Arousal Index Research Articles

0544 Polysomnography characteristics of children with obesity: A single center retrospective study

Abstract Introduction The constellations of symptoms known as obstructive sleep apnea (OSA) results from either partial or complete airway obstruction during sleep. This affects effective gas exchange and disrupts sleep architecture resulting in sleep fragmentation with downstream immediate and long-term adverse effects. Obesity is a significant risk factor in childhood OSA, especially in post-pubertal children. Obese/overweight children have been found to have significantly higher rates of OSA than their normal-weight counterparts, independent of tonsillar size. Polysomnography characteristics (PSG) comparing children with obesity with and without comorbidities (Hypertension, Diabetes or Pre-diabetes) has not been previously described. Methods Retrospective analysis of 190 obese children (BMI>95th centile), age between 7-18 years with AHI ≥5/hour met the criteria for the data analysis. Clinical, demographic and PSG parameters of children with obesity with and without co-morbidities were compared using Wilcoxon rank sum test. Correlation (Spearman non-parametric) and regression model was employed to explore associations between demographic and PSG characteristics. Results Majority of the obese children (mean BMI 33.2) had mild OSA, with no significant difference in AHI between the two groups. Children with obesity and comorbidities were older with higher BMI. There was no difference in BMI between the two groups after adjusting for BMI z scores. AHI increased with increasing BMI centiles. In our regression model, peak ETCO2 was associated with Black race, AHI, rhinitis and inversely associated with asthma. Peak ETCO2 increased with BMI. Oxygen at baseline, nadir and desaturation duration inversely correlated with BMI-centiles. Older children had lower O2 nadir. Black race was associated with higher desaturation, supine AHI, and arousal index. Supine AHI was higher with rhinitis. Average heart rate when awake, NREM and REM increased with higher BMI. Conclusion In our study, majority of the children had mild OSA with no significant difference in AHI between obese children with and without comorbidities. AHI, average heart rate and peak ETCO2 increased with BMI. O2 nadir was lower in older children and with higher BMI. Black race was associated with higher peak ETCO2, higher desaturation and supine AHI. Children with obesity and comorbidities were older with higher BMI suggesting synergistic effect of BMI and duration of obesity. Support (If Any)

0730 Validation studies for scoring polysomnograms and home sleep apnea tests with artificial intelligence: Sleep stage probabilities (hypnodensity) derived from neurological or cardiorespiratory signals

Abstract Introduction There have been significant advances in machine learning in recent years. This means that powerful methods are now available for classification problems, such as scoring sleep stages from neurological or cardiorespiratory signals. In the present work, validation studies for both applications are presented. Methods To determine the 5 sleep stages from the neurological signals, 54 sleep-wake-related features were calculated and classified by a bidirectional long short-term memory (LSTM) network which had been trained on 1956 manual scorings of 588 PSGs from 294 subjects (supervised deep learning). To determine the 4 stages (wake, light sleep, deep sleep, REM) from cardiorespiratory signals, a convolutional neural network combined with LSTM layers was used for feature extraction and classification. This network had been trained on 685 PSGs from 391 subjects (Bakker et al. JCSM 2021). The networks obtained were validated in 428 PSGs with one and 10 PSGs with 12 manual scorings (neurological staging) as well as in 2 two datasets, each containing 296 ambulatory recordings (cardiorespiratory staging). Results Cohen’s kappa between autoscoring based on neurological signals and manual scoring was 0.74 (95%-confidence interval: 0.74-0.74) for the 428 PSGs. The intraclass correlation coefficient (ICC) for absolute agreement between autoscoring and manual scoring was for the AHI 0.97 (0.96-0.98), for the arousal index 0.79 (0.67-0.86) and for the PLMSI 0.91 (0.88-0.93). The ICC between the sleep stage probabilities derived from the 12 manual scorings and the artificial intelligence (AI) derived hypnodensity was 0.91 (0.91-0.91). Cohen’s kappa values for the cardiorespiratory sleep staging were 0.68 (0.68-0.68) and 0.64 (0.63-0.64) for the 2 datasets with 296 ambulatory recordings each. Conclusion All metrics from the PSG validation studies show substantial (Cohen’s kappa > 0.6) as well as good to excellent agreement (ICC > 0.75 or > 0.90) compared to manual scorings. As an added value of the AI-supported PSG evaluation, the probabilities of the sleep stages per epoch are determined (hypnodensity graph). The valid estimation of the sleep stages from cardiorespiratory signals by means of AI may result in improved clinical interpretation of home sleep apnea tests, which are increasingly used in the sleep-disordered breathing diagnostic pathway. Support (If Any)

0616 Retrospective Pain Reports in Obstructive Sleep Apnea Patients Relate to Age, Sex, BMI, Insomnia and Depression Scales, Not to Polysomnographic Measures of Sleep and Respiration

