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Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

Background: Phelan-McDermid syndrome (PMS) is a rare genetic syndrome characterized by developmental delay/intellectual disability, absent or delayed speech, physical dysmorphic features and high rates of autistic features. However, it is currently unknown whether people with PMS have similar neurocognitive atypicalities to those previously identified in idiopathic autism. Disruption in social orienting has previously been suggested as an early hallmark feature of idiopathic autism that impacts social learning and social interaction., Methods: This study used a semi-naturalistic task to explore orienting to social versus non-social stimuli and its relation to clinical features in individuals diagnosed with PMS, autism, and neurotypical children recruited in the United States and the United Kingdom., Results: At the group level, autistic and neurotypical children responded on average more often to social than non-social stimuli, while children with PMS responded similarly to both stimulus types. Both clinical groups responded significantly less often to social stimuli than neurotypical children. In addition, we found considerable variability in orienting responses within each group that were of clinical relevance. In the autism group, non-social orienting was associated with mental age, while in the PMS group social and non-social orienting were related to strength of autistic features., Conclusions: These findings do not support specific social motivation difficulties in either clinical group. Instead, they highlight the importance of exploring individual differences in orienting responses in Phelan-McDermid Syndrome in relation to autistic features., Trial Registration: NA., Competing Interests: Declarations Ethics approval and consent to participate In the UK, the project was approved by the National Research Ethics Service (NRES) Committee London – Queen Square, under reference 15/LO/0305. All volunteers and their families gave appropriate consent/assent to participate in the study. In the US, the project was approved by the Institutional Review Board at the Mount Sinai Hospital. All participants and their families gave appropriate consent to participate in the study. Consent for publication NA. Competing interests AK receives research support from AMO Pharma and consults to Ovid Therapeutics, Acadia, and Alkermes. ASJC has been a consultant for F. Hoffmann-La Roche Ltd, consults for Servier and Signant Health, and she has been involved in clinical trials conducted by Servier. The present work is unrelated to the above grants and relationships. All other authors have no competing interests to declare (EL, JC, JFF, PS, EW, DH, AD, DVC, VB, CB, DGM, MN)., (© 2024. The Author(s).)

Background: The prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) and amygdala are frequently implicated in ASD, depression, and social functioning, it is unknown if these regions explain differences between ASD adults with and without co-occurring depression., Methods: The present study contrasted observed vs. subjective perception of autism symptoms and social performances assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with depression and social functioning., Results: We found that ASD individuals with depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social interactions. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression., Limitations: Due to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task, which excluded many on the autism spectrum. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings., Conclusions: Our approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social interaction in ASD, in contributing to depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes., Competing Interests: Competing interests The authors declare that they have no competing interests

Unraveling the phenotypic and genetic complexity of autism is extremely challenging yet critical for understanding the biology, inheritance, trajectory, and clinical manifestations of the many forms of the condition. Here, we leveraged broad phenotypic data from a large cohort with matched genetics to characterize classes of autism and their patterns of core, associated, and co-occurring traits, ultimately demonstrating that phenotypic patterns are associated with distinct genetic and molecular programs. We used a generative mixture modeling approach to identify robust, clinically-relevant classes of autism which we validate and replicate in a large independent cohort. We link the phenotypic findings to distinct patterns of de novo and inherited variation which emerge from the deconvolution of these genetic signals, and demonstrate that class-specific common variant scores strongly align with clinical outcomes. We further provide insights into the distinct biological pathways and processes disrupted by the sets of mutations in each class. Remarkably, we discover class-specific differences in the developmental timing of genes that are dysregulated, and these temporal patterns correspond to clinical milestone and outcome differences between the classes. These analyses embrace the phenotypic complexity of children with autism, unraveling genetic and molecular programs underlying their heterogeneity and suggesting specific biological dysregulation patterns and mechanistic hypotheses.

