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Numerous candidate EEG biomarkers have been put forward for use in clinical research on autism spectrum disorder (ASD), but biomarker development has been hindered by limited attention to the psychometric properties of derived variables, inconsistent results across small studies, and variable methodology. The authors evaluated the basic psychometric properties of a battery of EEG assays for their potential suitability as biomarkers in clinical trials.This was a large, multisite, naturalistic study in 6- to 11-year-old children who either had an ASD diagnosis (N=280) or were typically developing (N=119). The authors evaluated an EEG battery composed of well-studied assays of resting-state activity, face perception (faces task), biological motion perception, and visual evoked potentials (VEPs). Biomarker psychometrics were evaluated in terms of acquisition rates, construct performance, and 6-week stability. Preliminary evaluation of use was explored through group discrimination and phenotypic correlations.Three assays (resting state, faces task, and VEP) show promise in terms of acquisition rates and construct performance. Six-week stability values in the ASD group were moderate (intraclass correlations ≥0.66) for the faces task latency of the P1 and N170, the VEP amplitude of N1 and P1, and resting alpha power. Group discrimination and phenotype correlations were primarily observed for the faces task P1 and N170.In the context of a large-scale, rigorous evaluation of candidate EEG biomarkers for use in ASD clinical trials, neural response to faces emerged as a promising biomarker for continued evaluation. Resting-state activity and VEP yielded mixed results. The study's biological motion perception assay failed to display construct performance. The results provide information about EEG biomarker performance that is relevant for the next stage of biomarker development efforts focused on context of use.

Children with autism spectrum disorder are prescribed various medications to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity and prevent contamination of clinical endpoints. However, this choice may compromise the representativeness of the sample. In a recent study designed to identify biomarkers and endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, providing the opportunity to examine characteristics of psychotropic medication use and guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the study and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Our findings suggest that exclusion of children taking concomitant psychotropic medications could limit the representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options. Lay abstract Children with autism spectrum disorder are prescribed a variety of medications that affect the central nervous system (psychotropic medications) to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity of the sample and prevent contamination of biomarkers or clinical endpoints. However, this choice may significantly diminish the clinical representativeness of the sample. In a recent multisite study designed to identify biomarkers and behavioral endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, thus providing a unique opportunity to examine characteristics of psychotropic medication use in a research cohort and to guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the ABC-CT and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half of these children. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Descriptive analysis showed that children taking antipsychotics displayed a trend toward greater overall impairment. Our findings suggest that exclusion of children taking concomitant psychotropic medications in trials could limit the clinical representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options.

Atypical neural response to faces is thought to contribute to social deficits in autism spectrum disorder (ASD). Compared to typically developing (TD) controls, individuals with ASD exhibit delayed brain responses to upright faces at a face-sensitive event-related potential (ERP), the N170. Given observed differences in patterns of visual attention to faces, it is not known whether slowed neural processing may simply reflect atypical looking to faces. The present study manipulated visual attention to facial features to examine whether directed attention to the eyes normalizes N170 latency in ASD. ERPs were recorded in 30 children and adolescents with ASD as well as 26 TD children and adolescents. Results replicated prior findings of shorter N170 latency to the eye region of the face in TD individuals. In contrast, those with ASD did not demonstrate modulation of N170 latency by point of regard to the face. Group differences in latency were most pronounced when attention was directed to the eyes. Results suggest that well-replicated findings of N170 delays in ASD do not simply reflect atypical patterns of visual engagement with experimental stimuli. These findings add to a body of evidence indicating that N170 delays are a promising marker of atypical neural response to social information in ASD. LAY SUMMARY: This study looks at how children's and adolescents' brains respond when looking at different parts of a face. Typically developing children and adolescents processed eyes faster than other parts of the face, whereas this pattern was not seen in ASD. Children and adolescents with ASD processed eyes more slowly than typically developing children. These findings suggest that observed inefficiencies in face processing in ASD are not simply reflective of failure to attend to the eyes.

Visual exploration paradigms involving object arrays have been used to examine salience of social stimuli such as faces in ASD. Recent work suggests performance on these paradigms may associate with clinical features of ASD. We evaluate metrics from a visual exploration paradigm in 4-to-11-year-old children with ASD (n = 23; 18 males) and typical development (TD; n = 23; 13 males). Presented with arrays containing faces and nonsocial stimuli, children with ASD looked less at (p = 0.002) and showed fewer fixations to (p = 0.022) faces than TD children, and spent less time looking at each object on average (p = 0.004). Attention to the screen and faces correlated positively with social and cognitive skills in the ASD group (ps .05). This work furthers our understanding of objective measures of visual exploration in ASD and its potential for quantifying features of ASD.

