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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Kaare Mikkelsen, Aarhus University, Denmark
- Second opponent: Associate Professor Morten Engstrøm, NTNU: Norwegian University of Science and Technology
- Third member and chair of the evaluation committee: Professor Shuo-Wang Qiao, University of Oslo
Chair of the Defence
Professor Emeritus Hans Erik Heier, University of Oslo
Principal Supervisor
Researcher Stine Knudsen Heier, University of Oslo
Summary
Narcolepsy type 1 (NT1) is a chronic neurological sleep disorder characterized by excessive daytime sleepiness, cataplexy, and disturbed nocturnal sleep. In Norway, a more than tenfold increase in new NT1 diagnoses occurred after the 2009/2010 H1N1 vaccination campaign. NT1 is caused by an autoimmune destruction of hypocretin-producing neurons in the hypothalamus, causing unstable sleep-wake regulation.
Night-time sleep fragmentation is a core feature of NT1, assessed by investigating sleep stages in 30-second epochs from an over-night polysomnography (PSG). As sleep is though biologically dynamic, 30-second epochs may be too coarse to capture brief transitions and microstructural dynamics.
In this PhD project, high-resolution sleep staging in 5-second mini-epochs was explored. Initial evaluation of existing automated sleep staging models showed that reliable mini-epoch scoring required model adaptation. By retraining the existing U-Sleep model using transfer learning on human-scored mini-epochs, performance comparable to human and automatic epoch scoring was achieved. Mini-epoch sleep staging with the optimized U-Sleep model was then applied to PSGs from NT1 patients and their non-narcoleptic siblings to assess sleep fragmentation.
Analyses showed that NT1 patients had significantly increased sleep fragmentation compared to their siblings, both with epochs and mini-epochs. Mini-epoch analyses, however, captured substantially more stage transitions and revealed patterns of sleep instability not detectable with epoch scoring.
With mini-epochs, but not epochs, sleep-wake fragmentation was significantly higher in patients with all core narcolepsy symptoms and increased significantly from the 1st to the 2nd night-half in patients with undetectable hypocretin-1 levels (<40 pg/ml) and/or all core narcolepsy symptoms.
These findings highlight the clinical value of high-resolution, temporally sensitive sleep stage analyses for detailed phenotyping and detection of future disease biomarkers.
Additional information
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