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

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

Sensory over-responsivity: parent report, direct assessment measures, and neural architecture.

Background: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. Methods: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. Results: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. Conclusions: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR.

Burden of de novo mutations and inherited rare single nucleotide variants in children with sensory processing dysfunction.

BACKGROUND: In children with sensory processing dysfunction (SPD), who do not meet criteria for autism spectrum disorder (ASD) or intellectual disability, the contribution of de novo pathogenic mutation in neurodevelopmental genes is unknown and in need of investigation. We hypothesize that children with SPD may have pathogenic variants in genes that have been identified as causing other neurodevelopmental disorders including ASD. This genetic information may provide important insight into the etiology of sensory processing dysfunction and guide clinical evaluation and care. METHODS: Eleven community-recruited trios (children with isolated SPD and both biological parents) underwent WES to identify candidate de novo variants and inherited rare single nucleotide variants (rSNV) in genes previously associated with ASD. Gene enrichment in these children and their parents for transmitted and non-transmitted mutation burden was calculated. A comparison analysis to assess for enriched rSNV burden was then performed in 2377 children with ASD and their families from the Simons Simplex Collection. RESULTS: Of the children with SPD, 2/11 (18%), were identified as having a de novo loss of function or missense mutation in genes previously reported as causative for neurodevelopmental disorders (MBD5 and FMN2). We also found that the parents of children with SPD have significant enrichment of pathogenic rSNV burden in high-risk ASD candidate genes that are inherited by their affected children. Using the same approach, we confirmed enrichment of rSNV burden in a large cohort of children with autism and their parents but not unaffected siblings. CONCLUSIONS: Our findings suggest that SPD, like autism, has a genetic basis that includes both de novo single gene mutations as well as an accumulated burden of rare inherited variants from their parents.