A generalizable connectome-based marker of in-scan sustained attention in neurodiverse youth.

Difficulty with attention is an important symptom in many conditions in psychiatry, including neurodiverse conditions such as autism. There is a need to better understand the neurobiological correlates of attention and leverage these findings in healthcare settings. Nevertheless, it remains unclear if it is possible to build dimensional predictive models of attentional state in a sample that includes participants with neurodiverse conditions. Here, we use 5 datasets to identify and validate functional connectome-based markers of attention. In dataset 1, we use connectome-based predictive modeling and observe successful prediction of performance on an in-scan sustained attention task in a sample of youth, including participants with a neurodiverse condition. The predictions are not driven by confounds, such as head motion. In dataset 2, we find that the attention network model defined in dataset 1 generalizes to predict in-scan attention in a separate sample of neurotypical participants performing the same attention task. In datasets 3-5, we use connectome-based identification and longitudinal scans to probe the stability of the attention network across months to years in individual participants. Our results help elucidate the brain correlates of attentional state in youth and support the further development of predictive dimensional models of other clinically relevant phenotypes.

Vulnerability to Ideologically-Motivated Violence Among Individuals With Autism Spectrum Disorder.

People with autism spectrum disorder (ASD) are represented among those who espouse extremist thought and have committed violent acts associated with their beliefs. Media often highlight a perpetrator's psychiatric diagnosis following acts of mass violence, which in some instances has included ASD. ASD may itself not provide useful information for understanding motivations. Instead, understanding specific traits and neuropsychological and other vulnerabilities may offer an opportunity to make sense of these very complex events.

What are we optimizing for in autism screening? Examination of algorithmic changes in the M-CHAT.

The present study objectives were to examine the performance of the new M-CHAT-R algorithm to the original M-CHAT algorithm. The main purpose was to examine if the algorithmic changes increase identification of children later diagnosed with ASD, and to examine if there is a trade-off when changing algorithms. We included 54,463 screened cases from the Norwegian Mother and Child Cohort Study. Children were screened using the 23 items of the M-CHAT at 18 months. Further, the performance of the M-CHAT-R algorithm was compared to the M-CHAT algorithm on the 23-items. In total, 337 individuals were later diagnosed with ASD. Using M-CHAT-R algorithm decreased the number of correctly identified ASD children by 12 compared to M-CHAT, with no children with ASD screening negative on the M-CHAT criteria subsequently screening positive utilizing the M-CHAT-R algorithm. A nonparametric McNemar's test determined a statistically significant difference in identifying ASD utilizing the M-CHAT-R algorithm. The present study examined the application of 20-item MCHAT-R scoring criterion to the 23-item MCHAT. We found that this resulted in decreased sensitivity and increased specificity for identifying children with ASD, which is a trade-off that needs further investigation in terms of cost-effectiveness. However, further research is needed to optimize screening for ASD in the early developmental period to increase identification of false negatives.

Celebrating 40 years since DSM-III.

This special section celebrates the first official recognition of Autism as a diagnostic concept in 1980 in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual. The articles in this special section note the many areas of significant progress made as well as areas that remain important topics for continued and future research. The official recognition of autism as a diagnostic concept has significantly advanced both clinical work and research.

Puppets facilitate attention to social cues in children with ASD.

Diminished visual attention to faces of social partners represents one of the early characteristics of autism spectrum disorder (ASD). Here we examine if the introduction of puppets as social partners alters attention to speakers' faces in young children with ASD and typically developing (TD) controls. Children with ASD (N = 37; Mage  = 49.44 months) and TD (N = 27; Mage  = 40.66 months) viewed a video depicting a puppet and a human engaged in a conversation. Dwell time on these faces was analyzed as a function of group and speaker's identity. Unlike TD controls, the ASD group exhibited limited visual attention to and chance-level visual preference for the human speaker. However, attention to and preference for the puppet speaker's face was greater than chance and comparable across the two groups. While there was a strong association between low human speaker preference and high autism severity, no association with autism severity was found for puppet speaker preference. Unlike humans, expressive and verbal puppets attracted the attention of children with ASD at levels comparable to that of TD controls. Considering that puppets can engage in reciprocal interactions and deliver simplified, salient social-communicative cues, they may facilitate therapeutic efforts in children with ASD. LAY SUMMARY: While studies have shown support for therapeutic uses of robots with children with autism, other similar agents such as puppets remain to be explored. When shown a video of a conversation between a puppet and a person, young children with ASD paid as much attention to the puppet's face as typically-developing (TD) children. Since puppets can engage in back-and-forth interactions and model social interactions and communication, they may play a promising role in therapeutic efforts for young children with ASD.

Seeing the forest and the trees: Disentangling autism phenotypes in the age of DSM-5.

This paper, written in honor of Professor Ed Zigler, focuses on some of the themes in developmental disabilities research that were so central to his work. It has now been nearly 80 years since Leo Kanner first identified the prototypic form - early infantile autism - of what is now autism spectrum disorder. In this article we summarize the development of the concept and the important accumulation of knowledge over time that has now led us to the recognition of a broader autism phenotype just as, at the same time, the current official diagnostic system in the USA has narrowed the concept. We also address current controversies regarding autism as the diagnosis is impacted by age and developmental factors, gender, and cultural issues. In parallel to the work on intellectual deficiency and development pioneered by Zigler and his colleagues, we summarize some of the challenges for the years ahead.

The Diagnosis of Autism: From Kanner to DSM-III to DSM-5 and Beyond.

