortical midline and in the occipital, temporal, parietal, and frontal lobes. GM increases at T2 correlated inversely with cortisol levels at T1 and positively with weight gain at T2. The strongest associations between regional GM increase and weight gain were found in the cerebellum. In addition, increases in GM volumes at T2 in the thalamus, hippocampus, and amygdala were associated with increases in follicle-stimulating hormone. CONCLUSIONS: Our data suggest that brain alterations in adolescents with acute AN are mostly reversible at T1 and that GM recovery in specific brain regions is associated with weight and hormonal normalization.

[Self-report and parental report of empathy in adolescents with autism]. / Selbst- und Fremdbeurteilung der Empathie bei Jugendlichen mit Autismus.

OBJECTIVE: A deficit in empathy has repeatedly been described as a central feature of autistic disorders. However, little is known about how adolescents with autism evaluate their own empathic abilities, and how their parents judge these skills. The present study assesses affective components of empathy via both self-report and parental report. METHOD: 18 boys with autism and 18 typically developing boys participated in the study. A German translation of the Bryant Index of Empathy was used for the self-assessment of empathy. Parents rated the empathic abilities of their sons using a German version of the Griffith Empathy Measure. Both questionnaires are comparable with regards to content and mainly tap into affective components of empathy. RESULTS: Self-reports of empathy in adolescents with autism did not differ from controls. In contrast, parents of adolescents with autism judged their sons to be less empathic compared to parents of typically developing adolescents. CONCLUSIONS: The discrepancy between unimpaired self-reported empathy and parental report of impaired empathy in adolescents with autism might result from their difficulties in effectively conveying empathic feelings to other people. Alternatively, the results may be explained by impaired introspection on inner experiences in individuals with autism.

Temporal Behavioral Parameters of On-Going Gaze Encounters in a Virtual Environment.

To navigate the social world, humans heavily rely on gaze for non-verbal communication as it conveys information in a highly dynamic and complex, yet concise manner: For instance, humans utilize gaze effortlessly to direct and infer the attention of a possible interaction partner. Many traditional paradigms in social gaze research though rely on static ways of assessing gaze interaction, e.g., by using images or prerecorded videos as stimulus material. Emerging gaze contingent paradigms, in which algorithmically controlled virtual characters can respond flexibly to the gaze behavior of humans, provide high ecological validity. Ideally, these are based on models of human behavior which allow for precise, parameterized characterization of behavior, and should include variable interactive settings and different communicative states of the interacting agents. The present study provides a complete definition and empirical description of a behavioral parameter space of human gaze behavior in extended gaze encounters. To this end, we (i) modeled a shared 2D virtual environment on a computer screen in which a human could interact via gaze with an agent and simultaneously presented objects to create instances of joint attention and (ii) determined quantitatively the free model parameters (temporal and probabilistic) of behavior within this environment to provide a first complete, detailed description of the behavioral parameter space governing joint attention. This knowledge is essential to enable the modeling of interacting agents with a high degree of ecological validity, be it for cognitive studies or applications in human-robot interaction.

Brain and motor synchrony in children and adolescents with ASD-a fNIRS hyperscanning study.

Brain-to-brain synchrony has been proposed as an important mechanism underlying social interaction. While first findings indicate that it may be modulated in children with autism spectrum disorder (ASD), no study to date has investigated the influence of different interaction partners and task characteristics. Using functional near-infrared spectroscopy hyperscanning, we assessed brain-to-brain synchrony in 41 male typically developing (TD) children (8-18 years; control sample), as well as 18 children with ASD and age-matched TD children (matched sample), while performing cooperative and competitive tasks with their parents and an adult stranger. Dyads were instructed either to respond jointly in response to a target (cooperation) or to respond faster than the other player (competition). Wavelet coherence was calculated for oxy- and deoxyhemoglobin brain signals. In the control sample, a widespread enhanced coherence was observed for parent-child competition, and a more localized coherence for parent-child cooperation in the frontopolar cortex. While behaviorally, children with ASD showed a lower motor synchrony than children in the TD group, no significant group differences were observed on the neural level. In order to identify biomarkers for typical and atypical social interactions in the long run, more research is needed to investigate the neurobiological underpinnings of reduced synchrony in ASD.

Neural mechanisms of empathy in adolescents with autism spectrum disorder and their fathers.

A deficit in empathy has been repeatedly described in individuals with autism spectrum disorder (ASD) and also, albeit less markedly, in their unaffected relatives. Here, we aimed to investigate the neural mechanisms of empathy in ASD, and to explore familial contributions to empathy correlates. Using functional magnetic resonance imaging, 15 boys with ASD, 11 fathers of adolescents with ASD, and two control groups comparable for age and IQ (n=15 typically developing boys and their fathers (n=9)) were investigated during an empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). When attributing emotions to self and other, the ASD group showed diminished fusiform gyrus activation compared to controls. Neural activity in the fusiform gyrus was inversely related to social deficits in ASD subjects. Moreover, when ASD subjects inferred their own emotional response to faces, they showed less congruent reactions and inferior frontal gyrus activity was decreased. Although fathers of ASD children scored higher on a self-rating scale for autistic symptoms compared to control fathers, their task performance was unimpaired. However, neurally, fathers of affected children also showed reduced fusiform gyrus activation when inferring others' emotions. Shared abnormalities in fusiform gyrus activation in affected adolescents and first-degree relatives suggest that this dysfunction constitutes a fundamental deviation in ASD. Moreover, the findings provide evidence that both aberrant neural face and mirroring mechanisms are implicated in empathy impairments in ASD.

Developmental Differences in Probabilistic Reversal Learning: A Computational Modeling Approach.

