Cerebral grey matter may not explain sleep slow-wave characteristics after severe brain injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that grey matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between grey matter volume (GMV) and slow-wave characteristics in 27 moderate to severe traumatic brain injury patients (TBI; 32.0 ± 12.2 years old, eight women) compared to 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3-tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6  Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and grey matter in regions implicated in the generation and/or propagation of slow waves. Compared to controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.Significance Statement Because sleep slow waves play a key role in cognition, synaptic plasticity, and restorative sleep, understanding how they relate to cerebral matter integrity is especially important in the context of brain atrophy following moderate to severe traumatic brain injury (TBI). We found that higher grey matter volume (GMV) in regions involved in slow-wave generation and propagation was associated with faster and steeper slow waves in healthy individuals. However, these associations were not observed in TBI participants, raising questions about the degree of contribution of GMV to slow-wave properties in patients with lower grey matter relative to controls. These findings challenge our current understanding of the link between grey matter integrity and slow waves, highlighting the complexity of this relationship.

Unrefreshing naps and sleep architecture during the multiple sleep latency test in idiopathic hypersomnia.

Patients with idiopathic hypersomnia frequently report having unrefreshing naps. However, whether they have abnormal sleep architecture during naps that may explain their unrefreshing aspect is unknown. We compared sleep architecture during short daytime naps in patients with idiopathic hypersomnia reporting unrefreshing and refreshing naps. One-hundred and thirty-four patients tested with one-night polysomnography, followed by an adapted version of the Multiple Sleep Latency Test with four naps, were included. They were asked about the refreshing aspect of their habitual naps during a clinical interview. They were classified as having objective (Multiple Sleep Latency Test ≤ 8 min) or subjective idiopathic hypersomnia (Multiple Sleep Latency Test > 8 min), and as presenting refreshing or unrefreshing naps. We tested Group differences (refreshing versus unrefreshing naps) on nap sleep architecture in the whole sample and for subjective and objective idiopathic hypersomnia subgroups separately using ANCOVAs. No Group effects were observed in the Multiple Sleep Latency Test architecture in the whole sample and in objective and subjective idiopathic hypersomnia subgroups. This study provides preliminary evidence that reporting unrefreshing naps is not associated with clinically significant findings in Multiple Sleep Latency Test sleep architecture in patients with idiopathic hypersomnia. Given that naps taken by patients with idiopathic hypersomnia are typically long, future studies should investigate longer daytime sleep episodes.

Brain white matter damage and its association with neuronal synchrony during sleep.

The restorative function of sleep partly relies on its ability to deeply synchronize cerebral networks to create large slow oscillations observable with EEG. However, whether a brain can properly synchronize and produce a restorative sleep when it undergoes massive and widespread white matter damage is unknown. Here, we answer this question by testing 23 patients with various levels of white matter damage secondary to moderate to severe traumatic brain injuries (ages 18-56; 17 males, six females, 11-39 months post-injury) and compared them to 27 healthy subjects of similar age and sex. We used MRI and diffusion tensor imaging metrics (e.g. fractional anisotropy as well as mean, axial and radial diffusivities) to characterize voxel-wise white matter damage. We measured the following slow wave characteristics for all slow waves detected in N2 and N3 sleep stages: peak-to-peak amplitude, negative-to-positive slope, negative and positive phase durations, oscillation frequency, and slow wave density. Correlation analyses were performed in traumatic brain injury and control participants separately, with age as a covariate. Contrary to our hypotheses, we found that greater white matter damage mainly over the frontal and temporal brain regions was strongly correlated with a pattern of higher neuronal synchrony characterized by slow waves of larger amplitudes and steeper negative-to-positive slopes during non-rapid eye movement sleep. The same pattern of associations with white matter damage was also observed with markers of high homeostatic sleep pressure. More specifically, higher white matter damage was associated with higher slow-wave activity power, as well as with more severe complaints of cognitive fatigue. These associations between white matter damage and sleep were found only in our traumatic brain injured participants, with no such correlation in controls. Our results suggest that, contrary to previous observations in healthy controls, white matter damage does not prevent the expected high cerebral synchrony during sleep. Moreover, our observations challenge the current line of hypotheses that white matter microstructure deterioration reduces cerebral synchrony during sleep. Our results showed that the relationship between white matter and the brain's ability to synchronize during sleep is neither linear nor simple.

BDNF Val66Met Polymorphism Interacts with Sleep Consolidation to Predict Ability to Create New Declarative Memories.

UNLABELLED: It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (ß-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (ß-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (ß = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition. SIGNIFICANCE STATEMENT: Individuals with the BDNF Val/Val (valine allele) polymorphism showed better memory performance after a night of consolidated sleep. However, we observed that middle-aged and older individuals who are carriers of the BDNF Met allele displayed no positive association between sleep quality and their ability to learn the next morning. This interaction between sleep and BDNF polymorphism was more salient for hippocampus-dependent tasks than for other cognitive tasks. Our results support the hypothesis that reduced activity-dependent secretion of BDNF impairs the benefits of sleep on synaptic plasticity and next-day memory. Our work advances the field by revealing new evidence of a clear genetic heterogeneity in how sleep consolidation contributes to the ability to learn.

Sleep architecture in idiopathic hypersomnia: the influence of age, sex, and body mass index.

This study aimed to progress the understanding of idiopathic hypersomnia (IH) by assessing the moderating influence of individual characteristics, such as age, sex, and body mass index (BMI) on sleep architecture. In this retrospective study, 76 IH participants (38.1 ± 11.3 years; 40 women) underwent a clinical interview, an in-laboratory polysomnography with a maximal 9-h time in bed and a multiple sleep latency test (MSLT). They were compared to 106 healthy controls (38.1 ± 14.1 years; 60 women). Multiple regressions were used to assess moderating influence of age, sex, and BMI on sleep variables. We used correlations to assess whether sleep variables were associated with Epworth Sleepiness Scale scores and mean sleep onset latency on the MSLT in IH participants. Compared to controls, IH participants had shorter sleep latency (p = 0.002), longer total sleep time (p < 0.001), more time spent in N2 sleep (p = 0.008), and showed trends for a higher sleep efficiency (p = 0.023) and more time spent in rapid eye movement (REM) sleep (p = 0.022). No significant moderating influence of age, sex, or BMI was found. More severe self-reported sleepiness in IH patients was correlated with shorter REM sleep latency and less N1 sleep in terms of proportion and duration (ps < 0.01). This study shows that, when compared to healthy controls, patients with IH had no anomalies in their sleep architecture that can explain their excessive daytime sleepiness. Moreover, there is no moderating influence of age, sex, and BMI, suggesting that the absence of major group differences is relatively robust.

A 10-day theta burst stimulation intervention facilitates the clinical rehabilitation of patients following an isolated limb fracture: A longitudinal SHAM-controlled pilot study.

OBJECTIVE: We investigated if theta burst stimulation (TBS) could enhance recovery by reducing key symptoms when implemented acutely post-fracture in participants with an isolated upper limb fracture (IULF). METHODS/DESIGN: This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous TBS protocol. Two main groups were included: I) participants with IULF receiving active TBS; and II) patients with IULF receiving SHAM/placebo. Another group (III) of healthy individuals were the reference group. Disability and pain intensity were collected through questionnaires (DASH & NRA) at three timepoints (baseline; 72 h post-intervention & 3 months post-injury). Group III completed the baseline assessment. RESULTS: 79 participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between Intervention and Time approached significance (F = 2.33; p = 0.11), whereas it was significant for pain (F = 3.42; p = 0.04). At 3 months post-injury, the ACTIVE group reported reduced disability (F = 4.71; p = 0.04) and pain (F = 5.84; p = 0.02) at three months post-injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. CONCLUSIONS: In IULF patients, a 10-day TBS intervention implemented acutely post-trauma had beneficial effects on symptoms of functional recovery and pain at 3 months post-trauma.

Are unrefreshing naps associated with nocturnal sleep architecture specificities in idiopathic hypersomnia?