Objective: Despite the frequent occurrence of depressive symptoms in children and adolescents with autism spectrum disorder (ASD), few studies have investigated the relationship between depressive ...

Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright faces, the face specificity effect (difference between face and object processing), and the inversion effect (difference between face upright and inverted processing) in relation to age. First, linear mixed models (LMMs) were fitted with fixed effect of age at testing and random effect of participant, using all available data points to characterize general age-based development in the TD and ASD groups. Second, LMM models using only the TD group were used to calculate age-based residuals in both groups. The purpose of residualization was to assess how much variation in ASD participants could be accounted for by chronological age-related changes. Our data demonstrate that the N170L and P100L responses to upright faces appeared to follow a roughly linear relationship with age. In the ASD group, the distribution of the age-adjusted residual values suggest that ASD participants were more likely to demonstrate slower latencies than would be expected for a TD child of the same age, similar to what has been identified using unadjusted values. Lastly, using age-adjusted values for stratification, we found that children who demonstrated slowed age-adjusted N170L had lower verbal and non-verbal IQ and worse face memory. These data suggest that age must be considered in assessing the N170L and P100L response to upright faces as well, and these adjusted values may be used to stratify children within the autism spectrum.

BackgroundSocial symptomatology quantified by clinical interview (Autism Diagnostic Observation Schedule, ADOS) and self-report (Social Responsiveness Scale, SRS) indicate symptom severity in autism spectrum disorder (ASD). Reluctance to engage in interpersonal eye contact is a frequently observed behavioral hallmark, though neural bases for these difficulties and relation to symptomatology are not understood. We test the hypothesis that eye contact in ASD activates atypical neural mechanisms that are related to individual differences in symptomatology.MethodsNeural activity represented by hemodynamic signals was acquired by functional near-infrared spectroscopy (fNIRS) during real person-to-person eye contact (confirmed by eye-tracking) for 17 adult ASD (3 female, 14 male) and 19 typically-developed (TD) participants (8 female, 11 male). Assessment of social function was based on ADOS scores for ASD participants and SRS scores for the combined group of ASD and TD participants.ResultsIndividual ADOS scores were negatively correlated (r = -0.69) with individual fNIRS beta-values (representing strength of hemodynamic signals) within clusters in the right dorsal stream regions: somatosensory cortices, angular gyrus, and supramarginal gyrus. Hemodynamic responses in the right dorsolateral prefrontal cortex (DLPFC) were also negatively correlated (r = -0.77) with ADOS scores. Similarly, SRS scores for the combined ASD and TD groups were also negatively correlated (r = -0.58) with somatosensory cortices and the supramarginal gyrus.ConclusionsThese findings are consistent with the hypothesis that neural mechanisms in the dorsal stream and DLPFC are related to social symptomatology and implicate high-level interactive face and eye-processing systems as potential neurobiological markers of ASD.

Reluctant eye contact and reduced social interactions characteristic of autism spectrum disorder (ASD) are consistent with deficits in oculomotor and face processing systems. We test the hypothesis that these deficits are interrelated ASD. Eye-tracking and hyperscanning with functional near-infrared spectroscopy (fNIRS) were used to acquire neuroimaging data during live, dynamic eye-to-eye contacts in 17 ASD and 19 typically-developed (TD) adults. Real eye contact conditions were contrasted with conditions where eye gaze was directed at a comparable dynamic face video. These findings were regressed with eye-contact dwell-time, i.e., times when gaze of both partners was in the eye-box of the other, to confirm the relationship between visual sensing and neural coding. Visual fixations and positional variance were also determined. Average gaze dwell-times in the "eye-box" did not vary between ASD and TD participants but were longer for the Real Eye than Video Eye condition for both groups. However, positional gaze variability, "jitter", was higher for ASD in both conditions. Neural findings for TD [Real Eye > Video Eye] were consistent with previous findings for interactive face-gaze with activity in right temporal and dorsal parietal regions. However, in ASD ventral temporal regions were observed for this contrast without evidence for dorsal parietal activity. This neural difference was enhanced when regressed by eye-contact dwell-times. Together findings are consistent with the hypothesis that unstable bottom-up oculomotor signals contribute to deficits in live face processing and reduced dorsal stream activity in ASD.

