Investigating sensory response to physical discomfort in children with autism spectrum disorder using near-infrared spectroscopy.

Self-reporting of pain can be difficult in populations with communication challenges or atypical sensory processing, such as children with autism spectrum disorder (ASD). Consequently, pain can go untreated. An objective method to identify discomfort would be valuable to individuals unable to express or recognize their own bodily distress. Near-infrared spectroscopy (NIRS) is a brain-imaging modality that is suited for this application. We evaluated the potential of detecting a cortical response to discomfort in the ASD population using NIRS. Using a continuous-wave spectrometer, prefrontal and parietal measures were collected from 15 males with ASD and 7 typically developing (TD) males 10-15 years of age. Participants were exposed to a noxious cold stimulus by immersing their hands in cold water and tepid water as a baseline task. Across all participants, the magnitude and timing of the cold and tepid water-induced brain responses were significantly different (p < 0.001). The effect of the task on the brain response depended on the study group (group x task: p < 0.001), with the ASD group exhibiting a blunted response to the cold stimulus. Findings suggest that NIRS may serve as a tool for objective pain assessment and atypical sensory processing.

Pitch direction ability predicts melodic perception in autism.

Individuals with autism spectrum disorders (ASDs) often present atypical auditory perception. Previous work has reported both enhanced low-level pitch discrimination and superior abilities to detect local pitch structure on higher-level melodic tasks in ASD. However, it is unclear how low and high levels of auditory perception are related in ASD or typical development (TD), or how this relationship might change across development and stimulus presentation rates. To these aims, in the present study, children with ASD and TD were tested on a low-level pitch direction discrimination task and a high-level melodic global-local task. Groups performed similarly on both of these auditory tasks. Moreover, individual differences in low-level pitch direction ability predicted performance on the higher-level global-local task, with a stronger relationship in ASD. Age did not affect the relationship between low-level and high-level pitch performance in either ASD or TD. However, there was a more positive effect of age on the high-level global-local task performance in TD than ASD. Finally, there was no effect of stimulus rate on the relationship between low-level and high-level pitch performance in either group. These findings provide a better understanding of how perception is associated across levels of processing in ASD versus TD. This work helps to better understand individual differences in auditory perception and to refine ASD phenotypes.

Client and family engagement in rehabilitation research: a framework for health care organizations.

PURPOSE: To describe the development and implementation of an organizational framework for client and family-centered research. METHOD: Case report. RESULTS: While patient-centered care is now well established, patient-centered research remains underdeveloped. This is particularly true at the organizational level (e.g., hospital based research institutes). In this paper we describe the development of an organizational framework for client and family centered research at Holland Bloorview Kids Rehabilitation Hospital in Toronto, Canada. CONCLUSION: It is our hope that, by sharing our framework other research institutions can learn from our experience and develop their own research patient/client/family engagement programs. Implications for rehabilitation Family engagement in rehabilitation research •Rehabilitation research is crucial to the development and improvement of rehabilitative care. •The relevance, appropriateness, and accountability of research to patients, clients and families could be improved. •Engaging clients and families as partners in all aspects of the research process is one way to address this problem. •In this paper, we describe a framework for engaging clients and families in research at the organizational level.

Auditory Pitch Perception in Autism Spectrum Disorder Is Associated With Nonverbal Abilities.

Atypical sensory perception and heterogeneous cognitive profiles are common features of autism spectrum disorder (ASD). However, previous findings on auditory sensory processing in ASD are mixed. Accordingly, auditory perception and its relation to cognitive abilities in ASD remain poorly understood. Here, children with ASD, and age- and intelligence quotient (IQ)-matched typically developing children, were tested on a low- and a higher level pitch processing task. Verbal and nonverbal cognitive abilities were measured using the Wechsler's Abbreviated Scale of Intelligence. There were no group differences in performance on either auditory task or IQ measure. However, there was significant variability in performance on the auditory tasks in both groups that was predicted by nonverbal, not verbal skills. These results suggest that auditory perception is related to nonverbal reasoning rather than verbal abilities in ASD and typically developing children. In addition, these findings provide evidence for preserved pitch processing in school-age children with ASD with average IQ, supporting the idea that there may be a subgroup of individuals with ASD that do not present perceptual or cognitive difficulties. Future directions involve examining whether similar perceptual-cognitive relationships might be observed in a broader sample of individuals with ASD, such as those with language impairment or lower IQ.

Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder.

There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto-temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD.

How and why should we engage parents as co-researchers in health research? A scoping review of current practices.

BACKGROUND: The importance of engaging parents in health research as co-researchers is gaining growing recognition. While a number of benefits of involving parents as co-researchers have been proposed, guidelines on exactly how effective engagement can be achieved are lacking. The objectives of this scoping review were to (i) synthesize current evidence on engaging parents as co-researchers in health research; (ii) identify the potential benefits and challenges of engaging parent co-researchers; and (iii) identify gaps in the literature. METHODS: A scoping literature review was conducted using established methodology. Four research databases and one large grey literature database were searched, in addition to hand-searching relevant journals. Articles meeting specific inclusion criteria were retrieved and data extracted. Common characteristics were identified and summarized. RESULTS: Ten articles were included in the review, assessed as having low-to-moderate quality. Parent co-researchers were engaged in the planning, design, data collection, analysis and dissemination aspects of research. Structural enablers included reimbursement and childcare. Benefits of engaging parent co-researchers included enhancing the relevance of research to the target population, maximizing research participation and parent empowerment. Challenges included resource usage, wide-ranging experiences, lack of role clarity and power differences between parent co-researchers and researchers. Evaluation of parent co-researcher engagement was heterogeneous and lacked rigour. CONCLUSIONS: A robust evidence base is currently lacking in how to effectively engage parent co-researchers. However, the review offers some insights into specific components that may form the basis of future research to inform the development of best practice guidelines.

Novel mechanisms and treatment approaches in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by marked heterogeneity in biology, expression, and response to treatment. The past decade has yielded considerable progress in understanding the underlying biological mechanisms, in characterizing the earliest behavioral phenotype(s), and in developing and evaluating effective treatments for ASD. This review highlights recent research advances in genetics and neuroimaging, as well as in novel behavioral and psychopharmacological treatment approaches, arguing for the value of trans-disciplinary initiatives to move the field forward exponentially. Despite considerable complexity, patterns are beginning to emerge that can inform the identification of novel treatment targets and approaches. The next generation of major innovations in ASD research will involve collaborations across genetics/genomics, neuroimaging, and intervention science. Such efforts, currently under way, hold tremendous promise for exponentially increasing our capacity to understand the mechanisms that contribute to the emergence of ASD and to develop and evaluate personalized interventions that yield maximal impact in a meaningful way.

Effects of Age and Attention on Auditory Global-Local Processing in Children with Autism Spectrum Disorder.

In vision, typically-developing (TD) individuals perceive "global" (whole) before "local" (detailed) features, whereas individuals with autism spectrum disorder (ASD) exhibit a local bias. However, auditory global-local distinctions are less clear in ASD, particularly in terms of age and attention effects. To these aims, here ASD and TD children judged local and global pitch structure in nine-tone melodies. Both groups showed a similar global precedence effect, but ASD children were less sensitive to global interference than TD children at younger ages. There was no effect of attention task. These findings provide novel evidence of developmental differences in auditory perception and may help to refine sensory phenotypes in ASD.

Structural Gray Matter Differences During Childhood Development in Autism Spectrum Disorder: A Multimetric Approach.