While allowing for rapid recruitment of large samples, online psychiatric and neurodevelopmental research relies heavily on participants' self-report of neuropsychiatric symptoms, foregoing the rigorous clinical characterization of laboratory settings. Autism spectrum disorder (ASD) research is one example where the clinical validity of such an approach remains elusive. Here, we compared participants characterized online via self-reports against in-person participants evaluated by clinicians. Despite having comparable self-reported autism symptoms, the online high-trait group reported significantly more social anxiety and avoidant behavior than in-person ASD subjects. Within the in-person sample, there was no relationship between self-rated and clinician-rated autism symptoms, suggesting these approaches may capture different aspects of ASD. The online high-trait and in-person ASD participants also differed in their behavior in well-validated social decision-making tasks: the in-person group perceived having less social control and acted less affiliative towards virtual characters. Our study aimed to draw comparisons at three levels: methodological platform (online versus in-person), symptom measurement (self- versus clinician-report), and social behavior. We identified a lack of agreement between self- and clinician-rated measures of symptoms and divergent social tendencies in groups ascertained by each method, highlighting the need for differentiation between in-person versus online samples in autism research., Competing Interests: Additional Declarations: There is NO Competing Interest.

As early identification of autism improves, there is a critical need for interventions to support the development of social communication skills in toddlers. Caregiver coaching and parental involvement is crucial for improving outcomes and providing children with adequate hours of planned active engagement. This pilot study assessed a 4-week intervention for individual caregiver-child dyads. Eight toddlers 21- to 45-months of age participated. Standardized assessments were collected at four study visits to assess autism symptomatology, language development, and both caregiver knowledge and engagement. Results demonstrated the feasibility of the intervention. Social communication, receptive and expressive language all improved as measured by direct assessment. Caregiver knowledge and caregivers' subjective feelings of engagement with their toddlers also improved., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autism (ASD) and schizophrenia spectrum disorders (SCZ) are neurodevelopmental conditions with overlapping and interrelated symptoms. A network analysis approach that represents clinical conditions as a set of "nodes" (symptoms) connected by "edges" (relations among symptoms) was used to compare symptom organization in the two conditions. Gaussian graphical models were estimated using Bayesian methods to model separate symptom networks for adults with confirmed ASD or SCZ diagnoses. Though overall symptom organization differed by diagnostic group, both symptom networks demonstrated high centrality of social communication difficulties. Autism-relevant restricted and repetitive behaviors and schizophrenia-related cognitive-perceptual symptoms were uniquely central to the ASD and SCZ networks, respectively. Results offer recommendations to improve differential diagnosis and highlight potential treatment targets in ASD and SCZ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SZ) are characterized by difficulty with social cognition and atypical reception of facial communication - a key area in the Research Domain Criteria framework. To identify areas of overlap and dissociation between ASD and SZ, we review studies of event-related potentials (ERP) to faces across ASD and SZ populations, focusing on ERPs implicated in social perception: P100, N170, N250, and P300. There were many inconsistent findings across studies; however, replication was strongest for delayed N170 latency in ASD and attenuated N170 amplitude in SZ. These results highlight the challenges of replicating research findings in heterogeneous clinical populations and the need for transdiagnostic research that continuously quantifies behavior and neural activity across neurodevelopmental disorders., Competing Interests: CONFLICT-OF-INTEREST STATEMENT The authors declare that they have no conflict of interest.

