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Individuals with autism spectrum condition (ASC) are suggested to experience difficulties with categorization and generalization. However, empirical studies have mainly focused on one process at a time, and neglected underlying neural mechanisms. Here, we investigated categorization and generalization at a behavioral and neural level in 38 autistic and 38 neurotypical (NT) adults. By presenting shapes sampled from an artificial multidimensional stimulus space, we investigated (1) behavioral and neural underpinnings of category learning and (2) behavioral generalization of trained categorization to both an extended version of the stimulus space and a novel stimulus space. Our previous findings showed that individuals with autism were slower in category learning. In this study, we demonstrate that this slower learning in autism was not related to differences in applied categorization strategy. In contrast, electroencephalography recordings during training did reveal a reduced amplitude of the N1 component in the right occipital temporal cortex after stimulus presentation in autistic participants, which suggests atypical categorical proficiency. In addition, we observed delayed and higher activation in the frontal regions after receiving (negative) feedback in the autistic group, potentially suggesting more explicit feedback processing or a higher salience of prediction errors in autism. Finally, autistic and NT individuals were able to generalize their learned categorization after training. However, when generalizing to a novel set of shapes, autistic individuals were significantly less accurate. Reduced generalization significantly correlated with increased intolerance to uncertainty scores. This multi-level approach reveals behavioral and neural differences in learning and generalization that could be related to clinical symptoms in autism., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Background: Childhood adversity poses a major transdiagnostic risk for a host of psychiatric disorders. Altered threat-related information processing has been put forward as a potential process underlying the association between childhood adversity and psychiatric disorders, with previous research providing support for decreased discrimination between threat and safety cues, in both children and adults exposed to adversity. This altered threat-safety discrimination has been hypothesized to stem from increased generalization of fear, yet to date, this hypothesis has not been tested in youth., Methods: Here, we investigate whether childhood adversity is associated with fear generalization during adolescence. 119 adolescents between 12 and 16 years of age (mean = 13.95), of whom 63 exposed to childhood adversity, completed a fear generalization paradigm. Fear conditioning was assessed through trial-by-trial US expectancy ratings and post-experimental ratings of fear, valence and arousal. Additionally, we administered a perceptual discrimination task to assess the potential impact of perceptual discrimination abilities upon fear generalization., Results: In line with our hypotheses, results showed that childhood adversity is associated with (1) reduced threat-safety differentiation during fear acquisition and (2) increased fear generalization in both boys and girls, albeit to a different extent, as boys showed more generalization towards safety cues while girls showed more generalization towards dangerous cues. Moreover, this overgeneralization of fear could not be attributed to group differences in perceptual discrimination., Conclusions: Altered fear learning may be an important process through which adversity increases risk for the development of psychopathology. Longitudinal research is essential to elucidate risk and resilience patterns following childhood adversity., (© 2024 Association for Child and Adolescent Mental Health.)

Background: Research suggests that most mental health conditions have their onset in the critically social period of adolescence. Yet, we lack understanding of the potential social processes underlying early psychopathological development. We propose a conceptual model where daily-life social interactions and social skills form an intermediate link between known risk and protective factors (adverse childhood experiences, bullying, social support, maladaptive parenting) and psychopathology in adolescents - that is explored using cross-sectional data., Methods: N = 1913 Flemish adolescent participants (Mean age = 13.8; 63% girls) were assessed as part of the SIGMA study, a large-scale, accelerated longitudinal study of adolescent mental health and development. Self-report questionnaires (on risk/protective factors, social skills, and psychopathology) were completed during class time; daily-life social interactions were measured during a subsequent six-day experience-sampling period., Results: Registered uncorrected multilevel linear regression results revealed significant associations between all risk/protective factors and psychopathology, between all risk/protective factors and social processes, and between all social processes and psychopathology. Social processes (social skills, quantity/quality of daily social interactions) were uniquely predicted by each risk/protective factor and were uniquely associated with both general and specific types of psychopathology. For older participants, some relationships between social processes and psychopathology were stronger., Conclusions: Unique associations between risk/protective factors and psychopathology signify the distinct relevance of these factors for youth mental health, whereas the broad associations with social processes support these processes as broad correlates. Results align with the idea of a social pathway toward early psychopathology, although follow-up longitudinal research is required to verify any mediation effect.

Background: Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross-frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of "harmonic" cross-frequency couplings, whereas "nonharmonic" decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings., Methods: Within this exploratory, randomized, placebo-controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak-frequencies in the alpha (8-14 Hz) and theta (4-8 Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting-state electroencephalography was acquired before and after 4 weeks of oxytocin administration (12 IU twice-daily) in children with autism spectrum disorder (8-12 years, n = 33 oxytocin; n = 34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism (n = 40)., Results: Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha-theta cross-frequency decoupling, indicating a higher incidence of spurious "noisy" coupling in their resting brain (p = .001). Dimensionally, increased neural coupling was associated with more social difficulties (p = .002) and lower activity of the parasympathetic "rest & digest" branch of the autonomic nervous system (p = .018), indexed with high-frequency heart-rate-variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross-frequency configurations was increased in the cohort of autistic children (p < .001), indicating a beneficial effect of oxytocin on reducing spurious cross-frequency-interactions. Furthermore, parallel epigenetics changes of the oxytocin receptor gene indicated that the neural effects were likely mediated by changes in endogenous oxytocinergic signaling (p = .006)., Conclusions: Chronic oxytocin induced important homeostatic changes in the resting-state intrinsic neural frequency architecture, reflective of reduced noisy oscillatory couplings and improved signal-to-noise properties., (© 2024 Association for Child and Adolescent Mental Health.)