BACKGROUND: Autism spectrum disorder is a complex neurodevelopmental disorder characterized by impaired social interaction and communication, repetitive behaviors, and restricted interests. Gray matter differences linked to autism spectrum disorder have been studied using a variety of structural imaging methods, but yielded little consensus; the extent to which disparate results reflect differences in methodology or heterogeneity within autism spectrum disorder is not yet clear. Moreover, very few studies have examined gray matter changes as a function of age in autism spectrum disorder. METHOD: A detailed investigation of gray matter structural development was performed via voxel-based morphometry, cortical thickness, and cortical surface area analyses in 38 autism spectrum disorder versus 46 typically developing children. RESULTS: Relative to typically developing children, the autism spectrum disorder group showed gray matter increases most prominently in the frontal and temporal lobes (including regions such as medial frontal gyrus, Broca's area and posterior temporal cortex), as well as certain parietal and occipital subcortical regions. Gray matter decreases were found only near the temporoparietal junction. Subcortical gray matter increases were found in the putamen and caudate nucleus, while decreases were found in cerebellum. There were age-dependent GM differences in distributed regions including prefrontal cortex, primary sensorimotor cortex, and temporoparietal junction. CONCLUSION: The results underline the distributed nature of gray matter structural differences in autism spectrum disorder and provide a more comprehensive characterization of autism spectrum disorder-related cortical and subcortical gray matter structural differences during childhood and adolescent development.

Examining and comparing social perception abilities across childhood-onset neurodevelopmental disorders.

OBJECTIVE: Several neurodevelopmental disorders are associated with social processing deficits. The objective of this study was to compare patterns of social perception abilities across obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and control participants. METHOD: A total of 265 children completed the Reading the Mind in the Eyes Test-Child Version (RMET). Parents or caregivers completed established trait/symptom scales. The predicted percentage of accuracy on the RMET was compared across disorders and by item difficulty and item valence (i.e., positive/negative/neutral mental states), then analyzed for associations with trait/symptom scores. RESULTS: The percentage of correct RMET scores varied significantly between diagnostic groups (p < .0001). On pairwise group comparisons controlling for age and sex, children with ADHD and ASD scored lower than the other groups (p < .0001). When IQ was also controlled for in the model, participants with OCD performed better than controls (p < .001), although differences between other groups were less pronounced. Participants with ASD scored lowest on easy items. Those with ASD and ADHD scored significantly lower than other groups on items with positive valence (p < .01). Greater social communication impairment and hyperactivity/impulsivity, but not OCD traits/symptoms, were associated with lower scores on the RMET, irrespective of diagnosis. CONCLUSION: Social perception abilities in neurodevelopmental disorders exist along a continuum. Children with ASD have the greatest deficits, whereas children with OCD may be hypersensitive to social information. Social communication deficits and hyperactive/impulsive traits are associated with impaired social perception abilities; these findings highlight overlapping cognitive and behavioral manifestations across disorders.

Atypical functional brain connectivity during rest in autism spectrum disorders.

OBJECTIVE: Connectivity atypicalities in autism spectrum disorders (ASD) have been extensively proposed. The default mode network (DMN) is critical in this study, given the insight it provides for long-distance connectivity, and the importance of regions in this network for introspection and social emotion processing, areas affected in ASD. However, study of this network has largely been limited to adults; research earlier in development is lacking. The objective of this study was to examine DMN connectivity in children/adolescents with ASD. METHODS: A total of 115 children/adolescents, aged 6 to 17 years (71 males with ASD and 44 group age-matched TD males) were included in these analyses. We examined group differences in (1) functional connectivity between the posterior cingulate cortex and regions across the brain, (2) connectivity within the DMN as a function of age and intelligence quotient (IQ), and (3) the association between DMN connectivity and empathic accuracy. RESULTS: Individuals with ASD, relative to controls, showed either stronger or weaker connectivity between the posterior cingulate cortex (PCC) and DMN regions, depending on the region, but also showed stronger connectivity with non-DMN regions. A significant group-by-age interaction was observed in functional connectivity between the PCC and medial prefrontal cortex; connectivity increased with age in controls, but decreased in individuals with ASD. No effects of IQ were found. There was a significant group difference in the relation between DMN connectivity and empathic accuracy. INTERPRETATION: Differences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities.

