Symbolic dynamics of sleep heart rate variability is associated with cognitive decline in older men.

We aimed to investigate the association between autonomic and cognitive functions in older men. We investigated heart rate variability (HRV) during sleep using time domain metrics and symbolic dynamics analysis of inter-beat intervals. These metrics were statistically analysed for associations with cognitive function which was elicited by administering the modified mini-mental state examination (3MS) and the Trail making test part-B in older men participating in the MrOS sleep study.Multivariable linear regression adjusted for age, body-mass-index (BMI), apnea-hypopnea index (AHI) and arousal index (A.I.) showed that symbolic dynamics of HRV especially the 0V% which is a measure of sympathetic outflow to the heart during rapid eye movement (REM) sleep is significantly associated with 3MS and Trail B scores. In conclusion, nonlinear HRV during sleep provides a unique window to probe the association between cognitive and autonomic function.Clinical Relevance- This study shows that cognitive decline is associated with altered cardiac autonomic function.

Differences in Temporal Relapse Characteristics Between Affective and Non-affective Psychotic Disorders: Longitudinal Analysis.

Objective: Multiple relapses over time are common in both affective and non-affective psychotic disorders. Characterizing the temporal nature of these relapses may be crucial to understanding the underlying neurobiology of relapse. Materials and Methods: Anonymized records of patients with affective and non-affective psychotic disorders were collected from SA Mental Health Data Universe and retrospectively analyzed. To characterize the temporal characteristic of their relapses, a relapse trend score was computed using a symbolic series-based approach. A higher score suggests that relapse follows a trend and a lower score suggests relapses are random. Regression models were built to investigate if this score was significantly different between affective and non-affective psychotic disorders. Results: Logistic regression models showed a significant group difference in relapse trend score between the patient groups. For example, in patients who were hospitalized six or more times, relapse score in affective disorders were 2.6 times higher than non-affective psychotic disorders [OR 2.6, 95% CI (1.8-3.7), p < 0.001]. Discussion: The results imply that the odds of a patient with affective disorder exhibiting a predictable trend in time to relapse were much higher than a patient with recurrent non-affective psychotic disorder. In other words, within recurrent non-affective psychosis group, time to relapse is random. Conclusion: This study is an initial attempt to develop a longitudinal trajectory-based approach to investigate relapse trend differences in mental health patients. Further investigations using this approach may reflect differences in underlying biological processes between illnesses.

Composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular mortality in older community-dwelling men.

AIMS: To investigate the composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular (CV) mortality in community-dwelling older men. METHODS AND RESULTS: We analysed overnight oximetry data from polysomnograms obtained in 2840 men from the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study (ClinicalTrials.gov Identifier: NCT00070681) to determine the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and time spent below 90% oxygen saturation (T90) attributed to acute desaturations (T90desaturation) and to non-specific drifts in oxygen saturation (T90non-specific), respectively, and their relationship with CV mortality. After 8.8 ± 2.7 years follow-up, 185 men (6.5%) died from CV disease. T90 [hazard ratio (HR) 1.21, P < 0.001], but not ODI (HR 1.13, P = 0.06), was significantly associated with CV death in univariate analysis. T90 remained significant when adjusting for potential confounders (HR 1.16, P = 0.004). Men with T90 > 12 min were at an elevated risk of CV mortality (HR 1.59; P = 0.006). Approximately 20.7 (5.7-48.5) percent of the variation in T90 could be attributed to non-specific drifts in oxygen saturation. T90desaturation and T90non-specific were individually associated with CV death but combining both variables did not improve the prediction. CONCLUSION: In community-dwelling older men, T90 is an independent predictor of CV mortality. T90 is not only a consequence of frank desaturations, but also reflects non-specific drifts in oxygen saturation, both contributing towards the association with CV death. Whether T90 can be used as a risk marker in the clinical setting and whether its reduction may constitute a treatment target warrants further study.

The effect of adenotonsillectomy for childhood sleep apnoea on cardiorespiratory control.

The efficacy of adenotonsillectomy for relieving obstructive sleep apnoea symptoms in children has been firmly established, but its precise effects on cardiorespiratory control are poorly understood. In 375 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either adenotonsillectomy (n=194) or a strategy of watching waiting (n=181), respiratory rate, respiratory sinus arrhythmia and heart rate were analysed during quiet, non-apnoeic and non-hypopnoeic breathing throughout sleep at baseline and at 7 months using overnight polysomnography. Children who underwent early adenotonsillectomy demonstrated an increase in respiratory rate post-surgery while the watchful waiting group showed no change. Heart rate and respiratory sinus arrhythmia were comparable between both arms. On assessing cardiorespiratory variables with regard to normalisation of clinical polysomnography findings during follow-up, heart rate was reduced in children who had resolution of obstructive sleep apnoea syndrome, while no differences in their respiratory rate or respiratory sinus arrhythmia were observed. Adenotonsillectomy for obstructive sleep apnoea increases baseline respiratory rate during sleep. Normalisation of apnoea-hypopnoea index, spontaneously or via surgery, lowers heart rate. Considering the small average effect size, the clinical significance is uncertain.

Effect of respiration on heartbeat-evoked potentials during sleep in children with sleep-disordered breathing.

OBJECTIVE: Heartbeat-evoked potentials (HEPs) in electroencephalogram (EEG) provide a quantitative measure of cardiac interoception during sleep. We previously reported reduced HEPs in children with sleep-disordered breathing (SDB), indicative of attenuated cardiac information processing. The objective of this study was to investigate the link between HEP and respiration. PATIENTS/METHODS: From the overnight polysomnograms of 40 healthy children and 40 children with SDB, we measured HEPs during epochs of stage 2, slow-wave and rapid eye movement (REM) sleep free of abnormal respiratory events. HEPs were analysed with respect to respiratory phase. RESULTS: We observed a marked association between respiratory phase and HEP in children with SDB during REM sleep, but not in normal children. In children with SDB, HEP waveforms were attenuated during expiration compared to inspiration. Following adenotonsillectomy, expiratory HEP peak amplitude increased in the SDB children and was no longer different from those of normal children. CONCLUSIONS: The expiratory phase of respiration is primarily associated with attenuated cardiac information processing in children with SDB, establishing a pathophysiological link between breathing and HEP attenuation.

Symbolic dynamics of pulse transit time and heart period in children with upper airway obstruction.

Upper airway obstruction (UAO) is a relatively common condition during childhood that is characterized by periods of partial or complete upper airway closure, resulting in restless sleep. It has also been suggested that UAO triggers early cardiovascular changes that may predispose to an increased risk of developing cardiovascular diseases later in life. The aim of this study was to assess the temporal dynamics of heart period (HP) and pulse transit time (PTT) during quite, event-free periods of sleep in children with UAO (n = 40) and matched healthy controls. The dynamics of HP and PTT were symbolized based on the sextiles of their distribution and words of length three were formed and classified into four types based on their patterns. Joint symbolic dynamics represent the concomitant occurrence of words in HP and PTT. Children with UAO showed a significantly increased frequency in word types of monotonously increasing and decreasing HP and PTT as well as joint dynamics across all stages of sleep. The dynamics of HP showed a marked sleep stage dependence, while PTT dynamics appeared to be relatively unaffected. In conclusion, cardiovascular dynamics are altered in children with UAO during scored event-free sleep, indicative of frequent bursts in sympathetic nervous system activity, possibly reflecting subcortical arousal responses to brief and subtle increases in UAO.

Increased thoracoabdominal asynchrony during breathing periods free of discretely scored obstructive events in children with upper airway obstruction.

OBJECTIVE: This study aims to investigate the impact of upper airway obstruction (UAO) in children by measuring thoracoabdominal asynchrony (TAA) during periods of sleep apnea/hypopnea and during scored-event-free (SEF) breathing periods. METHODS: Respiratory inductive plethysmographic signals were extracted from polysomnographic data, recorded before and after adenotonsillectomy in 40 children with UAO and 40 healthy, matched children at equivalent time points. Thoracoabdominal asynchrony was computed using a Hilbert transform-based phase difference estimation method in SEF periods during stage 2, stage 4 non-rapid eye movement (NREM), and rapid eye movement (REM) sleep and compared between the groups. RESULTS: At baseline, in the UAO group, TAA during obstructions were significantly higher than TAA during SEF periods in both stage 2 and REM sleep. Compared to controls, children with UAO had a significantly higher TAA during SEF periods in stage 2, stage 4 sleep, and REM sleep. This between-group difference was not significant post adenotonsillectomy. UAO group showed a significant decrease in TAA compared to their baseline during SEF stage 2 and 4 NREM, but not in REM. CONCLUSION: Upper airway obstruction in children is associated with increased TAA during SEF periods, indicative of continuous partial obstruction of the upper airway. Adenotonsillectomy decreased this effect significantly in non-REM sleep as evidenced by reduced asynchrony levels post-surgery. TAA assessment during sleep may therefore provide additional diagnostic information.