Background: Childhood adversity has been associated with alterations in threat-related information processing, including heightened perceptual sensitivity and attention bias towards threatening facial expressions, as well as hostile attributions of neutral faces, although there is a large degree of variability and inconsistency in reported findings., Methods: Here, we aimed to implicitly measure neural facial expression processing in 120 adolescents between 12 and 16 years old with and without exposure to childhood adversity. Participants were excluded if they had any major medical or neurological disorder or intellectual disability, were pregnant, used psychotropic medication or reported acute suicidality or an ongoing abusive situation. We combined fast periodic visual stimulation with electroencephalography in two separate paradigms to assess the neural sensitivity and responsivity towards neutral and expressive, i.e. happy and angry, faces. Linear mixed effects models were used to assess the impact of childhood adversity on facial expression processing., Results: Sixty-six girls, 53 boys and one adolescent who identified as 'other', between 12 and 16 years old (M = 13.93), participated in the current study. Of those, 64 participants were exposed to childhood adversity. In contrast to our hypotheses, adolescents exposed to adversity show lower expression-discrimination responses for angry faces presented in between neutral faces and higher expression-discrimination responses for happy faces presented in between neutral faces than unexposed controls. Moreover, adolescents exposed to adversity, but not unexposed controls, showed lower neural responsivity to both angry and neutral faces that were simultaneously presented., Conclusions: We therefore conclude that childhood adversity is associated with a hostile attribution of neutral faces, thereby reducing the dissimilarity between neutral and angry faces. This reduced threat-safety discrimination may increase risk for psychopathology in individuals exposed to childhood adversity., (© 2024. The Author(s).)

Aim: Childhood adversity may result in a negative expectation of future interactions with others, also referred to as 'threat anticipation'. It may also negatively impact on identity development, which subsequently may influence how individuals deal with their environment. Here, we examine the hypotheses that (1) identity synthesis is associated with reduced anticipation of threat, whereas the opposite would be true for identity confusion, and (2) that identity confusion exacerbates the association between childhood adversity and threat anticipation., Methods: One thousand nine hundred and thirteen adolescents from the general population (mean age = 13.8 years, SD = 1.86, range = 11-20) completed self-report questionnaires assessing exposure to childhood adversity, identity development and threat anticipation., Results and Discussion: Identity development was significantly associated with threat anticipation in the expected direction: identity synthesis was associated with reduced anticipation of threat (β = -.0013, p < .001), whereas identity confusion was association with increased threat anticipation (β = .0017, p < .001). Furthermore, childhood adversity was positively associated with threat anticipation (β = .0018, p < .001). However, no evidence for an interaction effect of identity on the association between childhood adversity and threat anticipation was found, suggesting childhood adversity and identity development have an independent rather than synergistic effect on threat anticipation., Conclusion: The current study illustrates the importance of exposure to childhood adversity and identity development for threat anticipation in adolescence. Further research is needed to clarify how both factors influence each other within a developmental framework., (© 2024 John Wiley & Sons Australia, Ltd.)

Oxytocin (OXT) modulates social behaviors. However, the administration of exogenous OXT in humans produces inconsistent behavioral changes, affecting future consideration of OXT as a treatment for autism and other disorders with social symptoms. Inter-individual variability in social functioning traits might play a key role in how OXT changes brain activity and, therefore, behavior. Here, we investigated if inter-individual variability might dictate how single-dose intranasal OXT administration (IN-OXT) changes spontaneous neural activity during the eyes-open resting state. We used a double-blinded, randomized, placebo-controlled, cross-over design on 30 typically developing young adult men to investigate the dynamics of EEG microstates corresponding to activity in defined neural networks. We confirmed previous reports that, at the group level, IN-OXT increases the representation of the attention and salience microstates. Furthermore, we identified a decreased representation of microstates associated with the default mode network. Using multivariate partial least square statistical analysis, we found that social functioning traits associated with IN-OXT-induced changes in microstate dynamics in specific spectral bands. Correlation analysis further revealed that the higher the social functioning, the more IN-OXT increased the appearance of the visual network-associated microstate, and suppressed the appearance of a default mode network-related microstate. The lower the social functioning, the more IN-OXT increases the appearance of the salience microstate. The effects we report on the salience microstate support the hypothesis that OXT regulates behavior by enhancing social salience. Moreover, our findings indicate that social functioning traits modulate responses to IN-OXT and could partially explain the inconsistent reports on IN-OXT effects., (© 2024 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Background: Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization., Methods: The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures., Results: Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results., Limitations: Data-collection occurred during the COVID-19 pandemic., Conclusions: Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC., (© 2024. The Author(s).)

