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.

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.

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.

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.

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.

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.

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.

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.

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.

Inferring Interactivity From Gaze Patterns During Triadic Person-Object-Agent Interactions.

Observing others' gaze informs us about relevant matters in the environment. Humans' sensitivity to gaze cues and our ability to use this information to focus our own attention is crucial to learning, social coordination, and survival. Gaze can also be a deliberate social signal which captures and directs the gaze of others toward an object of interest. In the current study, we investigated whether the intention to actively communicate one's own attentional focus can be inferred from the dynamics of gaze alone. We used a triadic gaze interaction paradigm based on the recently proposed classification of attentional states and respective gaze patterns in person-object-person interactions, the so-called "social gaze space (SGS)." Twenty-eight participants interacted with a computer controlled virtual agent while they assumed to interact with a real human. During the experiment, the virtual agent engaged in various gaze patterns which were determined by the agent's attentional communicative state, as described by the concept of SGS. After each interaction, participants were asked to judge whether the other person was trying to deliberately interact with them. Results show that participants were able to infer the communicative intention solely from the agent's gaze behavior. The results substantiate claims about the pivotal role of gaze in social coordination and relationship formation. Our results further reveal that social expectations are reflected in differential responses to the displayed gaze patterns and may be crucial for impression formation during gaze-based interaction. To the best of our knowledge, this is the first study to document the experience of interactivity in continuous and contingent triadic gaze interactions.

Neural modulation of social reinforcement learning by intranasal oxytocin in male adults with high-functioning autism spectrum disorder: a randomized trial.

Reduced social motivation is a hallmark of individuals with autism spectrum disorders (ASDs). Although the exact neural mechanisms are unclear, oxytocin has been shown to enhance motivation and attention to social stimuli, suggesting a potential to augment social reinforcement learning as the central mechanism of behavioral interventions in ASD. We tested how reinforcement learning in social contexts and associated reward prediction error (RPE) signals in the nucleus accumbens (NAcc) were modulated by intranasal oxytocin. Male adults with a childhood diagnosis of ASD (n = 15) and healthy controls (n = 24; aged 18-26 years) performed a probabilistic reinforcement learning task during functional magnetic resonance imaging in a single-center (research center in Germany), randomized double-blind, placebo-controlled cross-over trial. The interventions were intranasal oxytocin (Syntocinon®, Novartis; 10 puffs = 20 international units (IUs) per treatment) and placebo spray. Using computational modeling of behavioral data, trial-by-trial RPE signals were assessed and related to brain activation in NAcc during reinforcing feedback in social and non-social contexts. The order of oxytocin/placebo was randomized for 60 participants. Twenty-one participants were excluded from analyses, leaving 39 for the final analysis. Behaviorally, individuals with ASD showed enhanced learning under oxytocin when the learning target as well as feedback was social as compared to non-social (social vs. non-social target: 87.09% vs. 71.29%, 95% confidence interval (CI): 7.28-24.33, p = .003; social vs. non-social feedback: 81.00% vs. 71.29%, 95% CI: 2.81-16.61, p = .027). Correspondingly, oxytocin enhanced the correlation of the RPE signal with NAcc activation during social (vs. non-social) feedback in ASD (3.48 vs. -1.12, respectively, 95% CI: 2.98-6.22, p = .000), whereas in controls, this effect was found in the placebo condition (2.90 vs. -1.14, respectively, 95% CI: 1.07-7.01, p = .010). In ASD, a similar pattern emerged when the learning target was social (3.00 vs. -0.64, respectively, 95% CI: -0.13 to 7.41, p = .057), whereas controls showed a reduced correlation for social learning targets under oxytocin (-0.70 vs. 2.72, respectively, 95% CI: -5.86 to 0.98, p = .008). The current data suggest that intranasal oxytocin has the potential to enhance social reinforcement learning in ASD. Future studies are warranted that investigate whether oxytocin can potentiate social learning when combined with behavioral therapies, resulting in greater treatment benefits than traditional behavior-only approaches.

The "Social Gaze Space": A Taxonomy for Gaze-Based Communication in Triadic Interactions.