In this paper we review the impact of DSM-III and its successors on the field of autism-both in terms of clinical work and research. We summarize the events leading up to the inclusion of autism as a "new" official diagnostic category in DSM-III, the subsequent revisions of the DSM, and the impact of the official recognition of autism on research. We discuss the uses of categorical vs. dimensional approaches and the continuing tensions around broad vs. narrow views of autism. We also note some areas of current controversy and directions for the future.

Functional Outcomes of Children Identified Early in the Developmental Period as at Risk for ASD Utilizing the The Norwegian Mother, Father and Child Cohort Study (MoBa).

Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk¼ range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.

Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol.

Performing functional magnetic resonance imaging (fMRI) scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in fMRI connectivity analyses. One approach to limit motion has been to use shorter MRI protocols, though this reduces the reliability of results. Hence, there is a need to implement methods to achieve high-quality, low-motion data while not sacrificing data quantity. Here we show that by using a mock scan protocol prior to a scan, in conjunction with other in-scan steps (weighted blanket and incentive system), it is possible to achieve low-motion fMRI data in pediatric participants (age range: 7-17 years old) undergoing a 60 min MRI session. We also observe that motion is low during the MRI protocol in a separate replication group of participants, including some with autism spectrum disorder. Collectively, the results indicate it is possible to conduct long scan protocols in difficult-to-scan populations and still achieve high-quality data, thus potentially allowing more reliable fMRI findings.

Enhancing the understanding of clinically meaningful results: A clinical research perspective.

Published research often address aspects related to "statistical significance" but fail to address the clinical and practical importance and meaning of results. Our main objectives in this article are to investigate the merit of common measures of Effect Size in statistical research and to highlight the importance of the simple Relative Risk ratio. In this article we present data where we consider two widely utilized effect size measures (Cohen's d and Pearson's r) in relations to relative risk. We conclude that probability analyses of risk surpass the most commonly used statistical approach used in clinical trials today and should thus be the preferred compared to the misuse and misunderstanding of reporting for instance p-values alone.

Clinical Features of Children With Autism Who Passed 18-Month Screening.

OBJECTIVES: We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). METHODS: We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. RESULTS: Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. CONCLUSIONS: This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.

An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder.

Nicotinic acetylcholine receptors (nAChRs), particularly the α7 nAChR, are implicated in the pathophysiology of both autism spectrum disorder (ASD) and aggressive behavior. We explored the feasibility, tolerability, and preliminary efficacy of targeting nAChRs using transdermal nicotine to reduce aggressive symptoms in adults with ASD. Eight subjects were randomized in a double-blind crossover trial of 7 mg transdermal nicotine or placebo, each for 1 week. All participants tolerated nicotine treatment well. Five subjects contributed data to the primary outcome, Aberrant Behavior Checklist-Irritability (ABC-I) subscale change from baseline, which was improved by nicotine compared to placebo. Sleep ratings were also improved by nicotine and correlated with ABC-I improvement. These findings support further investigation of nAChR agonists for aggression and sleep in ASD.

Neural mechanisms of behavioral change in young adults with high-functioning autism receiving virtual reality social cognition training: A pilot study.

Measuring treatment efficacy in individuals with Autism Spectrum Disorder (ASD) relies primarily on behaviors, with limited evidence as to the neural mechanisms underlying these behavioral gains. This pilot study addresses this void by investigating neural and behavioral changes in a Phase I trial in young adults with high-functioning ASD who received an evidence-based behavioral intervention, Virtual Reality-Social Cognition Training over 5 weeks for a total of 10 hr. The participants were tested pre- and post-training with a validated biological/social versus scrambled/nonsocial motion neuroimaging task, previously shown to activate regions within the social brain networks. Three significant brain-behavior changes were identified. First, the right posterior superior temporal sulcus, a hub for socio-cognitive processing, showed increased brain activation to social versus nonsocial stimuli in individuals with greater gains on a theory-of-mind measure. Second, the left inferior frontal gyrus, a region for socio-emotional processing, tracked individual gains in emotion recognition with decreased activation to social versus nonsocial stimuli. Finally, the left superior parietal lobule, a region for visual attention, showed significantly decreased activation to nonsocial versus social stimuli across all participants, where heightened attention to nonsocial contingencies has been considered a disabling aspect of ASD. This study provides, albeit preliminary, some of the first evidence of the harnessable neuroplasticity in adults with ASD through an age-appropriate intervention in brain regions tightly linked to social abilities. This pilot trial motivates future efforts to develop and test social interventions to improve behaviors and supporting brain networks in adults with ASD. Autism Res 2018, 11: 713-725. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: This study addresses how the behavioral changes after treatment for ASD reflect underlying brain changes. Before and after receiving VR-SCT, young adults with high-functioning ASD passively viewed biological motion stimuli in a MRI scanner, tapping changes in the social brain network. The results reveal neuroplasticity in this age population, extending the window of opportunity for interventions to impact social competency in adults with ASD.

Sex-Differences in Children Referred for Assessment: An Exploratory Analysis of the Autism Mental Status Exam (AMSE).

The autism mental status exam is an eight-item observational assessment that structures the way we observe and document signs and symptoms of ASD. Investigations of test performance indicate strong sensitivity and specificity using gold-standard assessment as reference standard. This study aims to explore potential sex differences in AMSE test performance and observations of 123 children referred for autism assessment. Results indicates more language deficits in females with ASD than in males with ASD and less sensory symptoms in females compared to males with ASD. The AMSE performance is similar in identifying ASD and non-ASD in females compared to males. Less disruptive behaviors in females, might cause a need for a bigger hit to other areas of development to raise concern.