Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

INTRODUCTION: In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants. METHODS: Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group-level and subject-level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio. RESULTS: Group-level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject-level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function. CONCLUSIONS: The group-level and subject-level approaches employed here demonstrate the value of examining inter-individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.

Brain-Computer Interface Training of mu EEG Rhythms in Intellectually Impaired Children with Autism: A Feasibility Case Series.

Prior studies show that neurofeedback training (NFT) of mu rhythms improves behavior and EEG mu rhythm suppression during action observation in children with autism spectrum disorder (ASD). However, intellectually impaired persons were excluded because of their behavioral challenges. We aimed to determine if intellectually impaired children with ASD, who were behaviorally prepared to take part in a mu-NFT study using conditioned auditory reinforcers, would show improvements in symptoms and mu suppression following mu-NFT. Seven children with ASD (ages 6-8; mean IQ 70.6 ± 7.5) successfully took part in mu-NFT. Four cases demonstrated positive learning trends (hit rates) during mu-NFT (learners), and three cases did not (non-learners). Artifact-creating behaviors were present during tests of mu suppression for all cases, but were more frequent in non-learners. Following NFT, learners showed behavioral improvements and were more likely to show evidence of a short-term increase in mu suppression relative to non-learners who showed little to no EEG or behavior improvements. Results support mu-NFT's application in some children who otherwise may not have been able to take part without enhanced behavioral preparations. Children who have more limitations in demonstrating learning during NFT, or in providing data with relatively low artifact during task-dependent EEG tests, may have less chance of benefiting from mu-NFT. Improving the identification of ideal mu-NFT candidates, mu-NFT learning rates, source analyses, EEG outcome task performance, population-specific artifact-rejection methods, and the theoretical bases of NFT protocols, could aid future BCI-based, neurorehabilitation efforts.

Development of a culturally and linguistically sensitive virtual reality educational platform to improve vaccine acceptance within a refugee population: the SHIFA community engagement-public health innovation programme.

OBJECTIVES: To combat misinformation, engender trust and increase health literacy, we developed a culturally and linguistically appropriate virtual reality (VR) vaccination education platform using community-engaged approaches within a Somali refugee community. DESIGN: Community-based participatory research (CBPR) methods including focus group discussions, interviews, and surveys were conducted with Somali community members and expert advisors to design the educational content. Co-design approaches with community input were employed in a phased approach to develop the VR storyline. PARTICIPANTS: 60 adult Somali refugees and seven expert advisors who specialise in healthcare, autism research, technology development and community engagement. SETTING: Somali refugees participated at the offices of a community-based organisation, Somali Family Service, in San Diego, California and online. Expert advisors responded to surveys virtually. RESULTS: We find that a CBPR approach can be effectively used for the co-design of a VR educational programme. Additionally, cultural and linguistic sensitivities can be incorporated within a VR educational programme and are essential factors for effective community engagement. Finally, effective VR utilisation requires flexibility so that it can be used among community members with varying levels of health and technology literacy. CONCLUSION: We describe using community co-design to create a culturally and linguistically sensitive VR experience promoting vaccination within a refugee community. Our approach to VR development incorporated community members at each step of the process. Our methodology is potentially applicable to other populations where cultural sensitivities and language are common health education barriers.

The revised 2019 standards for psychopharmacological training: Model education and training program in psychopharmacology for prescriptive authority.

The American Psychological Association (APA), under the oversight of the Board of Educational Affairs, and the Board of Professional Affairs, is responsible for the education and training of psychologists in prescriptive authority. All APA standards and guidelines are required by Association Rule 30-8.3 to be revised at least every 10 years. The standards for training psychologists in the safe and responsible practice of prescribing psychotropic medication have been recently updated (Model Education and Training Program in Psychopharmacology for Prescriptive Authority, APA, 2019). A departure from the 1996 and 2009 versions of that document is that training may now be conducted at the doctoral level; however, a postdoctoral supervised clinical fellowship can only occur after the attainment of licensure as a practicing psychologist. Two novel features of the 2019 revision are the use of a competency-based model of learning and assessment, and increased emphasis on supervised clinical experiences in physical assessment and medication management. By the time of completion of their fellowships, practicing psychologists are expected to have clinical competence in the measurement and interpretation of vital signs; neurological examination; therapeutic drug monitoring; systems of care; pharmacology; clinical pharmacology; psychopharmacological research; and finally, professional, ethical, and legal issues. The updated standards were approved as APA policy in February 2019. This article briefly reviews the revision process and highlights the updates made in the most recent version of the standards. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impaired motor skills and atypical functional connectivity of the sensorimotor system in 40- to 65-year-old adults with autism spectrum disorders.

