Sympathetic Nervous System Responses Research Articles

Mindfulness-Based Stress Reduction and Autonomic Modulation in Chronic Kidney Disease

Intro: Chronic kidney disease (CKD) is characterized by chronic overactivation of the sympathetic nervous system (SNS) that leads to increased blood pressure and cardiovascular disease risk. Mindfulness-Based Stress Reduction (MBSR) is an 8-week mindfulness meditation training program that has previously been shown to reduce blood pressure and improve autonomic balance in healthy and some clinical populations; however, MBSR has never previously been tested in CKD and the long-term effects of mindfulness mediation on SNS activity are unknown. Thus, we tested the hypothesis that 8 weeks of MBSR reduces SNS activity and reactivity in CKD patients. Method: In a randomized controlled trial, participants with CKD stages III-IV were randomized to 8 weeks of MBSR (n=17, 64±8 yr, 88% males) or a health education program (HEP, n=12, 63±10 yr, 83% males) that served as the active control intervention. MBSR was comprised of eight 2.5-hour group meetings and a retreat session focused on mindfulness training. HEP was administered in a similar structure and focused on health education. Direct intraneural measures of SNS activity directed to muscle (MSNA) was recorded via microneurography with concomitant beat-to-beat blood pressure and EKG monitoring at rest and during mental stress before and after the 8-week intervention. MSNA reactivity during mental arithmetic-induced stress (3 minutes) was compared between baseline and end of study (EOS) in the MBSR and HEP groups. Results. Baseline characteristics, kidney function, and comorbidities were comparable between groups. There was a significant Group (MBSR vs. HEP) by Time (baseline vs. EOS) interaction in the change in MSNA reactivity to mental stress. The MBSR group had a significant reduction in MSNA reactivity during the 1st, 2nd and 3rd minute of mental arithmetic at EOS (p<0.05 for all), while no change was observed within the HEP group. Resting MSNA and reactivity in blood pressure and heart rate during mental arithmetic remained unchanged in both groups from baseline to EOS. Conclusion. Patients with CKD had an amelioration of sympathetic reactivity during mental stress following 8-weeks of MBSR but not after HEP (control intervention). Our findings demonstrate that mindfulness training is feasible and may have potential beneficial effects on autonomic function in CKD. NIH R01HL135183; NIH R61AT10457; NIH KL2TR002381; VA Merit I01CX001065. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Salt-Sensitive Hypertension and the Kidney.

Salt-sensitive hypertension (SS-HT) is characterized by blood pressure elevation in response to high dietary salt intake and is considered to increase the risk of cardiovascular and renal morbidity. Although the mechanisms responsible for SS-HT are complex, the kidneys are known to play a central role in the development of SS-HT and the salt sensitivity of blood pressure (SSBP). Moreover, several factors influence renal function and SSBP, including the renin-angiotensin-aldosterone system, sympathetic nervous system, obesity, and aging. A phenotypic characteristic of SSBP is aberrant activation of the renin-angiotensin system and sympathetic nervous system in response to excessive salt intake. SSBP is also accompanied by a blunted increase in renal blood flow after salt loading, resulting in sodium retention and SS-HT. Obesity is associated with inappropriate activation of the aldosterone mineralocorticoid receptor pathway and renal sympathetic nervous system in response to excessive salt, and mineralocorticoid receptor antagonists and renal denervation attenuate sodium retention and inhibit salt-induced blood pressure elevation in obese dogs and humans. SSBP increases with age, which has been attributed to impaired renal sodium handling and a decline in renal function, even in the absence of kidney disease. Aging-associated changes in renal hemodynamics are accompanied by significant alterations in renal hormone levels and renal sodium handling, resulting in SS-HT. In this review, we focus mainly on the contribution of renal function to the development of SS-HT.

Trauma film viewing and intrusive memories: Relationship between salivary alpha amylase, endocannabinoids, and cortisol

The endogenous cannabinoid (ECB) system is a small molecule lipid signalling system that is involved in stress response activation and is associated with PTSD, but it is unclear whether salivary ECBs are part of the sympathetic nervous system response to stress. We conducted an adapted trauma film paradigm, where participants completed a cold pressor test (or control) while watching a 10-minute trauma film. We also collected saliva and hair samples and tested them for ECBs, cortisol, and salivary alpha amylase (sAA). As hypothesised, there were significant positive correlations between sAA activity and salivary ECB levels, particularly 2-arachidonoyl glycerol (2-AG), though ECBs were not correlated with sAA stress reactivity. Participants who had a significant cortisol response to the trauma film/stressor reported less intrusive memories, which were also less distressing and less vivid. This effect was moderated by arachidonoyl ethanolamide (AEA), where decreases in AEA post-stress were associated with more intrusive memories in cortisol non-responders only. This study provides new evidence for the role of ECBs in the sympathetic nervous system.

