Pediatric obstructive sleep apnea (OSA) is associated with impaired executive function, and manifests clinically as impairments in learning, attention, memory, and school performance, along with abnormal neuropsychological development. OSA in adults has been associated with regional alterations (both increases and decreases) in functional brain activation, cortical grey matter volume reductions on voxel-based morphometry, and altered subcortical white matter integrity on diffusion tensor imaging. It is unknown if the effects of OSA on a developing brain are similar, and if these consequences are reversible. The central hypothesis is that pediatric OSA causes direct brain injury that result in cortical grey matter loss, altered white matter integrity, impaired resting state interactions, and task-related functional brain activation. Moreover, these abnormalities may not be readily reversible. Experimental sleep fragmentation causes impaired hippocampal long-term potentiation of memory and neurogenesis, while sleep deprivation further leads to cellular stress. Hypoxia can cause cell loss, enhance apoptosis and activate multiple mechanisms of neuronal injury. Disruption of the normal <1 Hz slow cortical neuronal oscillation can alter calcium kinetics in the synapses and perhaps prevent a putative synaptic downscaling function of sleep. OSA can plausibly result in significant neuronal, myelin, and synaptic injury. The long-term goals of our research are to determine the impact of OSA on brain development and pediatric cognitive morbidity, and as a risk factor for executive and affective dysfunction in adulthood. Our research will use cutting edge magnetic resonance imaging (MRI) based anatomical and functional neuroimaging techniques, measure standard polysomnographic and neuropsychological variables, and compute standard and novel sleep quality and sleep-breathing indices.
Our specific aims for this application are to demonstrate the impact of pediatric OSA on 1) cortical grey matter and subcortical white matter, using high resolution anatomical magnetic resonance imaging at 3 Tesla;2) working memory (executive network including the lateral prefrontal cortex) and encoding (encoding network including the hippocampus) task- related activation on functional MRI. Resting state brain activation assessments will complement the above approaches. We will assess differences from healthy age, body mass index, gender, and Tanner stage matched controls, pre and 6-months post treatment (tonsillectomy or positive airway pressure). Correlations of neuroanatomical indices (cortical thickness, fractional anisotropy, fiber length, apparent diffusion coefficient) and functional activation volumes and % blood oxygen level dependent signal change, in areas of the executive network (e.g., dorsolateral prefrontal, posterior parietal, anterior cingulate) will be explored in relation to neuropsychological performance, neuroanatomical abnormalities, functional imaging abnormalities, and polysomnographic disease severity.

Public Health Relevance

Sleep apnea is associated with repeated obstructions of airflow during sleep, resulting in sleep disruption and drops in oxygen during sleep. There is concern that such changes can harm the developing brain. This research project will use magnetic resonance imaging, a technique that uses powerful but safe magnetic fields to look at brain structure and function, to study the impact of sleep apnea on the child's (age 8-13 years) brain.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Developmental Brain Disorders Study Section (DBD)
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Twery, Michael
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Beth Israel Deaconess Medical Center
United States
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