Impairments in fine and gross motor function, coordination, and balance in early development are common in autism spectrum disorders (ASDs). It is unclear whether these deficits persist into adulthood and whether they may be exacerbated by additional motor problems that often emerge in typical aging. We assessed motor skills and used resting-state functional magnetic resonance imaging to study intrinsic functional connectivity of the sensorimotor network in 40- to 65-year-old adults with ASDs (n = 17) and typically developing matched adults (n = 19). Adults with ASDs scored significantly lower on assessments of motor skills compared with an age-matched group of typical control adults. In addition, functional connectivity of the sensorimotor system was reduced and the pattern of connectivity was more heterogeneous in adults with ASDs. A negative correlation between functional connectivity of the motor system and motor skills, however, was only found in the typical control group. Findings suggest behavioral impairment and atypical brain organization of the motor system in middle-age adults with ASDs, accompanied by pronounced heterogeneity.

Facilitating Neurofeedback in Children with Autism and Intellectual Impairments Using TAGteach.

Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial.

OBJECTIVE: No drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low-dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment-1 (SAT-1) trial was a double-blind, placebo-controlled, translational pilot study to examine the safety and activity of low-dose suramin in children with ASD. METHODS: Ten male subjects with ASD, ages 5-14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS-2 comparison scores and Expressive One-Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire. RESULTS: Blood levels of suramin were 12 ± 1.5 µmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 µmol/L after 6 weeks. The terminal half-life was 14.7 ± 0.7 days. A self-limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS-2 comparison scores improved by -1.6 ± 0.55 points (n = 5; 95% CI = -2.3 to -0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors. INTERPRETATION: The safety and activity of low-dose suramin showed promise as a novel approach to treatment of ASD in this small study.

Under-reactive but easily distracted: An fMRI investigation of attentional capture in autism spectrum disorder.

For individuals with autism spectrum disorder (ASD), salient behaviorally-relevant information often fails to capture attention, while subtle behaviorally-irrelevant details commonly induce a state of distraction. The present study used functional magnetic resonance imaging (fMRI) to investigate the neurocognitive networks underlying attentional capture in sixteen high-functioning children and adolescents with ASD and twenty-one typically developing (TD) individuals. Participants completed a rapid serial visual presentation paradigm designed to investigate activation of attentional networks to behaviorally-relevant targets and contingent attention capture by task-irrelevant distractors. In individuals with ASD, target stimuli failed to trigger bottom-up activation of the ventral attentional network and the cerebellum. Additionally, the ASD group showed no differences in behavior or occipital activation associated with contingent attentional capture. Rather, results suggest that to-be-ignored distractors that shared either task-relevant or irrelevant features captured attention in ASD. Results indicate that individuals with ASD may be under-reactive to behaviorally-relevant stimuli, unable to filter irrelevant information, and that both top-down and bottom-up attention networks function atypically in ASD. Lastly, deficits in target-related processing were associated with autism symptomatology, providing further support for the hypothesis that non-social attentional processes and their neurofunctional underpinnings may play a significant role in the development of sociocommunicative impairments in ASD.

Sensory Symptoms and Processing of Nonverbal Auditory and Visual Stimuli in Children with Autism Spectrum Disorder.