Similar to the gut microbiome, oral microbiome compositions have been suggested to play an important role in the etiology of autism. However, empirical research on how variations in the oral microbiome relate to clinical-behavioral difficulties associated with autism remains sparse. Furthermore, it is largely unknown how potentially confounding lifestyle variables, such as oral health and nutrition, may impact these associations. To fill this gap, the current study examined diagnosis-related differences in oral microbiome composition between 80 school-aged autistic children (8-12 years; 64 boys, 16 girls) versus 40 age-matched typically developing peers (32 boys, 8 girls). In addition, associations with individual differences in social functioning (SRS-2), repetitive behavior (RBS-R) and anxiety (SCARED) were explored, as well as the impact of several lifestyle variables regarding nutrition and oral health. Results provide important indications that the bacterial genera Solobacterium , Stomatobaculum , Ruminococcaceae UCG.014, Tannerella and Campylobacter were significantly more abundant in autistic compared to non-autistic children. Furthermore, the former four bacteria that were significantly more abundant in the autistic children showed significant associations with parent-reported social difficulties, repetitive and restrictive behavior and with parent-reported anxiety-like behavior. Importantly, associations among oral microbiome and quantitative diagnostic characteristics were not significantly driven by differences in lifestyle variables. This exploratory study reveals significant differences in oral microbiome composition between autistic and non-autistic children, even while controlling for potential confounding lifestyle variables. Furthermore, the significant associations with clinical characteristics suggest that individual differences in microbiome composition might be involved in shaping the clinical phenotype of autism. However, these associations warrant further exploration of the oral microbiome's potential beyond the oral cavity and specifically with respect to neuropsychiatric conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Categorization is an essential cognitive and perceptual process, which happens spontaneously. However, earlier research often neglected the spontaneous nature of this process by mainly adopting explicit tasks in behavioral or neuroimaging paradigms. Here, we use frequency-tagging (FT) during electroencephalography (EEG) in 22 healthy human participants (both male and female) as a direct approach to pinpoint spontaneous visual categorical processing. Starting from schematic natural visual stimuli, we created morph sequences comprising 11 equal steps. Mirroring a behavioral categorical perception discrimination paradigm, we administered a FT-EEG oddball paradigm, assessing neural sensitivity for equally sized differences within and between stimulus categories. Likewise, mirroring a behavioral category classification paradigm, we administered a sweep FT-EEG oddball paradigm, sweeping from one end of the morph sequence to the other, thereby allowing us to objectively pinpoint the neural category boundary. We found that FT-EEG can implicitly measure categorical processing and discrimination. More specifically, we could derive an objective neural index of the required level to differentiate between the two categories, and this neural index showed the typical marker of categorical perception (i.e., stronger discrimination across as compared with within categories). The neural findings of the implicit paradigms were also validated using an explicit behavioral task. These results provide evidence that FT-EEG can be used as an objective tool to measure discrimination and categorization and that the human brain inherently and spontaneously (without any conscious or decisional processes) uses higher-level meaningful categorization information to interpret ambiguous (morph) shapes., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Objective: Our objective was to investigate the executive function and its relationship with gestational age, sex, maternal education, and neurodevelopmental outcome at 2 years corrected age in children born preterm., Method: Executive function was assessed by means of the Multisearch Multilocation Task (MSML), Reversed Categorization Task (RevCat), and Snack Delay Task (SDT). Infant and maternal characteristics were gathered from the child's record. The developmental outcome was measured by the Bayley Scales and a multidisciplinary risk evaluation for autism., Results: The executive function battery was completed by 97 children. The majority were able to successfully complete the MSML and SDT but failed RevCat. The lower the gestational age and the maternal education, the lower the executive function scores. Better cognition and motor function, as well as low autism risk, were associated with better executive function scores. Executive function was not related to sex., Interpretation: This cohort study provides evidence that it is feasible to assess executive function in 2-year-olds born preterm. Executive function is related to gestational age and maternal education and is positively correlated with behavioral outcome. Therefore, executive functions can be a valuable target for early intervention, resulting in improvements in neurodevelopmental outcomes in children born preterm., Competing Interests: None declared., (Thieme. All rights reserved.)

Clinical efficacy of intranasal administration of oxytocin is increasingly explored in autism spectrum disorder, but to date, the biological effects of chronic administration regimes on endogenous oxytocinergic function are largely unknown. Here exploratory biological assessments from a completed randomized, placebo-controlled trial showed that children with autism (n = 79, 16 females) receiving intranasal oxytocin for four weeks (12 IU, twice daily) displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at a four-week follow up session. Regarding salivary oxytocin receptor gene (OXTR) epigenetics (DNA-methylation), oxytocin-induced reductions in OXTR DNA-methylation were observed, suggesting a facilitation of oxytocin receptor expression in the oxytocin compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reduced OXTR DNA-methylation and improved feelings of secure attachment. These findings indicate that four weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism., (© 2024. The Author(s).)

