Anxiety-related shifts in smell function in children and adolescents.

Anxious adults show changes in smell function that are consistent with a durable shift in sensitivity toward particular odorants and away from others. Little is known regarding the development of these changes, including whether they exist in youth, are stable during the transition from childhood to adolescence, and whether odorant properties (e.g. trigeminal features, hedonic valence) affect anxiety-related differences in detection. To address this, we measured smell detection thresholds to phenyl ethyl alanine (PEA), a rose-like odorant with little trigeminal properties, and guaiacol (GUA), a smoke-like odorant with high trigeminal properties. These thresholds were measured at baseline and after an acute stress challenge, the Trier Social Stress Tests, in 131 healthy youth (in 4th, 7th, and 10th grades, age 9-16 years) that reported normal to elevated levels of anxiety. At baseline, high anxious youth exhibited heightened sensitivity to GUA coupled with reduced sensitivity to PEA, as well as a further exaggeration of this bias with acute stress. Importantly, sex, age, and hedonic valence moderated the relationship between trait anxiety and sensitivity to both odorants. Smell function and its aberrations are often overlooked in the literature on biomarkers of stress and anxiety. Taken together with the extant literature, these findings suggest that greater attention is warranted to characterize potential novel olfactory therapeutic targets-across the lifespan.

Paradoxical olfactory function in combat veterans: The role of PTSD and odor factors.

Stress- and trauma-related disorders, including posttraumatic stress disorder (PTSD), are characterized by an increased sensitivity to threat cues. Given that threat detection is a critical function of olfaction and that combat trauma is commonly associated with burning odors, we sought a better understanding of general olfactory function as well as response to specific trauma-related (i.e. burning) odors in combat-related PTSD. Trauma-exposed combat veterans with (N = 22) and without (N = 25) PTSD were assessed for general and specific odor sensitivities using a variety of tools. Both groups had similar general odor detection thresholds. However, the combat veterans with PTSD, compared to combat veterans with comparable trauma exposure, but without PTSD, had increased ratings of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with a blunted heart rate in response to burning rubber odor. These findings are discussed within the context of healthy versus pathological changes in olfactory processing that occur over time after psychological trauma.

Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD.

Structural and functional changes in the olfactory system are increasingly implicated in the expression of PTSD. Still, very little is known about the neurobiological networks of trauma-related odor sensitivity or how they relate to other objective and subjective measures of olfaction and PTSD. The purpose of this study was to replicate prior findings and further characterize olfactory function in trauma-exposed combat veterans with and without PTSD. We also sought to extend this area of research by exploring the effects of time since the combat-related index trauma (TST) on post-trauma olfactory function, as well as by correlating odor-elicited brain activity to general olfactory ability and odor-elicited PTSD symptoms. Participants included combat veterans with PTSD (CV+PTSD; n = 21) or without any psychiatric disorder (CV-PTSD; n = 27). TST was coded as greater (n = 24) or less (n = 24) than 5 years. There were main effects and/or interaction for PTSD-status and TST across several parameters of olfactory function: odor detection, odor identification, ratings for trauma-related odor intensity and triggered PTSD symptoms, and trauma odor-elicited brain activation. Overall, results suggest olfactory impairment in chronic PTSD, but not necessarily in the earlier stages of the disorder, although some early-stage olfactory findings may be predictive of later olfactory impairment. Results also suggest that trauma-exposed individuals who never develop PTSD may demonstrate olfactory resiliency. Finally, results highlight a potentially unique role of trigeminal odor properties in the olfactory-PTSD relationship.

Quantifying cardio-respiratory phase synchronization-a comparison of five methods using ECGs of post-infarction patients.

OBJECTIVE: Phase synchronization between two weakly coupled oscillators occurs in many natural systems. Since it is difficult to unambiguously detect such synchronization in experimental data, several methods have been proposed for this purpose. Five popular approaches are systematically optimized and compared here. APPROACH: We study and apply the automated synchrogram method, the reduced synchrogram method, two variants of a gradient method, and the Fourier mode method, analyzing 24h data records from 1455 post-infarction patients, the same data with artificial inaccuracies, and corresponding surrogate data generated by Fourier phase randomization. MAIN RESULTS: We find that the automated synchrogram method is the most robust of all studied approaches when applied to records with missing data or artifacts, whereas the gradient methods should be preferred for noisy data and low-accuracy R-peak positions. We also show that a strong circadian rhythm occurs with much more frequent phase synchronization episodes observed during night time than during day time by all five methods. SIGNIFICANCE: In specific applications, the identified characteristic differences as well as strengths and weaknesses of each method in detecting episodes of cardio-respiratory phase synchronization will be useful for selecting an appropriate method with respect to the type of systematic and dynamical noise in the data.

