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Ian M. Colrain

SRI Author

Biomedical sciences publications

Physiological Responses to Acute Psychosocial Stress in Women with Menopausal Insomnia

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Introduction: Insomnia disorder is a common sleep disorder and frequently emerges in the context of menopause, being associated with menopause-specific factors such as hot flashes and other psychosocial variables. Increased vulnerability to stress may also contribute to the development of insomnia in midlife women. Here, we aimed to investigate whether there are differences in physiological reactivity to acute psychosocial stress in women with menopausal insomnia compared with controls.

Methods: We investigated cortisol and heart rate [HR] responses to an acute experimental psychosocial stress (Trier Social Stress Test, TSST) approximately 1 h after waking in the morning in midlife women with ( n = 22) and without ( n = 16) DSM-IV insomnia disorder (Age: 50.05 ± 3.10 years), developed in the context of menopause.

Results: Despite similar perceived stress levels, women with insomnia showed blunted HR increases (~29% HR acceleration) to the TSST compared to controls (~44% HR acceleration) ( p = 0.026). No group differences in HR were detected at baseline or during post-task recovery. Cortisol stress responses were inconclusive, with most of the women (60%) failing to exhibit significant cortisol increases in response to the TSST. A greater magnitude of the cortisol awakening response (CAR) predicted the likelihood of being a non-responder ( p = 0.036), showing the confounding effect of CAR on cortisol stress responses.

Discussion: Women with menopausal insomnia show blunted cardiac responses to stress, suggesting alterations in the autonomic reactivity to acute stress. Whether these alterations are pre-existing or are a consequence of insomnia, needs to be determined.

Biomedical sciences publications

Stress, Sleep, and Autonomic Function in Healthy Adolescent Girls and Boys: Findings from the NCANDA Study

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Objectives : Starting in adolescence, female sex is a strong risk factor for the development of insomnia. Reasons for this are unclear but could involve altered stress reactivity and/or autonomic nervous system (ANS) dysregulation, which are strongly associated with the pathophysiology of insomnia. We investigated sex differences in the effect of stress on sleep and ANS activity in adolescents, using the first night in the laboratory as an experimental sleep-related stressor.

Design : Repeated measures (first night vs. a subsequent night) with age (older/younger) and sex (males/females) as between factors.

Setting: Recordings were performed at the human sleep laboratory at SRI International.

Participants : One hundred six healthy adolescents (Age, mean ± SD: 15.2 ± 2.0 years; 57 boys).

Measures: Polysomnographic sleep, nocturnal heart rate (HR), and frequency-domain spectral ANS HR variability (HRV) indices.

Results : Boys and girls showed a first-night effect, characterized by lower sleep efficiency, lower %N1 and %N2 sleep, more wake after sleep onset and %N3 sleep, altered sleep microstructure (increased high-frequency sigma and Beta1 electroencephalographic activity), and reduced vagal activity ( P < .05) on the first laboratory night compared to a subsequent night. The first night ANS stress effect (increases in HR and suppression in vagal HRV during rapid eye movement sleep) was greater in girls than boys P < .05). Conclusions: Sleep and ANS activity were altered during the first laboratory night in adolescents, with girls exhibiting greater ANS alterations than boys. Findings suggest that girls may be more vulnerable than boys to sleep-specific stressors, which could contribute to their increased risk for developing stress-related sleep disturbances.

Biomedical sciences publications

Impact of evening alcohol consumption on nocturnal autonomic and cardiovascular function in adult men and women: A dose–response laboratory investigation

