Shared and distinct biological mechanisms for anxiety and sensory over-responsivity in youth with autism versus anxiety disorders.

Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants' SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.

Urbanisation process generates more independently-acting stressors and ecosystem functioning impairment in tropical Andean streams.

The tropical Andes are experiencing rapid population growth and urbanisation has become a major driver impairing stream ecosystems. However, knowledge about multiple-stressors effects on urbanised Andean streams is lacking. In southern Ecuador, we assessed how multiple stressors determine the structural (aquatic invertebrate metrics) and functional (organic matter breakdown and delta N of primary consumers) attributes of streams in a densely populated watershed without wastewater treatment and with contrasting land uses. We found that urbanised streams exhibited individual-stressor effects and that stressor interactions were rare. While structural and function attributes responded negatively to urbanisation, ecosystem functioning metrics were influenced most. Stream ecosystem functions were influenced by water-chemistry stressors, whereas aquatic invertebrate metrics were influenced by physical-habitat stressors. We suggest that managers of urbanised streams in the Andes immediately focus on the most important stressors by reducing inputs of inorganic N and P, re-establishing stream flow and substrate heterogeneity, and restoring riparian vegetation instead of attempting to elucidate intricate interactions among stressors. Our result also demonstrate that stream biomonitoring programs would benefit from a combination of structural and functional indicators to assess anthropogenic effects in a multiple-stressors scenario.

Associations between physiological and neural measures of sensory reactivity in youth with autism.

BACKGROUND: Individuals with Autism Spectrum Disorder (ASD) commonly show sensory over-responsivity (SOR), an impairing condition related to over-reactive brain and behavioral responses to aversive stimuli. While individuals with ASD often show atypically high physiological arousal, it is unclear how this relates to sensory reactivity. We therefore investigated how physiological arousal relates to brain and behavioral indices of SOR, to inform understanding of the biological mechanisms underlying SOR and to determine whether physiological measures are associated with SOR-related brain responses. METHODS: Youth aged 8-18 (49 ASD; 30 age- and performance-IQ-matched typically developing (TD)) experienced mildly aversive tactile and auditory stimuli first during functional magnetic resonance imaging (N = 41 ASD, 26 TD) and then during skin conductance (SCR) (N = 48 ASD, 28 TD) and heart rate (HR) measurements (N = 48 ASD, 30 TD). Parents reported on their children's SOR severity. RESULTS: Autism Spectrum Disorder youth overall displayed greater SCR to aversive sensory stimulation than TD youth and greater baseline HR. Within ASD, higher SOR was associated with higher mean HR across all stimuli after controlling for baseline HR. Furthermore, the ASD group overall, and the ASD-high-SOR group in particular, showed reduced HR deceleration/greater acceleration to sensory stimulation compared to the TD group. Both SCR and HR were associated with brain responses to sensory stimulation in regions previously associated with SOR and sensory regulation. CONCLUSIONS: Autism Spectrum Disorder youth displayed heightened physiological arousal to mildly aversive sensory stimulation, with HR responses in particular showing associations with brain and behavioral measures of SOR. These results have implications for using psychophysiological measures to assess SOR, particularly in individuals with ASD who cannot undergo MRI.

Differential Effects of REM Sleep on Emotional Processing: Initial Evidence for Increased Short-term Emotional Responses and Reduced Long-term Intrusive Memories.

Background: Rapid eye movement (REM) sleep has been postulated to facilitate emotional processing of negative stimuli. However, empirical evidence is mixed and the conditions under which higher amounts of REM sleep lead to decreased or increased emotional responses are unclear. We proposed that the time course between REM sleep and measurement of emotional responses is a crucial factor and hypothesized that more REM sleep will enhance emotional responses shortly after sleep, but will lead to decreased emotional responses in the long-term. Participants and Methods: Seventy-six healthy young women watched negative and neutral pictures before a polysomnographically-recorded nap including three different groups (1: no REM sleep, 2: REM sleep awakening, 3: REM sleep). Short-term emotional responses were measured using aversiveness ratings of negative pictures; aversiveness ratings of intrusive picture memories on the three subsequent evenings were used to measure long-term emotional responses. Results: For short-term emotional responses, no significant interaction indicating group differences was found. However, we found correlations between longer REM sleep duration and higher aversiveness ratings of negative pictures. In contrast, lower aversiveness of intrusive picture memories after two days was found in participants with a full REM sleep period compared to individuals without REM sleep. Correlational analyses also supported this pattern of results. Conclusions: Results suggest that REM sleep may increase reactivity to emotional stimuli in the short-term and this effect of REM sleep appears to facilitate emotional processing during subsequent nights leading to reduced intrusive picture memories in the long-term.

Bad mood food? Increased versus decreased food cue reactivity in anorexia nervosa and bulimia nervosa during negative emotions.

OBJECTIVE: Emotion regulation difficulties in anorexia nervosa (AN) and bulimia nervosa (BN) might underlie bingeing and purging in BN, extreme fasting in AN, or combinations of these symptoms in binge-purge type AN. In this study, we tested for decreased food cue reactivity in response to negative emotions in AN, and the opposite pattern for BN. Furthermore, we explored subgroup differences (restrictive vs. binge-purging AN; history of AN in BN). METHOD: Patients with AN (n = 41), BN (n = 39), and matched controls (n = 70) completed an emotional eating questionnaire. In a laboratory experiment, we induced negative emotions and measured food cue reactivity (pleasantness, desire to eat (DTE), and corrugator muscle activity). RESULTS: AN reported emotional undereating, while BN reported emotional overeating. In the laboratory task, BN showed increased DTE and an appetitive corrugator response during negative emotions, selectively towards high-calorie foods. AN showed generalized reduced cue reactivity to high-calorie food regardless of emotional state. This pattern appears to be characteristic of restrictive AN, while cue reactivity of both BN subgroups pointed towards emotional overeating. CONCLUSIONS: The emotional over- versus undereating framework might help to explain bingeing and restricting along the anorectic-bulimic disorder spectrum, which calls for novel transdiagnostic theories and subgroup-specific treatments.

Procedural memory consolidation is associated with heart rate variability and sleep spindles.

Sleep and memory studies often focus on overnight rather than long-term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para-)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long-term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R-R interval [RRI], standard deviation of R-R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, Mage  = 23.40 ± 2.78 years) were trained on a mirror-tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full-night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2-R1) indicated significantly higher accuracy after sleep, whereas a significant long-term (R3-R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only "SpA enhancers" exhibited overnight improvements for accuracy and long-term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning.

Recover your smile: Effects of a beauty care intervention on depressive symptoms, quality of life, and self-esteem in patients with early breast cancer.

OBJECTIVE: Medical cancer treatment is often accompanied by appearance-related side effects such as hair loss, skin irritation, and paleness, which can subsequently lead to psychosocial distress. Initial evidence suggests that beauty care interventions may reduce distress and improve quality of life (QoL), body image, and self-esteem immediately. METHODS: We investigated the effects of a brief beauty care intervention on self-reported symptoms of depression, quality of life, body image, and self-esteem in 39 female primary breast cancer patients with appearance-related treatment side effects. Patients were randomly assigned either to an immediate intervention group (IG) or to a wait-list control (WL). The intervention consisted of a single-session group makeup workshop, a photo shooting, and of receiving professionally edited portrait and upper-body photos. RESULTS: While groups did not differ regarding any measure at the pretreatment baseline assessment, IG patients reported less symptoms of depression, higher QoL, and higher self-esteem compared with baseline and compared with WL. Follow-up at 8 weeks indicated moderate stability of these improvements. CONCLUSIONS: In contrast to previous research, results indicate beneficial short-term and midterm effects of beauty care on psychological outcomes in patients with early breast cancer. These results emphasize the utility of this type of brief, low-cost intervention in women undergoing medical cancer treatment in order to improve their well-being.

Wearables and the Quantified Self: Systematic Benchmarking of Physiological Sensors.

Wearable sensors are increasingly used in research, as well as for personal and private purposes. A variety of scientific studies are based on physiological measurements from such rather low-cost wearables. That said, how accurate are such measurements compared to measurements from well-calibrated, high-quality laboratory equipment used in psychological and medical research? The answer to this question, undoubtedly impacts the reliability of a study's results. In this paper, we demonstrate an approach to quantify the accuracy of low-cost wearables in comparison to high-quality laboratory sensors. We therefore developed a benchmark framework for physiological sensors that covers the entire workflow from sensor data acquisition to the computation and interpretation of diverse correlation and similarity metrics. We evaluated this framework based on a study with 18 participants. Each participant was equipped with one high-quality laboratory sensor and two wearables. These three sensors simultaneously measured the physiological parameters such as heart rate and galvanic skin response, while the participant was cycling on an ergometer following a predefined routine. The results of our benchmarking show that cardiovascular parameters (heart rate, inter-beat interval, heart rate variability) yield very high correlations and similarities. Measurement of galvanic skin response, which is a more delicate undertaking, resulted in lower, but still reasonable correlations and similarities. We conclude that the benchmarked wearables provide physiological measurements such as heart rate and inter-beat interval with an accuracy close to that of the professional high-end sensor, but the accuracy varies more for other parameters, such as galvanic skin response.

Detecting Moments of Stress from Measurements of Wearable Physiological Sensors.

There is a rich repertoire of methods for stress detection using various physiological signals and algorithms. However, there is still a gap in research efforts moving from laboratory studies to real-world settings. A small number of research has verified when a physiological response is a reaction to an extrinsic stimulus of the participant's environment in real-world settings. Typically, physiological signals are correlated with the spatial characteristics of the physical environment, supported by video records or interviews. The present research aims to bridge the gap between laboratory settings and real-world field studies by introducing a new algorithm that leverages the capabilities of wearable physiological sensors to detect moments of stress (MOS). We propose a rule-based algorithm based on galvanic skin response and skin temperature, combing empirical findings with expert knowledge to ensure transferability between laboratory settings and real-world field studies. To verify our algorithm, we carried out a laboratory experiment to create a "gold standard" of physiological responses to stressors. We validated the algorithm in real-world field studies using a mixed-method approach by spatially correlating the participant's perceived stress, geo-located questionnaires, and the corresponding real-world situation from the video. Results show that the algorithm detects MOS with 84% accuracy, showing high correlations between measured (by wearable sensors), reported (by questionnaires and eDiary entries), and recorded (by video) stress events. The urban stressors that were identified in the real-world studies originate from traffic congestion, dangerous driving situations, and crowded areas such as tourist attractions. The presented research can enhance stress detection in real life and may thus foster a better understanding of circumstances that bring about physiological stress in humans.

Temporal Patterns of Infant Regulatory Behaviors in Relation to Maternal Mood and Soothing Strategies.

This study investigates the temporal patterning of infant self-regulatory behaviors (crying/fussing, sleeping) in relation to both infant (age, sex, regulatory problems) and maternal variables (soothing behaviors, mood). Self-regulatory and soothing behaviors were assessed in 121 mother-infant dyads (4-44 weeks) by the Baby's Day Diary at 5 min intervals over 3 days. Further infant characteristics and maternal mood were assessed by questionnaires (DASS, CES-D, STAI) and the Diagnostic Interview for the Assessment of Regulatory Problems in Infancy and Toddlerhood. Data were analyzed using generalized additive mixed models. Negative maternal mood was associated with a deviant course of crying/fussing during the day. Body contact was associated with reduced variability in the 24 h course of sleep. Mother-infant transactional processes-above and beyond known relationships with overall levels of crying/fussing and sleeping-might play out on the temporal dimension of infant regulatory behaviors.

Associations between interoceptive sensitivity, intuitive eating, and body mass index in patients with anorexia nervosa and normal-weight controls.

Reduced perception of bodily signals and low levels of intuitive eating have been reported in patients with anorexia nervosa (AN) compared with normal-weight individuals. However, findings have been inconsistent and treatment progress might account for some of these inconsistencies. Thirty-seven inpatients with AN and 39 normal-weight controls completed a heartbeat perception task and the Intuitive Eating Scale-2. Patients with AN reported lower intuitive eating than controls, whereas interoceptive sensitivity did not differ between groups. Higher interoceptive sensitivity was related to higher intuitive eating across both groups. In patients with AN, both higher interoceptive sensitivity and intuitive eating correlated with the number of days in the hospital and with higher body mass index (BMI), when controlling for BMI at admission. These relationships suggest that interoceptive sensitivity and intuitive eating improve during treatment. Future research should determine whether these improvements promote weight gain or follow it.

Tunable, Flexible, and Efficient Optimization of Control Pulses for Practical Qubits.

Quantum computation places very stringent demands on gate fidelities, and experimental implementations require both the controls and the resultant dynamics to conform to hardware-specific constraints. Superconducting qubits present the additional requirement that pulses must have simple parameterizations, so they can be further calibrated in the experiment, to compensate for uncertainties in system parameters. Other quantum technologies, such as sensing, require extremely high fidelities. We present a novel, conceptually simple and easy-to-implement gradient-based optimal control technique named gradient optimization of analytic controls (GOAT), which satisfies all the above requirements, unlike previous approaches. To demonstrate GOAT's capabilities, with emphasis on flexibility and ease of subsequent calibration, we optimize fast coherence-limited pulses for two leading superconducting qubits architectures-flux-tunable transmons and fixed-frequency transmons with tunable couplers.

Suppressing images of desire: Neural correlates of chocolate-related thoughts in high and low trait chocolate cravers.

Chocolate is the most often craved food in Western societies and many individuals try to resist its temptation due to weight concerns. Suppressing chocolate-related thoughts might, however, lead to paradoxical enhancements of these thoughts and this effect might be more pronounced in individuals with frequent chocolate cravings. In the current study, neural and cognitive correlates of chocolate thought suppression were investigated as a function of trait chocolate craving. Specifically, 20 high and 20 low trait chocolate cravers followed suppression vs. free thinking instructions after being exposed to chocolate and neutral images. Enhanced cue reactivity was evident in high trait chocolate cravers in that they reported more chocolate-related thoughts selectively after chocolate images compared to their low trait craving counterparts. This cue reactivity was mirrored neurally by higher activation in the ventral and dorsal striatum, demonstrating enhanced reward system activity. Unexpectedly, high trait chocolate cravers successfully reduced their elevated chocolate thoughts in the suppression condition. This lends support for the use of thought suppression as a means of regulating unwanted thoughts, cravings and imagery. Whether this thought manipulation is able to curb the elevated cue reactivity and the underlying reward sensitivity in chocolate cravers in applied settings remains to be shown.

Cardiac Vagal Control and Depressive Symptoms: The Moderating Role of Sleep Quality.

Lower cardiac vagal control (CVC) has been linked to greater depression. However, this link has not been consistently demonstrated, suggesting the presence of key moderators. Sleep plausibly is one such factor. Therefore, we investigated whether sleep quality moderates the link between CVC (quantified by high-frequency heart rate variability, HF-HRV) and depressive symptoms (assessed using established questionnaires) in 29 healthy women. Results revealed a significant interaction between HF-HRV and sleep quality in predicting depressive symptoms: participants with lower HF-HRV reported elevated depressive symptoms only when sleep quality was also low. In contrast, HF-HRV was not associated with depressive symptoms when sleep quality was high, suggesting a protective function of high sleep quality in the context of lower CVC.

Quality Predictors of Abdominal Fetal Electrocardiography Recording in Antenatal Ambulatory and Bedside Settings.