Interoceptive beliefs moderate the link between physiological and emotional arousal during an acute stressor.

Growing work suggests that interoception, that is, representations of one's internal bodily changes, plays a role in shaping emotional experiences. Past studies primarily examine how behavioral accuracy in detecting interoceptive signals (interoceptive ability) relates to emotional states, with less work examining self-reported interoceptive facets such as the characterizations of one's interoceptive abilities (interoceptive sensibility) or evaluative beliefs about the value versus danger of interoceptive signals (interoceptive beliefs). However, existing studies rarely examine physiological reactivity, behavioral, and self-reported dimensions of interoception together in the same sample. As such, it remains unclear whether and how much individual differences in interoceptive facets uniquely and in interaction with physiological reactivity may matter for emotional experience. Herein, 250 healthy young adults completed a heartbeat detection task assessing interoceptive ability and questionnaire measures of interoceptive sensibility and beliefs during an initial laboratory visit. At a follow-up session, 227 participants returned to undergo an acute psychosocial stressor. Measures of physiological arousal such as preejection period (PEP) and heart rate variability were acquired throughout the stressor with self-reported emotions acquired immediately after. Linear regressions revealed that greater sympathetic nervous system reactivity (i.e., PEP), poorer interoceptive ability (i.e., accuracy), and less positive interoceptive beliefs were related to more intense high arousal emotions during the stressor. Importantly, across models, interoceptive beliefs was the only interoceptive facet to moderate the concordance between physiological and emotional arousal. Implications for psychological theories of emotion, stress, and interoception are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapytargeting LMCG represented a promising strategy for the treatment of AMI.

Interoceptive ability moderates the effect of physiological reactivity on social judgment.

Social judgments-that others are kind or cruel, well intentioned, or conniving-can ease or disrupt social interactions. And yet a person's internal state can alter these judgments-a phenomenon known as affective realism. We examined the factors that contribute to, and mitigate, affective realism during a stressful interview. Using data collected between 2015 and 2019, we hypothesized and found that individuals' ability (N = 161; 57.6% female; 57.6% European American, 13.6% African American, 13.6% Asian American, 6.4% Latinx, 6.0% biracial, and 2.8% that identified with none or 1 + of the races presented; Mage = 19.20 years) to accurately perceive their own internal sensations (i.e., heartbeats) influenced whether they attributed their own heightened stress reactions (i.e., sympathetic nervous system reactivity) to the behavior of two impassive interviewers. Participants who were poor heartbeat detectors perceived their interviewers as less helpful, polite, or professional, and more apathetic, judgmental, and aggressive when experiencing heightened levels of cardiovascular sympathetic nervous system reactivity during their interview. Being aware of one's internal state may be one pathway to reducing bias in social perceptions in circumstances where such biases may lead us astray. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sympathetic nervous system responses during complex walking tasks and community ambulation post-stroke

Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 μs), high-change SCR (ΔSCR ≥ 0.2 μs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 μs), low-change SCR (ΔSCR < 0.2 μs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire.

Psychologically aggressive parenting and later aggression: Salivary alpha-amylase reactivity and sex as moderators

Psychologically aggressive parenting (PAP) exposure negatively affects children's development of aggression. Nevertheless, not all children exposed to PAP display aggressive behaviors. Sympathetic nervous system (SNS) activity may influence the impact of early adversity on aggression. This study examines whether SNS reactivity and sex moderate the link between psychologically aggressive parenting (PAP) during childhood and later aggression. Emerging adults (N = 182, mean age = 19.03 years, 53 % female) retrospectively reported on their childhood PAP and current aggression. Salivary alpha-amylase (sAA) collected from a social stress task indexed SNS reactivity to stress. Childhood PAP was associated with emerging adulthood anger, hostility, physical, and verbal aggression. Moreover, males were more likely to exhibit anger, verbal, and physical aggression and had higher levels of sAA reactivity than females. A significant three-way interaction between childhood PAP, sAA reactivity, and sex accounted for participants' current verbal aggression. The link between childhood PAP and later verbal aggression was stronger for males at higher levels of sAA reactivity. Females with higher levels of sAA reactivity displayed lower levels of verbal aggression regardless of PAP exposure. Males and females with lower levels of sAA reactivity were at elevated risk for verbal aggression regardless of PAP exposure. Moreover, we found a significant two-way interaction between PAP and sex on anger, such that higher levels of PAP exposure were associated with more anger among males, but not females. These findings highlight the importance of examining interactions between biological and environmental factors and sex in accounting for later aggression.

