Sleep and extra-axial cerebrospinal fluid in early development.

• In Event: Functional and structural findings from the Baby Connectome Project

Abstract

The distribution of cerebrospinal fluid (CSF) has been the focus of increased research in neurodevelopmental and neurodegenerative disorders, but there is limited evidence on the development and disbursement of CSF in early typical development. Abnormally increased volume of CSF in the subarachnoid space surrounding the brain (i.e., extra-axial CSF, or EA-CSF) is associated with elevated risk for autism spectrum disorder (ASD) and some social communicative competencies. The circulation of CSF between the brain and extra-axial spaces has been linked with sleep (in adult and animal model studies), but little is known about how early sleep dysregulation may impact EA-CSF in infancy. To inform our developmental understanding of EA-CSF and any potential links with sleep dysregulation, the present study utilized a subset of data from Baby Connectome Project (BCP) – infants (n = 119) with at least one assessment with an MRI scan and the Brief Infant Sleep Questionnaire (BISQ). Infants completed from 1 to 6 assessments, M(SD) = 1.81(1.21) assessments. Infants (ages 1 to 36 months) were classified into groups with regulated (n = 103) or dysregulated (n = 16) sleep using the BISQ. Total CSF, EA-CSF, and total cerebral volume (TCV) were generated from T1 and T2 MRIs using the open-source tool autoEACSF. Multilevel models were utilized to explore the associations of EA-CSF volumes and EA-CSF/TCV ratios with infant sex, age, and sleep. Infants with dysregulated sleep had comparable EA-CSF, total CSF, and TCV volumes when compared to infants with regulated sleep (Figure 1). Developmental trajectories of EA-CSF volumes or EA-CSF/TCV ratios (Figure 2) were also comparable across the sleep groups. There was an age-related decline in the ratio of EA-CSF to TCV from 9 to 30 months of age (b = -0.064, t = -3.73, p < 0.001) (Figure 2). Findings from the present study do not support sleep problems as a mechanism through which CSF distribution is altered in this normative sample of infants. Although elevated EA-CSF is associated with developmental and neurodegenerative pathology, its links with sleep dysregulation do not appear robust in early typical development. Notably, this is the first study to document changes in EA-CSF in a sample of well-characterized typically developing infants/toddlers. Although there is a large range of EA-CSF/TCV ratios across early development (Figure 2), the results demonstrate that the proportion of CSF to brain volume decreases across the first two years of life in typical development.

Authors

• Pearlynne Chong, Purdue University, West Lafayette

• Juan Carlos Prieto

• Sun Hyung Kim, University of North Carolina

• Martin Styner, University of North Carolina at Chapel Hill

• Jed T. Elison, University of Minnesota - Twin Cities

• Mark D. Shen, University of North Carolina at Chapel Hill

• AJ Schwichtenberg, Purdue University, West Lafayette
  Presenting Author