Background Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). Methods The Autism Biomarkers Consortium for Clinical Trials conducted a multisite, observational study of 6–11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. Results All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. Limitations No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. Conclusions All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

Autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SCZ) have overlapping symptomatology related to difficulties with social cognition. Yet, few studies have directly compared social cognition in ASD, SCZ, and typical development (TD). The current study examined individual differences in face recognition and its relation to affective theory of mind (ToM) in each diagnostic group. Adults with ASD (n = 31), SCZ (n = 43), and TD (n = 47) between the ages of 18 and 48 years-old with full scale IQ above 80 participated in this study. The Reading the Mind in the Eyes Test (RMET) measured affective ToM, and the Benton Facial Recognition Test (BFRT) measured face perception. Adults with ASD and SCZ did not differ in their affective ToM abilities, and both groups showed affective ToM difficulties compared with TD. However, better face recognition ability uniquely predicted better affective ToM ability in ASD. Results suggest that affective ToM difficulties may relate to face processing in ASD but not SCZ. By clarifying the complex nature of individual differences in affective ToM and face recognition difficulties in these disorders, the present study suggests there may be divergent mechanisms underlying pathways to social dysfunction in ASD compared with SCZ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A hierarchical model of temporal dynamics was examined in adults (n = 34) and youth (n = 46) across the stages of face processing during the perception of static and dynamic faces. Three ERP components (P100, N170, N250) and spectral power in the mu range were extracted, corresponding to cognitive stages of face processing: low-level vision processing, structural encoding, higher-order processing, and action understanding. Youth and adults exhibited similar yet distinct patterns of hierarchical temporal dynamics such that earlier cognitive stages predicted later stages, directly and indirectly. However, latent factors indicated unique profiles related to behavioral performance for adults and youth and age as a continuous factor. The application of path analysis to electrophysiological data can yield novel insights into the cortical dynamics of social information processing.

Social neuroscience research investigating autism spectrum disorder (ASD) has yielded inconsistent findings, despite ASD being well-characterized by difficulties in social interaction and communication through behavioral observation. In particular, specific etiologies and functional and structural assays of the brain in autism have not been consistently identified. To date, most social neuroscience research has focused on a single person viewing static images. Research utilizing interactive social neuroscience featuring dual-brain recording offers great promise for the study of neurodevelopmental disabilities. Reward processing has been implicated in the pathology of ASD, yet mixed findings have brought uncertainty about the role reward processing deficits may play in ASD. The current study employed dual-brain EEG recording to examine reward processing during live interaction and its relation to autistic traits. Sixteen typically developing (TD) adults played a competitive treasure-hunt game against a computer and against a human partner. EEG results revealed enhanced neural sensitivity to reward outcome during live interaction with a human competitor. Further, individuals with higher levels of autistic traits demonstrated reduced sensitivity to reward outcome during live interaction. These findings provide novel insight into reward processing mechanisms associated with autistic traits, as well as support the necessary utility of interactive social neuroscience techniques to study developmental disorders.

Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with autism spectrum disorder (ASD) and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA’s Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.

Biomarker development is currently a high priority in neurodevelopmental disorder research. For many types of biomarkers (particularly biomarkers of diagnosis), reliability over short time periods is critically important. In the field of autism spectrum disorder (ASD), resting electroencephalography (EEG) power spectral densities (PSD) are well-studied for their potential as biomarkers. Classically, such data have been decomposed into pre-specified frequency bands (e.g., delta, theta, alpha, beta, and gamma). Recent technical advances, such as the Fitting Oscillations and One-Over-F (FOOOF) algorithm, allow for targeted characterization of the features that naturally emerge within an EEG PSD, permitting a more detailed characterization of the frequency band-agnostic shape of each individual’s EEG PSD. Here, using two resting EEGs collected a median of 6 days apart from 22 children with ASD and 25 typically developing (TD) controls during the Feasibility Visit of the Autism Biomarkers Consortium for Clinical Trials, we estimate within visit test-retest reliability based on characterization of the PSD shape in two ways: (1) Using the FOOOF algorithm we estimate six parameters (offset, slope, number of peaks, and amplitude, center frequency and bandwidth of the largest alpha peak) that characterize the shape of the EEG PSD; and (2) using nonparametric functional data analyses, we decompose the shape of the EEG PSD into a reduced set of basis functions that characterize individual power spectrum shapes. We show that individuals exhibit idiosyncratic PSD signatures that are stable over recording sessions using both characterizations. Our data show that EEG activity from a brief two-minute recording provides an efficient window into understanding brain activity at the single-subject level with desirable psychometric characteristics that persist across different analytical decomposition methods. This is a necessary step towards analytical validation of biomarkers based on the EEG PSD, and provides insights into parameters of the PSD that offer short-term reliability (and thus promise as potential biomarkers of trait or diagnosis) versus those that are more variable over the short term (and thus may index state or other rapidly dynamic measures of brain function). Future research should address longer-term stability of the PSD, for purposes such as monitoring development or response to treatment.