Sympathetic nervous system responses to acute psychosocial stress in male physicians with clinical burnout

BackgroundOccupational burnout has been associated with an increased risk of cardiovascular disease, with sympathetic nervous system (SNS) dysfunction as one explanation. This study examined the effects of burnout on responses of SNS activity measures to acute psychosocial stress in male physicians, a population at risk for burnout. MethodsStudy participants were 60 male physicians, 30 with clinical burnout, assessed with the Maslach Burnout Inventory, and 30 without burnout (controls). All participants underwent the 15-min Trier Social Stress Test. Heart rate, blood pressure, salivary alpha-amylase, and plasma levels of epinephrine (EPI) and norepinephrine were assessed pre-stress, immediately post-stress, and 15 min and 45 min post-stress. ResultsPhysicians with burnout and controls differed in EPI changes over time, controlling for age, job stress and anxiety symptoms (F (3,147) = 5.18, p = .002 for 'Time by Group' interaction; η2p = .096). Burnout was associated with a smaller increase in EPI from pre-stress to immediately post-stress (r(54) = −.40, p = .004). The emotional exhaustion dimension of burnout was a significant driver of this effect. The area under the curve with respect to increase in EPI was also smaller in the burnout group (F (1,49) = 6.06, p = .017, η2p = .110). Group differences were not significant for the other SNS activity measures. ConclusionsBurnout may be linked to dysfunction of the sympathoadrenal medullary (SAM) system, when exposed to acute psychosocial stress. In keeping with the allostatic load concept, an insufficient SAM stress response in burnout could potentially contribute to cardiovascular disease.

Biological stress responses to multitasking and work interruptions: A randomized controlled trial

In the course of digitalization, new stressors are emerging. In modern working and living environments, two ubiquitous, technology-mediated stressors are multitasking demands and work interruptions. However, biological stress response patterns to multitasking and work interruptions have been sparsely investigated so far. We thus aimed to comprehensively assess biological stress response patterns to both stressors and, additionally, test whether responses differ between digital and partially non-digital settings. A controlled experimental set-up was established and humans’ biological markers of the Sympathetic Nervous System (SNS), the hypothalamic-pituitary adrenal (HPA) axis, and the immune system were assessed. N = 186 healthy participants (mean age: 23.2 ± 4.3 years, 74.7% female, body mass-index: 22.3 ± 3.1 kg/m2) took part in this pre-registered study. Each participant was randomly assigned to one of 6 experimental conditions (1 digital single-task, 3 dual-tasks [2 parallel tasks and 1 interruption], 1 multitasking, and 1 passive, control condition). Each one of the dual-tasking as well as the multitasking conditions included a non-digital sub-task, i.e., performing a task in presence of an examiner. All other conditions involved digital tasks only. Salivary alpha-amylase (sAA) levels as a marker for SNS reactivity significantly changed in work interruptions, parallel dual-tasking, and multitasking conditions. No changes were found for control conditions. Furthermore, no significant changes over time and no differences between the conditions were identified for three biological markers: cortisol as marker for HPA axis activity as well as for two immune system markers (secretory Immunoglobulin-A, C-reactive protein). A time course similar to sAA was found for perceived stress: with increases during task execution and decreases afterwards in multitasking and parallel dual-tasking. Yet, it did not change for the work interruption, passive control, and single-tasking condition. Overall, our findings show that dual- and multitasking are perceived as stressful and are associated with an activation of the SNS, but not with responses of HPA axis or immune system. This was consistent for digital as well as partially digital task demands. Our findings will also inform future research into the differential stress effects of digital and non-digital tasks to advance our understanding of biological stress response-patterns to multitasking and work interruptions. Therefore, our findings are highly relevant for understanding the long-term biological health effects of stress in modern (digitalized) environments.

Reference gene recommendations and PACAP receptor expression in murine sympathetic ganglia of the autonomic nervous system that innervate adipose tissues after chronic cold exposure.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an important regulator of the stress response in mammals, influencing both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). PACAP has been reported to influence energy homeostasis, including adaptive thermogenesis, an energy burning process in adipose tissue regulated by the SNS in response to cold stress and overfeeding. While research suggests PACAP acts centrally at the level of the hypothalamus, knowledge of PACAP's role within the sympathetic nerves innervating adipose tissues in response to metabolic stressors is limited. This work shows, for the first time, gene expression of PACAP receptors in stellate ganglia and highlights some differential expression with housing temperature. Additionally, we present our dissection protocol, analysis of tyrosine hydroxylase gene expression as a molecular biomarker for catecholamine producing tissue and recommend three stable reference genes for the normalization of quantitative real time-polymerase chain reaction (qRT-PCR) data when working with this tissue. This study adds to information about neuropeptide receptor expression in peripheral ganglia of the sympathetic nervous system innervating adipose tissue and provides insight into PACAP's role in the regulation of energy metabolism.