Children born very preterm (VPT, < 32 weeks of gestation) have an increased risk of developing socio-emotional difficulties. Possible neural substrates for these socio-emotional difficulties are alterations in the structural connectivity of the social brain due to premature birth. The objective of the current study was to study microstructural white matter integrity in VPT versus full-term (FT) born school-aged children along twelve white matter tracts involved in socio-emotional processing. Diffusion MRI scans were obtained from a sample of 35 VPT and 38 FT 8-to-12-year-old children. Tractography was performed using TractSeg, a state-of-the-art neural network-based approach, which offers investigation of detailed tract profiles of fractional anisotropy (FA). Group differences in FA along the tracts were investigated using both a traditional and complementary functional data analysis approach. Exploratory correlations were performed between the Social Responsiveness Scale (SRS-2), a parent-report questionnaire assessing difficulties in social functioning, and FA along the tract. Both analyses showed significant reductions in FA for the VPT group along the middle portion of the right SLF I and an anterior portion of the left SLF II. These group differences possibly indicate altered white matter maturation due to premature birth and may contribute to altered functional connectivity in the Theory of Mind network which has been documented in earlier work with VPT samples. Apart from reduced social motivation in the VPT group, there were no significant group differences in reported social functioning, as assessed by SRS-2. We found that in the VPT group higher FA values in segments of the left SLF I and right SLF II were associated with better social functioning. Surprisingly, the opposite was found for segments in the right IFO, where higher FA values were associated with worse reported social functioning. Since no significant correlations were found for the FT group, this relationship may be specific for VPT children. The current study overcomes methodological limitations of previous studies by more accurately segmenting white matter tracts using constrained spherical deconvolution based tractography, by applying complementary tractometry analysis approaches to estimate changes in FA more accurately, and by investigating the FA profile along the three components of the SLF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Hypothesis: Childhood adversity is associated with a myriad of psychiatric symptoms, including psychotic experiences (PEs), and with multiple psychological processes that may all mediate these associations., Study Design: Using a network approach, the present study examined the complex interactions between childhood adversity, PEs, other psychiatric symptoms, and multiple psychological mediators (ie, activity-related and social stress, negative affect, loneliness, threat anticipation, maladaptive cognitive emotion regulation, attachment insecurity) in a general population, adolescent sample (n = 865, age 12-20, 67% female)., Study Results: Centrality analyses revealed a pivotal role of depression, anxiety, negative affect, and loneliness within the network and a bridging role of threat anticipation between childhood adversity and maladaptive cognitive emotion regulation. By constructing shortest path networks, we found multiple existing paths between different categories of childhood adversity and PEs, with symptoms of general psychopathology (ie, anxiety, hostility, and somatization) as the main connective component. Sensitivity analyses confirmed the robustness and stability of the networks. Longitudinal analysis in a subsample with Wave 2 data (n = 161) further found that variables with higher centrality (ie, depression, negative affect, and loneliness) better predicted follow-up PEs., Conclusions: Pathways linking childhood adversity to PEs are complex, with multifaceted psychological and symptom-symptom interactions. They underscore the transdiagnostic, heterotypic nature of mental ill-health in young people experiencing PEs, in agreement with current clinical recommendations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Individuals with autism spectrum disorder (ASD) exhibit atypical speech-in-noise (SiN) perception, but the scope of these impairments has not been clearly defined. We conducted a systematic review of the behavioural research on SiN perception in ASD, using a comprehensive search strategy across databases (Embase, Pubmed, Web of Science, APA PsycArticles, LLBA, clinicaltrials.gov and PsyArXiv). We withheld 20 studies that generally revealed intact speech perception in stationary noise, while impairments in speech discrimination were found in temporally modulated noise, concurrent speech, and audiovisual speech perception. An association with auditory temporal processing deficits, exacerbated by suboptimal language skills, is shown. Speech-in-speech perception might be further impaired due to deficient top-down processing of speech. Further research is needed to address remaining challenges and gaps in our understanding of these impairments, including the developmental aspects of SiN processing in ASD, and the impact of gender and social attentional orienting on this ability. Our findings have important implications for improving communication in ASD, both in daily interactions and in clinical and educational settings., Competing Interests: Declaration of Competing Interest We have no known conflict of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and interaction. Crucial for efficient social interaction is the ability to quickly and accurately extract information from a person's face. Frequency-tagging electroencephalography (EEG) is a novel tool to quantify face-processing sensitivity in a robust and implicit manner. In terms of intervention approaches, intranasal administration of oxytocin (OT) is increasingly considered as a potential pharmacological approach for improving socio-communicative difficulties in ASD, through enhancing social salience and/or reducing (social) stress and anxiety., Methods: In this randomized, double-blind, placebo-controlled, mechanistic pharmaco-neuroimaging clinical trial, we implemented frequency-tagging EEG to conduct an exploratory investigation into the impact of repeated OT administration (4 weeks, 12 IU, twice daily) on neural sensitivity towards happy and fearful facial expressions in children with ASD (8-12 years old; OT: n = 29; placebo: n = 32). Neural effects were assessed at baseline, post-nasal spray (24 hr after the last nasal spray) and at a follow-up session, 4 weeks after the OT administration period. At baseline, neural assessments of children with ASD were compared with those of an age- and gender-matched cohort of neurotypical (NT) children (n = 39)., Results: Children with ASD demonstrated reduced neural sensitivity towards expressive faces, as compared to NT children. Upon nasal spray administration, children with ASD displayed a significant increase in neural sensitivity at the post- and follow-up sessions, but only in the placebo group, likely reflecting an implicit learning effect. Strikingly, in the OT group, neural sensitivity remained unaffected from the baseline to the post-session, likely reflecting a dampening of an otherwise typically occurring implicit learning effect., Conclusions: First, we validated the robustness of the frequency-tagging EEG approach to assess reduced neural sensitivity towards expressive faces in children with ASD. Furthermore, in contrast to social salience effects observed after single-dose administrations, repeated OT administration dampened typically occurring learning effects in neural sensitivity. In line with OT's social anxiolytic account, these observations possibly reflect a predominant (social) stress regulatory effect towards emotionally evocative faces after repeated OT administration., (© 2023 Association for Child and Adolescent Mental Health.)

