0460 Dose-response Relationship Between Thalamic Activity During Sustained Attention and Excessive Daytime Sleepiness

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by sleep fragmentation and intermittent hypoxia. Both are known causes of sleepiness and poor sustained attention, i.e., lapses in vigilance, which can be measured using the psychomotor vigilance test (PVT). Crucial to vigilance, the thalamus plays a key role by regulating sensory information essential for sustaining attention. However, to date, the relationship between thalamic activity underlying PVT and its relationship to sleepiness in OSA has not been investigated systematically. Methods A total of 5 newly diagnosed OSA subjects (mean AHI4% = 51±24, 5M, age 42±3 yrs., ESS [Epworth Sleepiness Scale] 11 ± 3.4), 3 healthy controls (1M/2F, age 35±2 yrs., ESS 3±3) and 9 PAP treated OSA subjects (diagnostic AHI4% = 15±12, 6M/3F, age 57±10 yrs., ESS 8±5) who demonstrated >4 hours nightly PAP adherence were studied. Participants performed a PVT during fMRI after an in-lab nocturnal polysomnography. Each fMRI session consisted of 4 runs: two PVT runs interleaved with two control runs. Analyses in AFNI were restricted to the bilateral thalamus with percent signal change used as the primary metric of thalamic activity. Results There was a dose response relationship of ESS to thalamic activity during PVT such that subjects with lowest levels of sleepiness (ESS) exhibited the greatest thalamic activity: untreated OSA (3±2%), CPAP treated OSA subjects (7.2±1.9%), healthy controls (21.8±1.1%); χ2(3) = 7.13, p< 0.05. CPAP treated OSA subjects with persistent sleepiness (ESS≥10) exhibited lower thalamic activity than those without persistent sleepiness (ESS< 10), however it did not reach statistical significance (5.3±3.4% vs. 6.9±2.9%). Conclusion Based on the collected data, the thalamic activity underlying PVT shows a dose response relationship with level of sleepiness. The lower degree of thalamic activity in CPAP treated patients with persistent sleepiness as compared to those without suggesting a level of irreversible injury to the thalamus due to OSA. Our findings should be further validated with a larger sample size with varying degrees of sleep apnea severity. Support (if any) NIH K25HL151912, NIH R01HL171813, NIH R21HL165320