Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and the role of neuroinflammation in autism behaviors needs to be further investigated. The aim of the present study was to test the possible association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and nuclear kappa B (NF-κB) and the severity of cognitive disorders, social impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and NF-κB as biochemical parameters related to neuroinflammation were determined in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46 neurotypical controls. The data indicated that ASD patients have remarkably higher levels of the measured parameters compared to neurotypical controls, except for EP2 receptors that showed an opposite trend. While the measured parameter did not correlate with the severity of social and cognitive dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the dysfunction in sensory processing. NF-κB was significantly increased in relation to age. Based on the discussed data, the positive correlation between PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as biomarkers of autism severity. NF-κB as inflammatory inducer showed an elevated level in plasma of ASD individuals. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of biochemical correlates to ASD.

The cerebellum, which forms widespread functional networks with many areas in the cerebral cortices and subcortical structures, is one of the brain regions most consistently reported to exhibit neuropathological features in patients with autism spectrum disorder (ASD). However, cerebellar functional connectivity (FC) studies in patients with ASD have been very sparse. Using resting state functional connectivity (rsFC) analysis, we investigated the FC of the hemispheric/vermal subregions and the dentate nucleus of the cerebellum with the cerebral regions in 36 children and adolescents [16 participants with ASD, 20 typically developing (TD) participants, age: 6–15 years]. Furthermore, an independent larger sample population (42 participants with ASD, 88 TD participants, age: 6–15 years), extracted from the Autism Brain Imaging Data Exchange (ABIDE) II, was included for replication. The ASD group showed significantly increased or decreased FC between “hubs” in the cerebellum and cerebral cortices, when compared with the TD group. Findings of aberrant FCs converged on the posterior hemisphere, right dentate nucleus, and posterior inferior vermis of the cerebellum. Furthermore, these aberrant FCs were found to be related to motor, executive, and socio-communicative functions in children and adolescents with ASD when we examined correlations between FC and behavioral measurements. Results from the original dataset were partially replicated in the independent larger sample population. Our findings suggest that aberrant cerebellar–cerebral FC is associated with motor, socio-communicative, and executive functions in children and adolescents with ASD. These observations improve the current knowledge regarding the neural substrates that underlie the symptoms of ASD.

Developmental changes in large-scale network connectivity in autism

Sensory processing disorders have been linked to stereotypical behaviours in children with intellectual disability (ID) and autism spectrum disorders (ASD) and to anxiety in children with ASD. In earlier phases of this study with the same participants, we found that those with both ASD and ID were more motivated than those with ID alone to engage in stereotypical behaviour to alleviate anxiety. In this phase, we confirmed that children with both ASD and ID and those with ID alone process sensation differently than typically developing children. We asked: Do the sensory processing difficulties of children with ASD and ID differ significantly from those of children with ID alone in a way that would help explain the increased anxiety of the former group? Parents of children with ASD and ID (n = 29; mean age 9.7 years) and with ID alone (n = 23; mean age 9.5 years) completed a Sensory Profile (SP) to provide information about their children's sensory processing abilities. SP quadrant scores for each group were compared with each other and with the published norms of typically developing children. Children with ASD and ID and with ID alone processed sensory information differently than typically developing children (P=0.0001;d= >2.00). Children with both ASD and ID were significantly more sensitive (P=0.007;d=0.70) and avoidant (P < 0.05;d=0.47) than the children with ID alone. We conclude that increased sensitivity and the tendency to avoid sensation may help explain anxiety in children with autism.