The fluent processing of faces can be challenging for autistic individuals. Here, we assessed the neural sensitivity to rapid changes in subtle facial cues in 23 autistic men and 23 age and IQ matched non-autistic (NA) controls using frequency-tagging electroencephalography (EEG). In oddball paradigms examining the automatic and implicit discrimination of facial identity and facial expression, base rate images were presented at 6 Hz, periodically interleaved every fifth image with an oddball image (i.e. 1.2 Hz oddball frequency). These distinctive frequency tags for base rate and oddball stimuli allowed direct and objective quantification of the neural discrimination responses. We found no large differences in the neural sensitivity of participants in both groups, not for facial identity discrimination, nor for facial expression discrimination. Both groups also showed a clear face-inversion effect, with reduced brain responses for inverted versus upright faces. Furthermore, sad faces generally elicited significantly lower neural amplitudes than angry, fearful and happy faces. The only minor group difference is the larger involvement of high-level right-hemisphere visual areas in NA men for facial expression processing. These findings are discussed from a developmental perspective, as they strikingly contrast with robust face processing deficits observed in autistic children using identical EEG paradigms., (© 2023 International Society for Autism Research and Wiley Periodicals LLC.)

Speech-in-noise perception seems aberrant in individuals with autism spectrum disorder (ASD). Potential aggravating factors are the level of linguistic skills and impairments in auditory temporal processing. Here, we investigated autistic adolescents with and without language delay as compared to non-autistic peers, and we assessed speech perception in steady-state noise, temporally modulated noise, and concurrent speech. We found that autistic adolescents with intact language capabilities and not those with language delay performed worse than NT peers on words-in-stationary-noise perception. For the perception of sentences in stationary noise, we did not observe significant group differences, although autistic adolescents with language delay tend to perform worse in comparison to their TD peers. We also found evidence for a robust deficit in speech-in-concurrent-speech processing in ASD independent of language ability, as well as an association between early language delay in ASD and inadequate temporal speech processing. We propose that reduced voice stream segregation and inadequate social attentional orienting in ASD result in disproportional informational masking of the speech signal. These findings indicate a speech-in-speech processing deficit in autistic adolescents with broad implications for the quality of social communication., (© 2023 International Society for Autism Research and Wiley Periodicals LLC.)

Alterations in the brain's oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD., (© 2023. The Author(s).)

Introduction: Childhood adversity is a major risk factor for psychiatric disorders and has especially been associated with an admixture of depressive, anxiety, and psychosis symptoms. Identity formation, a main developmental task during adolescence, may be impacted by these adverse experiences and act as an important process in the association between childhood adversity and psychopathology., Methods: We investigated the association between childhood adversity, identity formation, and depressive, anxiety, and psychosis symptoms cross-sectionally in 1913 Flemish adolescents between 11 and 20 years old (mean = 13.76, SD = 1.86). Adolescents completed questionnaires during the first wave of the SIGMA study between January 2018 and May 2019., Results: Childhood interpersonal adversity was associated with increased identity confusion and decreased identity synthesis. Additionally, identity confusion was associated with increased self-reported levels of psychopathology and potentially mediated the association between childhood adversity and psychopathology., Conclusion: This study highlights the importance of promoting healthy identity formation in adolescents with and without exposure to adverse childhood experiences., (© 2023 The Foundation for Professionals in Services for Adolescents.)

We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, [Formula: see text] = 0.13), latency to constriction (F(3,326.41) = 3.84, p = 0.010, [Formula: see text] = 0.03) and relative constriction amplitude(F(3,282.53) = 3.70, p = 0.012, [Formula: see text] = 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001, [Formula: see text] = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, [Formula: see text] = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established., Methods: A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin., Results: In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness., Limitations: Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities., Conclusions: Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE )., (© 2023. The Author(s).)

The present study investigated transparency estimation, that is, the ability to estimate how observable one's emotions are, in patients diagnosed with borderline personality disorder (BPD) ( n = 35) and healthy controls (HCs; n = 35). Participants watched emotionally evocative video clips and estimated the transparency of their own emotional experience while watching the clip. Facial expression coding software (FaceReader) quantified their objective transparency. BPD patients felt significantly less transparent than HCs, but there were no differences in objective transparency. BPD patients tended to underestimate the transparency of their emotions compared to HCs, who in turn overestimated their transparency. This suggests that BPD patients expect that others will not know how they feel, irrespective of how observable their emotions actually are. We link these findings to low emotional awareness and a history of emotional invalidation in BPD, and we discuss their impact on BPD patients' social functioning.

Successfully engaging in social communication requires efficient processing of subtle socio-communicative cues. Voices convey a wealth of social information, such as gender, identity, and the emotional state of the speaker. We tested whether our brain can systematically and automatically differentiate and track a periodic stream of emotional utterances among a series of neutral vocal utterances. We recorded frequency-tagged EEG responses of 20 neurotypical male adults while presenting streams of neutral utterances at a 4 Hz base rate, interleaved with emotional utterances every third stimulus, hence at a 1.333 Hz oddball frequency. Four emotions (happy, sad, angry, and fear) were presented as different conditions in different streams. To control the impact of low-level acoustic cues, we maximized variability among the stimuli and included a control condition with scrambled utterances. This scrambling preserves low-level acoustic characteristics but ensures that the emotional character is no longer recognizable. Results revealed significant oddball EEG responses for all conditions, indicating that every emotion category can be discriminated from the neutral stimuli, and every emotional oddball response was significantly higher than the response for the scrambled utterances. These findings demonstrate that emotion discrimination is fast, automatic, and is not merely driven by low-level perceptual features. Eventually, here, we present a new database for vocal emotion research with short emotional utterances (EVID) together with an innovative frequency-tagging EEG paradigm for implicit vocal emotion discrimination.

