EEG Slow Waves in Traumatic Brain Injury: Convergent Findings in Mouse and Man

OBJECTIVE: Evidence from previous studies suggests that greater sleep pressure, in the form of EEG-based slow waves, accumulates in specific brain regions that are more active during prior waking experience. We sought to quantify the number and coherence of EEG slow waves in subjects with mild traumatic brain injury (mTBI). METHODS: We developed a method to automatically detect individual slow waves in each EEG channel, and validated this method using simulated EEG data. We then used this method to quantify EEG-based slow waves during sleep and wake states in both mouse and human subjects with mTBI. A modified coherence index that accounts for information from multiple channels was calculated as a measure of slow wave synchrony. RESULTS: Brain-injured mice showed significantly higher theta:alpha amplitude ratios and significantly more slow waves during spontaneous wakefulness and during prolonged sleep deprivation, compared to sham-injured control mice. Human subjects with mTBI showed significantly higher theta:beta amplitude ratios and significantly more EEG slow waves while awake compared to age-matched control subjects. We then quantified the global coherence index of slow waves across several EEG channels in human subjects. Individuals with mTBI showed significantly less EEG global coherence compared to control subjects while awake, but not during sleep. EEG global coherence was significantly correlated with severity of post-concussive symptoms (as assessed by the Neurobehavioral Symptom Inventory scale). CONCLUSION AND IMPLICATIONS: Taken together, our data from both mouse and human studies suggest that EEG slow wave quantity and the global coherence index of slow waves may represent a sensitive marker for the diagnosis and prognosis of mTBI and post-concussive symptoms

EEG Slow Waves in Traumatic Brain Injury: Convergent Findings in Mouse and Man

OBJECTIVE: Evidence from previous studies suggests that greater sleep pressure, in the form of EEG-based slow waves, accumulates in specific brain regions that are more active during prior waking experience. We sought to quantify the number and coherence of EEG slow waves in subjects with mild traumatic brain injury (mTBI). METHODS: We developed a method to automatically detect individual slow waves in each EEG channel, and validated this method using simulated EEG data. We then used this method to quantify EEG-based slow waves during sleep and wake states in both mouse and human subjects with mTBI. A modified coherence index that accounts for information from multiple channels was calculated as a measure of slow wave synchrony. RESULTS: Brain-injured mice showed significantly higher theta:alpha amplitude ratios and significantly more slow waves during spontaneous wakefulness and during prolonged sleep deprivation, compared to sham-injured control mice. Human subjects with mTBI showed significantly higher theta:beta amplitude ratios and significantly more EEG slow waves while awake compared to age-matched control subjects. We then quantified the global coherence index of slow waves across several EEG channels in human subjects. Individuals with mTBI showed significantly less EEG global coherence compared to control subjects while awake, but not during sleep. EEG global coherence was significantly correlated with severity of post-concussive symptoms (as assessed by the Neurobehavioral Symptom Inventory scale). CONCLUSION AND IMPLICATIONS: Taken together, our data from both mouse and human studies suggest that EEG slow wave quantity and the global coherence index of slow waves may represent a sensitive marker for the diagnosis and prognosis of mTBI and post-concussive symptoms

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

Background: Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times.Results: in each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed sleep specific changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time.Conclusion: Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health SciencesNational Institutes of HealthAmerican Sleep Medicine FoundationNational Heart Lung Blood InstituteUniv Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USAUniversidade Federal de São Paulo UNIFESP, São Paulo, BrazilNIEHS, US Dept HHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USAUniversidade Federal de São Paulo UNIFESP, São Paulo, BrazilNational Institutes of Health: AG-17628National Heart Lung Blood Institute: HL090021: K12Web of Scienc

Aging is associated with an earlier arrival of reflected waves without a distal shift in reflection sites

Background-Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (T-INF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a "distal-shift" of reflection sites. T-INF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results-We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTTWSA) and partially distributed tube-load (TL) modeling (RWTTTL). Consistent with previous reports, T-INF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population -15.0 ms/decade, P<0.001; clinical population -9.07 ms/decade, P=0.003) and RWTTTL (general -15.8 ms/decade, P<0.001; clinical -11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions-RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging

Insomnia in untreated sleep apnea patients compared to controls.

