Assessing Spontaneous Categorical Processing of Visual Shapes via Frequency-Tagging EEG.

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.

Between faces: childhood adversity is associated with reduced threat-safety discrimination during facial expression processing in adolescence.

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.

Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT.

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.

Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: A double-blind, cross-over randomized clinical trial.

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.

Executive Function Assessment in 2-Year-Olds Born Preterm.

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.

Investigating the development of the autonomic nervous system in infancy through pupillometry.

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.

Can repeated intranasal oxytocin administration affect reduced neural sensitivity towards expressive faces in autism? A randomized controlled trial.

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.

At the Head and Heart of Oxytocin's Stress-Regulatory Neural and Cardiac Effects: A Chronic Administration RCT in Children with Autism.

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.

The role of identity in the development of depressive, anxiety, and psychosis symptoms in adolescents exposed to childhood adversity.

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.

Pinpointing the optimal spatial frequency range for automatic neural facial fear processing.

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 â€‹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 â€‹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 â€‹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.

Reduced task-dependent modulation of functional network architecture for positive versus negative affective touch processing in autism spectrum disorders.

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.

Rapid neural categorization of angry and fearful faces is specifically impaired in boys with autism spectrum disorder.

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.

Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder?

BACKGROUND: Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. METHODS: By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. RESULTS: For EF, ASD relatives - like ASD probands - showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. CONCLUSIONS: Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions.

Visuoperceptual processing in children with neurofibromatosis type 1: True deficit or artefact?

Impairments in visuoperceptual processing have long been considered a hallmark deficit of individuals with Neurofibromatosis type 1 (NF1). However, it is unclear which specific visuoperceptual subprocesses are impaired and whether impairments on these tasks really result from visuoperceptual impairments or rather from confounding factors like Executive Functioning (EF) impairments, lower intelligence (IQ) and/or co-occurring symptoms of Autism Spectrum Disorder (ASD). To answer these questions, we administered four visuoperceptual tasks and two control tasks in 39 children with NF1, 52 typically developing children and 52 children with ASD (8-18 years), all matched for age and gender. Furthermore, EF, IQ, and symptoms of ASD were assessed. Children with NF1 displayed intact visual form discrimination and intact information integration along the dorsal visual pathway. Moreover, their reduced performance on a task requiring integration of information along the ventral visual stream and their more detail-oriented processing style appeared to result from confounding EF impairments and not from visuoperceptual impairments per se. The co-occurring ASD symptoms and lower IQ of the children with NF1 did not impact substantially upon their visuoperceptual performance. These findings point to the large impact of EF impairments on the performance of visuoperceptual task and suggest that individuals with NF1 show intact visual form discrimination, intact visual integration, and typical visual processing style when potential confounding factors are controlled for. This may have large repercussions for the interpretation of other findings on visuoperceptual processing in individuals with NF1. © 2017 Wiley Periodicals, Inc.

Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity.

Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants' age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship.

Measuring quantitative autism traits in families: informant effect or intergenerational transmission?

Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results. In this paper, we focus on possible informant effects and, taking these into account, on possible intergenerational transmission of QAT. This study used multiple informant data retrieved via the Social Responsiveness Scale from 170 families with at least one member with ASD. Using intraclass correlations (ICCs) and mixed model analyses, we investigated inter-informant agreement and differences between parent and teacher reports on children and between self- and other-reports on adults. Using structural equation modelling (SEM), we investigated the relatedness of QAT between family members in ASD families. Parent-teacher agreement about social responsiveness was poor, especially for children with ASD, though agreement between parents was moderate to strong for affected and unaffected children. Agreement between self- and other-report in adult men was good, but only moderate in women. Agreement did not differ between adults with and without ASD. While accounting for informant effects, our SEM results corroborated the assortative mating theory and the intergenerational transmission of QAT from both fathers and mothers to their offspring.

Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning.

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.

Oral microbiota in autistic children: Diagnosis-related differences and associations with clinical characteristics.

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.

Subtle microstructural alterations in white matter tracts involved in socio-emotional processing after very preterm birth.

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.

Childhood Adversity and Emerging Psychotic Experiences: A Network Perspective.

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.