Abstract Introduction OSA was found to alter pain experience, presumably due to apnea-related hypoxia and sleep disturbance. However, types of pain measures, demographic and subjective variables, such as mood, may influence pain experience in OSA. Presently, retrospective pain reports of patients referred for OSA evaluation were analyzed as a function of PSG measures, demographic variables, and self-reported mood and insomnia symptoms. Methods On the evening of a diagnostic in-lab PSG, patients reported pain intensity in the preceding 6 months (PI, rage 0-10, Chronic Pain Grade Scale), symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised, CESDR) and insomnia (Insomnia Severity Index, ISI). PI was regressed on age, sex, BMI, total sleep time (TST), sleep stage percentages, sleep efficiency, WASO, awakenings, respiratory arousal index, AHI, SpO2% nadir, time below SpO2 90%, desaturation index, CESDR and ISI using a stepwise entry. Results A total of 1293 patients with ≥2 hours of PSG-defined sleep completed the questionnaires; 3% Asian, 42% black, 5% Hispanic, 32% white; 62% women; 66% had OSA (AHI≥5); Mage=58.7±13.8, MBMI=33.8±7.3, MPI=3.5±3.1; MISI=12.9±6.9; MCESDR=14.7±13.1, MAHI=17.6±22.9, MSpO2%nadir=84.9±9.0. Higher PI was associated with female sex (p<0.001, R2=2.6%), older age (p<0.001, R2=3.7%), higher BMI (p<0.001, R2=2.5%), higher ISI (p<0.001, R2=4.5%), higher CESDR (p<0.001, R2=2.3%) and longer TST (p=0.028, R2=0.4%). No other sleep or respiratory variables related to PI. No significant interactions with AHI≥5 were present. No differences between OSA (AHI≥5) and no-OSA groups were present on PI, ISI or CESDR after controlling for age, sex and BMI. Conclusion Retrospective reports of pain intensity were unrelated to PSG measures of sleep and respiratory disturbance. Female sex, older age and higher BMI related to higher PI regardless of the OSA diagnosis and collectively accounted for 8.8% of the PI variance. Symptoms of insomnia and depression related to higher PI independently of OSA, accounting for 4.5% and 2.3% of the PI variance, respectively. As in prior research OSA was associated with insomnia and depression, these variables may mediate the relationship between OSA and pain. Support (If Any) None

0523 Prevalence And Severity Of Sleep Disordered Breathing In Asthmatic Children

Abstract Introduction Children with severe and poorly controlled asthma have a higher predisposition for sleep disordered breathing (SDB). It can lead to cardiovascular, neurocognitive, and behavioral problems. Variable data exists currently whether demographic factors like age, sex, obesity, adeno-tonsillar hypertrophy tend to increase the risk of SDB in asthmatics. Our objective was to evaluate the risk factors and prevalence of SDB in asthmatics as compared to non - asthmatics and describe the polysomnographic parameters in asthmatics with SDB. Methods Asthmatic and non - asthmatic children aged 5 – 15 years, were recruited in this case – control study. Parameters like age, gender, body mass index, adeno-tonsillar hypertrophy, and the history of snoring were compared. All participants completed the Sleep-Related Breathing Disorder scale, extracted from the Pediatric Sleep Questionnaire (SDBS-PSQ) and prevalence of risk of SDB (defined as SDBS - PSQ ≥ 0.33) was calculated. A subset of asthmatics with risk of SDB underwent polysomnography, and subjects were classified into no, mild, moderate, and severe SDB [based on apnea-hypopnea index (AHI) ≤1, 1-5, 5-10, and ≥10, respectively]. Results 120 children, with 60 asthmatics were included. Amongst asthmatic group, 61.7% were male and mean age was 9.51 ± 2.50 years. Risk of SDB was significantly higher in asthmatics compared to non - asthmatics (18.33% vs 1.67%, p = 0.001; with mean SDBS-PSQ score 0.14 ± 0.17 vs 0.05 ± 0.08, p = 0.001). History of snoring was reported in 25% of asthmatic children versus 11.7% in non – asthmatics (p> 0.05). Other parameters were similar in both the groups (p> 0.05). Of the 11 asthmatics with risk of SDB, 10 underwent polysomnography. 9 patients (15% of asthmatics) were diagnosed with SDB, with a mean AHI of 4.21 ± 3.28, mean total sleep time of 279.23 ± 57.69 minutes and mean arousal index of 10.23 ± 8.67. In this subset, 60% had mild SDB. Conclusion Prevalence of SDB is higher in asthmatics, compared to general population. SDBS-PSQ is a useful screening tool for diagnosing SDB and should be incorporated in the daily practice, the gold standard being polysomnography. Further studies would help in a better understanding of SDB spectrum in children. Support (If Any) Nil

