Structural Covariance of Sensory Networks, the Cerebellum, and Amygdala in Autism Spectrum Disorder

Abstract

Sensory dysfunction is a core symptom of autism spectrum disorder (ASD), and abnormalities with sensory responsivity and processing can be extremely debilitating to ASD patients and their families. However, relatively little is known about the underlying neuroanatomical and neurophysiological factors that lead to sensory abnormalities in ASD. Investigation into these aspects of ASD could lead to significant advancements in our general knowledge about ASD, as well as provide targets for treatment and inform diagnostic procedures. Thus, the current study aimed to measure the covariation of volumes of brain structures (i.e., structural magnetic resonance imaging) that may be involved in abnormal sensory processing, in order to infer connectivity of these brain regions. Specifically, we quantified the structural covariation of sensory-related cerebral cortical structures, in addition to the cerebellum and amygdala by computing partial correlations between the structural volumes of these structures. These analyses were performed in participants with ASD (n = 36), as well as typically developing peers (n = 32). Results showed decreased structural covariation between sensory-related cortical structures, especially between the left and right cerebral hemispheres, in participants with ASD. In contrast, these same participants presented with increased structural covariation of structures in the right cerebral hemisphere. Additionally, sensory-related cerebral structures exhibited decreased structural covariation with functionally identified cerebellar networks. Also, the left amygdala showed significantly increased structural covariation with cerebral structures related to visual processing. Taken together, these results may suggest several patterns of altered connectivity both within and between cerebral cortices and other brain structures that may be related to sensory processing.

Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

“…A consistent observation of these studies includes reduced long-distance cortical FC in individuals with ASD, with effects most pronounced within sensorimotor, default mode, and visual perceptual networks (Assaf et al, 2010; Di Martino et al, 2014; Hahamy et al, 2015). Recent studies showed decreased cerebellar connectivity to somatomotor and visual cortices in ASD relative to controls that was related to more severe ASD symptoms (Khan et al, 2015; Cardon et al, 2017). These findings suggest that intrinsic functional communication between discrete regions of visual–motor brain networks may be selectively impaired in ASD and related to key clinical features of the disorder.…”

“…FC between brain regions identified as significant in our ALFF–force variability analysis was then compared between groups and examined in relation to visuomotor behavior. Given prior findings that more severe motor abnormalities (Haswell et al, 2009; Estes et al, 2015; Landa et al, 2016) and FC alterations (Khan et al, 2015; Cardon et al, 2017) of visuomotor networks are associated with more severe ASD symptoms, we also examined the relationship between visuomotor network ALFF and FC with clinical ratings of social–communication abnormalities and restricted and repetitive behaviors in individuals with ASD.…”

Altered Cerebellar White Matter in Sensory Processing Dysfunction Is Associated With Impaired Multisensory Integration and Attention

“…Several diffusion tensor imaging (DTI) studies of ASD have shown alterations of WM microstructure in the pathways linking the cerebellum to the brainstem and cerebral hemispheres (Brito et al, 2009 ; Shukla et al, 2010 ; Groen et al, 2011 ; Jeong et al, 2012 ). A 2017 structural MRI study of individuals with ASD showed differences in morphological connectivity among neuroanatomical areas implicated in sensory processing, including sensory regions of the cerebral cortex, the amygdala, and the cerebellum, with altered connectivity between the cerebellum and cortical areas (Cardon et al, 2017 ). Moreover, the cerebellum plays a role in multisensory processing, as its connectivity to the cerebral cortex is important for sensory integration across different modalities such as hearing, sight, touch and even smell (Cardon et al, 2017 ; Zhao et al, 2018 ; Sathyanesan et al, 2019 ).…”

“…A 2017 structural MRI study of individuals with ASD showed differences in morphological connectivity among neuroanatomical areas implicated in sensory processing, including sensory regions of the cerebral cortex, the amygdala, and the cerebellum, with altered connectivity between the cerebellum and cortical areas (Cardon et al, 2017 ). Moreover, the cerebellum plays a role in multisensory processing, as its connectivity to the cerebral cortex is important for sensory integration across different modalities such as hearing, sight, touch and even smell (Cardon et al, 2017 ; Zhao et al, 2018 ; Sathyanesan et al, 2019 ). While investigation of the structural and functional aspects of sensory processing has begun in children with isolated SPD and those with sensory over-responsivity and autism (Bar-Shalita et al, 2009 ; Marco et al, 2011 ; Brandes-Aitken et al, 2018 ; Molholm et al, 2020 ), there has so far been no exploration of the role of the cerebellum in children with isolated SPD.…”

“…DTI is a neuroimaging method that measures the diffusion of water in the brain's white matter. It allows us to visualize and quantify direction, uniformity, and orientation of WM tracts for the examination of structural connectivity, e.g., between cerebellum and sensory cortex areas in ASD (Jeong et al, 2012 ; Cardon et al, 2017 ; Mallott et al, 2019 ). Thus, DTI measures can serve as a proxy for connectivity, especially in studying distributed neural networks, and can reveal subtle microstructural anomalies undetectable by other non-invasive imaging methods (Payabvash et al, 2019 ).…”