Humans substantially rely on non-verbal cues in their communication and interaction with others. The eyes represent a "simultaneous input-output device": While we observe others and obtain information about their mental states (including feelings, thoughts, and intentions-to-act), our gaze simultaneously provides information about our own attention and inner experiences. This substantiates its pivotal role for the coordination of communication. The communicative and coordinative capacities - and their phylogenetic and ontogenetic impacts - become fully apparent in triadic interactions constituted in its simplest form by two persons and an object. Technological advances have sparked renewed interest in social gaze and provide new methodological approaches. Here we introduce the 'Social Gaze Space' as a new conceptual framework for the systematic study of gaze behavior during social information processing. It covers all possible categorical states, namely 'partner-oriented,' 'object-oriented,' 'introspective,' 'initiating joint attention,' and 'responding joint attention.' Different combinations of these states explain several interpersonal phenomena. We argue that this taxonomy distinguishes the most relevant interactional states along their distinctive features, and will showcase the implications for prominent social gaze phenomena. The taxonomy allows to identify research desiderates that have been neglected so far. We argue for a systematic investigation of these phenomena and discuss some related methodological issues.

Looking While Unhappy: A Mood-Congruent Attention Bias Toward Sad Adult Faces in Children.

A negative mood-congruent attention bias has been consistently observed, for example, in clinical studies on major depression. This bias is assumed to be dysfunctional in that it supports maintaining a sad mood, whereas a potentially adaptive role has largely been neglected. Previous experiments involving sad mood induction techniques found a negative mood-congruent attention bias specifically for young individuals, explained by an adaptive need for information transfer in the service of mood regulation. In the present study we investigated the attentional bias in typically developing children (aged 6-12 years) when happy and sad moods were induced. Crucially, we manipulated the age (adult vs. child) of the displayed pairs of facial expressions depicting sadness, anger, fear and happiness. The results indicate that sad children indeed exhibited a mood specific attention bias toward sad facial expressions. Additionally, this bias was more pronounced for adult faces. Results are discussed in the context of an information gain which should be stronger when looking at adult faces due to their more expansive life experience. These findings bear implications for both research methods and future interventions.

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.

BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health.

Reward: From Basic Reinforcers to Anticipation of Social Cues.

Reward processing plays a major role in goal-directed behavior and motivation. On the neural level, it is mediated by a complex network of brain structures called the dopaminergic reward system. In the last decade, neuroscientific researchers have become increasingly interested in aspects of social interaction that are experienced as rewarding. Recent neuroimaging studies have provided evidence that the reward system mediates the processing of social stimuli in a manner analogous to nonsocial rewards and thus motivates social behavior. In this context, the neuropeptide oxytocin is assumed to play a key role by activating dopaminergic reward pathways in response to social cues, inducing the rewarding quality of social interactions. Alterations in the dopaminergic reward system have been found in several psychiatric disorders that are accompanied by social interaction and motivation problems, for example autism, attention deficit/hyperactivity disorder, addiction disorders, and schizophrenia.

Intact mirror mechanisms for automatic facial emotions in children and adolescents with autism spectrum disorder.

It has been suggested that an early deficit in the human mirror neuron system (MNS) is an important feature of autism. Recent findings related to simple hand and finger movements do not support a general dysfunction of the MNS in autism. Studies investigating facial actions (e.g., emotional expressions) have been more consistent, however, mostly relied on passive observation tasks. We used a new variant of a compatibility task for the assessment of automatic facial mimicry responses that allowed for simultaneous control of attention to facial stimuli. We used facial electromyography in 18 children and adolescents with Autism spectrum disorder (ASD) and 18 typically developing controls (TDCs). We observed a robust compatibility effect in ASD, that is, the execution of a facial expression was facilitated if a congruent facial expression was observed. Time course analysis of RT distributions and comparison to a classic compatibility task (symbolic Simon task) revealed that the facial compatibility effect appeared early and increased with time, suggesting fast and sustained activation of motor codes during observation of facial expressions. We observed a negative correlation of the compatibility effect with age across participants and in ASD, and a positive correlation between self-rated empathy and congruency for smiling faces in TDC but not in ASD. This pattern of results suggests that basic motor mimicry is intact in ASD, but is not associated with complex social cognitive abilities such as emotion understanding and empathy. Autism Res 2017, 10: 298-310. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.