Sleep Problems in Preschoolers With Autism Spectrum Disorder Are Associated With Sensory Sensitivities and Thalamocortical Overconnectivity.

BACKGROUND: Projections between the thalamus and sensory cortices are established early in development and play an important role in regulating sleep as well as in relaying sensory information to the cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorder (ASD) might therefore be linked to sensory and sleep problems common in ASD. METHODS: Here, we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep functional magnetic resonance imaging, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5-5 years old) with ASD compared with a matched group of 46 typically developing children. RESULTS: In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high-quality magnetic resonance imaging data (n = 29). In addition, auditory cortex blood oxygen level-dependent signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. CONCLUSIONS: These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

Children with ASD show links between aberrant sound processing, social symptoms, and atypical auditory interhemispheric and thalamocortical functional connectivity.

Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by social and communicative deficits, as well as repetitive behaviors and atypical sensitivity to sensory stimulation. Alterations in network connectivity are widely recognized, but their interplay with social and sensory symptoms remains largely unclear. Here, functional magnetic resonance imaging and diagnostic and behavioral assessments were used in a cohort of children and adolescents with ASD (n=40) and matched typically developing (TD, n=38) controls to examine the relation between auditory processing, interhemispheric and thalamocortical network connectivity, and social-behavioral symptom severity. We found that atypical processing of sounds was related to social, cognitive, and communicative impairments. Additionally, severity of sensory processing deficits and lower verbal IQ were related to reduced interhemispheric connectivity of auditory cortices in ASD. Increased connectivity between the thalamus and auditory cortex in ASD, however, was associated with reduced cognitive and behavioral symptomatology, suggesting that thalamocortical overconnectivity might reflect a compensatory mechanism in ASD. These findings provide novel evidence for links between auditory sensory deficits and impairments in social interaction and communication.

Regional specificity of aberrant thalamocortical connectivity in autism.

Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions.