SLEEP

Warby, Simon C.; Mongrain, Valérie

doi: 10.5665/sleep.4056pmid: 25197802

Kezirian, Eric J.

doi: 10.5665/sleep.4058pmid: 25197800

Kirkness, Jason P.; Sowho, Mudiaga; Murano, Emi

doi: 10.5665/sleep.4060pmid: 25197803

Ramachandran, Satya Krishna

doi: 10.5665/sleep.4062pmid: 25197801

Arnardottir, Erna S.; Nikonova, Elena V.; Shockley, Keith R.; Podtelezhnikov, Alexei A.; Anafi, Ron C.; Tanis, Keith Q.; Maislin, Greg; Stone, David J.; Renger, John J.; Winrow, Christopher J.; Pack, Allan I.

doi: 10.5665/sleep.4064

Han, Fang; Lin, Ling; Schormair, Barbara; Pizza, Fabio; Plazzi, Giuseppe; Ollila, Hanna M.; Nevsimalova, Sona; Jennum, Poul; Knudsen, Stine; Winkelmann, Juliane; Coquillard, Cristin; Babrzadeh, Farbod; Strom, Tim M.; Wang, Chunlin; Mindrinos, Michael; Vina, Marcelo Fernandez;

Ma, Junshui; Svetnik, Vladimir; Snyder, Ellen; Lines, Christopher; Roth, Thomas; Herring, W. Joseph

doi: 10.5665/sleep.4068pmid: 25197807

AbstractStudy Objectives:Suvorexant, an orexin receptor antagonist, improves sleep in healthy subjects (HS) and patients with insomnia. We compared the electroencephalographic (EEG) power spectral density (PSD) profile of suvorexant with placebo using data from a phase 2 trial in patients with insomnia. We also compared suvorexant's PSD profile with the profiles of other insomnia treatments using data from 3 HS studiesDesign:Phase 2 trial—randomized, double-blind, two-period (4 w per period) crossover. HS studies—randomized, double-blind, crossover.Setting:Sleep laboratories.Participants:Insomnia patients (n = 229) or HS (n = 124).Interventions:Phase 2 trial—suvorexant 10 mg, 20 mg, 40 mg, 80 mg, placebo; HS study 1—suvorexant 10 mg, 50 mg, placebo; HS study 2— gaboxadol 15 mg, zolpidem 10 mg, placebo; HS study 3—trazodone 150 mg, placebo.Measurements and Results:The PSD of the EEG signal at 1–32 Hz of each PSG recording during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were calculated. The day 1 and day 28 PSD profiles of suvorexant at all four doses during NREM and REM sleep in patients with insomnia were generally flat and close to 1.0 (placebo) at all frequencies. The day 1 PSD profile of suvorexant in HS was similar to that in insomnia patients. In contrast, the other three drugs had distinct PSD profiles in HS that differed from each other.Conclusions:Suvorexant at clinically effective doses had limited effects on power spectral density compared with placebo in healthy subjects and in patients with insomnia, in contrast to the three comparison insomnia treatments. These findings suggest the possibility that antagonism of the orexin pathway might lead to improvements in sleep without major changes in the patient's neurophysiology as assessed by electroencephalographic.

Siclari, Francesca; Bernardi, Giulio; Riedner, Brady A.; LaRocque, Joshua J.; Benca, Ruth M.; Tononi, Giulio

doi: 10.5665/sleep.4070pmid: 25197810

AbstractObjectives:To assess how the characteristics of slow waves and spindles change in the falling-asleep process.Design:Participants undergoing overnight high-density electroencephalographic recordings were awakened at 15- to 30-min intervals. One hundred forty-one falling-asleep periods were analyzed at the scalp and source level.Setting:Sleep laboratory.Participants:Six healthy participants.Interventions:Serial awakenings.Results:The number and amplitude of slow waves followed two dissociated, intersecting courses during the transition to sleep: slow wave number increased slowly at the beginning and rapidly at the end of the falling-asleep period, whereas amplitude at first increased rapidly and then decreased linearly. Most slow waves occurring early in the transition to sleep had a large amplitude, a steep slope, involved broad regions of the cortex, predominated over frontomedial regions, and preferentially originated from the sensorimotor and the posteromedial parietal cortex. Most slow waves occurring later had a smaller amplitude and slope, involved more circumscribed parts of the cortex, and had more evenly distributed origins. Spindles were initially sparse, fast, and involved few cortical regions, then became more numerous and slower, and involved more areas.Conclusions:Our results provide evidence for two types of slow waves, which follow dissociated temporal courses in the transition to sleep and have distinct cortical origins and distributions. We hypothesize that these two types of slow waves result from two distinct synchronization processes: (1) a “bottom-up,” subcorticocortical, arousal system-dependent process that predominates in the early phase and leads to type I slow waves, and (2) a “horizontal,” corticocortical synchronization process that predominates in the late phase and leads to type II slow waves. The dissociation between these two synchronization processes in time and space suggests that they may be differentially affected by experimental manipulations and sleep disorders.

