Publication guidelines for human heart rate and heart rate variability studies in psychophysiology-Part 1: Physiological underpinnings and foundations of measurement.

This Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV. Along with this guidance, the Report reviews what is known about the origin of the heartbeat and its neural control, including factors that produce and influence HRV metrics. The Report concludes with checklists to guide authors in study design and analysis considerations, as well as guidance on the reporting of key methodological details and characteristics of the samples under study. It is expected that rigorous and transparent recording and reporting of HR and HRV measures will strengthen inferences across the many applications of these metrics in psychophysiology. The prior Committee Reports on HR and HRV are several decades old. Since their appearance, technologies for human cardiac and vascular monitoring in laboratory and daily life (i.e., ambulatory) contexts have greatly expanded. This Committee Report was prepared for the Society for Psychophysiological Research to provide updated methodological and interpretive guidance, as well as to summarize best practices for reporting HR and HRV studies in humans.

Cost-utility of real-time continuous glucose monitoring versus self-monitoring of blood glucose and intermittently scanned continuous glucose monitoring in people with type 1 diabetes receiving multiple daily insulin injections in Denmark.

AIMS: To determine the cost-effectiveness of the Dexcom G6 real-time continuous glucose monitoring (rt-CGM) system compared with both the self-monitoring of blood glucose (SMBG) and the Abbott FreeStyle Libre 1 and 2 intermittently scanned CGM (is-CGM) devices in people with type 1 diabetes receiving multiple daily insulin injections in Denmark. MATERIALS AND METHODS: The analysis was performed using the IQVIA Core Diabetes Model, which associates rt-CGM use with glycated haemoglobin reductions of 0.6% and 0.36% based on data from the DIAMOND and ALERTT1 trials, respectively, compared with SMBG and is-CGM use. The analysis was performed from the payer perspective over a 50-year time horizon; future costs and clinical outcomes were discounted at 4% per annum. RESULTS: The use of rt-CGM was associated with an incremental gain of 1.37 quality-adjusted life years (QALYs) versus SMBG. Total mean lifetime costs were Danish Krone (DKK) 894 535 for rt-CGM and DKK 823 474 for SMBG, resulting in an incremental cost-utility ratio of DKK 51 918 per QALY gained versus SMBG. Compared with is-CGM, the use of rt-CGM led to a gain of 0.87 QALYs and higher mean lifetime costs resulting in an incremental cost-utility ratio of DKK 40 879 to DKK 34 367 per QALY gained. CONCLUSIONS: In Denmark, the rt-CGM was projected to be highly cost-effective versus both SMBG and is-CGM, based on a willingness-to-pay threshold of 1× per capita gross domestic product per QALY gained. These findings may help inform future policies to address regional disparities in access to rt-CGM.

Impact of stereotype threat on brain activity during memory tasks in older adults.

We report the first neuroimaging experiment to investigate the impact of explicitly activating aging stereotypes (i.e., stereotype threat) on brain activity during cognitive tasks. Cognitively normal older adults read about aging stereotypes or a control passage prior to taking episodic memory, working memory, and a non-demanding control task during fMRI. At the group level, stereotype activation did not impact cognitive performance or measures sensitive to stress and anxiety (physiological or self-report), but like prior work, highly educated and retired adults exhibited greater stereotype effects on episodic memory. At the neural level, stereotype activation did not impact brain activity in executive control or emotional regulation regions previously linked to stereotype threat effects in younger adults, suggesting that stereotype threat operates differently in older adults. Instead, on each task, the stereotype group showed more brain activity than the control group in parietal midline regions (e.g., precuneus, posterior cingulate). Although activity in these regions can arise from many processes, they have previously been associated with self-referential thinking and error-prevention focus, and in our study, brain activity in these regions was associated with slower responses and lower false alarm errors on the episodic memory task. Collectively, these findings are more consistent with the regulatory fit hypothesis than an executive control interference hypothesis of stereotype threat effects in older adults, whereby older adults adopt an error-prevention mindset in response to explicit stereotype threat.

Text messaging and brief phone calls for weight loss in overweight and obese English- and Spanish-speaking adults: A 1-year, parallel-group, randomized controlled trial.

BACKGROUND: Weight loss interventions based solely on text messaging (short message service [SMS]) have been shown to be modestly effective for short periods of time and in some populations, but limited evidence is available for positive longer-term outcomes and for efficacy in Hispanic populations. Also, little is known about the comparative efficacy of weight loss interventions that use SMS coupled with brief, technology-mediated contact with health coaches, an important issue when considering the scalability and cost of interventions. We examined the efficacy of a 1-year intervention designed to reduce weight among overweight and obese English- and Spanish-speaking adults via SMS alone (ConTxt) or in combination with brief, monthly health-coaching calls. ConTxt offered 2-4 SMS/day that were personalized, tailored, and interactive. Content was theory- and evidence-based and focused on reducing energy intake and increasing energy expenditure. Monthly health-coaching calls (5-10 minutes' duration) focused on goal-setting, identifying barriers to achieving goals, and self-monitoring. METHODS AND FINDINGS: English- and Spanish-speaking adults were recruited from October 2011 to March 2013. A total of 298 overweight (body mass index [BMI] 27.0 to 39.9 kg/m2) adults (aged 21-60 years; 77% female; 41% Hispanic; 21% primarily Spanish speaking; 44% college graduates or higher; 22% unemployed) were randomly assigned (1:1) to receive either ConTxt only (n = 101), ConTxt plus health-coaching calls (n = 96), or standard print materials on weight reduction (control group, n = 101). We used computer-based permuted-block randomization with block sizes of three or six, stratified by sex and Spanish-speaking status. Participants, study staff, and investigators were masked until the intervention was assigned. The primary outcome was objectively measured percent of weight loss from baseline at 12 months. Differences between groups were evaluated using linear mixed-effects regression within an intention-to-treat framework. A total of 261 (87.2%) and 253 (84.9%) participants completed 6- and 12-month visits, respectively. Loss to follow-up did not differ by study group. Mean (95% confidence intervals [CIs]) percent weight loss at 12 months was -0.61 (-1.99 to 0.77) in the control group, -1.68 (-3.08 to -0.27) in ConTxt only, and -3.63 (-5.05 to -2.81) in ConTxt plus health-coaching calls. At 12 months, mean (95% CI) percent weight loss, adjusted for baseline BMI, was significantly different between ConTxt plus health-coaching calls and the control group (-3.0 [-4.99 to -1.04], p = 0.003) but not between the ConTxt-only and the control group (-1.07 [-3.05 to 0.92], p = 0.291). Differences between ConTxt plus health-coaching calls and ConTxt only were not significant (-1.95 [-3.96 to 0.06], p = 0.057). These findings were consistent across other weight-related secondary outcomes, including changes in absolute weight, BMI, and percent body fat at 12 months. Exploratory subgroup analyses suggested that Spanish speakers responded more favorably to ConTxt plus health-coaching calls than English speakers (Spanish contrast: -7.90 [-11.94 to -3.86], p < 0.001; English contrast: -1.82 [-4.03 to 0.39], p = 0.107). Limitations include the unblinded delivery of the intervention and recruitment of a predominantly female sample from a single site. CONCLUSIONS: A 1-year intervention that delivered theory- and evidence-based weight loss content via daily personalized, tailored, and interactive SMS was most effective when combined with brief, monthly phone calls. TRIAL REGISTRATION: ClinicalTrials.gov NCT01171586.

Visual cues to fertility are in the eye (movements) of the beholder.

Past work demonstrates that humans behave differently towards women across their menstrual cycles, even after exclusively visual exposure to women's faces. People may look at women's faces differently as a function of women's menstrual cycles. Analyses of participants' scanpaths (eye movement patterns) while they looked at women at different phases of their menstrual cycles revealed that observers exhibit more consistent scanpaths when examining women's faces when women are in a menstrual cycle phase that typically corresponds with peak fertility, whereas they exhibit more variable patterns when looking at women's faces when they are in phases that do not correspond with fertility. A multivariate classifier on participants' scanpaths predicted whether they were looking at the face of a woman in a more typically fertile- versus non-fertile-phase of her menstrual cycle with above-chance accuracy. These findings demonstrate that people look at women's faces differently as a function of women's menstrual cycles, and suggest that people are sensitive to fluctuating visual cues associated with women's menstrual cycle phase.

Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans.

Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to acute psychosocial stress in humans. Now we extend this to study the effects of a pure mu-opioid agonist, hydromorphone, and a non-opioid analgesic, acetaminophen, on response to social stress. We compared the effect of hydromorphone (2 and 4 mg), acetaminophen (1000 mg) to a placebo using a between subject design. Healthy adult volunteers were randomly assigned to receive placebo (N = 13), 2 mg hydromorphone (N = 12), 4 mg hydromorphone (N = 12), or 1000 mg acetaminophen (paracetamol; N = 13) under double-blind conditions before undergoing a stress task or a control task on two separate sessions. The stress task, consisting of a standardized speaking task and the non-stressful control task were presented in counterbalanced order. Dependent measures included mood ratings, subjective appraisal of the stress (or no-stress) task, salivary cortisol, pupil diameter, heart rate, and blood pressure. The stress task produced its expected increase in heart rate, blood pressure, salivary cortisol, pupil diameter, and subjective ratings of anxiety and negative mood. Hydromorphone dose-dependently dampened cortisol responses to stress, and decreased ratings of how "challenging" participants found the task. Acetaminophen did not affect physiological responses, but, like hydromorphone, decreased ratings of how "challenging" the task was. The hydromorphone results support the idea that the mu-opioid system is involved in physiological responses to acute stress in humans, in line with results from preclinical studies. The non-opioid analgesic acetaminophen did not dampen physiological responses, but did reduce some components of psychological stress. It remains to be determined how both opioid and non-opioid systems mediate the complex physiological and psychological responses to social stress.

Performance during competition and competition outcome in relation to testosterone and cortisol among women.

A contribution to a special issue on Hormones and Human Competition. This study investigated the relation between competition, testosterone (T), and cortisol (C) in women. One hundred and twenty female participants competed against a male confederate in a computerized laboratory task. The task was preprogrammed so that half the women won and half of the women lost the competition. T and C concentrations were measured in saliva samples collected at four time points before and after the competition. Accuracy and reaction time during the competition were recorded. T and C increased directly after the competition, though not significantly for C, and then decreased over time regardless of the competition outcome. Regression analyses demonstrated that baseline T was significantly and positively associated with competition accuracy, though only in individuals who were low in C. Individuals who were high in C showed no relation between T and accuracy. This relation was further qualified by competition outcome. Losers of the competition showed a significant positive relation between baseline T levels and competition accuracy, though only if they were low in C. No relation was found between T and accuracy in losers who were high in C. Winners of the competition showed no relation between T and accuracy, regardless of whether C levels were high or low. These results are in line with the dual-hormone hypothesis, whereby the effects of T on status-seeking behaviors are dependent on C levels for individuals whose status is threatened.

The complexity of empathy during medical school training: evidence for positive changes.

CONTEXT: Empathy is an essential aspect of clinical care, associated with improved patient satisfaction, increased adherence to treatment, and fewer malpractice complaints. Previous studies suggest that empathy declines during medical training. However, past research relied on a single narrowly operationalised, self-report measure of empathy. As empathy is a complex socio-emotional construct, it is critical to assess changes across its distinct components using multiple measures in order to better understand how it is influenced by medical training. METHODS: In a longitudinal study, medical students completed a series of self-report and behavioural measures twice per year during the first 3 years of their study (2012-2015). These included the previously used Jefferson Scale of Physician Empathy (JSPE), designed to assess empathy in the clinical context, the Questionnaire of Cognitive and Affective Empathy (QCAE), designed to assess overall empathy and its main components, and behavioural measures of sensitivity to others' pain and understanding of others' emotions, both of which are important aspects of empathy. The employment of multiple measures allowed for a more complete assessment of medical students' empathy and related processes. RESULTS: In reflection of findings in previous work, students' empathy assessed by the JSPE decreased over training. However, on the QCAE, aspects of students' empathy, specifically overall cognitive empathy and its subcomponent perspective taking, and the emotion contagion subcomponent of affective empathy improved, whereas the remaining subcomponents remained stable. During medical school, students also exhibited comparable growth in their understanding of others' emotions and increased sensitivity to others' pain. CONCLUSIONS: Changes in empathy during medical school cannot be simply characterised as representing an overall decline. Indeed, aspects of empathy thought to be valuable in positive physician-patient interactions improve during training. Overall, this study points to the importance of assessing the distinct components of empathy using multiple forms of measurement in order to better understand the mechanisms involved in empathy changes in medical practice.

Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity.

RATIONALE: Dopamine ß-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine in the central nervous system and peripherally. DBH variants are associated with large changes in circulating DBH and implicated in multiple disorders; yet causal relationships and tissue-specific effects remain unresolved. OBJECTIVE: To characterize regulatory variants in DBH, effect on mRNA expression, and role in modulating sympathetic tone and disease risk. METHODS AND RESULTS: Analysis of DBH mRNA in human tissues confirmed high expression in the locus coeruleus and adrenal gland, but also in sympathetically innervated organs (liver>lung>heart). Allele-specific mRNA assays revealed pronounced allelic expression differences in the liver (2- to 11-fold) attributable to promoter rs1611115 and exon 2 rs1108580, but only small differences in locus coeruleus and adrenals. These alleles were also associated with significantly reduced mRNA expression in liver and lung. Although DBH protein is expressed in other sympathetically innervated organs, mRNA levels were too low for analysis. In mice, hepatic Dbh mRNA levels correlated with cardiovascular risk phenotypes. The minor alleles of rs1611115 and rs1108580 were associated with sympathetic phenotypes, including angina pectoris. Testing combined effects of these variants suggested protection against myocardial infarction in 3 separate clinical cohorts. CONCLUSIONS: We demonstrate profound effects of DBH variants on expression in 2 sympathetically innervated organs, liver and lung, but not in adrenals and brain. Preliminary results demonstrate an association of these variants with clinical phenotypes responsive to peripheral sympathetic tone. We hypothesize that in addition to endocrine effects via circulating DBH and norepinephrine, the variants act in sympathetically innervated target organs.

Click "like" to change your behavior: a mixed methods study of college students' exposure to and engagement with Facebook content designed for weight loss.

BACKGROUND: Overweight or obesity is prevalent among college students and many gain weight during this time. Traditional face-to-face weight loss interventions have not worked well in this population. Facebook is an attractive tool for delivering weight loss interventions for college students because of its popularity, potential to deliver strategies found in successful weight loss interventions, and ability to support ongoing adaptation of intervention content. OBJECTIVE: The objective of this study was to describe participant exposure to a Facebook page designed to deliver content to overweight/obese college students in a weight loss randomized controlled trial (N=404) and examine participant engagement with behavior change campaigns for weight loss delivered via Facebook. METHODS: The basis of the intervention campaign model were 5 self-regulatory techniques: intention formation, action planning, feedback, goal review, and self-monitoring. Participants were encouraged to engage their existing social network to meet their weight loss goals. A health coach moderated the page and modified content based on usage patterns and user feedback. Quantitative analyses were conducted at the Facebook post- and participant-level of analysis. Participant engagement was quantified by Facebook post type (eg, status update) and interaction (eg, like) and stratified by weight loss campaign (sequenced vs nonsequenced). A subset of participants were interviewed to evaluate the presence of passive online engagement or "lurking." RESULTS: The health coach posted 1816 unique messages to the study's Facebook page over 21 months, averaging 3.45 posts per day (SD 1.96, range 1-13). In all, 72.96% (1325/1816) of the posts were interacted with at least once (eg, liked). Of these, approximately 24.75% (328/1325) had 1-2 interactions, 23.39% (310/1325) had 3-5 interactions, 25.13% (333/1325) had 6-8 interactions, and 41 posts had 20 or more interactions (3.09%, 41/1325). There was significant variability among quantifiable (ie, visible) engagement. Of 199 participants in the final intervention sample, 32 (16.1%) were highly active users and 62 (31.2%) never visibly engaged with the intervention on Facebook. Polls were the most popular type of post followed by photos, with 97.5% (79/81) and 80.3% (386/481) interacted with at least once. Participants visibly engaged less with posts over time (partial r=-.33; P<.001). Approximately 40% of the participants interviewed (12/29, 41%) reported passively engaging with the Facebook posts by reading but not visibly interacting with them. CONCLUSIONS: Facebook can be used to remotely deliver weight loss intervention content to college students with the help of a health coach who can iteratively tailor content and interact with participants. However, visible engagement with the study's Facebook page was highly variable and declined over time. Whether the level of observed engagement is meaningful in terms of influencing changes in weight behaviors and outcomes will be evaluated at the completion of the overall study.

Social interaction modulates autonomic, inflammatory, and depressive-like responses to cardiac arrest and cardiopulmonary resuscitation.

Psychological factors, including depression and social isolation, are important determinants of cardiovascular health. The current study uses a well-validated mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) to examine the effect of social environment on several pathophysiological and behavioral responses to cerebral ischemia. Male experimental mice were either housed in pairs with an ovariectomized female or socially isolated for the duration of the experiment. Cardiac arrest increased the mRNA expression of the proinflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as the microglia marker MAC-1; expression of each of these factors, except IL-6, was further increased among socially isolated mice. Furthermore, socially isolated animals exposed to the CA/CPR procedure displayed significantly higher levels of neuronal cell death and microglia staining within the hippocampus at 7 d following surgery. Social isolation also exacerbated CA/CPR-induced depressive-like behavior and cardiac autonomic dysregulation. In the absence of ischemic damage, social environment had no significant effect on the expression of neuronal cell death, autonomic cardiac control, or behavior. Together, these data suggest that social factors influence the pathophysiological trajectory following cardiac arrest.