STUDY OBJECTIVES: Unrefreshing naps are supportive clinical features of idiopathic hypersomnia (IH) and are reported by more than 50% of IH patients. They are, however, not mandatory for the diagnosis, and their pathophysiological nature is not understood. This study aimed at verifying whether IH patients with and without unrefreshing naps constitute two subtypes of IH based on their demographic/clinical characteristics, and sleep architecture. METHODS: One hundred twelve IH patients underwent a polysomnography (PSG) followed by a multiple sleep latency test (MSLT). They completed questionnaires on excessive daytime sleepiness, mood, and sleep quality. They were met by sleep medicine physicians who conducted a semi-structured clinical interview and questioned them on refreshing aspects of their naps. Patients who reported unrefreshing naps were compared to patients reporting refreshing naps on questionnaires, MSLT and PSG variables, with age as a covariable. As sensitivity analyses, we performed the same comparisons in participants presenting objective markers of IH and those diagnosed with IH based only on clinical judgment (subjective IH), separately. RESULTS: In the whole sample, 61% of patients reported unrefreshing naps. These participants had less awakenings, a lower percentage of N1 sleep, less sleep stage transitions, and a higher percentage of REM sleep on the nighttime PSG compared to the refreshing naps subgroup. When subjective and objective IH patients were tested separately, more group differences were observed on PSG for subjective IH patients. CONCLUSIONS: Patients with unrefreshing naps have less fragmented sleep compared to those with refreshing naps. Future studies should investigate whether this group difference indicates a weaker arousal drive.

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals.

BACKGROUND: Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer's disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. METHODS: Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. RESULTS: In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (ß = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (ß = 0.48, p = 0.012) and total BF volumes (ß = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. DISCUSSION: These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.

Sleep from acute to chronic traumatic brain injury and cognitive outcomes.

STUDY OBJECTIVES: Traumatic brain injuries (TBIs) cause persistent cerebral damage and cognitive deficits. Because sleep may be a critical factor for brain recovery, we characterized the sleep of patients with TBI from early hospitalization to years post-injury and explored the hypothesis that better sleep during hospitalization predicts more favorable long-term cognitive outcomes. METHODS: We tested patients with moderate-to-severe TBI in the hospitalized (n = 11) and chronic (n = 43) stages using full-night polysomnography, with 82% of the hospitalized group being retested years post-injury. Hospitalized patients with severe orthopedic and/or spinal cord injury (n = 14) and healthy participants (n = 36) were tested as controls for the hospitalized and chronic TBI groups, respectively. Groups had similar age and sex and were compared for sleep characteristics, including slow waves and spindles. For patients with TBI, associations between sleep during hospitalization and long-term memory and executive function were assessed. RESULTS: Hospitalized patients with TBI or orthopedic injuries had lower sleep efficiency, higher wake after sleep onset, and lower spindle density than the chronic TBI and healthy control groups, but only hospitalized patients with brain injury had an increased proportion of slow-wave sleep. During hospitalization for TBI, less fragmented sleep, more slow-wave sleep, and higher spindle density were associated to more favorable cognitive outcomes years post-injury, while injury severity markers were not associated with these outcomes. CONCLUSION: These findings highlight the importance of sleep following TBI, as it could be a strong predictor of neurological recovery, either as a promoter or an early marker of cognitive outcomes.

Medial temporal lobe and obstructive sleep apnea: Effect of sex, age, cognitive status and free-water.

Medial temporal structures, namely the hippocampus, the entorhinal cortex and the parahippocampal gyrus, are particularly vulnerable to Alzheimer's disease and hypoxemia. Here, we tested the associations between obstructive sleep apnea (OSA) severity and medial temporal lobe volumes in 114 participants aged 55-86 years (35 % women). We also investigated the impact of sex, age, cognitive status, and free-water fraction correction on these associations. Increased OSA severity was associated with larger hippocampal and entorhinal cortex volumes in women, but not in men. Greater OSA severity also correlated with increased hippocampal volumes in participants with amnestic mild cognitive impairment, but not in cognitively unimpaired participants, regardless of sex. Using free-water corrected volumes eliminated all significant associations with OSA severity. Therefore, the increase in medial temporal subregion volumes may possibly be due to edema. Whether these structural manifestations further progress to neuronal death in non-treated OSA patients should be investigated.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

BACKGROUND: Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. METHODS: In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. RESULTS: On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. CONCLUSIONS: As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder.

