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Autism spectrum disorder (ASD) is characterized by abnormal functional organization of brain networks, which may underlie the cognitive and social impairments observed in affected individuals. The present study characterizes unique intrinsic connectivity within- and between- neural networks in children through to adults with ASD, relative to controls. Resting state fMRI data were analyzed in 204 subjects, 102 with ASD and 102 age- and sex-matched controls (ages 7-40 years), acquired on a single scanner. ASD was assessed using the autism diagnostic observation schedule (ADOS). BOLD correlations were calculated between 47 regions of interest, spanning seven resting state brain networks. Partial least squares (PLS) analyses evaluated the association between connectivity patterns and ASD diagnosis as well as ASD severity scores. PLS demonstrated dissociable connectivity patterns in those with ASD, relative to controls. Similar patterns were observed in the whole cohort and in a subgroup analysis of subjects under 18 years of age. Greater inter-network connectivity was seen in ASD with greater intra-network connectivity in controls. In conclusion, stronger inter-network and weaker intra-network resting state-fMRI BOLD correlations characterize ASD and may differentiate control and ASD cohorts. These findings are relevant to understanding ASD as a disruption of network topology.

This study examined functional changes longitudinally over 2 years in neural correlates associated with working memory in youth with and without autism spectrum disorder, and the impact of increasing cognitive load. We used functional magnetic resonance imaging and a visuo-spatial 1-back task with four levels of difficulty. A total of 14 children with autism spectrum disorder and 15 typically developing children (ages 7–13) were included at baseline and followed up approximately 2 years later. Despite similar task performance between groups, differences were evident in the developmental trajectories of neural responses. Typically developing children showed greater load-dependent activation which intensified over time in the frontal, parietal and occipital lobes and the right fusiform gyrus, compared to those with autism spectrum disorder. Children with autism spectrum disorder showed minimal age-related changes in load-dependent activation, but greater longitudinal load-dependent deactivation in default mode network compared to typically developing children. Results suggest inadequate modulation of neural activity with increasing cognitive demands in children with autism spectrum disorder, which does not mature into adolescence, unlike their typically developing peers. Diminished ability for children with autism spectrum disorder to modulate neural activity during this period of maturation suggests that they may be more vulnerable to the increasing complexity of social and academic demands as they progress through adolescence than their peers.

Background Adults with Autism Spectrum Disorder (ASD) encounter many difficulties finding and accessing health care services. Despite this, few studies have considered the health service use patterns of adults with ASD without intellectual disability (ID). Objectives The current study examines a diverse range of medical and mental health services and supports, as well as adults' personal experiences accessing and using these services, barriers to service use, and reported unmet service needs. Methods Forty adults (ages 18–61 years) with ASD without ID completed surveys every two months about their health service use for a total of 12–18 months. Bivariate analyses were conducted to understand the individual demographic and clinical factors associated with rate of service use, satisfaction with services, and barriers to health care. Results Results indicated that, beyond a family doctor, the most commonly used services were dentistry, individual counseling, and psychiatry. Individuals who had medical problems experienced significantly more barriers to service use than those who did not, and those who had medical and mental health problems were less satisfied with services. Conclusions Findings highlight the challenges adults with ASD without ID face accessing appropriate, quality services to meet their needs, particularly those with complex medical and mental health issues. Service providers must strive to provide adequate health care to this population who may become distressed if their needs are left unmet.

Objective. There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear if and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder. Methods. To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography (MEG) from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity). Results. While no overall group differences were observed, significant alterations in linear and non-linear age-related changes in resting oscillatory power and network synchrony were found. These differences were frequency- and region-specific and implicated brain systems thought to play a prominent role in ASD, such as the frontal cortex and cerebellum. We also found correlations between the Autism Diagnostic Observation Schedule (ADOS) scores and the degree to which connectivity in cerebellar networks is ‘idiosyncratic' in an individual with autism. Interpretation. We provide the first evidence that it is the curvatures of maturational changes in neurophysiological oscillations and synchrony, rather than disturbances in a particular direction, which characterizes the brain function in individuals with ASD. Moreover, the patterns of idiosyncratic distortions of network synchrony relative to the group curve are associated with behavioral symptoms of ASD. This article is protected by copyright. All rights reserved.