Sedentary behavior and food cravings in diverse overweight women: a pilot study.

UNLABELLED: Obesity rates have risen sharply in the United States, with minority women among those most affected. Although a majority of Americans are considered inactive, little attention has been devoted to studying the correlation of sedentary behavior with dietary cravings in adults. OBJECTIVE: The current study used objective and self-report methods to measure sedentary behavior and its relationship to food cravings in a sample of overweight African American and Caucasian women. DESIGN: Thirty-nine adult women (54% African American) with an average body mass index of 33.7 wore accelerometers for one week and completed self-report measures of sedentary behavior, physical activity, and food cravings. RESULTS: Self-reported television viewing time was slightly longer (3.0 versus 2.5 hours), although total sedentary time was shorter (6.7 versus 8.0 hours) on weekends versus weekdays. Weekend but not weekday sedentary time and television viewing were associated with stable aspects of food cravings rather than craving for specific foods. CONCLUSION: In this small sample, only a third of all sedentary time was attributed to viewing television. Assessing whether sedentary behavior occurs by necessity versus choice may be a factor to consider in examining its relationship to food cravings.

Longitudinal measurement invariance of psychosocial measures in physical activity research: An application to adolescent data.

The current study served as a practical and substantive guide to establishing longitudinal measurement invariance of psychosocial measures commonly used in adolescent physical activity (PA) research. Psychosocial data on an initial sample of 878 adolescents (ages 11 - 15) recruited through primary care providers were provided at baseline, 6, 12, and 24 months. The target measures included family support, peer support, decisional balance (pros, cons), self-efficacy, and behavioral strategies. Five of the six psychosocial measures exhibited strict longitudinal measurement invariance, with the 6th measure (self-efficacy) exhibiting strong longitudinal measurement invariance. These findings support the equivalence of these measures across time, and provide the foundation to substantively interpret group differences and associations involving these measures and PA.

Triad multisystem phenotype with high risk for developing temporomandibular disorders-characteristics and potential pathophysiology results from the Orofacial Pain: Prospective Evaluation and Risk Assessment dataset.

ABSTRACT: A multisystem phenotype with the Triad of bodily pain, psychological distress, and sleep disturbance was found to have high risk for developing initial onset of painful temporomandibular disorders (TMDs) in the multicenter Orofacial Pain: Prospective Evaluation and Risk Assessment dataset. In this study, we systemically examined phenotypic characteristics and explored potential pathophysiology in quantitative sensory testing and autonomic nervous system domains in this multisystem Triad phenotype. Secondary analysis was performed on 1199 non-Triad and 154 Triad TMD-free Orofacial Pain: Prospective Evaluation and Risk Assessment enrollees at baseline. Results indicated that before developing TMDs, the Triad phenotype demonstrated both orofacial and systemic signs and symptoms that can only be captured through multisystem assessment. In addition, we found significantly lower resting heart rate variability and higher resting heart rate in the Triad phenotype as compared with the non-Triad group. However, pain sensitivity measured by quantitative sensory testing was not different between groups. These findings highlight the importance of whole-person multisystem assessment at the stage before developing complex pain conditions, such as TMDs, and suggest that, in addition to a "tissue damage monitor," pain should be considered in a broader context, such as a component within a "distress monitoring system" at the whole-person level when multisystem issues copresent. Therefore, the presence or absence of multisystem issues may carry critical information when searching for disease mechanisms and developing mechanism-based intervention and prevention strategies for TMDs and related pain conditions. Cardiovascular autonomic function should be further researched when multisystem issues copresent before developing TMDs.

Resting parasympathetic activity is associated with malodor-induced change in perceived foreignness of speakers.

INTRODUCTION: To protect against infection, individuals have evolved context-dependent pathogen-avoidant strategies, including selective social behaviors aimed at avoiding foreign individuals who may possess greater risk of infection. Parasympathetic nervous system (PNS) activity is associated with social engagement and regulation of the classical immune system but has not been widely investigated in relation to changes in intergroup perception and the behavioral immune system. METHOD: The current research investigated the relationship between parasympathetic activity and perceived foreignness of in and outgroup speakers during exposure to a pathogen-relevant odor (butyric acid). High-frequency heart rate variability was measured at rest and while participants rated foreignness of speakers with and without the odor present. RESULTS: Findings show that exposure to the odor was associated with higher foreignness perceptions of outgroup speakers and lower foreignness perceptions of ingroup speakers. This effect was especially evident among individuals with higher resting parasympathetic activity. CONCLUSION: These results suggest that the PNS may play a role in changes in social perceptions during a behavioral immune response.