Parametric study of transcranial alternating current stimulation for brain alpha power modulation.

Transcranial alternating current stimulation, a non-invasive brain stimulation technique, has been used to increase alpha (8-12 Hz) power, the latter being associated with various brain functions and states. Heterogeneity among stimulation parameters across studies makes it difficult to implement reliable transcranial alternating current stimulation protocols, explaining the absence of consensus on optimal stimulation parameters to modulate the alpha rhythm. This project documents the differential impact of controlling for key transcranial alternating current stimulation parameters, namely the intensity, the frequency and the stimulation site (anterior versus posterior). Phase 1:20 healthy participants underwent 4 different stimulation conditions. In each experimental condition, stimulation via 2 electrodes was delivered for 20 min. Stimulation conditions were administered at PO7-PO8 or F3-F4 at individual's alpha frequency, or at individual's theta frequency or sham. Stimulation intensity was set according to each participant's comfort following a standardized unpleasantness scale (≤ 40 out of 100) and could not exceed 6 mA. All conditions were counterbalanced. Phase 2: participants who tolerated higher intensity of stimulation (4-6 mA) underwent alpha-frequency stimulation applied over PO7-PO8 at 1 mA to investigate within-subject modulation of stimulation response according to stimulation intensity. Whether set over posterior or anterior cortical sites, alpha-frequency stimulation showed greater increase in alpha power relative to stimulation at theta frequency and sham stimulation. Posterior alpha-frequency stimulation showed a greater increase in alpha power relative to the adjacent frequency bands over frontal and occipito-parietal brain areas. Low intensity (1 mA) posterior alpha stimulation showed a similar increase in alpha power than at high (4-6 mA) intensity when measured immediately after stimulation. However, when tested at 60 min or 120 min, low intensity stimulation was associated with significantly superior alpha power increase relative to high intensity stimulation. This study shows that posterior individual's alpha frequency stimulation at higher intensities is well tolerated but fails to increase stimulation aftereffects recorded within 2 h of stimulation on brain oscillations of the corresponding frequency band. In sharp contrast, stimulating at 1 mA (regardless of phosphene generation or sensory perception) effectively and selectively modulates alpha power within that 2-h time window, thus validating that it as a reliable stimulus intensity for future studies. This study also shows that posterior alpha-frequency stimulation preferentially modulates endogenous brain oscillations of the corresponding frequency band. Moreover, our data suggest that posterior alpha-frequency transcranial alternating current stimulation is a reliable and precise non-invasive brain stimulation technique for persistent modulation of both frontal and occipito-parietal alpha power.

Slow wave activity moderates the association between new learning and traumatic brain injury severity.

STUDY OBJECTIVES: Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity. METHODS: Forty-two moderate to severe TBI participants, 12-47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance. RESULTS: We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI. CONCLUSIONS: This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.

Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder.

More than 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson's disease or Lewy body dementia. Symptom screens and metaiodobenzylguanine (MIBG)-scintigraphy suggest autonomic abnormalities in idiopathic RBD, but it is unclear whether autonomic abnormalities can predict neurodegenerative disease. From a cohort of 99 patients with idiopathic RBD, we selected those who developed parkinsonism or dementia. These were matched by age, sex, and follow-up duration to patients with RBD who remained disease free and to matched controls. From the polysomnographic trace performed at baseline evaluation, measures of beat-to-beat RR variability including time domains (mean RR-interval and RR-standard deviation) and frequency domains (low and high frequency components) were retrospectively assessed. Twenty-one patients with idiopathic RBD who developed neurodegenerative disease were included (Parkinson's disease-11, multiple system atrophy-1, and dementia-9). Age at PSG was 66 years, and 86% were male. PSG was performed on average 6.7 years before defined neurodegenerative disease. Comparing all patients with idiopathic RBD to controls, there were significant reductions in RR-standard deviation (24.6 ± 2.2 ms vs. 35.2 ± 3.5 ms, P = 0.006), very low frequency components (238.6 ± 99.6 ms(2) vs. 840.1 ± 188.3 ms(2), P < 0.001), and low frequency components (127.8 ± 26.3 ms(2) vs. 288.7 ± 66.2 ms(2), P = 0.032). However, despite clear differences between patients with idiopathic RBD and controls, there were no differences in any measure between those who did or did not develop disease. RR-variability analysis demonstrates substantial autonomic dysfunction in idiopathic RBD. However, this dysfunction is identical in patients who will or will not develop defined neurodegenerative disease. This suggests that autonomic dysfunction is linked with RBD independent of associated Parkinson's disease or Lewy body dementia.