Atypical sensory responses are common in autism spectrum disorder (ASD). While evidence suggests impaired auditory-visual integration for verbal information, findings for nonverbal stimuli are inconsistent. We tested for sensory symptoms in children with ASD (using the Adolescent/Adult Sensory Profile) and examined unisensory and bisensory processing with a nonverbal auditory-visual paradigm, for which neurotypical adults show bisensory facilitation. ASD participants reported more atypical sensory symptoms overall, most prominently in the auditory modality. On the experimental task, reduced response times for bisensory compared to unisensory trials were seen in both ASD and control groups, but neither group showed significant race model violation (evidence of intermodal integration). Findings do not support impaired bisensory processing for simple nonverbal stimuli in high-functioning children with ASD.

The Association of Intelligence, Visual-Motor Functioning, and Personality Characteristics With Adaptive Behavior in Individuals With Williams Syndrome.

Williams syndrome (WS) is associated with deficits in adaptive behavior and an uneven adaptive profile. This study investigated the association of intelligence, visual-motor functioning, and personality characteristics with the adaptive behavior in individuals with WS. One hundred individuals with WS and 25 individuals with developmental disabilities of other etiologies were included in this study. This study found that IQ and visual-motor functioning significantly predicted adaptive behavior in individuals of WS. Visual-motor functioning especially predicted the most amount of unique variance in overall adaptive behavior and contributed to the variance above and beyond that of IQ. Present study highlights the need for interventions that address visual-motor and motor functioning in individuals with WS.

Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND: The cerebellum plays important roles in sensori-motor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. METHODS: We used resting-state functional connectivity magnetic resonance imaging in 56 children and adolescents (28 subjects with ASD, 28 typically developing subjects) 8-17 years old. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensori-motor (premotor/primary motor, somatosensory, superior temporal, and occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). RESULTS: There were three main findings: 1) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; 2) partial correlation analyses that emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared with the typically developing group) for sensori-motor ROIs but predominantly reduced connectivity for supramodal ROIs; and 3) this atypical pattern of connectivity was supported by significantly increased noncanonical connections (between sensori-motor cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group. CONCLUSIONS: Our findings indicate that sensori-motor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition.

The Influence of Task Difficulty and Participant Age on Balance Control in ASD.

Impairments in sensorimotor integration are reported in Autism Spectrum Disorder (ASD). Poor control of balance in challenging balance tasks is one suggested manifestation of these impairments, and is potentially related to ASD symptom severity. Reported balance and symptom severity relationships disregard age as a potential covariate, however, despite its involvement in balance development. We tested balance control during increasingly difficult balance conditions in children with ASD and typically developing peers, and investigated relationships between balance control and diagnostic/symptom severity metrics for participants with ASD, including age as a covariate. Balance deficits in ASD were exacerbated by stance alterations, but were not related to symptom severity when age was considered. These findings support impaired balance in ASD, especially in challenging conditions, but question a link between balance and symptom severity.

Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder.

IMPORTANCE: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition. OBJECTIVE: To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ. MAIN OUTCOMES AND MEASURES: Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures. RESULTS: Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction. CONCLUSIONS AND RELEVANCE: Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.

Assessing bioenergetic compromise in autism spectrum disorder with 31P magnetic resonance spectroscopy: preliminary report.

We sought to examine, via Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in a case-control design, whether bioenergetic deficits in autism spectrum disorders extend to the brain and muscle. Six cases with autism spectrum disorder with suspected mitochondrial dysfunction (age 6-18 years) and 6 age/sex-matched controls underwent (31)P magnetic resonance spectroscopy. The outcomes of focus were muscle resting phosphocreatine and intracellular pH as well as postexercise phosphocreatine recovery time constant and frontal brain phosphocreatine. Intracellular muscle pH was lower in each autism spectrum disorder case than their matched control (6/6, P = .03; P = .0048, paired t test). Muscle phosphocreatine (5/6), brain phosphocreatine (3/4), and muscle phosphocreatine recovery time constant (3/3) trends were in the predicted direction (not all participants completed each). This study introduces (31)P magnetic resonance spectroscopy as a noninvasive tool for assessment of mitochondrial function in autism spectrum disorder enabling bioenergetic assessment in brain and provides preliminary evidence suggesting that bioenergetic defects in cases with autism spectrum disorder are present in muscle and may extend to brain.

The Coping Cat program for children with anxiety and autism spectrum disorder: a pilot randomized controlled trial.