INTRODUCTION: Sensory processing dysfunction (SPD) has only recently been described in women with genito-pelvic pain/penetration disorder (GPPPD). However, female sexual pain is a virtually unknown area of practice for occupational therapists providing intervention for adults with SPD AIM: To describe the experiences of women with GPPPD with identified sensory processing dysfunction (SPD) who followed a sensory-based home programme METHODS: Purposive, non-probability sampling was used to recruit participants for the qualitative arm of the study after they presented with SPD in the quantitative part of the study. Semi-structured individual interviews were used to gather information and sufficient information power was reached after five participants were interviewed. Data were analysed descriptively using inductive thematic and saliency analyses RESULTS: Two themes were identified. Theme one: Changes experienced after participating in a sensory-based home programme, reflected increased insight into SPD (allowing participants to identify sensory triggers) and intra-personal changes (increased tolerance of sensory stimuli, feelings of control and I can breathe again). Theme two: Coping strategies employed by women with SPD and GPPPD, included sensory seeking, changes to home and work environments, positive reinterpretation/growth, acceptance, and socio-emotional support (you're not the only one. There are plenty of us out there CONCLUSION: A sensory-based home programme, catering to specific sensory profiles is beneficial as a non-invasive occupational therapy intervention approach (based on sensory integrative therapy) for women with both SPD and GPPPD Implications for occupational therapy: • SPD in the context of sexual pain is an emergent field in occupational therapy, thus occupational therapists need to expand service-delivery to this population and other practitioners such as gynaecologists must be alerted to occupational therapy as a non-invasive, and non-pharmaceutical intervention option for patients. • Contribute to the knowledgebase of sensory integration in the adult population. • Improve the occupational therapist's role in sexuality. • Emphasize the importance of insight as part of a treatment programme.

Background Sensory processing dysfunction in children has been linked to attention-deficit/hyperactivity disorder, autism, feeding disorders, and functional abdominal pain. However, little is known about sensory processing in the broader pediatric gastroenterology population. Objective To characterize frequency and type of sensory processing dysfunction seen in pediatric gastroenterology compared to a general pediatric population. Methods The Short Sensory Profile 2 was administered to the parents of children ranging 3-14 years, being seen in a pediatric gastrointestinal (GI) subspecialty clinic or general pediatric clinic. Short Sensory Profile 2 scores from age- and gender-matched groups were compared with nonparametric statistics. Results Sensory processing dysfunction was increased in children seen in the GI clinic compared to children in the general pediatric clinic. Short Sensory Profile 2 quadrant analysis revealed greatest differences in avoiding, primarily in young females of the GI population. Conclusion Children presenting to a pediatric GI clinic demonstrate greater sensory processing dysfunction compared to children in a general pediatric practice.

Sensory reactivity is a diagnostic criterion for Autism Spectrum Disorder (ASD), and has been associated with poorer functional outcomes, behavioral difficulties, and autism severity across the lifespan. Yet, there is little consensus on best practice approaches to assessing sensory processing dysfunction in adolescents and adults with ASD. Despite growing evidence that sensory symptoms persist into adolescence and adulthood, there is a lack of norms for older age groups, and pediatric assessments may not target appropriate functional outcomes or environments. This review identified approaches used to measure sensory processing in the scientific literature, and to describe and compare these approaches to current best practice guidelines that can be incorporated into evidence-based practice. Method and Analysis: A search of scientific databases and grey literature (professional association and ASD society websites), from January 1987–May 2017, uncovered 4769 articles and 12 clinical guidelines. Study and sample characteristics were extracted, charted, and categorized according to assessment approach. Results: There were 66 articles included after article screening. Five categories of assessment approaches were identified: Self- and Proxy-Report Questionnaires, Psychophysical Assessment, Direct Behavioral Observation, Qualitative Interview Techniques, and Neuroimaging/EEG. Sensory research to date has focused on individuals with high-functioning ASD, most commonly through the use of self-report questionnaires. The Adolescent and Adult Sensory Profile (AASP) is the most widely used assessment measure (n = 22), however, a number of other assessment approaches may demonstrate strengths specific to the ASD population. Multi-method approaches to assessment (e.g., combining psychophysical or observation with questionnaires) may have clinical applicability to interdisciplinary clinical teams serving adolescents and adults with ASD. Contribution: A comprehensive knowledge of approaches is critical in the clinical assessment of a population characterized by symptomatic heterogeneity and wide-ranging cognitive profiles. This review should inform future development of international interdisciplinary clinical guidelines on sensory processing assessment in ASD across the lifespan.