Introduction: Intranasal administration of oxytocin presents a promising new approach to reduce disability associated with an autism spectrum disorder diagnosis. Previous investigations have emphasized the amygdala as the neural foundation for oxytocin's acute effects. However, to fully understand oxytocin's therapeutic potential, it is crucial to gain insight into the neuroplastic changes in amygdala circuitry induced from chronic oxytocin administrations, particularly in pediatric populations., Objective: We aimed to examine the impact of a 4-week course of intranasal oxytocin on amygdala functional connectivity in children with autism, compared to placebo. Additionally, we investigated whether oxytocin improves cardiac autonomic arousal, as indexed by high-frequency heart rate variability., Methods: Fifty-seven children with autism aged 8-12 years (45 boys, 12 girls) participated in a double-blind, randomized pharmaco-neuroimaging trial involving twice-daily administrations of intranasal oxytocin or placebo. Resting-state fMRI scans and simultaneous, in-scanner heart rate recordings were obtained before, immediately after, and 4 weeks after the nasal spray administration period., Results: Significant reductions in intrinsic amygdala-orbitofrontal connectivity were observed, particularly at the 4-week follow-up session. These reductions were correlated with improved social symptoms and lower cardiac autonomic arousal. Further, oxytocin's neural and cardiac autonomic effects were modulated by epigenetic modifications of the oxytocin receptor gene. The effects were more pronounced in children with reduced epigenetic methylation, signifying heightened expression of the oxytocin receptor., Conclusion: These findings underscore that a 4-week oxytocin administration course decreases amygdala connectivity and improves cardiac autonomic balance. Epigenetic modulators may explain inter-individual variation in responses to oxytocin., (© 2023 S. Karger AG, Basel.)

The social salience hypothesis proposes that the neuropeptide oxytocin (OT) can impact human social behavior by modulating the salience of social cues. Here, frequency-tagging EEG was used to quantify the neural responses to social versus non-social stimuli while administering a single dose of OT (24 IU) versus placebo treatment. Specifically, two streams of faces and houses were superimposed on one another, with each stream of stimuli tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). These distinctive frequency tags allowed unambiguously disentangling and objectively quantifying the respective neural responses elicited by the different streams of stimuli. This study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Based on four trials of 60 s, we detected robust frequency-tagged neural responses in each individual, with entrainment to faces being more pronounced in lateral occipito-temporal regions and entrainment to houses being focused in medial occipital regions. However, contrary to our expectation, a single dose of OT did not modulate these stimulus-driven neural responses, not in terms of enhanced social processing nor in terms of generally enhanced information salience. Bayesian analyses formally confirmed these null findings. Possibly, the baseline ceiling level performance of these neurotypical adult participants as well as the personal irrelevance of the applied stimulation streams might have hindered the observation of any OT effect.

The neuropeptide oxytocin (OXT) is suggested to exert an important role in human social behaviors by modulating the salience of social cues. To date, however, there is mixed evidence whether a single dose of OXT can improve the behavioral and neural sensitivity for emotional face processing. To overcome difficulties encountered with classic event-related potential studies assessing stimulus-saliency, we applied frequency-tagging EEG to implicitly assess the effect of a single dose of OXT (24 IU) on the neural sensitivity for positive and negative facial emotions. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, and happy, in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinctive frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the neural expression-categorization responses. The study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Contrary to our expectations, we did not find an effect of OXT on facial emotion processing, neither at the neural, nor at the behavioral level. A single dose of OXT did not evoke social enhancement in general, nor did it affect social approach-avoidance tendencies. Possibly ceiling performances in facial emotion processing might have hampered further improvement., (© 2022 Society for Psychophysiological Research.)

Transparency estimation, that is, estimating the extent to which one's mental states are observable to others, requires the simultaneous representation of the self and of others' perspective on the self. Individuals with borderline personality disorder (BPD) have difficulty integrating multiple perspectives when mentalizing, which may be reflected in impaired transparency estimation. A total of 62 participants high and low in BPD features watched emotionally evocative video clips and estimated the transparency of their emotional experience while facial expression coding software (FaceReader) quantified their objective transparency. Individuals high in BPD features showed a larger discrepancy between estimated and objective transparency than individuals low in BPD features, showing that they both over- and underestimated their transparency. Indeed, estimated transparency positively predicted objective transparency in individuals low in BPD features, but not in individuals high in BPD features. Moreover, the ability to estimate intraindividual variability in one's own objective transparency was moderated by self-reported arousal in the participants high in BPD features. Impairments in transparency estimation were correlated with self-report measures of borderline features, attachment, and mentalizing. In conclusion, we found that borderline features relate to a reduced capacity to estimate the extent to which one's own emotional states are observable to others. Although replication in clinical samples of BPD patients is needed, the present study provides evidence for problems in mentalizing the (embodied) self from another person's perspective in BPD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis evaluated potential group differences in endogenous OT levels between individuals with ASD and neurotypical (NT) controls. We included 18 studies comprising a total of 1422 participants. We found that endogenous OT levels are lower in children with ASD as compared to NT controls (n = 1123; g = -0.60; p = 0.006), but this effect seems to disappear in adolescent (n = 152; g = -0.20; p = 0.53) and adult populations (n = 147; g = 0.27; p = 0.45). Secondly, while no significant subgroup differences were found in regard to sex, the group difference in OT levels of individuals with versus without ASD seems to be only present in the studies with male participants (n = 814; g = -0.44; p = 0.08) and not female participants (n = 192; g = 0.11; p = 0.47). More research that employs more homogeneous methods is necessary to investigate potential developmental changes in endogenous OT levels, both in typical and atypical development, and to explore the possible use of OT level measurement as a diagnostic marker of ASD.