0629 Metabolic syndrome in narcoleptic children

Abstract Introduction Narcolepsy is a disabling neurological disorder characterized primarily by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis, rapid eye movement (REM) behavior disorder (RBD) and disturbed nocturnal sleep. Over 50% of children with narcolepsy are obese. Metabolic syndrome (MetS), a constellation of disturbances associated with obesity, is increasingly seen in narcolepsy. A higher prevalence of MetS was revealed both in adults and children with narcolepsy. The objective of the present study was to compare clinical and sleep characteristics in children with narcolepsy with different components of MetS to clarify the mechanisms in MetS in these children. Methods This retrospective study included 58 children with narcolepsy. Data on blood pressure, High density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin and anthropometry (height and weight) were collected. MetS was defined when ≥3 of the following criteria were met: (1) Body mass index (BMI) ≥IOTF-30, (2) Blood pressure ≥90th percentile, (3) HDL-C ≤0.4 g/L, (4) Triglycerides ≥1.3 g/L, (5) homeostasis model assessment of insulin resistance (HOMA-IR) ≥75th percentile. Then, clinical and sleep characteristics were compared in groups with different MetS components. Results A total of 17 % of children with narcolepsy had MetS including 79% with high HOMA, 26% with high BMI, 24% with low HDL cholesterol and 12% with high triglycerides, but no patient with high blood pressure. 58% of the patients without obesity had at least 1, 2 or ≥3 MetS risk factors (78%, 15% and 6%, respectively). 55% of them were overweight. In children with narcolepsy with at least two MetS risk factors, there was a higher proportion of night eating, a lower percentage of N3 sleep, a higher arousal index, a shorter mean sleep latency and more sleep onset REM periods (SOREMPs) compared to patients with fewer MetS risk factors. Conclusion Altered sleep architecture and eating behavior are closely associated with risk factors of MetS in children with narcolepsy, even without obesity. We recommend to evaluate MetS risk in all children with narcolepsy to prevent complications such as type 2 diabetes and cardiovascular outcomes. Support (If Any)

0843 Sexsomnia in a female patient with nightmares and obstructive sleep apnea: a case report

Abstract Introduction Sexsomnia has been described as various sleep-related abnormal sexual behaviors primarily associated with confusional arousals and more rarely linked to rapid eye movement (REM) sleep behavior disorder (RBD). Clinical descriptions are based on case reports and review series, which leads to diagnostic ambiguity, challenges with appropriate classification, and forensic and legal ramifications Report of Cases: We report a 34 year old female with a past medical history of polycystic ovarian syndrome and childhood post-traumatic stress disorder. Family history significant for parent with lifelong parasomnias. The patient was referred to Sleep Medicine with concern for snoring, sleepiness, and sleep behaviors. The patient reports sleep talking since childhood which predate trauma, traumatic themed nightmares, and ex-husband and current spouse reporting sleep-related masturbation, sexual advances described as coital-like pelvic movements which often lead to intercourse and subsequent amnesia. In addition, spouse describes bruxism and ongoing night terrors. Physical examination notable for body mass index 44 kg/m2, high arched palate, Mallampati class III, and 18 inch neck circumference. The patient underwent a polysomnagram which demonstrated fragmented sleep architecture, total arousal index up to 20.3/hr, and totalsleep time in stage N3 20%, Four awakenings fromN3, and findings of N3 partial arousal. The patient was observed in v-PSG to have periods of nocturnal lagophthalmos, finger movements, and vocalizations during NREM sleep. However, many of these observations were in the setting of respiratory events. The apnea-hypopnea index was 16.9/hr and a minimum oxygen saturation of 81% and mean saturation of 95%. A total of 3.1 minutes were spent less than or equal to 90%. TCO2 was without concern for hypoventilation. The patient was started on Auto CPAP 5-15cmH2O with resolution of snoring and some improvement to sleepiness. However, spouse reports ongoing sexsomnia in the same frequency despite treatment of obstructive sleep apnea. Conclusion This case reports a female adult with persistent sexsomnia despite early treatment of obstructive sleep apnea which highlights the possibility of co-occurring sleep disorder. The case does support current limited literature around sexsomnias having features of partial arousals from NREM sleep given the co-occuring history of night terrors, elevated N3 awakenings, and evidence of cortico-cortical dissociation. Support (If Any) None

0625 Characterization of Obstructive Sleep Apnea in Active-Duty US Military Personnel Receiving Interdisciplinary Care at the National Intrepid Center of Excellence

Abstract Introduction Among active-duty service members (ADSMs), obstructive sleep apnea (OSA) is associated with decreased quality of life and military readiness/retention. Limited evidence suggests mild traumatic brain injury (mTBI) patients have increased OSA incidence, but little is known about the underlying physiology. This study aims to characterize OSA in treatment-seeking ADSMs with a history of remote mTBI and/or persistent neurobehavioral symptoms to improve detection and early intervention. Methods This is a retrospective analysis of data collected from ADSMs attending the National Intrepid Center of Excellence Intensive Outpatient Program for persistent symptoms associated with mTBI. Sleep assessment included overnight polysomnography and self-report assessments of sleep quality, somatic and mood symptoms. OSA severity was determined by apnea-hypopnea index (negative: <5, mild: 5-15, moderate/severe: ≥15). Group differences were assessed using analysis of covariance and pairwise least squares regression, controlling for age and body mass index, and corrected for multiple comparisons. Results Analyses included 574 ADSMs, mostly male (99%), with a mean age of 39.7. The majority (n=288; 50.2%) were OSA negative (OSA-neg); a third had mild OSA (m-OSA) (n=216; 38%); and a tenth were diagnosed with moderate/severe OSA (mod/s-OSA) (n=70; 12%). Mod/s-OSA patients had increased arousal index (p<0.01), hypoxia time (p<0.001), reduced total sleep time (p<0.01) and sleep efficiency (p<0.001) compared to m-OSA and OSA-neg patients. M-OSA patients had an increased arousal index compared to OSA-neg patients (p<0.01). Patient groups did not significantly differ on subjective measures of sleep (i.e., quality, sleepiness), post-concussive, or behavioral health symptoms (anxiety, depression, post-traumatic stress symptoms, alcohol misuse). Conclusion In our sample of treatment-seeking ADSMs, nearly half presented with OSA according to cut-scores derived for AHI, greater than that expected in the general population. As reported in civilian populations, mod/s-OSA patients demonstrated worse objective sleep measures compared to m-OSA and OSA-neg patients, yet in our sample their self-reported symptom severity did not differ. These findings suggest a low threshold for OSA screening is needed in the symptomatic mTBI population and that multiple factors other than OSA likely contribute to perceived sleep disturbances and neurobehavioral symptoms. Support (If Any) None.