The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder (ASD). Twenty-two children (ages 8-14; IQ ≥ 70) with ASD and clinically significant anxiety were randomly assigned to 16 sessions of the Coping Cat program (cognitive-behavioral therapy; CBT) or a 16-week waitlist. Children in the CBT condition evidenced significantly larger reductions in anxiety than those in the waitlist. Treatment gains were largely maintained at two-month follow-up. Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinically significant levels of anxiety in children with high-functioning ASD.

Callosal fiber length and interhemispheric connectivity in adults with autism: brain overgrowth and underconnectivity.

Typical adults show an inverse relation between callosal fiber length and degree of interhemispheric connectivity. This has been hypothesized to be a consequence of the influence of conduction delays and cellular costs during development on axonal pruning, both of which increase with fiber length. Autism spectrum disorder (ASD) provides a test of this hypothesis: Children with ASD are known to have enlarged brains; thus, adults with ASD should show reductions in interhemispheric connectivity proportional to their degree of brain overgrowth during development. This prediction was tested by assessing the relation between both the size and structure of the corpus callosum and callosal fiber length, adjusting for intracranial volume, which is thought to reflect maximum brain size achieved during development. Using tractography to estimate the length of callosal fibers emanating from all areas of cortex, and through which region of the corpus callosum they pass, we show that adults with ASD show an inverse relation between callosal fiber length, adjusted for intracranial volume, and callosum size, and a positive relation between adjusted callosal fiber length and radial diffusivity. The results provide support for the hypothesized impact of fiber length during development.

Brief report: approaches to 31P-MRS in awake, non-sedated children with and without autism spectrum disorder.

We piloted a suite of approaches aimed to facilitate a successful series of up to four brain and muscle (31)Phosphorus-Magnetic Resonance Spectroscopy ((31)P-MRS) scans performed in one session in 12 awake, non-sedated subjects (ages 6-18), 6 with autism spectrum disorders (ASD) and 6 controls. We targeted advanced preparation, parental input, physical comfort, short scan protocols, allocation of extra time, and subject emotional support. 100% of subjects completed at least one brain scan and one leg muscle scan: 42 of 46 attempted scans were completed (91%), with failures dominated by exercise muscle scans (completed in 6/6 controls but 3/6 cases). One completed scan lacked usable data unrelated to subject/scan procedure (orthodonture affected a frontal brain scan). As a group, these methods provide a foundation for conduct and enhancement of future MR studies in pediatric subjects with ASD.

Considerations for the effects of military deployment on children and families.

Children of deployed military personnel represent a unique subculture in the United States. While many children exhibit high levels of resiliency, others will struggle with the impact of a parent who has gone to war. This article looks at some of the stressors of deployment as experienced by children and offers three case examples as well as clinical considerations for those who work with the children and families of the deployed.

Contrasting patterns of language-associated brain activity in autism and Williams syndrome.

Two neurodevelopmental disorders, Williams syndrome (WS) and autism, are both commonly described as having opposite social profiles: social avoidance in autism vs hypersociability in individuals with WS. The goal of this study was to contrast the brain activity associated with language processing in these two populations, in order to understand the very likely interplay between the use of language and the sociability dimension, on which these disorders diverge. Towards this aim, the N400 component of the event-related potentials was used to quantify the processing of semantic integration in these two populations. Results revealed that individuals with WS showed a significantly larger N400 effect, as compared to both typical controls and individuals with autism, while the latter group demonstrated the smallest N400 effect. The findings demonstrate quite opposite profiles of neural correlates of language processing in WS and autism, mirroring their contrasting social phenotypes.

White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study.

OBJECTIVE: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children. METHOD: DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, the genu, body, and splenium of the corpus callosum, the genu and anterior and posterior limbs of the internal capsule, and the middle cerebellar peduncle. RESULTS: Children with ASD had reduced FA and increased radial diffusion for whole-brain white matter and all three segments of the corpus callosum and internal capsule, compared with those in TD children. Increased MD was found for the whole brain and for anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for the middle cerebellar peduncle. CONCLUSIONS: Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for the internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.