Heartbeat evoked potentials during sleep and daytime behavior in children with sleep-disordered breathing.

RATIONALE: Event-related brain potentials allow probing of cortical information processing, but when evoked with externally induced stimuli may disrupt sleep homeostasis and do not provide insight into intrinsic cortical information processing. To investigate if cortical processing of intrinsic information in children with sleep-disordered breathing (SDB) is different from healthy children and, if so, whether it resolves with treatment, we used heartbeat as a source of interoceptive event-related brain potentials. OBJECTIVES: To investigate heartbeat evoked potentials (HEP) during sleep in healthy children and in children with SDB before and after treatment and to explore if there are any associations between HEP and daytime behavioral deficits in children with SDB. METHODS: Heartbeat-aligned EEG was assessed for presence of HEP within stage 2, slow-wave sleep, and REM sleep in 40 children with primarily mild to moderate SDB before and after adenotonsillectomy and in 40 matched control subjects at similar time points. MEASUREMENTS AND MAIN RESULTS: In both groups, nonrandom HEP were present in all sleep stages analyzed; however, amplitude of HEP were significantly lower in children with SDB during non-REM sleep (stage 2: P = 0.03; slow-wave sleep: P = 0.001). This between-group difference was not significant post adenotonsillectomy. Significant negative associations between HEP and daytime behavioral scores were observed at baseline. CONCLUSIONS: Children with SDB displayed reduced HEP amplitude during sleep, which might be indicative of changes in afferent sensory inputs to the brain and/or signify differences in sensory gating of cardiac-related information in the insular cortex. Adenotonsillectomy appears to reverse this effect.

Respiratory cycle-related electroencephalographic changes during sleep in healthy children and in children with sleep disordered breathing.

STUDY OBJECTIVE: To investigate respiratory cycle-related electroencephalographic changes (RCREC) in healthy children and in children with sleep disordered breathing (SDB) during scored event-free (SEF) breathing periods of sleep. DESIGN: Interventional case-control repeated measurements design. SETTING: Paediatric sleep laboratory in a hospital setting. PARTICIPANTS: Forty children with SDB and 40 healthy, age- and sex-matched children. INTERVENTIONS: Adenotonsillectomy in children with SDB and no intervention in controls. MEASUREMENTS AND RESULTS: Overnight polysomnography; electroencephalography (EEG) power variations within SEF respiratory cycles in the overall and frequency band-specific EEG within stage 2 nonrapid eye movement (NREM) sleep, slow wave sleep (SWS), and rapid eye movement (REM) sleep. Within both groups there was a decrease in EEG power during inspiration compared to expiration across all sleep stages. Compared to controls, RCREC in children with SDB in the overall EEG were significantly higher during REM and frequency band specific RCRECs were higher in the theta band of stage 2 and REM sleep, alpha band of SWS and REM sleep, and sigma band of REM sleep. This between-group difference was not significant postadenotonsillectomy. CONCLUSION: The presence of nonrandom respiratory cycle-related electroencephalographic changes (RCREC) in both healthy children and in children with sleep disordered breathing (SDB) during NREM and REM sleep has been demonstrated. The RCREC values were higher in children with SDB, predominantly in REM sleep and this difference reduced after adenotonsillectomy. CITATION: Immanuel SA, Pamula Y, Kohler M, Martin J, Kennedy D, Saint DA, Baumert M. Respiratory cycle-related electroencephalographic changes during sleep in healthy children and in children with sleep disordered breathing.

Effect of resistive inspiratory and expiratory loading on cardio-respiratory interaction in healthy subjects.

Resistive loading affects the breathing pattern and causes an increase in negative intrathoracic pressure. The aim of this paper was to study the influence inspiratory and expiratory loading on cardio-respiratory interaction. We recorded electrocardiogram (ECG) and respiratory inductance plethysmogram (RIP) in 11 healthy male subjects under normal and resistive loading conditions. The R-R time series were extracted from the ECG and respiratory phases were calculated from the ribcage and abdominal RIP using the Hilbert transform. Both the series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals or respiratory phases, respectively. Subsequently, words of length `3 digits' were formed and the correspondence between words of the two series was determined to quantify cardio-respiratory interaction. Adding inspiratory and expiratory resistive loads resulted in an increase in inspiratory and expiatory time, respectively. Furthermore, we observed a significant increase in cardio-respiratory interaction during inspiratory resistive loading as compared to expiratory resistive loading (ribcage: 22.1±7.2 vs. 12.5±4.3 %, p<;0.0001; abdomen: 18.8±8.5 vs. 12.1±3.1 %, p<;0.05, respectively). Further studies may aid in better understanding the underlying physiological mechanisms and management of patients with breathing disorders.