Cognitive flexibility helps us to navigate through our ever-changing environment and has often been examined by reversal learning paradigms. Performance in reversal learning can be modeled using computational modeling which allows for the specification of biologically plausible models to infer psychological mechanisms. Although such models are increasingly used in cognitive neuroscience, developmental approaches are still scarce. Additionally, though most reversal learning paradigms have a comparable design regarding timing and feedback contingencies, the type of feedback differs substantially between studies. The present study used hierarchical Gaussian filter modeling to investigate cognitive flexibility in reversal learning in children and adolescents and the effect of various feedback types. The results demonstrate that children make more overall errors and regressive errors (when a previously learned response rule is chosen instead of the new correct response after the initial shift to the new correct target), but less perseverative errors (when a previously learned response set continues to be used despite a reversal) adolescents. Analyses of the extracted model parameters of the winning model revealed that children seem to use new and conflicting information less readily than adolescents to update their stimulus-reward associations. Furthermore, more subclinical rigidity in everyday life (parent-ratings) is related to less explorative choice behavior during the probabilistic reversal learning task. Taken together, this study provides first-time data on the development of the underlying processes of cognitive flexibility using computational modeling.

Study protocol for a randomised-controlled study on emotion regulation training for adolescents with major depression: the KONNI study.

INTRODUCTION: Major depression (MD) often has its onset during adolescence and is associated with significant morbidity and mortality. One important factor for the development and maintenance of adolescent MD are disturbances in emotion regulation and the underlying neural processes. Cognitive reappraisal (CR) is a particular adaptive emotion regulation strategy. Previously, it has been shown in healthy adults that a task-based training in CR is efficient to reduce negative affect, and that these effects translate into everyday life.This randomised controlled trial examines for the first time whether a task-based training in CR proves effective in MD adolescents. Specifically, we will investigate whether the CR training improves the ability to downregulate negative affect in MD individuals as assessed by behavioural and neurobiological indices, and whether training effects generalise outside the laboratory. METHODS AND ANALYSIS: Adolescents with MD will be randomly allocated to a group that either receives a task-based training in CR or a control training. Both involve four training sessions over a time period of 2 weeks. In the CR training, participants will be instructed to downregulate negative affective responses to negative pictures via CR, while the control training involves picture viewing. During the training sessions, the Late Positive Potential, gaze fixations on negative picture aspects and affective responses to pictures will be collected. Before and after the training programmes, and at a 2-week follow-up, overall negative and positive affect, rumination and perceived stress will be assessed as primary outcomes. Analyses of variance will be conducted to test the effectiveness of the CR training with regard to both primary outcomes and task-based behavioural and neurobiological parameters. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Medical Faculty of the LMU Munich, Germany. The results will be published in peer-reviewed journals and disseminated through conferences, social media and public events. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT03957850, registered 21st May 2019; URL: https://clinicaltrials.gov/ct2/show/NCT03957850.

Neural Correlates of Empathy in Boys With Early Onset Conduct Disorder.

Background: A deficit in empathy has repeatedly been described in individuals with conduct disorder (CD), and in particular in those with callous unemotional traits. Until now, little is known about the neural basis of empathy in children and adolescents with early onset conduct disorder. The aim of this study was to examine neural responses during empathizing in children and adolescents with CD with a task that allowed to differentiate between the judgment of the emotional states of other people and the own emotional response to other people's emotional state. Moreover, we investigated associations of callous-unemotional traits and neural activations during empathizing. Methods: Using functional magnetic resonance imaging (fMRI) we investigated 14 boys with early onset CD and 15 typically developing (TDC) age matched controls between 8 and 16 years of age. Happy and sad faces were presented, and participants were asked to either infer the emotional state from the face (other-task) or to judge their own emotional response (self-task). A perceptual decision on faces was used as a control task. Individual empathic abilities and callous unemotional traits were assessed. Results: During the other task, TDC boys showed significantly larger right amygdala responses than CD boys. Higher empathic abilities (as assessed with the Bryant Index of Empathy) were associated with higher responses in the right amygdala within the CD boys and across the entire sample. Moreover, across the entire sample, callous-unemotional traits were negatively related to the BOLD-response in the right amygdala. CD boys showed larger responses in the dorsal and ventral medial prefrontal cortex across tasks and increased activation in dorsal medial prefrontal cortex specifically during the self-conditions, which were also related to empathic abilities within the CD boys. Conclusions: The data emphasize the important role of the amygdala in empathy related emotional processing. Diminished amygdala responses and their association with low empathy suggest a pivotal influence of impaired amygdala processing in early-onset CD, in particular for deficits in empathic behavior and related callous-unemotional-traits. Elevated response in the medial prefrontal cortex in boys with CD point toward increased involvement of brain areas related to self-referential processing and cognitive empathy during empathizing.

Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder.

Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2-0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3-3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits-partially replicating previous findings-and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.

Neurofunctional modulation of brain regions by distinct forms of motor cognition and movement features.

Extrastriate, parietal, and frontal brain regions are differentially involved in distinct kinds of body movements and motor cognition. Using functional magnetic resonance imaging, we investigated the neural mechanisms underlying the observation and mental imagery of meaningful face and limb movements with or without objects. The supplementary motor area was differentially recruited by the mental imagery of movements while there were differential responses of the extrastriate body area (EBA) during the observation conditions. Contrary to most previous reports, the EBA responded to face movements, albeit to a lesser degree than to limb movements. The medial wall of the intraparietal sulcus and adjacent intraparietal cortex was selectively recruited by the processing of meaningful upper limb movements, irrespective of whether these were object-related or not. Besides reach and grasp movements, the intraparietal sulcus may thus be involved in limb gesture processing, that is, in an important aspect of human social communication. We conclude that subregions of a frontal-parietal network differentially interact during the cognitive processing of body movements according to the specific motor-related task at hand and the particular movement features involved.