Evaluating motor cortical oscillations and age-related change in autism spectrum disorder

Autism spectrum disorder (ASD) is primarily characterized by impairments in social communication and the appearance of repetitive behaviors with restricted interests. Increasingly, evidence also points to a general deficit of motor tone and coordination in children and adults with ASD; yet the neural basis of motor functional impairment in ASD remains poorly characterized. In this study we used magnetoencephalography (MEG) to (1) assess potential group differences between typically developing (TD) and ASD participants in motor cortical oscillatory activity observed on a simple button-press task and (2) to do so over a sufficiently broad age-range so as to capture age-dependent changes associated with development. Event-related desynchronization was evaluated in Mu (8-13 Hz) and Beta (15-30 Hz) frequency bands (Mu-ERD, Beta-ERD). In addition, post-movement Beta rebound (PMBR), and movement-related gamma (60-90 Hz) synchrony (MRGS) were also assessed in a cohort of 123 participants (63 typically developing (TD) and 59 with ASD) ranging in age from 8 to 24.9 years. We observed significant age-dependent linear trends in Beta-ERD and MRGS power with age for both TD and ASD groups; which did not differ significantly between groups. However, for PMBR, in addition to a significant effect of age, we also observed a significant reduction in PMBR power in the ASD group (p 13.2 years (p < 0.001) and this group difference was not observed when assessing PMBR activity for the younger PMBR groups (ages 8-13.2 years; p = 0.48). Moreover, for the older ASD cohort, hierarchical regression showed a significant relationship between PMBR activity and clinical scores of ASD severity (SRS-T scores), after regressing out the effect of age (p < 0.05). Our results show substantial age-dependent changes in motor cortical oscillations (Beta-ERD and MRGS) occur for both TD and ASD children and diverge only for PMBR, and most significantly for older adolescents and adults with ASD. While the functional significance of PMBR and reduced PMBR signaling remains to be fully elucidated, these results underscore the importance of considering age as a factor when assessing motor cortical oscillations and group differences in children with ASD

Screening for Meares-Irlen sensitivity in adults: can assessment methods predict changes in reading speed?

Two methods of assessing candidates for coloured overlays were compared with the aim of determining which method had the most practical utility. A total of 58 adults were assessed as potential candidates for coloured overlays, using two methods; a questionnaire, which identified self-reported previous symptoms, and a measure of perceptual distortions immediately prior to testing. Participants were classified as normal, Meares-Irlen sensitive, and borderline sensitive. Reading speed was measured with and without coloured overlays, using the Wilkins Rate of Reading Test and the change in speed was calculated. Participants classified as normal did not show any significant benefit from reading with an overlay. In contrast, a significant reading advantage was found for the borderline and Meares-Irlen participants. Current symptom rating was found to be a significant predictor of the change in reading speed, however the previous symptom rating was not found to be a reliable predictor. These data indicate that the assessment of perceptual distortions immediately prior to measuring colour preference and reading speed is the most meaningful method of assessing pattern glare and determining the utility of coloured overlays

The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case–control design with population-based ascertainment of children aged 2–5 years with an autism spectrum disorder (ASD) and children in two control groups—one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers

Background and purposeDeletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency.Materials and methodsThirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation.ResultsIn controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency.ConclusionsThese results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity

Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers

BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders (ASD), and deletion subjects exhibit a large (20ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study is to use a multimodal approach to test if changes in white matter microstructure are associated with delayed M100 latency. MATERIALS AND METHODS: 30 pediatric deletion carriers, 9 duplication carriers and 39 control children were studied with both MEG and diffusion MR. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation. RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 CNV carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency. CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure which modulate conduction velocity