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare genetic condition associated with intellectual disability and autism spectrum disorder. Preclinical evidence suggests that low-dose ketamine may induce expression of ADNP and that neuroprotective effects of ketamine may be mediated by ADNP. The goal of the proposed research was to evaluate the safety, tolerability, and behavioral outcomes of low-dose ketamine in children with ADNP syndrome. We also sought to explore the feasibility of using electrophysiological markers of auditory steady-state response and computerized eye tracking to assess biomarker sensitivity to treatment. This study utilized a single-dose (0.5 mg/kg), open-label design, with ketamine infused intravenously over 40 min. Ten children with ADNP syndrome ages 6 to 12 years were enrolled. Ketamine was generally well tolerated, and there were no serious adverse events. The most common adverse events were elation/silliness (50%), fatigue (40%), and increased aggression (40%). Using parent-report instruments to assess treatment effects, ketamine was associated with nominally significant improvement in a wide array of domains, including social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities, a week after administration. Results derived from clinician-rated assessments aligned with findings from the parent reports. Overall, nominal improvement was evident based on the Clinical Global Impressions - Improvement scale, in addition to clinician-based scales reflecting key domains of social communication, attention deficit and hyperactivity, restricted and repetitive behaviors, speech, thinking, and learning, activities of daily living, and sensory sensitivities. Results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to index change with ketamine treatment. Findings are intended to be hypothesis generating and provide preliminary support for the safety and efficacy of ketamine in ADNP syndrome in addition to identifying useful endpoints for a ketamine clinical development program. However, results must be interpreted with caution given limitations of this study, most importantly the small sample size and absence of a placebo-control group., Competing Interests: Alexander Kolevzon is on the scientific advisory boards of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences. Paige M. Siper and Mount Sinai licensed the Sensory Assessment for Neurodevelopmental Disorders (SAND) developed by PMS to Stoelting, Co. Sandra Sermone is on the board of directors of ADNP Kids Research Foundation, has patent applications filed for ketamine and ketamine/NAP for the treatment of ADNP syndrome and related neurological conditions, and is a parent of a child with ADNP syndrome. Matthew Davis is on the scientific advisory board of ADNP Kids Research Foundation, has patent applications filed for ketamine and ketamine/NAP for the treatment of ADNP syndrome and related neurological conditions, and is a parent of a child with ADNP syndrome. Joseph D. Buxbaum consults for BridgeBio Pharma. The remainder of the authors declare no competing interests., (© 2022 The Author(s).)