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Study Objectives: To investigate the dose-dependent impact of moderate alcohol intake on sleep-related cardiovascular (CV) function, in adult men and women.
Methods: A total of 26 healthy adults (30–60 years; 11 women) underwent 3 nights of laboratory polysomnographic (PSG) recordings in which different doses of alcohol (low: 1 standard drink for women and 2 drinks for men; high: 3 standard drinks for women and 4 drinks for men; placebo: no alcohol) were administered in counterbalanced order before bedtime. These led to bedtime average breath alcohol levels of up to 0.02% for the low doses and around 0.05% for the high doses. Autonomic and CV function were evaluated using electrocardiography, impedance cardiography, and beat-to-beat blood pressure monitoring.
Results: Presleep alcohol ingestion resulted in an overall increase in nocturnal heart rate (HR), suppressed total and high-frequency (vagal) HR variability, reduced baroreflex sensitivity, and increased sympathetic activity, with effects pronounced after high-dose alcohol ingestion (p’s < 0.05); these changes followed different dose- and measure-dependent nocturnal patterns in men and women. Systolic blood pressure showed greater increases during the morning hours of the high-alcohol dose night compared to the low-alcohol dose night and placebo, in women only (p’s < 0.05). Conclusions: Acute evening alcohol consumption, even at moderate doses, has marked dose- and time-dependent effects on sleep CV regulation in adult men and women. Further studies are needed to evaluate the potential CV risk of repeated alcohol-related alterations in nighttime CV restoration in healthy individuals and in those at high risk for CV diseases, considering sex and alcohol dose and time effects.

Biomedical sciences publications

Automatic Artifact Detection in Impedance Cardiogram Using Pulse Similarity Index

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Impedance cardiography (ICG) is a noninvasive technique for evaluation of cardiac hemodynamic parameters such as cardiac output and pre-ejection period. However, the sensitivity of the technique to motion artifact, electrode displacement, and cardiovascular pathologies can severely impact the accuracy of hemodynamic parameter estimates. In this paper, we proposed a new algorithm for the automatic detection and exclusion of corrupted ICG cardiac cycles by defining a pulse similarity index that quantifies the level of pulse corruption and its diversion from a typical-shaped pulse. The index considers different features (activity, structure, shape, and pattern) of the ICG cardiac cycles. The algorithm is compared on sleep data collected from 20 participants against expert identified corrupted cycles. The artifact rejection algorithm achieved a high accuracy of 96% in detection of expert-identified corrupted ICG cycles, including those with normal amplitude as well as out-of-range values, and was robust to different types and levels of artifact. The algorithm shows promise toward applications requiring accurate and reliable automatic measurement of cardiac hemodynamic parameters from prolonged data sets.

Biomedical sciences publications

Wearable Sleep Technology in Clinical and Research Settings

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The accurate assessment of sleep is critical to better understand and evaluate its role in health and disease. The boom in wearable technology is part of the digital health revolution and is producing many novel, highly sophisticated and relatively inexpensive consumer devices collecting data from multiple sensors and claiming to extract information about users’ behaviors, including sleep. These devices are now able to capture different biosignals for determining, for example, HR and its variability, skin conductance, and temperature, in addition to activity. They perform 24/7, generating overwhelmingly large data sets (big data), with the potential of offering an unprecedented window on users’ health. Unfortunately, little guidance exists within and outside the scientific sleep community for their use, leading to confusion and controversy about their validity and application. The current state-of-the-art review aims to highlight use, validation and utility of consumer wearable sleep-trackers in clinical practice and research. Guidelines for a standardized assessment of device performance is deemed necessary, and several critical factors (proprietary algorithms, device malfunction, firmware updates) need to be considered before using these devices in clinical and sleep research protocols. Ultimately, wearable sleep technology holds promise for advancing understanding of sleep health; however, a careful path forward needs to be navigated, understanding the benefits and pitfalls of this technology as applied in sleep research and clinical sleep medicine.

Biomedical sciences publications

Reducing bedtime physiological arousal levels using immersive audio-visual respiratory bio-feedback: a pilot study in women with insomnia symptoms

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Hyperarousal is a critical component of insomnia, particularly at bedtime when individuals are trying to fall asleep. The current study evaluated the effect of a novel, acute behavioral experimental manipulation (combined immersive audio-visual relaxation and biofeedback) in reducing bedtime physiological hyperarousal in women with insomnia symptoms. After a clinical/adaptation polysomnographic (PSG) night, sixteen women with insomnia symptoms had two random-order PSG nights: immersive audio-visual respiratory bio-feedback across the falling asleep period (manipulation night), and no pre-sleep arousal manipulation (control night). While using immersive audio-visual respiratory bio-feedback, overall heart rate variability was increased and heart rate (HR) was reduced (by ~ 5 bpm; p < 0.01), reflecting downregulation of autonomic pre-sleep arousal, relative to no-manipulation. HR continued to be lower during sleep, and participants had fewer awakenings and sleep stage transitions on the manipulation night relative to the control night (p < 0.05). The manipulation did not affect sleep onset latency or other PSG parameters. Overall, this novel behavioral approach targeting the falling asleep process emphasizes the importance of pre-sleep hyperarousal as a potential target for improving sleep and nocturnal autonomic function during sleep in insomnia.