Background Atypical face processing is a prominent feature of autism spectrum disorder (ASD) but is not universal and is subject to individual variability. This heterogeneity could be accounted for by reliable yet unidentified subgroups within the diverse population of individuals with ASD. Alexithymia, which is characterized by difficulties in emotion recognition and identification, serves as a potential grouping factor. Recent research demonstrates that emotion recognition impairments in ASD are predicted by its comorbidity with alexithymia. The current study assessed the relative influence of autistic versus alexithymic traits on neural indices of face and emotion perception. Methods Capitalizing upon the temporal sensitivity of event-related potentials (ERPs), it investigates the distinct contributions of alexithymic versus autistic traits at specific stages of emotional face processing in 27 typically developing adults (18 female). ERP components reflecting sequential stages of perceptual processing (P100, N170 and N250) were recorded in response to fear and neutral faces. Results The results indicated that autistic traits were associated with structural encoding of faces (N170), whereas alexithymic traits were associated with more complex emotion decoding (N250). Conclusions These findings have important implications for deconstructing heterogeneity within ASD.

In adults with autism spectrum disorder, co-occurring psychiatric conditions are prevalent, and depression is one of the most common co-occurring disorders. This study examined the relationship between depression and cognitive ability, autism symptom severity, and self-reported social impairments in autism spectrum disorder. A total of 33 adults with autism spectrum disorder and 28 adults with typical development completed a standardized psychiatric interview, cognitive test, measure of clinician-rated autism symptom severity, and self-report of social impairments. Nine participants with autism spectrum disorder (27%) met the criteria for a depressive disorder (autism spectrum disorder + depressive disorder). Relatively more females with autism spectrum disorder had a co-occurring depressive disorder. The typical development group had a higher intelligence quotient than the autism spectrum disorder group, but the autism spectrum disorder + depressive disorder group did not differ from the typical development or autism spectrum disorder group. While the autism spectrum disorder + depressive disorder group had lower clinician-rated autism symptom severity than the autism spectrum disorder group, the autism spectrum disorder + depressive disorder group reported more social impairments than the autism spectrum disorder group. Self-reported social impairments predicted depression in adults with autism spectrum disorder when accounting for symptom severity and cognitive ability. These findings suggest that more self-perceived social impairments are related to depressive disorders in autism spectrum disorder, and may help clinicians identify individuals who are vulnerable in developing a co-occurring depressive disorder. Future directions include follow-up studies with larger cohorts and longitudinal designs to support inferences regarding directionality of these relationships.

Difficulty with emotion perception is a core feature of autism spectrum disorder (ASD) that is also associated with the broader autism phenotype. The current study explored the neural underpinnings of conscious and nonconscious perceptions of affect in typically developing individuals with varying levels of autistic-like traits, as measured by the Autism Quotient (AQ). We investigated the relationship between autistic traits and face processing efficiency using event-related potentials (ERPs). In 20 typically developing adults, we utilized ERPs (the P100, N170, and P300) to measure differences in face processing for emotional faces that were presented either (a) too quickly to reach conscious awareness (16 ms) or (b) slowly enough to be consciously observed (200 ms). All individuals evidenced increased P100 and P300 amplitude and shorter N170 latencies for nonconscious versus consciously presented faces. Individuals with high AQ scores evidenced delayed ERP components. Nonconsciously perceived emotional faces elicited enhanced neural responses regardless of AQ score. Higher levels of autistic traits were associated with inefficient face perception (i.e., longer latency of ERP components). This delay parallels processing delays observed in ASD. These data suggest that inefficient social perception is present in individuals with subclinical levels of social impairment.