0736 Mandibular Movements Are a Reliable Noninvasive Alternative to Esophageal Pressure for Measuring Respiratory Effort in Patients with Sleep Apnea Syndrome

Abstract Introduction Differentiation between obstructive and central apneas and hypopneas requires quantitative measurement of respiratory effort (RE) using esophageal pressure (PES), which is rarely implemented. This study investigated whether the sleep mandibular movements (MM) signal recorded with a tri-axial chin sensor (Sunrise, Namur, Belgium) is a reliable surrogate of PES in patients with suspected obstructive sleep apnea (OSA). Methods In-laboratory polysomnography (PSG) with PES and concurrent MM monitoring was performed. PSGs were scored manually using AASM 2012 rules. Data blocks (n=8042) were randomly sampled during normal breathing (NB), obstructive or central apnea/hypopnea (OA/OH/CA/CH), respiratory effort-related arousal (RERA), and mixed apnea (MxA). Analyses were: evaluation of the similarity and linear correlation between PES and MM using the longest common subsequence (LCSS) algorithm and Pearson’s coefficient; description of signal amplitudes; estimation of the marginal effect for crossing from NB to a respiratory disturbance for a given change in MM signal using a mixed linear-regression. Results Participants (n=38) had mild to severe OSA (median AH index 28.9/h; median arousal index 23.2/h). MM showed a high level of synchronization with concurrent PES signals. Distribution of gyroscope MM signal amplitude differed significantly between event types: median (95% confidence interval) values of 0.60 (0.17–2.43) for CA, 0.83 (0.23–4.71) for CH, 1.93 (0.54–5.57) for MxA, 3.23 (0.72–18.09) for OH, and 6.42 (0.88–26.81) units for OA. Mixed regression indicated that crossing from NB to central events would decrease gyroscope MM signal amplitude by –1.23 (CH) and –2.04 (CA) units, while obstructive events would increase gyroscope MM signal amplitude by +3.27 (OH) and +6.79 (OA) units (all p<10-6). Conclusion In OSA patients, MM signals facilitated the measurement of specific levels of RE associated with obstructive, central or mixed apneas and/or hypopneas. A high degree of similarity was observed with the PES gold-standard signal. Support (If Any)

Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility

PurposePreliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA.MethodsThis trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation.ResultsOf 62 patients who were randomized, 60 were included in efficacy analyses. The apnea–hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone (p < .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden (p < .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater Vactive). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine).ConclusionAD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation.Trial registrationClinical trial registered with www.clinicaltrials.gov (NCT04445688).

Respiratory Arousals in Patients with Very Severe Obstructive Sleep Apnea and How They Change after a Non-Framework Surgery.

Respiratory arousal is the change from a state of sleep to a state of wakefulness following an apnea or hypopnea. In patients with obstructive sleep apnea (OSA), it could have a helpful role to activate upper airway muscles and the resumption of airflow and an opposing role to contribute to greater ventilatory instability, continue cycling, and likely exacerbate OSA. Patients with very severe OSA (apnea-hypopnea index (AHI) ≥ 60 events/h) may have specific chemical (e.g., possible awake hypercapnic hypoxemia) and mechanical (e.g., restricted dilator muscles) stimuli to initiate a respiratory arousal. Little was reported about how respiratory arousal presents in this distinct subgroup, how it relates to AHI, Epworth Sleepiness Scale (ESS), body mass index (BMI), and oxygen saturation, and how a non-framework surgery may change it. Here, in 27 patients with very severe OSA, we show respiratory arousal index was correlated with each of AHI, mean oxyhemoglobin saturation of pulse oximetry (SpO2), mean desaturation, and desaturation index, but not in BMI or ESS. The mean (53.5 events/h) was higher than other reports with less severe OSAs in the literature. The respiratory arousal index can be reduced by about half (45.3%) after a non-framework multilevel surgery in these patients.

Pupillary response in reward processing in adults with major depressive disorder in remission.