Insomnia and obstructive sleep apnea (OSA) often coexist, but the nature of their relationship is unclear. The aims of this study were to compare the prevalence of initial and middle insomnia between OSA patients and controls from the general population as well as to study the influence of insomnia on sleepiness and quality of life in OSA patients. Two groups were compared, untreated OSA patients (n = 824) and controls ≥ 40 years from the general population in Iceland (n = 762). All subjects answered the same questionnaires on health and sleep and OSA patients underwent a sleep study. Altogether, 53% of controls were males compared to 81% of OSA patients. Difficulties maintaining sleep (DMS) were more common among men and women with OSA compared to the general population (52 versus 31% and 62 versus 31%, respectively, P < 0.0001). Difficulties initiating sleep (DIS) and DIS + DMS were more common among women with OSA compared to women without OSA. OSA patients with DMS were sleepier than patients without DMS (Epworth Sleepiness Scale: 12.2 versus 10.9, P < 0.001), while both DMS and DIS were related to lower quality of life in OSA patients as measured by the Short Form 12 (physical score 39 versus 42 and mental score 36 versus 41, P < 0.001). DIS and DMS were not related to OSA severity. Insomnia is common among OSA patients and has a negative influence on quality of life and sleepiness in this patient group. It is relevant to screen for insomnia among OSA patients and treat both conditions when they co-occur.NIH HL072067, HL09430

Aging in Mice Reduces the Ability to Sustain Sleep/Wake States

One of the most significant problems facing older individuals is difficulty staying asleep at night and awake during the day. Understanding the mechanisms by which the regulation of sleep/wake goes awry with age is a critical step in identifying novel therapeutic strategies to improve quality of life for the elderly. We measured wake, non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in young (2-4 months-old) and aged (22-24 months-old) C57BL6/NIA mice. We used both conventional measures (i.e., bout number and bout duration) and an innovative spike-and-slab statistical approach to characterize age-related fragmentation of sleep/wake. The short (spike) and long (slab) components of the spike-and-slab mixture model capture the distribution of bouts for each behavioral state in mice. Using this novel analytical approach, we found that aged animals are less able to sustain long episodes of wakefulness or NREM sleep. Additionally, spectral analysis of EEG recordings revealed that aging slows theta peak frequency, a correlate of arousal. These combined analyses provide a window into the mechanisms underlying the destabilization of long periods of sleep and wake and reduced vigilance that develop with aging

Objective Snoring Time and Carotid Intima-Media Thickness in Non-Apneic Female Snorers

Controversy persists about whether snoring can affect atherosclerotic changes in adjacent vessels, independently of obstructive sleep apnea and other cardiovascular risk factors. This study examined the independent association between snoring and carotid artery intima-media thickness (IMT) in non-apneic snorers and non-snorers. We studied 180 non-apneic snorers and non-snorers participating in a full-night home-based sleep study. Snoring sound was measured objectively by a microphone. Based on snoring time across the night, participants were classified as non-snorers (snoring time: 0%), mild snorers (1-25%) and moderate to heavy snorers (≥25%). We measured IMT on both common carotid arteries. The three groups were matched by age, body mass index, cholesterol, blood pressure and glucose levels, using weights from generalized boosted-propensity score models. Mean carotid IMT increased with increased snoring time across the night in women: non-snorers (0.707 mm), mild (0.718 mm) and moderate to heavy snorers (0.774 mm), but not in men. Snoring during at least one-fourth of a night\u27s sleep is associated independently with subclinical changes in carotid IMT in women only

Nocturnal sweating--a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner

The different clinical faces of obstructive sleep apnoea: a cluster analysis.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAlthough commonly observed in clinical practice, the heterogeneity of obstructive sleep apnoea (OSA) clinical presentation has not been formally characterised. This study was the first to apply cluster analysis to identify subtypes of patients with OSA who experience distinct combinations of symptoms and comorbidities. An analysis of baseline data from the Icelandic Sleep Apnoea Cohort (822 patients with newly diagnosed moderate-to-severe OSA) was performed. Three distinct clusters were identified. They were classified as the "disturbed sleep group" (cluster 1), "minimally symptomatic group" (cluster 2) and "excessive daytime sleepiness group" (cluster 3), consisting of 32.7%, 24.7% and 42.6% of the entire cohort, respectively. The probabilities of having comorbid hypertension and cardiovascular disease were highest in cluster 2 but lowest in cluster 3. The clusters did not differ significantly in terms of sex, body mass index or apnoea-hypopnoea index. Patients with OSA have different patterns of clinical presentation, which need to be communicated to both the lay public and the professional community with the goal of facilitating care-seeking and early identification of OSA. Identifying distinct clinical profiles of OSA creates a foundation for offering more personalised therapies in the future

Agreement in the scoring of respiratory events and sleep among international sleep centers.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Abstract STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers. DESIGN: Prospective study of interrater agreement of PSG scoring. SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC). MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85). CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.NHLBI P01 HL094307 HL093463 Tzagournis Medical Research Endowment Funds of The Ohio State Universit