Previous research suggests that variation in at-rest neural activity correlates with specific domains of the ASD phenotype; however, few studies have linked patterns of brain activity with autistic trait expression in typically developing populations. The purpose of this study was to examine associations between resting-state electroencephalography (EEG) and three domains of the broader autism phenotype (social interest, rigidity, and pragmatic language) in typically developing individuals. High-density scalp EEG was recorded in thirty-seven typically developing adult participants (13 male, aged 18–52 years). The Broad Autism Phenotype Questionnaire (BAP-Q) was used to measure autistic trait expression. Absolute alpha power (8–13 Hz) was extracted from eyes-closed epochs using spectral decomposition techniques. Analyses revealed a specific positive association between scores on the BAP-Q Rigidity subscale and alpha power in the parietal scalp region. No significant associations were found between alpha power and the BAP-Q Aloofness or Pragmatic Language subscales. Furthermore, the association between EEG power and behavioral rigidity was specific to the alpha frequency band. This study demonstrates that specific traits within the broader autism phenotype are associated with dissociable patterns of at-rest neural activity.

BACKGROUND Patients with single-suture craniosynostosis (SSC) are at an elevated risk for long-term learning disabilities. Such adverse outcomes indicate that the early development of neural processing in SSC may be abnormal. At present, however, the precise functional derangements of the developing brain remain largely unknown. Event-related potentials (ERPs) are a form of noninvasive neuroimaging that provide direct measurements of cortical activity and have shown value in predicting long-term cognitive functioning. The current study used ERPs to examine auditory processing in infants with SSC to help clarify the developmental onset of delays in this population. METHODS Fifteen infants with untreated SSC and 23 typically developing controls were evaluated. ERPs were recorded during the presentation of speech sounds. Analyses focused on the P150 and N450 components of auditory processing. RESULTS Infants with SSC demonstrated attenuated P150 amplitudes relative to typically developing controls. No differences in the N450 component were identified between untreated SSC and controls. CONCLUSIONS Infants with untreated SSC demonstrate abnormal speech sound processing. Atypicalities are detectable as early as 6 months of age and may represent precursors to long-term language delay. Electrophysiological assessments provide a precise examination of neural processing in SSC and hold potential as a future modality to examine the effects of surgical treatment on brain development.

The prevalence of deformational plagiocephaly has risen dramatically in recent years, now affecting 15 percent or more of infants. Prior research using developmental scales suggests that these children may be at elevated risk for developmental delays. However, the low positive predictive value of such instruments in identifying long-term impairment, coupled with their poor reliability in infants, warrants the development of methods to more precisely measure brain function in craniofacial patients. Event-related potentials offer a direct measure of cortical activity that is highly applicable to young populations and has been implemented in other disorders to predict long-term cognitive functioning. The current study used event-related potentials to contrast neural correlates of auditory perception in infants with deformational plagiocephaly and typically developing children.Event-related potentials were recorded while 16 infants with deformational plagiocephaly and 18 nonaffected controls passively listened to speech sounds. Given prior research suggesting their association with subsequent functioning, analyses focused on the P150 and N450 event-related potential components.Deformational plagiocephaly patients and normal controls showed comparable cortical responses to speech sounds at both auditory event-related potential components.Children with deformational plagiocephaly demonstrate neural responses to language that are consistent with normative expectations and comparable to those of typical children. These results indicate that head shape deformity secondary to supine sleep is not associated with impairments in auditory processing. The applicability of the current methods in early infancy suggests that electrophysiologic brain recordings represent a promising method of monitoring brain development in children with cranial disorders.Risk, II.

Animal models of autism spectrum disorders (ASD) contribute to understanding of the role of genetics and the biological mechanisms underlying behavioral phenotypes and inform the development of potential treatments. Translational biomarkers are needed that can both validate these models and facilitate behavioral testing paradigms for ASD in humans. Automated video tracking of movement patterns and positions recorded from overhead cameras is routinely applied in behavioral paradigms designed to elicit core behavioral manifestations of ASD in rodent models. In humans, laboratory-based observations are a common semi-naturalistic context for assessing a variety of behaviors relevant to ASD such as social engagement, play, and attention. We present information learned and suggest guidelines for designing, recording, acquiring, and evaluating video tracking data of human movement patterns based on our experience in a multi-site video tracking study of children with ASD in the context of a parent-child, laboratory-based play interaction.