Symbolic dynamics of respiratory cycle related sleep EEG in children with sleep disordered breathing.

Childhood sleep disordered breathing (SDB) is characterized by an increased work of breathing, restless night sleep and excessive daytime sleepiness and has been associated with cognitive impairment, behavioral disturbances and early cardiovascular changes. Compared to normal controls, children with SDB have elevated arousal thresholds and their sleep EEG may elicit cortical activation associated with arousals but often too subtle to be visually scored. The aim of this study was to assess EEG complexity throughout the respiratory cycle based on symbolic dynamics in children with SDB (n=40) and matched healthy controls. EEG amplitude values were symbolized based on the quartiles of their distribution and words of length 3 were formed and classed into 4 types based on their patterns. Children with SDB showed less complex EEG dynamics in non-REM sleep that was unrelated to the respiratory phase. In REM sleep normal children showed a respiratory phase-related reduction in EEG variability during the expiratory phase compared to inspiration, which was not apparent in children with SDB. In conclusion, respiratory cycle related EEG dynamics are altered in children with SDB during REM sleep and indicate changes in cortical activity.

Increased variability in respiratory parameters heralds obstructive events in children with sleep disordered breathing.

Sleep disordered breathing (SDB) is characterized by repeated episodes of central or obstructive apneas, disturbing respiratory patterns. The purpose of this study is to quantify respiratory variability associated with apneic/hypopneic events by computing respiratory parameters and thoraco-abdominal asynchrony (TAA) over sleep periods preceding the occurrence of obstructive events in children with SDB. One minute artifact-free epochs of ribcage (RC) and abdominal (AB) signals were extracted from the respiratory inductive plethysmograph (RIP) channel of the PSG prior to the onset of each obstruction. Breath-by-breath values of TAA were computed using a Hilbert transform based technique that measures the phase shift between the RC and AB signals. In addition, the following parameters were computed breath-by-breath from the RC signal: inspiratory time (Ti), expiratory time (Te), total time (Ttot), and the inspiratory duty cycle (DC=Ti/Ttot). Standard deviation of the parameters (SD_TAA, SD_Ti, SD_Te, SD_Ttot, SD_DC) over each 1 min epoch were calculated and averaged over each subject with respect to sleep stage. For comparison, similar measures were computed from within quiet breathing periods of each subject. We found that breaths immediately before apnea/hypopneas were associated with a high degree of variability in respiratory timing and TAA. The proposed variability analysis of RIP signals may be useful for detecting acute epochs of respiratory instability in children with SDB.

Respiratory timing and variability during sleep in children with sleep-disordered breathing.

Sleep-disordered breathing (SDB) in children is assessed by quantification of hypopnea and apnea events. Little is known, however, about respiratory timing and breath-to-breath variability during sleep. The aim of this study was to investigate respiratory parameters across sleep stages in children with SDB before and after treatment compared with healthy children. Overnight polysomnography (PSG) was conducted in 40 children with SDB prior to and 6 mo following adenotonsillectomy. For comparison, a control group of 40 healthy sex- and age-matched children underwent two PSGs at equivalent time points but without intervention. The following variables were measured breath by breath during obstruction-free periods in stage 2 nonrapid eye movement (NREM), stage 4 NREM, and REM sleep: inspiratory time (Ti), expiratory time (Te), total time (Ttotal), inspiratory duty cycle (DC; =Ti/Ttotal), respiratory frequency (fR), and SD of the parameters Ti, Te, fR, and DC. Variability in waveform morphology was also computed using the residue of respiratory patterns. The severity of SDB was relatively mild in the study cohort (obstructive apnea hypopnea index: baseline, 5.1 ± 9.4 vs. 0.1 ± 0.2, P < 0.001; follow-up, 0.3 ± 0.3 vs. 0.8 ± 1.0, P < 0.01). Compared with healthy controls, children with SDB showed significantly longer Ti and Te and a lower fR at the baseline study. These differences were not significant after adenotonsillectomy. Sleep stages were associated with significant differences in all of the respiratory measures in both groups of children. In conclusion, children with relatively mild SDB showed prolonged inspiration and expiration indicative of chronic narrowing of the upper airway. Treatment of SDB normalizes respiratory timing. Documentation of these parameters may aid in both understanding and management of children with SDB.