BACKGROUND: Fetal electrocardiography using an abdominal monitor (Monica AN24™) could increase the diagnostic use of fetal heart rate (fHR) variability measurements. However, signal quality may depend on factors such as maternal physical activity, posture, and bedside versus ambulatory setting. METHODS: Sixty-three healthy women wore the monitor at home and 42 women during a hospital stay. All women underwent a posture experiment, and all home and 13 hospital participants wore the monitor during daytime and nighttime. The success rate (SR) of fHR detection was analyzed in relation to maternal physical activity, posture, daytime versus nighttime, and other maternal and fetal predictors. RESULTS: Ambulatorily, the SR was 86.8% for nighttime and 40.2% for daytime. The low daytime SR was largely due to effects of maternal physical activity and posture. The in-hospital SR was lower during nighttime (71.1%) and similar during daytime (43.3%). SR was related to gestational age, but not affected by pre-pregnancy and current body mass index or fetal growth restriction. CONCLUSIONS: The success of beat-to-beat fHR detection strongly depends on the home/hospital setting and predictors such as time of recording, activity levels, and maternal posture. Its clinical utility may be limited in periods of unsupervised recording with physical activity or posture shifts.

Criticism hurts everybody, praise only some: Common and specific neural responses to approving and disapproving social-evaluative videos.

Social evaluation is a ubiquitous feature of daily interpersonal interactions and can produce strong positive or negative emotional reactions. While previous research has highlighted neural correlates of static or dynamic facial expressions, little is known about neural processing of more naturalistic social interaction simulations or the modulating role of inter-individual differences such as trait fear of negative/positive evaluation. The present fMRI study investigated neural activity of 37 (21 female) healthy participants while watching videos of posers expressing a range of positive, negative, and neutral statements tapping into several basic and social emotions. Unpleasantness ratings linearly increased in response to positive to neutral to negative videos whereas arousal ratings were elevated in both emotional video conditions. At the whole brain level, medial prefrontal and rostral anterior cingulate cortex activated strongly in both emotional conditions which may be attributed to the cognitive processing demands of responding to complex social evaluation. Region of interest analysis for basic emotion processing areas revealed enhanced amygdala activation in both emotional conditions, whereas anterior and posterior insula showed stronger activity during negative evaluations only. Individuals with high fear of positive evaluation were characterized by increased posterior insula activity during positive videos, suggesting heightened interoception. Taken together, these results replicate and extend studies that used facial expression stimuli and reveal neurobiological systems involved in processing of more complex social-evaluative videos. Results also point to vulnerability factors for social-interaction related psychopathologies.

To eat or not to eat: Effects of food availability on reward system activity during food picture viewing.

Neuroimaging studies have started to explore the role of food characteristics (e.g., calorie-content) and psychological factors (e.g., restrained eating, craving) for the human appetitive system, motivated by the significant health implications of food-choice, overeating and overweight/obesity. However, one key aspect of modern food environments, food availability, especially of high energy foods, has not been adequately modeled in experimental research. Food that is immediately available for consumption could elicit stronger reward system activity and associated cognitive control than food that is not currently available for consumption and this could vary as a function of energy density. To examine this question, 32 healthy participants (16 women) underwent functional magnetic resonance imaging while passively viewing available foods - i.e. foods that could be eaten during and after the experiment - and unavailable foods of either high or low-caloric density in a 2 × 2 design. Available compared to unavailable foods elicited higher palatability ratings as well as stronger neural activation in the orbitofrontal cortex (OFC), amygdala, and left caudate nucleus as well as in the anterior cingulate cortex (ACC) - and thus structures implicated in reward and appetitive motivation as well as cognitive control, respectively. Availability effects in the caudate were mainly attributable to the high calorie condition (availability × calorie density interaction). These neuroimaging results support the contention that foods are particularly rewarding when immediately available and particularly so when high in caloric density. Thus, our results are consistent with health promoting interventions utilizing a nudging approach, i.e. aiming at decreasing accessibility of high calorie and increasing accessibility of low calorie foods in daily life. Results also imply that controlling/manipulating food availability may be an important methodological aspect in neuroscientific eating research.

Chronic Smoking, Trait Anxiety, and the Physiological Response to Stress.