This study addressed whether prior successes with educational interventions grounded in the theory of successful intelligence could be replicated on a larger scale as the primary basis for instruction in language arts, mathematics, and science. A total of 7,702 4th-grade students in the United States, drawn from 223 elementary school classrooms in 113 schools in 35 towns (14 school districts) located in 9 states, participated in the program. Students were assigned, by classroom, to receive units of instruction that were based either upon the theory of successful intelligence (SI; analytical, creative, and practical instruction) or upon teaching as usual (weak control), memory instruction (strong control), or critical-thinking instruction (strong control). The amount of instruction was the same across groups. In the 23 comparisons across 10 content units in 3 academic domains, there were only a small number of instances in which students in the SI instructional groups generally performed statistically better than students in other conditions. There were even fewer instances where the different control conditions outperformed the SI students. Implications for the future of SI theory and the scalability of research efforts in general are discussed.

Sensitivity to eye-contact is a foundation upon which social cognition is built. However, there are no known neural markers characterizing response to reciprocal gaze. Using co-registered EEG and eye-tracking, we measured brain activity while participants viewed faces that responded to their looking patterns. Contingent upon participant gaze, onscreen faces opened their eyes or mouths; in this way we measured brain response to reciprocal eye-contact. We identified two ERP components that were largest in response to reciprocal eye-contact: the N170 and the P300. The magnitude of the components’ differences between reciprocal eye-contact and mouth movement predicted self-reported social function. Individuals with greater brain response to reciprocal eye-contact reported more normative scores on measures of autistic traits. These results present the first neural markers of eye-contact, revealing that reciprocal eye-contact is identified in less than 500 ms. Furthermore, individual differences in brain response to eye-contact predict meaningful variability in self-reports of social performance.

Two methods for mixing AR features for EEG signal classification are proposed.Evolutionary and ensemble learning methods are considered.The results are assessed against a set of conventional order estimation methods.The feasibilities are investigated using several BCI competition datasets.Adequacy of Ensemble-based mixture and EA-based fusion methods are shown. Autoregressive (AR) models are of commonly utilized feature types in Electroencephalogram (EEG) studies due to offering better resolution, smoother spectra and being applicable to short segments of data. Identifying correct AR's modeling order is an open challenge. Lower model orders poorly represent the signal while higher orders increase noise. Conventional methods for estimating modeling order include Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and Final Prediction Error (FPE). This article assesses the hypothesis that appropriate mixture of multiple AR orders is likely to better represent the true signal compared to any single order. Better spectral representation of underlying EEG patterns can increase utility of AR features in Brain Computer Interface (BCI) systems by increasing timely & correctly responsiveness of such systems to operator's thoughts. Two mechanisms of Evolutionary-based fusion and Ensemble-based mixture are utilized for identifying such appropriate mixture of modeling orders. The classification performance of the resultant AR-mixtures are assessed against several conventional methods utilized by the community including (1) A well-known set of commonly used orders suggested by the literature, (2) conventional order estimation approaches (e.g., AIC, BIC and FPE), (3) blind mixture of AR features originated from a range of well-known orders. Five datasets from BCI competition III that contain 2, 3 and 4 motor imagery tasks are considered for the assessment. The results indicate superiority of Ensemble-based modeling order mixture and evolutionary-based order fusion methods within all datasets.

Processing speed is associated with reading performance. However, the literature is not clear either on the definition of processing speed or on why and how it contributes to reading performance. In this study we demonstrated that processing speed, as measured by reaction time, is not a unitary construct. Using the diffusion model of two-choice reaction time, we assessed processing speed in a series of same-different reaction time tasks for letter and number strings. We demonstrated that the association between reaction time and reading performance is driven by processing speed for reading-related information, but not motor or sensory encoding speed. Language: en

This report provides an overview of the development and preliminary evaluation of an educational placement screener for use in short-term juvenile detention facilities. The screener is designed to gauge levels of competence in reading (at the word and text level) and mathematics for juveniles in grades 3–12, and to serve as a rapid assessment device for subsequent educational placement within 48 h of admission. The psychometric properties of the screener were evaluated in a sample of 1,078 youths in detention and 157 youths in the community. The importance of the availability of easy-to-administer assessment devices that can accurately capture the level of academic functioning of youths in detention is discussed within the larger context of meeting the educational rights and needs of juvenile delinquents.

