Atypical Thalamocortical Connectivity and Its Relationship to Sleep Problems and Sound Processing in Young Children with Autism Spectrum Disorders
Abstract
The prevalence of autism spectrum disorders (ASD) in the United States is approaching 2% and is the most common chronic disability affecting military members and families. In addition to the core symptoms of ASD, co-occurring conditions and medical comorbidities are common. Sleep problems are reported by 50-80% of individuals with ASD or caregivers and are frequently cited as one of the biggest challenges impacting everyday function and quality of life. The unique challenges faced by military families, such as frequent deployments of a caregiver or relocations across time zones, are likely to exacerbate sleep problems in children with ASD. Despite the impact disrupted sleep has on development and quality of life for the affected child and family, the mechanism behind sleep problems in ASD is not understood. The proposed project will directly test such a potential mechanism and address the urgent need of identifying Mechanism(s) of underlying conditions co-occurring with ASD (FY21 ARP Career Development Award Area of Interest). We hypothesize that atypical sensory processing by the thalamus and primary sensory cortices is associated with disrupted sleep in children with ASD. The thalamus regulates the relay of sensory information from the periphery to cortex, a process termed sensory gating. During sleep, sensory gating typically increases and activity of sensory cortices decreases. Atypical sensory processing, and particularly abnormal processing of sounds, are present in 60% to 96% of children with ASD and are now recognized as part of the diagnostic criteria of ASD. Converging evidence from animal models and post-mortem and neuroimaging studies in humans suggests atypical functional and structural organization of the thalamus and sensory cortices and reduced sensory gating in ASD. For example, increased thalamocortical connectivity associated with sensory symptoms has been observed in children, adolescents, and adults with ASD in multiple studies utilizing functional magnetic resonance imaging (including our own). While relationships between disrupted sleep and atypical sensory processing (as reported on caregiver questionnaires) have been suggested, no systematic investigation of a potential mechanism is available to date. The proposed study will acquire multimodal MRI (to directly assess processing of sounds and thalamocortical connectivity), comprehensive diagnostic and behavioral measures (including testing of central auditory processing), and objective measures of sleep (utilizing wrist-worn sensors over a 2-week period) from a cohort of children (6-10 years-old) and a group of typically developing controls. The short-term impact of the proposed study will be to broaden understanding of the neurobiology of ASD and provide impetus for additional longitudinal, transdisciplinary, and ultimately intervention studies to address the current lack of evidence-based guidelines for the treatment of sleep problems in ASD. In the long term, identifying a mechanistic link between sensory processing and sleep disturbances in ASD might help inform pharmacological (e.g., targeting the GABAergic system) and non-pharmacological treatments to improve sleep. Simple modifications to sleep hygiene, reductions of noise during sleep and sensory training, for example, would be promising interventions to improve sleep in children with ASD. Importantly, while the current study will be conducted in children, it is anticipated that the findings will also be of relevance for infants at increased familial or environmental risk for ASD. Thalamocortical connectivity is established at birth and sensory maps mature within the first year of life. With disrupted sleep frequently observed in infants who are later diagnosed with ASD, understanding its relationship to sensory problems thus has the potential for much earlier interventions to lessen the cascading effects poor sleep has on behavior, cognitive function and development
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210220
Entities
People
- Annika Linke
Organizations
- San Diego State University
- United States Army