Kim, Andrew M.; Keenan, Brendan T.; Jackson, Nicholas; Chan, Eugenia L.; Staley, Bethany; Poptani, Harish; Torigian, Drew A.; Pack, Allan I.; Schwab, Richard J.

doi: 10.5665/sleep.4072pmid: 25197815

AbstractStudy Objectives:The objective of this study was to determine whether tongue fat is increased in obese sleep apneics compared to obese subjects without sleep apnea. We hypothesized that excess fat is deposited in the tongue in obese patients with sleep apnea.Design:Case-control design.Setting:Academic medical center.Patients:We examined tongue fat in 31 obese controls (apnea-hypopnea index, 4.1 ± 2.7 events/h) and 90 obese apneics (apnea-hypopnea index, 43.2 ± 27.3 events/h). Analyses were repeated in a subsample of 18 gender-, race-, age-, and BMI-matched case-control pairs.Interventions:All subjects underwent a MRI with three-point Dixon magnetic resonance imaging. We used sophisticated volumetric reconstruction algorithms to study the size and distribution of upper airway fat deposits in the tongue and masseter muscles within apneics and obese controls.Measurements and Results:The data supported our a priori hypotheses that after adjustment for age, BMI, gender, and race, the tongue in apneics was significantly larger (P = 0.001) and had an increased amount of fat (P = 0.002) compared to controls. Similar results were seen in our matched sample. Our data also demonstrate that within the apneic and normal tongue, there are regional differences in fat distribution, with larger fat deposits at the base of the tongue.Conclusions:There is increased tongue volume and deposition of fat at the base of tongue in apneics compared to controls. Increased tongue fat may begin to explain the relationship between obesity and obstructive sleep apnea.

McCarter, Stuart J.; St. Louis, Erik K.; Duwell, Ethan J.; Timm, Paul C.; Sandness, David J.; Boeve, Bradley F.; Silber, Michael H.

doi: 10.5665/sleep.4074pmid: 25197816

AbstractObjectives:We aimed to determine whether phasic burst duration and conventional REM sleep without atonia (RSWA) methods could accurately diagnose REM sleep behavior disorder (RBD) patients with comorbid OSA.Design:We visually analyzed RSWA phasic burst durations, phasic, “any,” and tonic muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and conducted automated REM atonia index (RAI) analysis. Group RSWA metrics were analyzed and regression models fit, with receiver operating characteristic (ROC) curves determining the best diagnostic cutoff thresholds for RBD. Both split-night and full-night polysomnographic studies were analyzed.Setting:N/A.Participants:Parkinson disease (PD)-RBD (n = 20) and matched controls with (n = 20) and without (n = 20) OSA.Interventions:N/A.Measurements and Results:All mean RSWA phasic burst durations and muscle activities were higher in PD-RBD patients than controls (P < 0.0001), and RSWA associations with PD-RBD remained significant when adjusting for age, gender, and REM AHI (P < 0.0001). RSWA muscle activity (phasic, “any”) cutoffs for 3-s mini-epoch scorings were submentalis (SM) (15.5%, 21.6%), anterior tibialis (AT) (30.2%, 30.2%), and combined SM/AT (37.9%, 43.4%). Diagnostic cutoffs for 30-s epochs (AASM criteria) were SM 2.8%, AT 11.3%, and combined SM/AT 34.7%. Tonic muscle activity cutoff of 1.2% was 100% sensitive and specific, while RAI (SM) cutoff was 0.88. Phasic muscle burst duration cutoffs were: SM (0.65) and AT (0.79) seconds. Combining phasic burst durations with RSWA muscle activity improved sensitivity and specificity of RBD diagnosis.Conclusions:This study provides evidence for REM sleep without atonia diagnostic thresholds applicable in Parkinson disease-REM sleep behavior disorder (PD-RBD) patient populations with comorbid OSA that may be useful toward distinguishing PD-RBD in typical outpatient populations.