BACKGROUND AND OBJECTIVES: Both chronic smoking and trait anxiety have been associated with dysregulations in psychobiological stress response systems. However, these factors have not been studied in conjunction. We expected trait anxiety and smoking status to attenuate stress reactivity. Furthermore, we expected an allostatic load effect resulting in particularly attenuated stress reactivity in high-anxious smokers. In addition, high-anxious smokers were expected to exhibit increased urges to smoke in response to stress. METHODS: 115 smokers and 37 nonsmokers, aged 18-64 years, completed a laboratory session including mental stressors such as evaluated public speaking and mental arithmetic. Trait anxiety was assessed using Spielberger's State-Trait Anxiety Inventory. Cardiovascular autonomic indices, salivary cortisol, and the desire to smoke were measured at baseline, during stressors, and at recovery. RESULTS: Regression analyses showed that smokers exhibited attenuated cardiovascular stress responses in comparison to nonsmokers. Higher trait anxiety predicted attenuated systolic blood pressure responses to stress. No interaction effect of smoking status and trait anxiety was found in stress response measures. Higher trait anxiety predicted an increased desire to smoke in response to stress among smokers. CONCLUSION: Results indicate that both smoking status and trait anxiety are associated with blunted sympatho-adrenal cardiovascular stress reactivity. Elevated urges to smoke in response to stress found among smokers with high trait anxiety suggest an important role of anxiety in smoking propensity and relapse.

ANSLAB: Integrated multichannel peripheral biosignal processing in psychophysiological science.

Psychophysiological science employs a large variety of signals from the human body that index the activity of the peripheral nervous system. This allows for studying interactions of psychological and physiological processes that are relevant for understanding cognition, emotion, and psychopathology. The multidimensional nature of the data and the interactions between different physiological signals represent a methodological and computational challenge. Analysis software in this domain is often limited in its coverage of the signals from different physiological systems, and therefore only partially addresses these challenges. ANSLAB (short for Autonomic Nervous System Laboratory) is an integrated software suite that supports data visualization, artifact detection, data reduction, automated processing, and statistical analysis for a large range of autonomic, respiratory, and muscular measures. Analysis modules for cardiovascular (e.g., electrocardiogram, heart rate variability, blood pressure wave, pulse wave, and impedance cardiography), electrodermal (skin conductance level and responses), respiratory (respiratory pattern, timing, and volume variables, as well as capnography), and muscular (eye-blink startle, facial and bodily electromyography) systems are complemented by specialized modules (e.g., body temperature and accelerometry, cross-spectral analysis of respiratory and cardiac measures, signal averaging, and statistical analysis) and productivity-enhancing features (batched processing, fully automatized analyses, and data management). ANSLAB also facilitates the analysis of long-term recordings from ambulatory assessment studies. The present article reviews several analysis modules included in ANSLAB and describes how these address some of the current needs and methodological challenges of psychophysiological science.

Higher vagal activity as related to survival in patients with advanced breast cancer: an analysis of autonomic dysregulation.

OBJECTIVE: High levels of high-frequency heart rate variability (HF-HRV), related to parasympathetic-nervous-system functioning, have been associated with longer survival in patients with myocardial infarction and acute trauma and in patients undergoing palliative care. From animal studies linking higher vagal activity with better immune system functioning and reduced metastases, we hypothesized that higher HF-HRV would predict longer survival in patients with metastatic or recurrent breast cancer (MRBC). METHODS: Eighty-seven patients with MRBC participated in a laboratory task including a 5-minute resting baseline electrocardiogram. HF-HRV was computed as the natural logarithm of the summed power spectral density of R-R intervals (0.15-0.50 Hz). In this secondary analysis of a study testing whether diurnal cortisol slope predicted survival, we tested the association between resting baseline HF-HRV on survival using Cox proportional hazards models. RESULTS: A total of 50 patients died during a median follow-up of 7.99 years. Higher baseline HF-HRV predicted significantly longer survival, with a hazard ratio of 0.75 (95% confidence interval = 0.60-0.92, p = .006). Visceral metastasis status and baseline heart rate were related to both HF-HRV and survival. However, a combination of HF-HRV and heart rate further improved survival prediction, with a hazard ratio of 0.64 (95% confidence interval = 0.48-0.85, p = .002). CONCLUSIONS: Vagal activity of patients with MRBC strongly predicted their survival, extending the known predictive window of HF-HRV in cancer beyond palliative care. Vagal activity can be altered by behavioral, pharmacological, and surgical interventions and may be a promising target for extending life expectancy in patients with metastasizing cancer.