Major depressive disorder (MDD) is associated with impaired reward processing and reward learning. The literature is inconclusive regarding whether these impairments persist after remission. The current study examined reward processing during a probabilistic learning task in individuals in remission from MDD (n = 19) and never depressed healthy controls (n = 31) matched for age and sex. The outcome measures were pupil dilation (an indirect index of noradrenergic activity and arousal) and computational modeling parameters. Participants completed two versions (facial/nonfacial feedback) of probabilistic reward learning task with changing contingencies. Pupil dilation was measured with a corneal reflection eye tracker. The hypotheses and analysis plan were preregistered. Healthy controls had larger pupil dilation following losses than gains (p <.001), whereas no significant difference between outcomes was found in individuals with a history of MDD, resulting in an interaction between group and outcome (β = 0.81, SE = 0.34, t = 2.37, p = .018). The rMDD group also achieved lower mean score at the last trial (t[46.77] = 2.12, p = .040) as well as a smaller proportion of correct choices (t[46.70] = 2.09, p = .041) compared with healthy controls. Impaired reward processing may persist after remission from MDD and could constitute a latent risk factor for relapse. Measuring pupil dilation in a reward learning task is a promising method for identifying reward processing abnormalities linked to MDD. The task is simple and noninvasive, which makes it feasible for clinical research.

Associations of the Severity of Obstructive Sleep Apnea With Age-Related Comorbidities: A Population-Based Study.

Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OSA) is also more prevalent in the older population. Although severe OSA has been linked to a higher risk of cardiovascular disease regardless of adult age, clinical consequences of mild-to-moderate OSA in the older adults are still uncertain.ObjectivesTo investigate the relationships between severity and metabolic, cognitive, and functional characteristics in community-dwelling older adults from a representative sample of the city of São Paulo.MethodsIn total, 199 participants of the first follow-up of the São Paulo Epidemiologic Sleep Study (EPISONO, São Paulo, Brazil) >60 years were cross-sectionally assessed through questionnaires, physical evaluations, laboratory tests, and full in-lab polysomnography (PSG). Three groups according to the OSA severity were compared according to sociodemographic characteristics, anthropometric measures, PSG parameters, the frequency of comorbidities, and the use of medications.ResultsParticipants' age ranged from 60 to 87 years with a mean of 70.02 ± 7.31, 59.8% female. In the univariate analysis, body mass index (BMI, kg/m2) (p = 0.049) and waist circumference (p = 0.005) were significantly higher in the participants with moderate OSA, but not among those with severe OSA. Participants with severe OSA had a higher arousal index (p = 0.007). Multivariate analysis showed that severe OSA was significantly associated with hypertension (p = 0.005), heart diseases (p = 0.025), and the use of two or more medications (p = 0.035).ConclusionIn a population-based study, severe, but not mild-to-moderate, OSA in older adults was associated with hypertension and the use of more medications. As age advances, anthropometric indicators of obesity may not increase the risk of severe OSA.

Prefrontal modulation of frustration-related physiology in preschool children ranging from low to severe irritability

Limbic-prefrontal connectivity during negative emotional challenges underpins a wide range of psychiatric disorders, yet the early development of this system is largely unknown due to difficulties imaging young children. Functional Near-Infrared Spectroscopy (fNIRS) has advanced an understanding of early emotion-related prefrontal activation and psychopathology, but cannot detect activation below the outer cortex. Galvanic skin response (GSR) is a sensitive index of autonomic arousal strongly influenced by numerous limbic structures. We recorded simultaneous lateral prefrontal cortex (lPFC) activation via fNIRS and GSR in 73 3- to 5-year-old children, who ranged from low to severe levels of irritability, during a frustration task. The goal of the study was to test how frustration-related PFC activation modulated psychophysiology in preschool children, and whether associations were moderated by irritability severity. Results showed lPFC activation significantly increased, and GSR levels significantly decreased, as children moved from frustration to rest, such that preschoolers with the highest activation had the steepest recovery. Further, this relation was moderated by irritability such that children with severe irritability showed no association between lPFC activation and GSR. Results suggest functional connections between prefrontal and autonomic nervous systems are in place early in life, with evidence of lPFC down-regulation of frustration-based stress that is altered in early psychopathology. Combining fNIRS and GSR may be a promising novel approach for inferring limbic-PFC processes that drive early emotion regulation and psychopathology.

The effect of laryngopharyngeal reflux on arousal in patients with obstructive sleep apnea

Background Laryngopharyngeal reflux (LPR) may be associated with the severity of obstructive sleep apnea (OSA). However, it is unknown whether LPR may be associated with arousal. Objective To clarify the effect of LPR on arousal in OSA. Methods This study included 120 OSA patients. The correlations between LPR scores and arousal index (ArI) were analyzed. Finally, to further clarify the effect of LPR on ArI, we analyzed the correlations between respiratory event-related arousal index (BERAI), leg-movement-related arousal index (LMRAI), snore-related arousal index (SRAI), spontaneous arousal index (SAI), and RSI score. Results Partial correlation analysis showed that the RSI score was positively correlated with ArI (p = .000), mainly correlated with BERAI and SAI (r = 0.422, p = .000; r = 0.212, p = .020). While controlling for apnea-hypopnea index (AHI), the RSI score was still positively correlated with ArI (p = .002), mainly correlated with BERAI and SAI (r = 0.252, p = .006; r = 0.200, p = .029). Conclusions and significance The effect of LPR symptoms on arousal in OSA exists. The more severe the LPR was, the more frequent the arousal in OSA patients was. Thereinto, respiratory event-related arousal and spontaneous arousal were the most obvious.