Children with autism spectrum disorder (ASD) exhibit social-communicative impairments. Less is known about the neuropsychological profile of ASD, although cognitive and neuropsychological deficits are evident. We modelled neuropsychological function in 20 children with ASD and 20 sex, age and IQ matched typically-developing controls (ages 7–14) as a network of interacting parameters. Graph theoretical analysis was applied to identify critical topographic regions within this network. Two areas were significantly stronger hubs in typically-developing children, the ability to shift attention (p

Working memory (WM) – temporary storage and manipulation of information in the mind – is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM.We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9–15yr) and sixteen young adults (ages 20–25yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.

Background Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterised by diminished social reciprocity and communication skills and the presence of stereotyped and restricted behaviours. Executive functioning deficits, such as working memory, are associated with core ASD symptoms. Working memory allows for temporary storage and manipulation of information and relies heavily on frontal-parietal networks of the brain. There are few reports on the neural correlates of working memory in youth with ASD. The current study identified the neural systems underlying verbal working memory capacity in youth with and without ASD using functional magnetic resonance imaging (fMRI). Methods Fifty-seven youth, 27 with ASD and 30 sex- and age-matched typically developing (TD) controls (9–16 years), completed a one-back letter matching task (LMT) with four levels of difficulty (i.e. cognitive load) while fMRI data were recorded. Linear trend analyses were conducted to examine brain regions that were recruited as a function of increasing cognitive load. Results We found similar behavioural performance on the LMT in terms of reaction times, but in the two higher load conditions, the ASD youth had lower accuracy than the TD group. Neural patterns of activations differed significantly between TD and ASD groups. In TD youth, areas classically used for working memory, including the lateral and medial frontal, as well as superior parietal brain regions, increased in activation with increasing task difficulty, while areas related to the default mode network (DMN) showed decreasing activation (i.e., deactivation). The youth with ASD did not appear to use this opposing cognitive processing system; they showed little recruitment of frontal and parietal regions across the load but did show similar modulation of the DMN. Conclusions In a working memory task, where the load was manipulated without changing executive demands, TD youth showed increasing recruitment with increasing load of the classic fronto-parietal brain areas and decreasing involvement in default mode regions. In contrast, although they modulated the default mode network, youth with ASD did not show the modulation of increasing brain activation with increasing load, suggesting that they may be unable to manage increasing verbal information. Impaired verbal working memory in ASD would interfere with the youths’ success academically and socially. Thus, determining the nature of atypical neural processing could help establish or monitor working memory interventions for ASD.

Psychotropic medications are frequently used to treat mental health and behavioral issues in adolescents and adults with an autism spectrum disorder (ASD). Although parents of individuals with ASD frequently take on medication management for their child, there is limited literature on parent perspectives of their child's medication use or their views about the healthcare services they receive, particularly in adulthood. The current study examined and compared parents of adolescents and of young adults with ASD regarding their child's psychotropic medication use and their views about healthcare services.One hundred parents of adolescents and young adults with ASD (ages 12-30 years) completed an online survey about their experience with their child's healthcare services and medication use.Parents of young adults were less likely to use nonpharmacological services before using a psychotropic medication than were parents of adolescents. Parents of young adults were also less likely to believe that their prescribing healthcare provider had adequate expertise in ASD, and were less satisfied with how their prescriber monitored their child's medication use.Findings highlight the need to build capacity among healthcare providers supporting individuals with ASD as they transition into adulthood. There is also a need for improved medication monitoring and increased awareness of the different mental health challenges that individuals with ASD encounter as they age.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by socio-communicative impairments. Executive dysfunction may explain some key characteristics of ASD, both social and nonsocial hallmarks. Limited research exists exploring the relations between executive function and social impairment in ASD and few studies have used a comparison control group. Thus, the objective of the present study was to investigate the relations between executive functioning using the Behavioral Rating Inventory of Executive Functioning (BRIEF), social impairment as measured by the Social Responsiveness Scale (SRS), and overall autistic symptomology as measured by the Autism Diagnostic Observation Schedule (ADOS) in children and adolescents with and without ASD. Seventy children and adolescents diagnosed with ASD and 71 typically developing controls were included in this study. Findings showed that behavioral regulation executive processes (i.e., inhibition, shifting, and emotional control) predicted social function in all children. However, metacognitive executive processes (i.e., initiation, working memory, planning, organization, and monitoring) predicted social function only in children with ASD and not in typically developing children. Our findings suggest a distinct metacognitive executive function-social symptom link in ASD that is not present in the typical population. Understanding components of executive functioning that contribute to the autistic symptomology, particularly in the socio-communicative domain, is crucial for developing effective interventions that target key executive processes as well as underlying behavioral symptoms.