Difficulties in automatic emotion processing in individuals with autism spectrum disorder (ASD) might remain concealed in behavioral studies due to compensatory strategies. To gain more insight in the mechanisms underlying facial emotion recognition, we recorded eye tracking and facial mimicry data of 20 school-aged boys with ASD and 20 matched typically developing controls while performing an explicit emotion recognition task. Proportional looking times to specific face regions (eyes, nose, and mouth) and face exploration dynamics were analyzed. In addition, facial mimicry was assessed. Boys with ASD and controls were equally capable to recognize expressions and did not differ in proportional looking times, and number and duration of fixations. Yet, specific facial expressions elicited particular gaze patterns, especially within the control group. Both groups showed similar face scanning dynamics, although boys with ASD demonstrated smaller saccadic amplitudes. Regarding the facial mimicry, we found no emotion specific facial responses and no group differences in the responses to the displayed facial expressions. Our results indicate that boys with and without ASD employ similar eye gaze strategies to recognize facial expressions. Smaller saccadic amplitudes in boys with ASD might indicate a less exploratory face processing strategy. Yet, this slightly more persistent visual scanning behavior in boys with ASD does not imply less efficient emotion information processing, given the similar behavioral performance. Results on the facial mimicry data indicate similar facial responses to emotional faces in boys with and without ASD. LAY SUMMARY: We investigated (i) whether boys with and without autism apply different face exploration strategies when recognizing facial expressions and (ii) whether they mimic the displayed facial expression to a similar extent. We found that boys with and without ASD recognize facial expressions equally well, and that both groups show similar facial reactions to the displayed facial emotions. Yet, boys with ASD visually explored the faces slightly less than the boys without ASD., (© 2021 International Society for Autism Research, Wiley Periodicals LLC.)

The ability to recognize faces and facial expressions is a common human talent. It has, however, been suggested to be impaired in individuals with autism spectrum disorder (ASD). The goal of this study was to compare the processing of facial identity and emotion between individuals with ASD and neurotypicals (NTs). Behavioural and functional magnetic resonance imaging (fMRI) data from 46 young adults (aged 17-23 years, N ASD  = 22, N NT  = 24) was analysed. During fMRI data acquisition, participants discriminated between short clips of a face transitioning from a neutral to an emotional expression. Stimuli included four identities and six emotions. We performed behavioural, univariate, multi-voxel, adaptation and functional connectivity analyses to investigate potential group differences. The ASD-group did not differ from the NT-group on behavioural identity and expression processing tasks. At the neural level, we found no differences in average neural activation, neural activation patterns and neural adaptation to faces in face-related brain regions. In terms of functional connectivity, we found that amygdala seems to be more strongly connected to inferior occipital cortex and V1 in individuals with ASD. Overall, the findings indicate that neural representations of facial identity and expression have a similar quality in individuals with and without ASD, but some regions containing these representations are connected differently in the extended face processing network., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pupillometry, measuring pupil size and reactivity, has been proposed as a measure of autonomic nervous system functioning, the latter which might be altered in individuals with autism spectrum disorder (ASD). This study aims to evaluate if pupillary responses differ in individuals with and without ASD. After performing a systematic literature search, we conducted a meta-analysis and constructed a qualitative synthesis. The meta-analysis shows a longer latency of the pupil response in the ASD-group as a substantial group difference, with a Hedges' g of 1.03 (95% CI 0.49-1.56, p = 0.008). Evidence on baseline pupil size and amplitude change is conflicting. We used the framework method to perform a qualitative evaluation of these differences. Explanations for the group differences vary between studies and are inconclusive, but many authors point to involvement of the autonomous nervous system and more specifically the locus coeruleus-norepinephrine system. Pupillometry reveals differences between people with and without ASD, but the exact meaning of these differences remains unknown. Future studies should align research designs and investigate a possible effect of maturation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Scanning faces is important for social interactions. Difficulty with the social use of eye contact constitutes one of the clinical symptoms of autism spectrum disorder (ASD). It has been suggested that individuals with ASD look less at the eyes and more at the mouth than typically developing (TD) individuals, possibly due to gaze aversion or gaze indifference. However, eye-tracking evidence for this hypothesis is mixed. While gaze patterns convey information about overt orienting processes, it is unclear how this is manifested at the neural level and how relative covert attention to the eyes and mouth of faces might be affected in ASD., Methods: We used frequency-tagging EEG in combination with eye tracking, while participants watched fast flickering faces for 1-min stimulation sequences. The upper and lower halves of the faces were presented at 6 Hz and 7.5 Hz or vice versa in different stimulation sequences, allowing to objectively disentangle the neural saliency of the eyes versus mouth region of a perceived face. We tested 21 boys with ASD (8-12 years old) and 21 TD control boys, matched for age and IQ., Results: Both groups looked longer at the eyes than the mouth, without any group difference in relative fixation duration to these features. TD boys looked significantly more to the nose, while the ASD boys looked more outside the face. EEG neural saliency data partly followed this pattern: neural responses to the upper or lower face half were not different between groups, but in the TD group, neural responses to the lower face halves were larger than responses to the upper part. Face exploration dynamics showed that TD individuals mostly maintained fixations within the same facial region, whereas individuals with ASD switched more often between the face parts., Limitations: Replication in large and independent samples may be needed to validate exploratory results., Conclusions: Combined eye-tracking and frequency-tagged neural responses show no support for the excess mouth/diminished eye gaze hypothesis in ASD. The more exploratory face scanning style observed in ASD might be related to their increased feature-based face processing style.