Perceived control, loneliness, early-life stress, and parents' perceptions of stress.

The COVID-19 pandemic has highlighted the importance of understanding what contributes to individual variability in experiences of stress. Increases in stress related to the pandemic have been especially pronounced in parents, indicating a need for research examining what factors contribute to parents' perceptions of stress. Here, we assessed the relationship between parents' perceptions of stress, control, loneliness, and experiences of childhood trauma in two populations of caregivers. In Study 1, we examined the relationship between perceptions of stress, control, loneliness, and history of early stress, along with indices of socioeconomic risk and resting parasympathetic nervous systema activity, which has been linked to variability in perceptions of stress, in caregivers of young children. Perceived control, loneliness, childhood stress, and resting parasympathetic nervous system activity predicted caregivers' stress. In Study 2, we replicated these initial findings in a second sample of caregivers. Additionally, we examined how these processes change over time. Caregivers demonstrated significant changes in perceptions of control, loneliness, and stress, and changes in control and childhood trauma history were associated with changes in perceptions of stress. Together these results indicate the importance of assessing how caregivers perceive their environment when examining what contributes to increased risk for stress. Additionally, they suggest that caregivers' stress-related processes are malleable and provide insight into potential targets for interventions aimed at reducing parents' stress.

Cardiopulmonary arrest and resuscitation disrupts cholinergic anti-inflammatory processes: a role for cholinergic α7 nicotinic receptors.

Cardiac arrest is a leading cause of death worldwide. While survival rates following sudden cardiac arrest remain relatively low, recent advancements in patient care have begun to increase the proportion of individuals who survive cardiac arrest. However, many of these individuals subsequently develop physiological and psychiatric conditions that likely result from ongoing neuroinflammation and neuronal death. The present study was conducted to better understand the pathophysiological effects of cardiac arrest on neuronal cell death and inflammation, and their modulation by the cholinergic system. Using a well validated model of cardiac arrest, here we show that global cerebral ischemia increases microglial activation, proinflammatory cytokine mRNA expression (interleukin-1ß, interleukin-6, tumor necrosis factor-α), and neuronal damage. Cardiac arrest also induces alterations in numerous cellular components of central cholinergic signaling, including a reduction in choline acetyltransferase enzymatic activity and the number of choline acetyltransferase-positive neurons, as well as, reduced acetylcholinesterase and vesicular acetylcholine transporter mRNA. However, treatment with a selective agonist of the α7 nicotinic acetylcholine receptor, the primary receptor mediating the cholinergic anti-inflammatory pathway, significantly decreases the neuroinflammation and neuronal damage resulting from cardiac arrest. These data suggest that global cerebral ischemia results in significant declines in central cholinergic signaling, which may in turn diminish the capacity of the cholinergic anti-inflammatory pathway to control inflammation. Furthermore, we provide evidence that pharmacological activation of α7 nicotinic acetylcholine receptors provide significant protection against ischemia-related cell death and inflammation within a clinically relevant time frame.

Effects of social isolation on glucocorticoid regulation in social mammals.

The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans.

Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function: a population based study.

Oxytocin (OT) is a nonapeptide neurohormone that is involved in a broad array of physiological and behavioral processes related to health including hypothalamic-pituitary-adrenal (HPA) axis functioning, autonomic nervous system (ANS) activity and social behaviors. The present study sought to explore the influence of genetic variation in the oxytocin receptor (SNP; rs53576) on autonomic and neurohormonal functioning across both resting and psychological stress conditions in a population based sample of older adults. Results revealed that A carrier males showed higher levels of resting sympathetic cardiac control as compared to their G/G counter parts. However, G/G participants displayed significantly higher levels of sympathetic reactivity to psychological stress with G/G males showing the highest levels of sympathetic response to stress. Although no significant effects were detected for heart rate or parasympathetic cardiac control across resting and stress conditions, results revealed that G/G participants generally displayed heightened stroke volume and cardiac output reactivity to the psychological stressor. Furthermore, analysis of diurnal fluctuations in salivary cortisol revealed that G/G participants displayed lower awakening cortisol levels and less variation in salivary cortisol across the day as compared to A carrier individuals.