Introduction: Sensory processing dysfunction (SPD) has only recently been described in women with genito-pelvic pain/penetration disorder (GPPPD). However, female sexual pain is a virtually unknown area of practice for occupational therapists providing intervention for aduls with sensory processing disorder (SPD). Aim: To describe the experiences of women with a GPPPD with identified SPD who followed a sensory-based home programme. Methods: Purposive, non-probability sampling was used to recruit participants for the qualitative arm of the study after they presented with SPD in the quantitative part of the study. Semi-structured individual interviews were used to gather information and sufficient information power was reached after five participants were interviewed. Data were analysed descriptively using inductive, thematic and saliency analyses. Results: Two themes were identified. Theme one: Changes experienced after participating in a sensory-based home programme, reflected increased insight into SPD (allowing participants to identify sensory triggers) and intra-personal changes (increased tolerance of sensory stimuli, feelings of control and "I can breathe again"). Theme two: Coping strategies employed by women with SPD and GPPPD, included sensory seeking, changes to home and work environments, positive reinterpretation/growth, acceptance and socio-emotional support ("you're not the only one. There are plenty of us out there"). Conclusion: A sensory-based home programme, catering to specific sensory profiles is beneficial as a non-invasive occupational therapy intervention approach (based on sensory integrative therapy) for women with both SPD and GPPPD. Implications for occupational therapy: • SPD in the context of sexual pain is an emergent field in occupational therapy, thus occupational therapis needd to expand service delivery to this population and other practitioners such as gynaecologists must be alerted to occupational therapy as a non-invasive and non-pharmaceutical intervention option for patients. * Contribute to the knowledge base of sensory integration in the adult population. *. Improve the occupational therapist's role in sexuality *. Emphasise the importance of insight as part of a treatment programme.

To investigate gender differences in functional connectivity during the unattended processing of facial expressions, we recorded visual mismatch negativity (vMMN) in 34 adults using a deviant-standard reverse oddball paradigm. Using wavelet analysis, we calculated the time-frequency (TF) power at each electrode associated with happy-deviant, sad-deviant, happy-standard and sad-standard conditions. We also calculated the phase lag index (PLI) between electrode pairs and analyzed the dynamic network topologies of the functional connectivity for happy and sad vMMNs in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–45 Hz) bands. The results showed that females induced stronger TF power and PLI values than males in only the alpha band over the whole brain regarding the vMMN. Moreover, females had a higher ratio of the number of connections between long-distance electrode pairs than males. While theoretical analysis of dynamic network topologies indicated that high node degree values were found in local brain regions of males and in almost the entire female brain, our findings suggested that female brain activation and connections between brain regions are not only stronger but also more widely distributed during the unattended processing of facial expressions than those in males.

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, and Neuroimaging Advancing the Field of Neurology.

Although atypical sensory motor processing has been investigated in children with autism spectrum disorder (ASD), whether or not atypical sensory motor processing is related to altered language function in children with ASD remains unclear. This study examined the relationship between sensory motor processing and language conceptual inference ability in 3-10-year-old children with (n = 61) and without (n = 114) ASD. Language performance was assessed using the language conceptual inference task of the Kaufman Assessment Battery for Children (K-ABC). Sensory processing was assessed using the Caregiver Sensory Profile. In children with ASD, altered processing of the fine motor/perceptual factor scored by sensory profile was found to be significantly related to language conceptual inference ability in the K-ABC, representing the integrated abilities of language comprehension and language expression, which reflect language semantic concept formation. For children with ASD, the results suggest a relationship between difficulties of integrating sensory information perceived from the body adjusting fine movement and deficiencies of language semantic conceptual formation.

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Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD.

Individuals with autism spectrum disorder (ASD) perform poorly in working memory (WM) tasks, with some literature suggesting that their impaired performance is modulated by WM load. While some neuroimaging and neurophysiological studies have reported altered functional connectivity during WM processing in individuals with autism, it remains largely unclear whether such alterations are moderated by WM load. The present study aimed to examine the effect of WM load on functional connectivity within the prefrontal cortex (PFC) in ASD using functional near-infrared spectroscopy (fNIRS). Twenty-two children with high-functioning ASD aged 8–12 years and 24 age-, intelligent quotient (IQ)-, sex- and handedness-matched typically developing (TD) children performed a number n-back task with three WM loads (0-back, 1-back, and 2-back). Hemodynamic changes in the bilateral lateral and medial PFC during task performance were monitored using a multichannel NIRS device. Children with ASD demonstrated slower reaction times, specifically during the “low load” condition, than TD children. In addition, the ASD and TD groups exhibited differential load-dependent functional connectivity changes in the lateral and medial PFC of the right but not the left hemisphere. These findings indicate that WM impairment in high-functioning ASD is paralleled by load-dependent alterations in right, but not left, intrahemispheric connectivity during WM processing in children with ASD. A disruption of functional neural connections that support different cognitive processes may underlie poor performance in WM tasks in ASD.