Obesity‐Induced Breathing Variability During Sleep Is Independent of Apneas and Sleep Fragmentation

IntroductionObesity is a major cause of sleep‐disordered breathing (SDB). Conventional metrics of SDB, such as the apnea‐hypopnea index, can be confounded by the effects of obesity on oxygenation and lack of standard definitions. Thus, the impact of SBD on sleep is often difficult to quantify. Sleep fragmentation is frequently observed in obese individuals, but whether it occurs independently of SDB remains unknown. Quantitative analysis of ventilation may delineate the effects of obesity on breathing patterns and sleep fragmentation. We aimed to examine the effects of obesity on respiratory patterns during sleep and the relationship between obesity‐related respiratory variability and sleep fragmentation.MethodsSleep recordings were performed in 15 male lean C57BL/6J mice and 17 male diet‐induced obese (DIO) mice on the same genetic background. We applied Poincaré analysis of minute ventilation (VE) during sleep to estimate the breathing variability. Apneas were scored as ≥90% reductions in airflow for two breath cycles or ≥0.7s regardless the presence of arousals. Arousals were defined as single waking events lasting less than 16s. Arousals were classified as respiratory when associated with ≥30% drops in VEfrom baseline.ResultsBreathing variability was significantly higher in DIO mice during NREM sleep, but not during REM sleep. Obesity was associated with an increased apnea severity and 45% greater sleep fragmentation. However, obesity‐induced breathing variability was not affected by apnea or arousal indexes. Respiratory arousals comprised 15% of the arousals in both strains.ConclusionsObesity increased respiratory variability during NREM sleep independently of apneas and macro‐sleep architecture. Obesity caused sleep fragmentation that was not fully explained by SDB severity. Our quantitative analysis of VE identified differences in breathing variability in obesity that were not captured by traditional SDB metrics, which may be applicable for human SDB.

Cues Associated with Social Defeat Stress Recruit CRF in the Nucleus Accumbens and Invigorate Drug‐Seeking following Abstinence from Cocaine

Cocaine‐dependent individuals experience intense drug cravings in anticipation of imminent drug availability. Notably, acute stressors can further exacerbate the heightened state of arousal produced by drug‐related stimuli and increase propensity to seek and consume drug – rendering individuals highly susceptible to relapse. The present studies extend ongoing work examining the stress peptide corticotropin releasing factor (CRF) as a candidate mechanism for maladaptive arousal evoked by drug‐predictive stimuli. In rats, CRF enhances instrumental behavior directed towards gaining access to cocaine, in part through local control of DA transmission in the nucleus accumbens (NAc). Because CRF modulates motivational states in both appetitive and aversive contexts, we explored the extent to which an ecologically relevant stressor (ie social defeat) augments cocaine self‐administration under a chained operant response sequence (ie seeking‐taking), and whether NAc‐CRF is recruited. On alternating days, male Long‐Evans rats were exposed to acute social defeat in the presence of a compound stimulus (CS+: peppermint odor + 3kHz tone) or placed in an empty cage (CS‐: almond odor + 25kHz tone) for 4 sessions each. Microdialysis conducted in the presence of the conditioned cues revealed that the stress‐CS+ produced a rapid increase in both CRF and DA in the NAc, which was temporally distinct from a delayed rise in corticosterone. Separate rats were trained to self‐administer cocaine under a chained schedule of reinforcement (FI‐FR) in order to dissociate anticipatory (‘drug‐seeking’) from consummatory (‘drug‐taking’) behavior. Completion of a fixed‐interval (5m) produced access to continuous cocaine reinforcement (FR1) on a separate lever (5m). Here, accelerating responding across the FI captures an index of arousal in anticipation of impending drug‐availability – ostensibly, when craving is heightened. After a 7d drug‐free (ABST) period, rats were reintroduced to the drug context to self‐administer cocaine in the presence of either the stress‐paired stimuli (CS+) or neutral cues (CS‐) in a counterbalanced manner. Compared to pre‐ABST baseline, responding during the FI was elevated under both stimulus conditions, presumably reflecting an “incubation”‐like enhancement of behavior. Critically, CS+ exposure produced significantly higher anticipatory responding for cocaine than the neutral condition (CS+&gt; CS‐ &gt; Baseline), suggesting that stress stimuli augmented the effects of ABST. Cocaine intake was unaffected by either condition. These data support the concept that environmental stressors can amplify the impact of being re‐exposed to a drug‐context after a period of abstinence, such to invigorate putative “drug‐seeking” behavior. Anticipation of threat may engage common motivational salience circuits that generate arousal during cocaine expectation, whereas the unconditioned aspects of drug‐reward are differentially controlled. Ongoing studies seek to further clarify the functional role of stress‐evoked NAc‐CRF in cocaine‐related behavior.