Approximately 1 in 88 individuals have an autism spectrum disorder (ASD), and the pro- portion of children diagnosed is on the rise (Centers for Disease Control and Prevention [CDC], 2012). ASD is a neurodevelopmental disorder characterized by social deficits, com- municative difficulties, and repetitive behaviors, with evidence of cognitive dysfunction (American Psychiatric Association [APA], 2013). Although ASD is most widely known as a childhood disability, symptoms persist into adolescence and adulthood, where individuals continue to experience social difficulties, com- municative impairments, stereotyped behavior (Ballaban-Gil, Rapin, Ruchman, & Shinnar, 1991; Fecteau, Mottron, Berthiaume, & Burack, 2003; Howlin, Goode, Hutton, & Rutter, 2004; Matson & Horovitz, 2010; see Seltzer, Shattuck, Abbeduto, & Greenburg, 2004, for a review), and comorbid mental health issues (Davis et al., 2011; Palucka & Lunsky, 2007; Seltzer et al., 2004). Adolescents and adults with ASD also have sustained impairments in academic per- formance, employment, social relationships (Howlin et al., 2004; Mao, 2012), and adap- tive functioning (Chadwick, Cuddy, Kusel, & Taylor, 2005). Despite these significant impair- ments, access to health services and supports become increasingly difficult as individuals with ASD age out of the pediatric system (Autism Ontario, 2008). After age 21, young adults are no longer integrated in public school and child health systems, and identification and coordination of appropriate structured daytime activities can become particularly challenging (Mao, 2012). Consequently, many young adults remain highly dependent on their families for support (Ballaban-Gil et al. 1991; Howlin et al., 2004; Levy & Perry, 2011; Mao, 2012). In a recent review of outcomes for adults with ASD, the number of adolescents and adults living with families ranged from approximately 22% to 70% (Howlin & Moss, 2012), leaving many parents with the responsibility of health care and social service provision for their adult child in addition to behavior management and assistance with daily living.Caring for an individual with ASD is associ- ated with high levels of caregiver burden-"the perception of psychological distress, anxiety, depression, demoralization, and generalized loss of personal freedom attributed directly to caregiving" (Lawton, Moss, Kleban, Glicks- man, & Rovine, 1991, p. 182)-from the time of diagnosis (Stuart & McGrew, 2008), and throughout childhood (Lee, Harrington, Louie, & Newschaffer, 2008; Rodrigue, Morgan, & Geffken, 1990), adolescence, and young adult- hood (Cadman et al., 2012; Kring, Greenberg, & Seltzer, 2008; Lee et al., 2008; Lin, 2011). Health care costs are substantially higher for children with ASD (Croen, Najjar, Ray, Lot- spiech, & Bernal, 2006), and parents report greater financial burden compared to care- givers of children with physical and intellectual disabilities (Xiong et al., 2011). Additionally, parents of individuals with ASD report lower personal well-being compared to parents of those with Fragile X syndrome (Abbedutto et al., 2004), Down syndrome (Abbedutto et al., 2004; Blacher & McIntyre, 2006), cerebral palsy (Blacher & McIntyre, 2006), attention-deficit/hyperactivity disorder (ADHD; Cadman et al., 2012), and undifferentiated intellectual disabilities (Blacher & McIntyre, 2006). Caregiver burden is also associated with parent depression, anxiety (Gallagher, Philips, Oliver, & Caroll, Gallagher et al., 2008; Kim, Greenberg, Seltzer, & Krauss, 2003; Luescher, Dede, Glitten, Fennell & Maria, 1999; Magana, Seltzer, Krauss, Rubert, & Szapocznick, 2002), and reduced caregiver satisfaction (Pruncho, 2003). In addition, evidence exists to suggest that psychological distress among families increases as children with ASD become older (Koegel et al., 1992; Marcus, 1984), yet the majority of literature focuses on the experiences of families in childhood. …