Validity of actigraphy for nighttime sleep monitoring in hospitalized patients with traumatic injuries.

STUDY OBJECTIVES: Sleep-wake disturbances are frequent among patients hospitalized for traumatic injuries but remain poorly documented because of the lack of tools validated for hospitalized patients. This study aimed to validate actigraphy for nighttime sleep monitoring of hospitalized patients with severe traumatic injuries, using ambulatory polysomnography (PSG). METHODS: We tested 17 patients (30.4 ± 14.7 years, 16.6 ± 8.2 days postinjury) who had severe orthopedic injuries and/or spinal cord injury, with or without traumatic brain injury. When medically stable, patients wore an actigraph on a nonparalyzed arm and underwent ambulatory PSG at the bedside. Data were converted to 1-minute epochs. The following parameters were calculated for the nighttime period: total sleep time, total wake time, sleep efficiency, and number of awakenings. Epoch-by-epoch concordance between actigraphy and PSG was analyzed to derive sensitivity, specificity, and accuracy. PSG sleep parameters were compared to those obtained from four actigraphy scoring algorithms by Bland-Altman plots. RESULTS: Sensitivity to detect sleep was ≥ 92% and accuracy was > 85% for all four actigraphy algorithms used, whereas specificity varied from 48% to 60%. The low-activity wake threshold (20 activity counts per epoch) was most closely associated with PSG on all sleep parameters. This scoring algorithm also had the highest specificity (59.9%) and strong sensitivity (92.8%). CONCLUSIONS: Actigraphy is valid for monitoring nighttime sleep and wakefulness in patients hospitalized with traumatic injuries, with sensitivity, specificity and accuracy comparable to actigraphic recordings in healthy individuals. A scoring algorithm using a low wake threshold is best suited for this population and setting.

Sleep-wake disturbances in hospitalized patients with traumatic brain injury: association with brain trauma but not with an abnormal melatonin circadian rhythm.

STUDY OBJECTIVES: To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) (1) is also found in patients with traumatic injuries other than TBI (non-TBI) and (2) is associated with a weaker or abnormal circadian clock signal. METHODS: Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate-to-severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4 ± 4.2 days, starting 19.3 ± 12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 hours, starting 18.3 ± 12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24-hour excretion, excretion onset, offset, duration, amplitude, and acrophase. Using Student's t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson's correlations. RESULTS: TBI patients had poorer daytime activity ratio (TBI: 77.5 ± 9.4%; non-TBI: 84.6 ± 6.9%), shorter nighttime total sleep time (TBI: 353.5 ± 96.6 min; non-TBI: 421.2 ± 72.2 min), and higher fragmentation index (TBI: 72.2 ± 30.0; non-TBI: 53.5 ± 23.6) (all p-values < 0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients. CONCLUSION: Moderate-to-severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleep-wake cycle. Despite their deregulated 24-hour sleep-wake cycle, TBI patients have a normal circadian clock signal.

Sleep spindles are resilient to extensive white matter deterioration.

Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury (n = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group (n = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.

Obstructive sleep apnea during REM sleep and daytime cerebral functioning: A regional cerebral blood flow study using high-resolution SPECT.