Objective: The current study used visual evoked potentials (VEPs) to examine excitatory and inhibitory postsynaptic activity in children with Phelan-McDermid syndrome (PMS) and the association with genetic factors. PMS is caused by haploinsufficiency of SHANK3 on chromosome 22 and represents a common single-gene cause of autism spectrum disorder (ASD) and intellectual disability., Method: Transient VEPs were obtained from 175 children, including 31 with PMS, 79 with idiopathic ASD, 45 typically developing controls, and 20 unaffected siblings of children with PMS. Stimuli included standard and short-duration contrast-reversing checkerboard conditions, and the reliability between these 2 conditions was assessed. Test-retest reliability and correlations with deletion size were explored in the group with PMS., Results: Children with PMS and, to a lesser extent, those with idiopathic ASD displayed significantly smaller amplitudes and decreased beta and gamma band activity relative to TD controls and PMS siblings. Across groups, high intraclass correlation coefficients were obtained between standard and short-duration conditions. In children with PMS, test-retest reliability was strong. Deletion size was significantly correlated with P 60 -N 75 amplitude for both conditions., Conclusion: Children with PMS displayed distinct transient VEP waveform abnormalities in both time and frequency domains that might reflect underlying glutamatergic deficits that were associated with deletion size. A similar response pattern was observed in a subset of children with idiopathic ASD. VEPs offer a noninvasive measure of excitatory and inhibitory neurotransmission that holds promise for stratification and surrogate endpoints in ongoing clinical trials in PMS and ASD., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate disorders, with distinct clinical profiles and natural histories. ASD, typically diagnosed in childhood, is characterized by restricted or repetitive interests or behaviors and impaired social communication, and it tends to have a stable course. SCZ, typically diagnosed in adolescence or adulthood, is characterized by hallucinations and delusions, and tends to be associated with declining function. However, youth with ASD are three to six times more likely to develop SCZ than their neurotypical counterparts, and increasingly, research has shown that ASD and SCZ converge at several levels. We conducted a systematic review of studies since 2013 relevant to understanding this convergence, and present here a narrative synthesis of key findings, which we have organized into four broad categories: symptoms and behavior, perception and cognition, biomarkers, and genetic and environmental risk. We then discuss opportunities for future research into the phenomenology and neurobiology of overlap between ASD and SCZ. Understanding this overlap will allow for researchers, and eventually clinicians, to understand the factors that may make a child with ASD vulnerable to developing SCZ. LAY SUMMARY: Autism spectrum disorder and schizophrenia are distinct diagnoses, but people with autism and people with schizophrena share several characteristics. We review recent studies that have examined these areas of overlap, and discuss the kinds of studies we will need to better understand how these disorders are related. Understanding this will be important to help us identify which autistic children are at risk of developing schizophrenia., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Background: FOXP1 syndrome is an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, speech and language delays, and externalizing behaviors. We previously evaluated nine children and adolescents with FOXP1 syndrome to better characterize its phenotype. We identified specific areas of interest to be further explored, namely autism spectrum disorder (ASD) and internalizing and externalizing behaviors., Methods: Here, we assess a prospective cohort of additional 17 individuals to expand our initial analyses and focus on these areas of interest. An interdisciplinary group of clinicians evaluated neurodevelopmental, behavioral, and medical features in participants. We report results from this cohort both alone, and in combination with the previous cohort, where possible., Results: Previous observations of intellectual disability, motor delays, and language deficits were confirmed. In addition, 24% of the cohort met criteria for ASD. Seventy-five percent of individuals met DSM-5 criteria for attention-deficit/hyperactivity disorder and 38% for an anxiety disorder. Repetitive behaviors were almost universally present (95%) even without a diagnosis of ASD. Sensory symptoms, in particular sensory seeking, were common., Limitations: As FOXP1 syndrome is a rare disorder, sample size is limited., Conclusions: These findings have important implications for the treatment and care of individuals with FOXP1 syndrome. Notably, standardized testing for ASD showed high sensitivity, but low specificity, when compared to expert consensus diagnosis. Furthermore, many individuals in our cohort who received diagnoses of attention-deficit/hyperactivity disorder or anxiety disorder were not being treated for these symptoms; therefore, our findings suggest that there may be immediate areas for improvements in treatment for some individuals., (© 2021. The Author(s).)

Background: Autism and intellectual disability may coincide and be preceded by global developmental delay or by motor delay., Hypothesis: Motor delay in the context of global developmental delay is an initial "red flag" for ASD, with added risk in girls., Objective: To assess early developmental milestones in girls with ASD as compared to diagnosed boys, considering prematurity risk., Method: Developmental milestones in a cohort of 467 children with ASD - diagnosed at mean age of 3.4 years (SD = 2.2) - were analyzed according to gender and prematurity risk., Results: 111 girls (24 %), 356 boys (76 %), presented with motor milestones acquisition grossly within the normal range. However, there was a shift towards acquisition of walking being at the later end of the norm range, with this shift being more prominent in girls. 60 % of girls and 47 % of boys with ASD had motor delay and 49 % of girls and 36 % of boys had global developmental delay. The extent of the delays was greater in the prematurity subgroup., Conclusion: Global delay of early milestones occurred in half of children with ASD and in 60 % of girls with ASD. Delayed acquisition of independent walking is relatively more common in girls subsequently diagnosed with ASD., Competing Interests: Declaration of Competing Interest All authors read and approved the final manuscript and do not have any conflict of interest with regards to this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Social Responsiveness Scale-2 (SRS-2) is a quantitative measure used to characterize symptoms of autism spectrum disorder (ASD). However, research suggests that SRS-2 scores are significantly influenced by language ability and intellectual disability (ID). Efforts to refine the SRS-2 by Sturm, Kuhfeld, Kasari, and Mccracken [Journal of Child Psychology and Psychiatry, 58(9), 1053-1061] yielded a shortened form, yet its psychometric properties in populations with severe ID remain unknown. This study aims to examine the psychometric properties of the SRS-2 in Phelan-McDermid syndrome (PMS), a genetic condition associated with ASD and ID, thereby guiding score interpretation in this population and future development of targeted scales. Analyses, including Item Response Theory (IRT), were conducted on a sample of individuals with PMS (n = 91) recruited at six sites nationally. Psychometric properties evaluated include measures of reliability (internal consistency, test-retest reliability) and validity (structural, construct, content). While both SRS-2 forms are reliable, the shortened SRS-2 shows superior validity to the full SRS-2 for measuring ASD symptoms in PMS. On IRT analysis, the shortened SRS-2 shows excellent discrimination and precisely evaluates respondents across a wide range of ASD symptomatology but interpretation is limited by uncertain content validity and small sample size. The shortened SRS-2 shows some promise for use in PMS, but future refinements and additions are needed to develop items that are tailored to identify ASD in children with severe ID and specifically PMS. LAY SUMMARY: This study determined that a shortened form of the Social Responsiveness Scale, Second Edition (SRS-2) shows both promise and limitations for the characterization of autism symptomatology in individuals with Phelan-McDermid syndrome (PMS), a population characterized by intellectual disability (ID). Caution should be used when interpreting SRS-2 scores in individuals with ID and future research should modify existing items and develop new items to improve the SRS-2's ability to accurately characterize autism symptomatology in PMS. Autism Res 2020, 13: 1383-1396. © 2020 International Society for Autism Research, Wiley Periodicals, Inc., (© 2020 International Society for Autism Research and Wiley Periodicals LLC.)