Autism spectrum disorder (ASD) and primary psychosis are classified as distinct neurodevelopmental disorders, yet they display overlapping epidemiological, environmental, and genetic components as well as endophenotypic similarities. For instance, both disorders are characterized by impairments in facial expression processing, a crucial skill for effective social communication, and both disorders display an increased prevalence of adverse childhood events (ACE). This narrative review provides a brief summary of findings from neuroimaging studies investigating facial expression processing in ASD and primary psychosis with a focus on the commonalities and differences between these disorders. Individuals with ASD and primary psychosis activate the same brain regions as healthy controls during facial expression processing, albeit to a different extent. Overall, both groups display altered activation in the fusiform gyrus and amygdala as well as altered connectivity among the broader face processing network, probably indicating reduced facial expression processing abilities. Furthermore, delayed or reduced N170 responses have been reported in ASD and primary psychosis, but the significance of these findings is questioned, and alternative frequency-tagging electroencephalography (EEG) measures are currently explored to capture facial expression processing impairments more selectively. Face perception is an innate process, but it is also guided by visual learning and social experiences. Extreme environmental factors, such as adverse childhood events, can disrupt normative development and alter facial expression processing. ACE are hypothesized to induce altered neural facial expression processing, in particular a hyperactive amygdala response toward negative expressions. Future studies should account for the comorbidity among ASD, primary psychosis, and ACE when assessing facial expression processing in these clinical groups, as it may explain some of the inconsistencies and confound reported in the field., (Copyright © 2020 Samaey, Van der Donck, van Winkel and Boets.)

Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.

Faces convey an assortment of emotional information via low and high spatial frequencies (LSFs and HSFs). However, there is no consensus on the role of particular spatial frequency (SF) information during facial fear processing. Comparison across studies is hampered by the high variability in cut-off values for demarcating the SF spectrum and by differences in task demands. We investigated which SF information is minimally required to rapidly detect briefly presented fearful faces in an implicit and automatic manner, by sweeping through an entire SF range without constraints of predefined cut-offs for LSFs and HSFs. We combined fast periodic visual stimulation with electroencephalography. We presented neutral faces at 6 ​Hz, periodically interleaved every 5th image with a fearful face, allowing us to quantify an objective neural index of fear discrimination at exactly 1.2 ​Hz. We started from a stimulus containing either only very low or very high SFs and gradually increased the SF content by adding higher or lower SF information, respectively, to reach the full SF spectrum over the course of 70 ​s. We found that faces require at least SF information higher than 5.93 cycles per image (cpi) to implicitly differentiate fearful from neutral faces. However, exclusive HSF faces, even in a restricted SF range between 94.82 and 189.63 cpi already carry the critical information to extract the emotional expression of the faces., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Individuals with autism spectrum disorders (ASD) experience impairments in social communication and interaction, and often show difficulties with receiving and offering touch. Despite the high prevalence of abnormal reactions to touch in ASD, and the importance of touch communication in human relationships, the neural mechanisms underlying atypical touch processing in ASD remain largely unknown. To answer this question, we provided both pleasant and unpleasant touch stimulation to male adults with and without ASD during functional neuroimaging. By employing generalized psychophysiological interaction analysis combined with an independent component analysis approach, we characterize stimulus-dependent changes in functional connectivity patterns for processing two tactile stimuli that evoke different emotions (i.e., pleasant vs. unpleasant touch). Results reveal that neurotypical male adults showed extensive stimulus-sensitive modulations of the functional network architecture in response to the different types of touch, both at the level of brain regions and large-scale networks. Conversely, far fewer stimulus-sensitive modulations were observed in the ASD group. These aberrant functional connectivity profiles in the ASD group were marked by hypo-connectivity of the parietal operculum and major pain networks and hyper-connectivity between the semantic and limbic networks. Lastly, individuals presenting more social deficits and a more negative attitude towards social touch showed greater hyper-connectivity between the limbic and semantic networks. These findings suggest that reduced stimulus-related modulation of this functional network architecture is associated with abnormal processing of touch in ASD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Difficulties with facial expression processing may be associated with the characteristic social impairments in individuals with autism spectrum disorder (ASD). Emotional face processing in ASD has been investigated in an abundance of behavioral and EEG studies, yielding, however, mixed and inconsistent results., Methods: We combined fast periodic visual stimulation (FPVS) with EEG to assess the neural sensitivity to implicitly detect briefly presented facial expressions among a stream of neutral faces, in 23 boys with ASD and 23 matched typically developing (TD) boys. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, happy, sad in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinguishable frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the expression-categorization responses, needing only four sequences of 60 s of recording per condition., Results: Both groups show equal neural synchronization to the general face stimulation and similar neural responses to happy and sad faces. However, the ASD group displays significantly reduced responses to angry and fearful faces, compared to TD boys. At the individual subject level, these neural responses allow to predict membership of the ASD group with an accuracy of 87%. Whereas TD participants show a significantly lower sensitivity to sad faces than to the other expressions, ASD participants show an equally low sensitivity to all the expressions., Conclusions: Our results indicate an emotion-specific processing deficit, instead of a general emotion-processing problem: Boys with ASD are less sensitive than TD boys to rapidly and implicitly detect angry and fearful faces. The implicit, fast, and straightforward nature of FPVS-EEG opens new perspectives for clinical diagnosis., (© 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)