Biomedical sciences publications

Insomnia in Women Approaching Menopause: Beyond Perception

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The menopausal transition is marked by increased prevalence in disturbed sleep and insomnia, present in 40-60% of women, but evidence for a physiological basis for their sleep complaints is lacking. We aimed to quantify sleep disturbance and the underlying contribution of objective hot flashes in 72 women (age range: 43-57 years) who had (38 women), compared to those who had not (34 women), developed clinical insomnia in association with the menopausal transition. Sleep quality was assessed with two weeks of sleep diaries and one laboratory polysomnographic (PSG) recording. In multiple regression models controlling for menopausal transition stage, menstrual cycle phase, depression symptoms, and presence of objective hot flashes, a diagnosis of insomnia predicted PSG-measured total sleep time (p<0.01), sleep efficiency (p=0.01) and wakefulness after sleep onset (WASO) (p=0.01). Women with insomnia had, on average, 43.5min less PSG-measured sleep time (p<0.001). There was little evidence of cortical EEG hyperarousal in insomniacs apart from elevated beta EEG power during REM sleep. Estradiol and follicle stimulating hormone levels were unrelated to beta EEG power but were associated with the frequency of hot flashes. Insomniacs were more likely to have physiological hot flashes, and the presence of hot flashes predicted the number of PSG-awakenings per hour of sleep (p=0.03). From diaries, women with insomnia reported more WASO (p=0.002), more night-to-night variability in WASO (p<0.002) and more hot flashes (p=0.012) compared with controls. Women who develop insomnia in the approach to menopause have a measurable sleep deficit, with almost 50% of the sample having less than 6h of sleep. Compromised sleep that develops in the context of the menopausal transition should be addressed, taking into account unique aspects of menopause like hot flashes, to avoid the known negative health consequences associated with insufficient sleep and insomnia in midlife women.

Biomedical sciences publications

Interaction between Reproductive Hormones and Physiological Sleep in Women

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CONTEXT:
The changing hormonal milieu around menopause is implicated in the development of sleep disturbances. No studies have assessed the association between concurrent physiological measures of sleep and serum hormone concentrations in perimenopausal women.
OBJECTIVE:
This study aimed to assess the interaction between physiological sleep and reproductive hormone measures in perimenopausal women.
DESIGN AND PARTICIPANTS:
This was a cross-sectional laboratory study of 33 perimenopausal women age 43-52 years (17 with no sleep complaints and 16 with a clinical diagnosis of insomnia). Eleven premenopausal women without sleep complaints (18-27 y), were included to determine whether hormone-sleep relationships differed depending on reproductive stage.
MAIN OUTCOME MEASURES:
Concurrent polysomnographic sleep indices and serum hormone levels (estradiol and follicle stimulating hormone [FSH]) were measured.
RESULTS:
FSH was positively associated with polysomnographic-defined wakefulness after sleep onset, and number of awakenings and arousals in perimenopausal women (P < .05) without sleep complaints independent of age, body mass index, and hot flashes. Similarly, FSH correlated with wakefulness after sleep onset and light N1 sleep in premenopausal women (P < .05). In contrast, in perimenopausal insomniacs amount of sleep correlated with anxiety and depression (P < .05) but not with FSH. Estradiol did not correlate with sleep in perimenopausal groups but correlated negatively with arousals in premenopausal women (P < .01). CONCLUSION: Our results suggest an interaction between the hypothalamic-pituitary-ovarian (HPO) axis and sleep-wake regulatory systems in pre- and peri-menopausal women without sleep complaints. There was no relationship between hormones and sleep in perimenopausal insomniacs, whose sleep may be influenced by other factors intrinsic to insomnia, such as hyperactivity, poor mood, and night-to-night variability.