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.

Pivotal Response Treatment (PRT) is an empirically validated behavioral treatment for individuals with autism spectrum disorders (ASD). The purpose of the current study was to assess the efficacy of PRT for ten cognitively-able preschool-aged children with ASD in the context of a short-duration (4-month) treatment model. Most research on PRT used individual behavioral goals as outcome measures, but the current study utilized standardized assessments of broader-based social communication and adaptive skills. The children made substantial gains; however, magnitude and consistency of response across measures were variable. The results provide additional support for the efficacy of PRT as well as evidence for improvements in higher-order social communication and adaptive skill development within the context of a short-duration PRT model.

The relation between early joint attention (in which a child coordinates attention between another person and an object or event) and later language and social outcomes was examined in younger siblings of children with autism spectrum disorder (Sibs-ASD) and younger siblings of children with typical development (Sibs-TD). Initial levels of joint attention (at a mean age of 15 months) as well as growth in levels of joint attention (between 15 months and 34 months) were used as potential predictors of outcomes at age 5. The results revealed that initial levels of initiating joint attention (IJA) were associated with language skills at outcome. In addition, growth of responding to joint attention (RJA) was associated with social skills at age 5. These patterns of associations were not significantly different between the Sibs-TD and Sibs-ASD groups. Although the Sibs-ASD group had lower joint attention scores than the Sibs-TD group at younger ages, significant group differences were not found for most measures at age 5.

We examined functional connectivity of the amygdala in preadolescent children with Autism Spectrum Disorders (ASDs) during spontaneous attention to eye-gaze in emotional faces. Children responded to a target word ("LEFT/RIGHT") printed on angry or fearful faces looking in a direction that was congruent, incongruent, or neutral with the target word. Despite being irrelevant to the task, gaze-direction facilitated (Congruent > Neutral) or interfered with (Incongruent > Congruent) performance in both groups. Despite similar behavioral performance, amygdala-connectivity was atypical and more widespread in children with ASD. In control children, the amygdala was more strongly connected with an emotional cognitive control region (subgenual cingulate) during interference, while during facilitation, no regions showed greater amygdala connectivity than in ASD children. In contrast, in children with ASD the amygdala was more strongly connected to salience and cognitive control regions (posterior and dorsal cingulate) during facilitation and with regions involved in gaze processing (superior temporal sulcus), cognitive control (inferior frontal gyrus), and processing of viscerally salient information (pregenual cingulate, anterior insula, and thalamus) during interference. These findings showing more widespread connectivity of the amygdala extend past findings of atypical functional anatomy of eye-gaze processing in children with ASD and challenge views of general underconnectivity in ASD.