Is inhibitory control a 'no-go' in adolescents with autism spectrum disorder?

BACKGROUND: Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents. METHODS: The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200 ms to 400 ms post-stimulus onset. Significant activations were determined using permutation testing. RESULTS: Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250 ms) followed by the left postcentral gyrus (250 to 300 ms) and finally the left middle frontal and right medial frontal gyri (300 to 400 ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250 ms), followed by the left superior and inferior frontal gyri (250 to 300 ms), then the right middle temporal gyrus (300 to 350 ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400 ms). CONCLUSIONS: Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls.

Metabolic mapping of deep brain structures and associations with symptomatology in autism spectrum disorders.

Structural neuroimaging studies in autism report atypical volume in deep brain structures which are related to symptomatology. Little is known about metabolic changes in these regions, and how they vary with age and sex, and/or relate to clinical behaviors. Using magnetic resonance spectroscopy we measured N-acetylaspartate, choline, creatine, myoinositol and glutamate in the caudate, putamen, and thalamus of 20 children with autism and 16 typically developing controls (7-18 years). Relative to controls, individuals with autism had elevated glutamate/creatine in the putamen. In addition, both groups showed age-related increases in glutamate in this region. Boys, relative to girls had increased choline/creatine in the thalamus. Lastly, there were correlations between glutamate, choline, and myoinositol in all three regions, and behavioral scores in the ASD group. These findings suggest changes in deep gray matter neurochemistry, which are sensitive to diagnosis, age and sex, and are associated with behavioral differences.

Neurofunctional underpinnings of audiovisual emotion processing in teens with autism spectrum disorders.

Despite successful performance on some audiovisual emotion tasks, hypoactivity has been observed in frontal and temporal integration cortices in individuals with autism spectrum disorders (ASD). Little is understood about the neurofunctional network underlying this ability in individuals with ASD. Research suggests that there may be processing biases in individuals with ASD, based on their ability to obtain meaningful information from the face and/or the voice. This functional magnetic resonance imaging study examined brain activity in teens with ASD (n = 18) and typically developing controls (n = 16) during audiovisual and unimodal emotion processing. Teens with ASD had a significantly lower accuracy when matching an emotional face to an emotion label. However, no differences in accuracy were observed between groups when matching an emotional voice or face-voice pair to an emotion label. In both groups brain activity during audiovisual emotion matching differed significantly from activity during unimodal emotion matching. Between-group analyses of audiovisual processing revealed significantly greater activation in teens with ASD in a parietofrontal network believed to be implicated in attention, goal-directed behaviors, and semantic processing. In contrast, controls showed greater activity in frontal and temporal association cortices during this task. These results suggest that in the absence of engaging integrative emotional networks during audiovisual emotion matching, teens with ASD may have recruited the parietofrontal network as an alternate compensatory system.

Effects of age and symptomatology on cortical thickness in autism spectrum disorders.

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours.

The effect of diagnosis, age, and symptom severity on cortical surface area in the cingulate cortex and insula in autism spectrum disorders.

Functional activity in the anterior cingulate cortex and insula has been reported to be abnormal during social tasks in autism spectrum disorders. However, few studies have examined surface morphometry in these regions and how this may be related to autism spectrum disorder symptomatology. In this study, 27 individuals with autism spectrum disorders and 25 controls between the ages of 7 to 39 years underwent structural magnetic resonance imaging. Our primary analysis examined differences in surface area in the cingulate and insula, between individuals with and without autism spectrum disorders, as well as age-related changes and associations with social impairments. Surface area in the right cingulate was significantly different between groups and decreased more rapidly with age in autism spectrum disorder participants. In addition, greater surface area in the insula and isthmus was associated with poorer social behaviors. Results suggest atypical surface morphometry in brain regions involved in social function, which appeared to be related to poorer social ability scores.