Obstructive sleep apnea (OSA) predominantly during rapid eye movement (REM) sleep may have impacts on brain health, even in milder OSA cases. Here, we evaluated whether REM sleep OSA is associated with abnormal daytime cerebral functioning using high-resolution single-photon emission computed tomography (SPECT). We tested 96 subjects (25 F, age: 65.2 ± 6.4) with a wide range of OSA severity from no OSA to severe OSA (apnea-hypopnea index: 0-97 events/h). More respiratory events during REM sleep were associated with reduced daytime regional cerebral blood flow (rCBF) in the bilateral ventromedial prefrontal cortex and in the right insula extending to the frontal cortex. More respiratory events during non-REM (NREM) sleep were associated with reduced daytime rCBF in the left sensorimotor and temporal cortex. In subjects with a lower overall OSA severity (apnea-hypopnea index<15), more respiratory events during REM sleep were also associated with reduced daytime rCBF in the insula and extending to the frontal cortex. Respiratory events that characterized OSA during NREM versus REM sleep are associated with distinct patterns of daytime cerebral perfusion. REM sleep OSA could be more detrimental to brain health, as evidenced by reduced daytime rCBF in milder forms of OSA.

Towards a better understanding of increased sleep duration in the chronic phase of moderate to severe traumatic brain injury: an actigraphy study.

INTRODUCTION: Most adults with moderate to severe traumatic brain injury (TBI) report persistent sleep-wake disturbances. Whether these complaints are either associated with abnormal sleep-wake patterns or can be explained by TBI-related characteristics is unclear. The present study aimed at characterising the subjective and objective sleep-wake patterns in TBI adults by taking into consideration the influence of TBI severity, common comorbidities and psychoactive medication. METHODS: Overall, 34 adults with moderate-severe TBI (one to four years post-injury) were compared to 34 controls. Sleepiness, fatigue, sleep quality, mood, and pain were assessed with questionnaires. A seven day sleep diary and actigraphy was used to document sleep and wake patterns. RESULTS: Compared to controls, TBI participants reported more sleepiness and fatigue, as well as poorer sleep quality. On actigraphy, they had earlier bedtime and longer time spent in bed, but equivalent sleep efficiency during the nighttime episode compared to controls. TBI participants also took more naps and accumulated more time asleep over the 24 h period than controls. These group differences were accentuated when only TBI adults using psychoactive medication were included. More comorbidities, more severe injuries and longer hospital stay were positively correlated with fatigue, sleepiness and sleep duration. CONCLUSIONS: Our results showed that despite complaints regarding sleep and diurnal functioning, TBI survivors have very marginal changes in their objective sleep-wake schedules. Prolonged time spent in bed may reflect an attempt to increase their sleep duration in response to fatigue and sleepiness. TBI adults who use psychoactive medication are those with more evident changes in their sleep-wake schedules.

Daytime vigilance in chronotypes: diurnal variations and effects of behavioral sleep fragmentation.

Vigilance levels of 12 morning types (M-types) and 12 evening types (E-types) were investigated after a baseline night, 2 nights of sleep fragmentation (5 min of forced awakening every half-hour) and a recovery night. Sleep timing was adjusted to the preferred sleep schedule of each subject. Daytime vigilance levels were assessed with test series including a scale of subjective alertness, a psychomotor vigilance task (PVT), a waking EEG recording, and a sleep latency test. Test series were administered every 4h, beginning 1.5h after wake time. On the baseline day, significant diurnal variations were found for each vigilance measure, except for the PVT. Diurnal variations were similar in M-types and E-types. Sleep fragmentation decreased vigilance levels on each measure, except the PVT. Effects of sleep fragmentation and recovery were similar in the two chronotypes. These results highlight the similarities in diurnal variations of vigilance in the two chronotypes when studied at their preferred sleep schedule. Results were also compared between chronotypes with extremely early or late circadian phases ("Extreme" subgroup) and between those with similar, intermediate circadian phases ("Intermediate" subgroup). Diurnal variations of subjective alertness and sleep latencies differed between "Extreme" chronotypes but were identical between "Intermediate" chronotypes. There were no major differences in the response to sleep fragmentation in any subgroup. Since phase angles differed by the same amount between chronotypes within each subgroup, the results suggest that a difference in phase angle cannot be the only source of the differences observed in diurnal variations between "Extreme" chronotypes.