Phase transitions in physiologic coupling.

Integrated physiological systems, such as the cardiac and the respiratory system, exhibit complex dynamics that are further influenced by intrinsic feedback mechanisms controlling their interaction. To probe how the cardiac and the respiratory system adjust their rhythms, despite continuous fluctuations in their dynamics, we study the phase synchronization of heartbeat intervals and respiratory cycles. The nature of this interaction, its physiological and clinical relevance, and its relation to mechanisms of neural control is not well understood. We investigate whether and how cardiorespiratory phase synchronization (CRPS) responds to changes in physiological states and conditions. We find that the degree of CRPS in healthy subjects dramatically changes with sleep-stage transitions and exhibits a pronounced stratification pattern with a 400% increase from rapid eye movement sleep and wake, to light and deep sleep, indicating that sympatho-vagal balance strongly influences CRPS. For elderly subjects, we find that the overall degree of CRPS is reduced by approximately 40%, which has important clinical implications. However, the sleep-stage stratification pattern we uncover in CRPS does not break down with advanced age, and surprisingly, remains stable across subjects. Our results show that the difference in CRPS between sleep stages exceeds the difference between young and elderly, suggesting that sleep regulation has a significantly stronger effect on cardiorespiratory coupling than healthy aging. We demonstrate that CRPS and the traditionally studied respiratory sinus arrhythmia represent different aspects of the cardiorespiratory interaction, and that key physiologic variables, related to regulatory mechanisms of the cardiac and respiratory systems, which influence respiratory sinus arrhythmia, do not affect CRPS.

Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages.

STUDY OBJECTIVES: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. DESIGN: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. SETTING: Data were collected in 7 laboratories in 5 European countries. PARTICIPANTS: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent alpha1 show characteristic age dependence with a maximum around 50-60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by alpha2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for alpha2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). CONCLUSION: The age dependence of alpha1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger alpha2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep.

Automated synchrogram analysis applied to heartbeat and reconstructed respiration.

Phase synchronization between two weakly coupled oscillators has been studied in chaotic systems for a long time. However, it is difficult to unambiguously detect such synchronization in experimental data from complex physiological systems. In this paper we review our study of phase synchronization between heartbeat and respiration in 150 healthy subjects during sleep using an automated procedure for screening the synchrograms. We found that this synchronization is significantly enhanced during non-rapid-eye-movement (non-REM) sleep (deep sleep and light sleep) and is reduced during REM sleep. In addition, we show that the respiration signal can be reconstructed from the heartbeat recordings in many subjects. Our reconstruction procedure, which works particularly well during non-REM sleep, allows the detection of cardiorespiratory synchronization even if only heartbeat intervals were recorded.

Cross-modulated amplitudes and frequencies characterize interacting components in complex systems.

The dynamics of complex systems is characterized by oscillatory components on many time scales. To study the interactions between these components we analyze the cross modulation of their instantaneous amplitudes and frequencies, separating synchronous and antisynchronous modulation. We apply our novel technique to brain-wave oscillations in the human electroencephalogram and show that interactions between the alpha wave and the delta or beta wave oscillators as well as spatial interactions can be quantified and related with physiological conditions (e.g., sleep stages). Our approach overcomes the limitation to oscillations with similar frequencies and enables us to quantify directly nonlinear effects such as positive or negative frequency modulation.

Phase-rectified signal averaging for the detection of quasi-periodicities and the prediction of cardiovascular risk.

We present the phase-rectified signal averaging (PRSA) method as an efficient technique for the study of quasi-periodic oscillations in noisy, nonstationary signals. It allows the assessment of system dynamics despite phase resetting and noise and in relation with either increases or decreases of the considered signal. We employ the method to study the quasi-periodicities of the human heart rate based on long-term ECG recordings. The center deflection of the PRSA curve characterizes the average capacity of the heart to decelerate (or accelerate) the cardiac rhythm. It can be measured by a central wavelet coefficient which we denote as deceleration capacity (DC). We find that decreased DC is a more precise predictor of mortality in survivors of heart attack than left ventricular ejection fraction, the current "gold standard" risk predictor. In addition, we discuss the dependence of the DC parameter on age and on diabetes.