Loop gain is Increased and the Arousal Threshold is Decreased in Caucasian Compared to African American Males with Obstructive Sleep Apnea

ObjectiveRace and ethnicity may impact the prevalence and treatment of obstructive sleep apnea (OSA). However, only a few studies have made direct comparisons of endotypic characteristics between African Americans and Caucasians. The comparisons completed have focused primarily on differences in anatomical traits (i.e. craniofacial morphology) that may exist between races. The present study was designed to explore if other endotypic traits [(i.e. loop gain (LG) and the arousal threshold (AT)] that influence sleep apnea differ in African American compared to Caucasian males with OSA.Methods26 African Americans [age = 34.9 ± 11.9 years; body mass index = 28.1 ± 4.4 kg/m2; apnea hypopnea index (AHI) = 37.7 ± 21.1 events/hour] and 26 Caucasian male participants (age = 31.2 ± 8.2 years; body mass index = 29.6 ± 3.6 kg/m2; AHI = 41.7 ± 16.5 events/hour) with untreated OSA completed a baseline nocturnal polysomnogram. Thereafter, sleep staging, respiratory events, and arousals were scored according to standard criteria. A MATLAB software program was used to quantify LG and the AT from the ventilatory and sleep measures obtained during non‐rapid eye movement (NREM) sleep throughout the night. LG at the natural frequency (LGn) of obstructive events and at a frequency of 1 cycle/min (LG1, i.e., 60 events/hour) were computed. Data was compared using Student t‐test and is presented as mean ± SD.ResultsAge (p = 0.19), BMI (p = 0.20), and the AHI (p = 0.44) was similar between the two groups. LG was significantly higher in Caucasians compared to African Americans (LGn: 0.44 ± 0.07 vs. 0.40 ± 0.06, p = 0.037; LG1: 0.61 ± 0.12 vs. 0.54 ± 0.12, p = 0.039). In contrast, the AT was significantly lower in Caucasians compared to African Americans (1.22 ± 0.17 vs. 1.38 ± 0.27, p = 0.009). The difference in the AT corresponded to an increased arousal index in Caucasians compared to African Americans (74.99 ± 5.36 vs. 51.13 ± 19.34 arousals/hour, p = 0.029). Furthermore, a subgroup analysis of participants with OSA and co‐existing hypertension also showed that Caucasian males (n = 11) had a higher LG (LGn: 0.45 ± 0.06 vs. 0.39 ± 0.07, p = 0.05; LG1: 0.62 ± 0.12 vs. 0.48 ± 0.09, p = 0.007) and lower AT (1.16 ± 0.12 vs. 1.37 ± 0.27, p = 0.033) than the African American participants (n =10).ConclusionDespite similar anthropometric measures and a similar apnea hypopnea index, loop gain and the arousal threshold were greater in Caucasian compared to African American males with OSA. Our results suggest that these endotypic characteristics may have a more prevalent role in initiating sleep disordered breathing in Caucasians compared to African Americans. Likewise, our findings suggest that Caucasians may be more responsive to therapies that target loop gain and the arousal threshold.

Effect of information-motivation-behavior skills on adherence of continuous positive airway pressure therapy in patients with obstructive sleep apnea hypopnea syndrome.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease that seriously affects health. Continuous positive airway pressure (CPAP) therapy is the preferred treatment for moderate-to-severe OSAHS patients. However, poor adherence to CPAP is a major obstacle in the treatment of OSAHS. Information-motivation-behavioral (IMB) skills, as a kind of mature technology to change the behavior, has been used in various health areas to improve treatment adherence. This study aims to explore the effects of the IMB skills intervention on CPAP adherence in OSAHS patients. Patients who were primary diagnosed with moderate-to-severe OSAHS were randomly divided into the IMB group (n=62) and the control group (n=58). The patients in the IMB group received CPAP therapy and the IMB skills intervention for 4 weeks. The patients in the control group received CPAP therapy and a usual health care provided by a registered nurse. We collected the baseline data of the general information, including age, sex, body mass index (BMI), the Epworth Sleepiness Scale (ESS) score, the Hospital Anxiety and Depression Scale (HADS) score, and indicators about disease severity [apnea-hypopnea index (AHI), percentage of time with arterial oxygen saturation SaO2<90% (T90), average SaO2, lowest SaO2, arousal index]. After CPAP titration, we collected CPAP therapy-relevant parameters (optimal pressure, maximum leakage, average leakage, 95% leakage, and residual AHI), score of satisfaction and acceptance of CPAP therapy, and score of willingness to continue CPAP therapy. After 4 weeks treatment, we collected the ESS score, HADS score, CPAP therapy-relevant parameters, effective CPAP therapy time per night, CPAP therapy days within 4 weeks, CPAP adherence rate, score of satisfaction and acceptance of CPAP therapy, and score of willingness to continue CPAP therapy. Visual analog scale (VAS) of 0-5 was used to evaluate the satisfaction and acceptance of IMB intervention measures in the IMB group. There were no significant differences in the baseline level of demographic parameters, ESS score, HADS score, disease severity, and CPAP therapy related parameters between the IMB group and the control group (all P>0.05). There were no significant differences in score of willingness to continue CPAP therapy, as well as score of satisfaction and acceptance of CPAP therapy after CPAP titration between the IMB group and the control group (both P>0.05). After 4 weeks treatment, the ESS score, HADS score, maximum leakage, average leakage, and 95% leakage of the IMB group were significantly decreased, while the score of satisfaction and acceptance of CPAP therapy and willingness to continue CPAP therapy of the IMB group were significantly increased (all P<0.05); while the above indexes in the control group were not different before and after 4 weeks treatment (all P<0.05). Compared with the control group, the ESS score, HADS score, maximum leakage, average leakage, and 95% leakage of the IMB group after 4 weeks treatment were significantly lower (all P<0.05); the effective CPAP therapy time, CPAP therapy days within 4 weeks, score of satisfaction and acceptance of CPAP therapy, score of willingness to continue CPAP therapy of the IMB group were significantly higher (all P<0.05). The rate of CPAP therapy adherence in 4 weeks of the IMB group was significantly higher than that of the control group (90.3% vs 62.1%, P<0.05). The VAS of overall satisfaction with IMB skills intervention measures was 4.46±0.35. IMB skills intervention measures can effectively improve the adherence of CPAP therapy in OSAHS patients, and is suitable for clinical promotion.