Both autism spectrum disorder (ASD) and psychopathy are primarily characterized by social dysfunction; overlapping phenotypic features may reflect altered function in common brain mechanisms. The current study examined the degree to which neural response to social and nonsocial feedback is modulated by autistic versus psychopathic traits in a sample of typically developing adults (N = 31, 11 males, 18-52 years). Event-related potentials were recorded whilst participants completed a behavioral task and received feedback on task performance. Both autistic and psychopathic traits were associated with alterations in the neural correlates of feedback processing. Sensitivity to specific forms of feedback (social, nonsocial, positively valenced, negatively valenced) differed between the two traits. Autistic traits were associated with decreased sensitivity to social feedback. In contrast, the antisocial domain of psychopathic traits was associated with an overall decrease in sensitivity to feedback, and the interpersonal manipulation domain was associated with preserved processing of positively valenced feedback. Results suggest distinct alterations within specific mechanisms of feedback processing may underlie similar difficulties in social behavior.

Individuals with autism spectrum disorder (ASD) demonstrate difficulty with social interactions and relationships, but the neural mechanisms underlying these difficulties remain largely unknown. While social difficulties in ASD are most apparent in the context of interactions with other people, most neuroscience research investigating ASD have provided limited insight into the complex dynamics of these interactions. The development of novel, innovative “interactive social neuroscience” methods to study the brain in contexts with two interacting humans is a necessary advance for ASD research. Studies applying an interactive neuroscience approach to study two brains engaging with one another have revealed significant differences in neural processes during interaction compared to observation in brain regions that are implicated in the neuropathology of ASD. Interactive social neuroscience methods are crucial in clarifying the mechanisms underlying the social and communication deficits that characterize ASD.

We compared the reading-related skills of children with Autism Spectrum Disorders who have hyperlexia (ASD + HPL) with age-matched children with ASD without HPL (ASD - HPL) and with single-word reading-matched typically developing children (TYP). Children with ASD + HPL performed (1) better than did children with ASD - HPL on tasks of single-word reading and pseudoword decoding and (2) equivalently well compared to word-reading-matched TYP children on all reading-related tasks except reading comprehension. It appears that the general underlying model of single-word reading is the same in principle for "typical" and hyperlexic reading. Yet, the study revealed some dissimilarities between these two types of reading when more fine-grained cognitive and linguistic abilities were considered; these dissimilarities warrant further investigations.

A sample of Swahili-speaking probands with reading difficulties was identified from a large representative sample of 1,500 school children in the rural areas of Tanzania. Families of these probands (n = 88) were invited to participate in the study. The proband and his/her siblings received a battery of reading-related tasks and performance on these tasks was recorded and treated as phenotypic data. Molecular-genetic analyses were carried out with 47 highly polymorphic markers spanning three previously identified regions of interest harboring susceptibility loci for reading difficulties: 2p, 6p, and 15q (DYX1–DYX3). The analyses revealed the involvement of these regions in the development of reading difficulties in Swahili. The linkage signals are especially pronounced for time (compared with error) indicators of reading difficulties. These findings are easily interpretable because in transparent languages such as Swahili deficits in reading are more related to the rate/speed of reading and reading-related processes than to the number of errors made. In short, the study incrementally advances the field by adding an understudied language and an understudied population to the variety of languages and populations in the field of molecular-genetic studies of reading difficulties.

Social cognitive and affective neuroscience : SCAN 10(10), 1357-1364 (2015). doi:10.1093/scan/nsv024, Published by Oxford Univ. Press, Oxford

Human faces are fundamentally dynamic, but experimental investigations of face perception have traditionally relied on static images of faces. Although naturalistic videos of actors have been used with success in some contexts, much research in neuroscience and psychophysics demands carefully controlled stimuli. In this article, we describe a novel set of computer-generated, dynamic face stimuli. These grayscale faces are tightly controlled for low- and high-level visual properties. All faces are standardized in terms of size, luminance, location, and the size of facial features. Each face begins with a neutral pose and transitions to an expression over the course of 30 frames. Altogether, 222 stimuli were created, spanning three different categories of movement: (1) an affective movement (fearful face), (2) a neutral movement (close-lipped, puffed cheeks with open eyes), and (3) a biologically impossible movement (upward dislocation of eyes and mouth). To determine whether early brain responses sensitive to low-level visual features differed between the expressions, we measured the occipital P100 event-related potential, which is known to reflect differences in early stages of visual processing, and the N170, which reflects structural encoding of faces. We found no differences between the faces at the P100, indicating that different face categories were well matched on low-level image properties. This database provides researchers with a well-controlled set of dynamic faces, controlled for low-level image characteristics, that are applicable to a range of research questions in social perception.