There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear whether and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder (ASD).To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity).Although no overall group differences were observed, significant alterations in linear and nonlinear age-related changes in resting oscillatory power and network synchrony were found. These differences were frequency- and region-specific and implicated brain systems thought to play a prominent role in ASD, such as the frontal cortex and cerebellum. We also found correlations between Autism Diagnostic Observation Schedule scores and the degree to which connectivity in cerebellar networks is "idiosyncratic" in an individual with autism.We provide the first evidence that it is the curvatures of maturational changes in neurophysiological oscillations and synchrony, rather than disturbances in a particular direction, that characterize the brain function in individuals with ASD. Moreover, the patterns of idiosyncratic distortions of network synchrony relative to the group curve are associated with behavioral symptoms of ASD. Ann Neurol 2017;81:199-211.

We investigated the mediating role of interference in developmental assessments of working memory (WM) capacity across childhood, adolescence, and young adulthood. One hundred and forty-two participants completed two versions of visuospatial (colour matching task, CMT) and verbal (letter matching task, LMT) WM tasks, which systematically varied cognitive load in a high and low interference condition. Results showed similar developmental trajectories across high interference contexts (CMT- and LMT-Complex) and divergent developmental growth patterns across low interference contexts (CMT- and LMT-Simple). Performance on tasks requiring greater cognitive control was in closer agreement with developmental predictions relative to simple recall guided tasks that rely solely on the storage components of WM. These findings suggest that developmental WM capacity, as measured by the CMT and LMT paradigms, can be better quantified using high interference contexts, in both content domains, and demonstrate steady increases in WM through to mid-adolescence.

Autism Spectrum Disorder (ASD) is a clinically diagnosed, heterogeneous, neurodevelopmental condition, whose underlying causes have yet to be fully determined. A variety of studies have investigated either cortical, subcortical, or cerebellar anatomy in ASD, but none have conducted a complete examination of all neuroanatomical parameters on a single, large cohort. The current study provides a comprehensive examination of brain development of children with ASD between the ages of 4 and 18 years who are carefully matched for age and sex with typically developing controls at a ratio of one-to-two. Two hundred and ten magnetic resonance images were examined from 138 Control (116 males and 22 females) and 72 participants with ASD (61 males and 11 females). Cortical segmentation into 78 brain-regions and 81,924 vertices was conducted with CIVET which facilitated a region-of-interest- (ROI-) and vertex-based analysis, respectively. Volumes for the cerebellum, hippocampus, striatum, pallidum, and thalamus and many associated subregions were derived using the MAGeT Brain algorithm. The study reveals cortical, subcortical and cerebellar differences between ASD and Control group participants. Diagnosis, diagnosis-by-age, and diagnosis-by-sex interaction effects were found to significantly impact total brain volume but not total surface area or mean cortical thickness of the ASD participants. Localized (vertex-based) analysis of cortical thickness revealed no significant group differences, even when age, age-range, and sex were used as covariates. Nonetheless, the region-based cortical thickness analysis did reveal regional changes in the left orbitofrontal cortex and left posterior cingulate gyrus, both of which showed reduced age-related cortical thinning in ASD. Our finding of region-based differences without significant vertex-based results likely indicates non-focal effects spanning the entirety of these regions. The hippocampi, thalamus, and globus pallidus, were smaller in volume relative to total cerebrum in the ASD participants. Various sub-structures showed an interaction of diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-age-range, in the case where age was divided into childhood (age, Highlights • Thorough analysis of neuroanatomical patterns in children and adolescents with ASD • Cortical, subcortical, and cerebellar development is assessed. • Total brain volume is smaller in males with ASD compared with Controls. • Cortical thickness in ASD does not decrease between childhood and adulthood. • Hippocampi, thalamus, globus pallidus and cerebellum are relatively smaller in ASD.

Background Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI). Methods We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7–13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load. Results Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends. Conclusions Children with ASD showed differences in activation in the frontal and parietal lobes—both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.