Prevalence and Risk Factors for Rapid Eye Movement-Related Obstructive Sleep Apnea in Children.

ObjectivesDifferent pathophysiological mechanisms and the distribution of respiratory events among rapid eye movement (REM) and non-rapid eye movement (NREM) sleep modulate the effect of obstructive sleep apnea (OSA). We aimed to study the prevalence and risk factors for REM-related OSA in children.Study DesignRetrospective, cross-sectional study.MethodsWe recruited 366 children with OSA confirmed by polysomnography (PSG) over a 5-year period. REM-related OSA is defined by an obstructive apnea-hypopnea index (OAHI) in the REM sleep ≥2× than during NREM sleep.ResultsThe prevalence of REM-related OSA in children was 50.3%. Children with REM-related OSA were more likely to be female (P = 0.042), and had lower prevalence of adenotonsillar hypertrophy (P = 0.043) compared with children with other OSA subtypes. Children with REM-related OSA slept longer in the supine position (P = 0.003), had shorter duration of NREM1 sleep (P = 0.018), lower nadir SpO2 (P = 0.005), and a higher oxygen desaturation index 3% (ODI3%) (P = 0.014), and lower arousal index (P = 0.034) compared with other OSA subtypes. Female gender and supine sleep was the independent risk factors for REM-related OSA.ConclusionThe prevalence of REM-related OSA was 50.3%. OAHIREM should be considered as an important parameter in future clinical research studies done in children with OSA.

Early signs of sleep-disordered breathing in healthy women predict carotid intima-media thickening after 10 years

BackgroundCardiovascular disease (CVD) is the leading cause of death in women. The risk of CVD increases in women after menopause. The aim was to study how sleep parameters and cardiovascular risk factors in 46-year-old women predict future carotid intima-media thickness (IMT) 10 years after. MethodsProspective study of 92 healthy women, aged 46 years, were studied at baseline and at 10-year follow-up. Polysomnography for sleep and breathing; blood samples for cholesterol, glucose and follicle stimulating hormone; blood pressure (BP), weight and height measurements; questionnaires for background variables and vasomotor symptoms were carried out at both time points. Carotid ultrasound was scanned for IMT at 10-year follow-up. ResultsAfter adjusting for conventional risk factors, apnea-hypopnea index (AHI) during rapid-eye-movement (REM) sleep was the only parameter at baseline that predicted IMT 10 years after (IMT mean: β 81.4 [95% CI, 14.0–148.8]; IMT max: β 104.7 [95% CI, 15.4–194.1]). At 10-year follow-up, higher arousal index (IMT mean: β 55.6 [95% CI, 19.5–91.8]; IMT max β 59.9 [95% CI, 11.4–108.4]) and lower vasomotor symptoms (IMT max: β −60.5 [95% CI, −119.0 to −2.0]) were associated with concurrent higher IMT. The conventional risk factors at baseline did not associate with future IMT but 10 years after higher concurrent HbA1c (IMT mean: β 11.0 [95% CI, 3.4–18.5]; IMT max β 14.0 [95% CI, 4.1–23.8]) and systolic BP (IMT mean: β 2.4 [95% CI, 1.1–3.7]; IMT max: β 2.7 [95% CI, 1.03 to 4.53]) were associated with higher IMT. ConclusionsIn healthy 46-year-old women, AHI during REM sleep predicted IMT 10 years after. The conventional risk factors (HbA1c and BP) only associated with the concurrent IMT at 10-year follow-up.