# Sleep, the glymphatic system, and social communication development

> **NIH NIH R03** · PURDUE UNIVERSITY · 2021 · $75,617

## Abstract

Project Summary:
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 st...

## Key facts

- **NIH application ID:** 10109259
- **Project number:** 1R03HD104084-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** AMY J SCHWICHTENBERG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,617
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109259

## Citation

> US National Institutes of Health, RePORTER application 10109259, Sleep, the glymphatic system, and social communication development (1R03HD104084-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10109259. Licensed CC0.

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