Head-mounted eye-tracking systems allow us to observe participants' gaze behaviors in largely unconstrained, real-world settings. We have developed novel, untethered, mobile, low-cost, lightweight, easily-assembled head-mounted eye-tracking devices, comprised entirely of off-the-shelf components, including untethered, point-of-view, sports cameras. In total, the parts we have used cost ~$153, and we suggest untested alternative components that reduce the cost of parts to ~$31. Our device can be easily assembled using hobbying skills and techniques. We have developed hardware, software, and methodological techniques to perform point-of-regard estimation, and to temporally align scene and eye videos in the face of variable frame rate, which plagues low-cost, lightweight, untethered cameras. We describe an innovative technique for synchronizing eye and scene videos using synchronized flashing lights. Our hardware, software, and calibration designs will be made publicly available, and we describe them in detail here, to facilitate replication of our system. We also describe novel smooth-pursuit-based calibration methodology, which affords rich sampling of calibration data while compensating for lack of information regarding the extent of visibility on participants' scene recordings. Validation experiments indicate accuracy within 0.752 degrees of visual angle on average.

Autism spectrum disorder (ASD) is more common in males than females. An underrepresentation of females in the ASD literature has led to limited knowledge of differences in social function across the sexes. Investigations of face perception represent a promising target for understanding variability in social functioning between males and females. The current study analyzed electrophysiological brain recordings during face perception to investigate sex differences in the neural correlates of face perception and their relationship to social function. Event related potentials (ERP) were recorded from children with ASD while viewing faces, inverted faces, and houses. Relative to males, females showed attenuated response at an ERP marker of face perception, the N170. Among females, but not males, atypical face response was associated with symptom severity. Observed sex differences reflect influential differences in social information processing, and impairment in these features correlates with deficits in social information processing in females, but not males, with ASD. These findings hold significance for future treatment protocols, which should account for differences in males and females with ASD in clinical presentation and neural phenotypes.

The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010–July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample ( n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research.

Based on numerous suggestions in the literature, we evaluated lexical decision (LD) as a putative endophenotype for reading comprehension by investigating heritability estimates and segregation analyses parameter estimates for both of these phenotypes. Specifically, in a segregation analysis of a large sample of families, we established that there is little to no overlap between genes contributing to LD and reading comprehension and that the genetic mechanism behind LD derived from this analysis appears to be more complex than that for reading comprehension. We conclude that in our sample, LD is not a good candidate as an endophenotype for reading comprehension, despite previous suggestions from the literature. Based on this conclusion, we discuss the role and benefit of the endophenotype approach in studies of complex human cognitive functions.

The World Wide Web is one of the most common methods used by parents to find information on autism spectrum disorders and most consumers find information through search engines such as Google or Bing. However, little is known about how the search engines operate or the consistency of the results that are returned over time. This study presents the results of analyses of searches from 2009, 2010, and 2011 for information on autism. We found that over time, consumers are likely to have different search experiences yielding different results, and we urge consumers to use caution when using the World Wide Web to obtain information on autism.

This work’s objective was to offer additional insights into the psychological and genetic bases of reading ability and disability, and to evaluate the plausibility of a variety of psychological models of reading involving phonological awareness (PA) and rapid naming (RN), both hypothesized to be principal components in such models. In Study 1, 488 unselected families were assessed with measures of PA and RN to investigate familial aggregation and to obtain estimates of both the number and effect-magnitude of genetic loci involved in these traits’ transmission. The results of the analyses from Study 1 indicated the presence of genetic effects in the etiology of individual differences for PA and RN and pointed to both the shared and unique sources of this genetic variance, which appeared to be exerted by multiple (3–6 for PA and 3–5 for RN) genes. These results were used in Study 2 to parameterize a simulation of 3,000 families with quantitatively distributed PA and RN, so that the robustness and generalizability of the Study 1 findings could be evaluated. The findings of both studies were interpreted according to established theories of reading and our own understanding of the etiology of complex developmental disorders.