Disrupted Nighttime Sleep (DNS) in Pediatric Narcolepsy - ABSTRACT
The proposal will support the research and further Dr. Kiran Maski's training as a physician-scientist in
sleep neurology. Dr. Maski's long-term objectives are to examine the neurophysiology of nocturnal sleep in
pediatric narcolepsy and its relationship to cognitive and psychological co-morbidities common to this disease,
to identify potential sleep neurophysiological diagnostic and predictive biomarkers, and develop and test sleep-
specific treatments to reduce disease burden of pediatric narcolepsy patients. To achieve these goals, a
training plan focused on (1) analytic skills to study sleep dynamics, (2) fundamental knowledge in cognitive and
behavioral neuroscience and sleep-wake physiology, (3) longitudinal and clinical trial research design to
facilitate rare disease research is proposed to complement Dr. Maski's background in child neurology and
sleep medicine. This training will be accomplished through formal coursework, hands on training, and multi-
disciplinary mentorship with world-renown experts in sleep-wake neurophysiology (Dr. Thomas Scammell) and
cognitive neuroscience (Dr. Robert Stickgold). Additional consultants and collaborators with expertise in
mathematical modeling, statistics, behavioral science, and research methodology utilizing remote audiovisual
technology will enrich Dr. Maski's training and proposed research. This training will occur in the context of the
rich scholarly environment of Harvard Medical School, Harvard T.H. Chan School of Public Health and Boston
Children's Hospital. The research plan is devised to test the central hypothesis that disrupted nighttime sleep
(DNS) in pediatric narcolepsy type 1 (NT1) is a specific and dynamic form of sleep pathology that impairs
normal emotional and memory processes that occur during sleep. To test this hypothesis, we propose three
complimentary but independent aims. In Aim 1, we conduct a cross-sectional study to define DNS with
measures unique to pediatric NT1 compared to other sleep disorders and controls. In Aim 2, we study changes
in DNS using translational analytic methods within a pediatric NT1 cohort. Lastly, in Aim 3, we investigate
predicted changes to sleep architecture between drug-free pediatric NT1 patients, pediatric NT1 patients on
established sodium oxybate therapy (a sedating drug that treats DNS) and healthy, aged-matched controls to
determine direct effects of sleep fragmentation on memory consolidation and post-sleep emotional processes.
Public Health: Substantial evidence links sleep with cognitive and emotional processes. Yet , little is known of
the specific pathologic sleep changes that occur in pediatric neurologic diseases and the role this pathology
plays in the development of burdensome cognitive and psychological co-morbidities. This proposal serves to
provide new analytic methods to characterize sleep pathology in neurological diseases like narcolepsy, test
novel methods that show direct cognitive and psychological effects of sleep disruption, and forms the
foundation for sleep-specific treatment strategies to reduce disease burden in neurological diseases.
