Sleep plays a crucial role in several biological processes including nervous, immune, and endocrine systems. One critical function of sleep is the removal of neuronal metabolic waste via cerebrospinal fluid (CSF) circulation within the glymphatic system (GS). The GS is a brain-wide system with functions that are enhanced during sleep to clear inflammatory proteins and metabolites. Recent advancements in our understanding of the GS highlight its role in neurodevelopmental disorders and developmental risk. Specifically, Shen and colleagues reported excessive CSF in the subarachnoid space (extra-axial CSF; EA-CSF) as an early marker of autism and a correlate of developmental risk and sleep problems. MRI extracted EA-CSF volume can serve as a non-invasive marker of GS anatomy. Although the precise mechanisms leading to excessive EA-CSF are unknown, it is known that GS processes are enhanced during sleep. Developmental periods marked by high sleep need (e.g., infancy), likely reflect an increased need for the clearance of neuronal metabolic waste. Disruptions in sleep, during early development likely influence GS function and have the potential to contribute to neurodevelopmental risk and resilience. This study aims to elucidate the relations between sleep dysregulation, EA-CSF growth patterns in infancy, and a known area of concern for children with autism - social communication development. Within this study, we will index volumetric EA-CSF data from the community sample followed within the Baby Connectome Project (U01MH110274) with high-resolution structural MRI scans from 1 to 26 months of age. The hybrid accelerated longitudinal design of this dataset is well-suited for developmental pattern estimation. With a newly-developed automated MRI pipeline, we will model EA-CSF patterns over the first two years of life. To describe the relations between EA-CSF development and sleep dysregulation (Aim 1), we will compare EA-CSF growth patterns across two groups of infants ? those with regulated (S-REG) and dysregulated (S-DYS) sleep. We predict a group by age interaction, with the S-DYS group showing a growth pattern of EA-CSF over time that is significantly increased relative to the S- REG group. We believe the greater increase of EA-CSF in the S-DYS group may reflect an imbalance of CSF circulation/clearance. To assess how sleep dysregulation and EA-CSF growth patterns relate to social communication development (Aim 2), we will complete another set of group-based analyses to assess if lower social communication scores are present in (1) the S-DYS group and (2) infants with atypical EA-CSF growth patterns. The overarching goal of this line of work is to inform mechanistic pathways between sleep dysregulation and neurodevelopmental risk. This study focuses on EA-CSF, based on its known connections to sleep, autism, and other indices of developmental risk. Using a developmental psychopathology approach, this study provides crucial first steps in translating how EA-CSF growth within a community sample can inform our understanding of a potential neuroanatomical marker of social communicative risk and resilience.

Public Health Relevance

The glymphatic system (GS) aids in neuronal metabolic waste removal and is implicated in autism and other developmental concerns. This system is more active at night and disruptions in sleep likely influence the efficiency/efficacy of the GS. Within a community sample, this study assesses how early sleep influences a marker of GS anatomy (extra-axial cerebrospinal fluid; EA-CSF) and how sleep and EA-CSF are associated with a core deficit area in autism ? social communication development.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Research Grants (R03)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Kau, Alice S
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Purdue University
Schools of Arts and Sciences
West Lafayette
United States
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