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures., (© 2010 Blackwell Publishing Ltd.)

Functional magnetic resonance imaging was used to examine functional anatomy of attention to social (eye gaze) and nonsocial (arrow) communicative stimuli in late childhood and in a disorder defined by atypical processing of social stimuli, Autism Spectrum Disorders (ASD). Children responded to a target word ('LEFT'/'RIGHT') in the context of a distracting arrow or averted gaze pointing in a direction that was congruent, incongruent, or neutral (bar without arrowheads, central gaze) relative to the target word. Despite being irrelevant to the target task, both arrow and averted gaze facilitated responses (Congruent vs. Neutral trials) to the same extent in the two groups and led to interference (Incongruent vs. Congruent trials), which was greater from arrows in ASD than control children. In the brain, interaction between group and distracter-domain was observed in frontal-temporal regions during facilitation and frontal-striatal regions during interference. During facilitation, regions associated with attention to gaze in control children (left superior temporal sulcus, premotor) were associated with attention to arrows in ASD children; gaze was associated with medial temporal involvement in ASD children. During interference, regions associated with arrows in control children (anterior cingulate, right caudate) were activated in response to gaze in ASD children; further, left dorsolateral prefrontal cortex, a region not observed in control children, was activated during gaze-interference in ASD children. Thus, functional anatomy was atypical in ASD children during spontaneous processing of social and nonsocial communicative cues., (© 2011 Blackwell Publishing Ltd.)

Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the dopamine transporter genotype (DAT1) is associated with Attention Deficit Hyperactivity Disorder, a childhood disorder marked by poor executive function. We examined whether functional anatomy underlying working memory, a component process of executive function, differed by DAT1 in 7-12 year-old typically developing children. 10/10 and 9/10 carriers performed a verbal n-back task in two functional magnetic resonance imaging (fMRI) runs varying in working memory load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy was superior in 9/10 than 10/10 carriers in the high but not low load runs. Examination of each run separately revealed that frontal-striatal-parietal regions were more activated in 9/10 than 10/10 carriers in the high load run; the groups did not differ in the low load run. Examination of load effects revealed a DAT1xLoad interaction in the right hemisphere in the caudate, our a priori region of interest. Exploratory analysis at a more liberal threshold revealed this interaction in other basal ganglia regions (putamen, and substantial nigra/subthalamic nuclei - SN/STN) and in medial parietal cortex (left precuneus). The striatal and parietal regions were more activated in 9/10 carriers under high than low load, and DAT1 differences (9/10>10/10) were evident only under high load. In contrast, SN/STN tended to be more activated in 10/10 carriers under low than high load and DAT1 differences (10/10>9/10) were evident only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with reduced performance and a lack of increased basal ganglia involvement under higher working memory demands., (Copyright 2010 Elsevier Inc. All rights reserved.)

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.

Superior performance on the Embedded Figures Task (EFT) has been attributed to weak central coherence in perceptual processing in Autism Spectrum Disorder (ASD). The present study used functional magnetic resonance imaging to examine the neural basis of EFT performance in 7- to 12-year-old ASD children and age- and IQ-matched controls. ASD children activated only a subset of the distributed network of regions activated in controls. In frontal cortex, control children activated left dorsolateral, medial and dorsal premotor regions whereas ASD children only activated the dorsal premotor region. In parietal and occipital cortices, activation was bilateral in control children but unilateral (left superior parietal and right occipital) in ASD children. Further, extensive bilateral ventral temporal activation was observed in control, but not ASD children. ASD children performed the EFT at the same level as controls but with reduced cortical involvement, suggesting that disembedded visual processing is accomplished parsimoniously by ASD relative to typically developing brains.