Diminished autonomic nervous system responses to acoustic startle in progressive supranuclear palsy (S8.003)

<h3>Objective:</h3> To examine possible autonomic changes associated with progressive supranuclear palsy in response to a strong, unanticipated stimulus. <h3>Background:</h3> Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that causes serious problems in eye movements, walking, and balance, and is also often associated with cognitive, emotional, and behavioral changes. In other movement disorders such as Parkinson’s disease, similar symptoms have often been associated with changes in autonomic nervous system (ANS) functioning. Despite this, previous studies have rarely examined ANS functioning in PSP.. In the present study, we determined whether ANS responses to an emotionally provocative stimulus were altered in PSP. We tested the hypothesis that ANS responses to an unanticipated aversive auditory stimulus (i.e., a brief, loud burst of white noise) designed to induce a startle response would differ between patients with PSP compared to healthy controls (HC). <h3>Design/Methods:</h3> Participants included 33 PSP patients and 38 HC. Participants sat still for a 60 second baseline and heard a brief (100-ms) loud (115-dB) burst of white noise without warning. Continuous measures of cardiac interbeat intervals (IBI; decreases in IBI correspond to increases in heart rate) and skin conductance levels (SCL) were obtained throughout the task. <h3>Results:</h3> Compared to HC, PSP patients showed significantly less decrease in IBI (i.e., less increase in heart rate) and less increase in SCL from baseline during the 10 seconds after stimulus onset. <h3>Conclusions:</h3> Less decrease in IBI and less increase in SCL in the face of a strong external stimulus suggests a diminished sympathetic nervous system response. In light of previous research suggesting that peripheral sympathetic responses are relatively preserved in the setting of orthostatic postural testing in PSP, we suspect this relates to a brainstem degeneration in a pontine circuit that is critical for startle reflexes during emotional challenges. <b>Disclosure:</b> The institution of Dr. Pressman has received research support from Premiere. Dr. Pressman has received personal compensation in the range of $100,000-$499,999 for serving as a Associate Professor with University of Colorado School of Medicine. The institution of Dr. Chen has received research support from National Institute on Aging. Ms. Bullard has nothing to disclose. The institution of Dr. Rankin has received research support from Marcus Foundation. Robert Levenson has nothing to disclose.

Long-term cortisol secretion in attention deficit hyperactivity disorder: roles of sex, comorbidity, and symptom presentation.

Low activity of the hypothalamic-pituitary-adrenal axis (HPAA) has been found in children with attention deficit hyperactivity disorder (ADHD). The condition may be related to the reduced attention regulation capacity and/or to comorbid oppositional defiant or conduct disorder (ODD/CD). Sex differences are probable but not sufficiently studied. We analyzed the HPAA activity and sympathetic nervous system reactivity (SR) in children with ADHD while accounting for ADHD symptom presentation, comorbidity, and sex differences. The sample comprised 205 children, 98 (61 boys, 37 girls) with ADHD and 107 (48 boys, 59 girls) healthy controls. DSM-5 phenotypic symptom presentation and comorbid ODD/CD were assessed using clinical interviews. Hair cortisol concentration (HCC) was used to assess the long-term, cumulative activity of the HPAA. SR was assessed via skin conductance response (SCR). For control purposes, comorbid internalizing symptoms and indicators of adverse childhood experiences (ACE) were assessed. Children were medication naive. Boys presenting with predominantly inattentive symptoms (ADHD-I) showed lower HCC than healthy boys. Girls presenting with combined symptoms (ADHD-C) showed higher HCC than did healthy girls (p's < 0.05, sex-by-group interaction, F (2,194) = 4.09, p = 0.018). Boys with ADHD plus ODD/CD showed a blunted SR (p < 0.001, sex-by-group interaction, F (2,172) = 3.08, p = 0.048). Adjustment for ACE indicators led to non-significant differences in HCC but did not affect differences in SR. HCC constitutes an easily assessable, reliable, and valid marker of phenotypic ADHD-related features (i.e. symptom presentation and comorbidity). It indicates more homogenous subgroups of ADHD and might point to specifically involved pathophysiological processes.

The role of youths' cardiac autonomic balance and parental responses to youth emotion in vulnerability to borderline personality disorder development.

Developmental models of borderline personality disorder (BPD) emphasize the effects of youths' biological vulnerabilities and their experiences of parental responses to emotion, as well as the interaction between these two elements. The current study evaluated the independent and interactive effects of two indices of autonomic nervous system response and parental responses to youth negative emotions on severity and exacerbation of youths' BPD features during the transition to adolescence. The sample consisted of 162 psychiatric youth (10-14 years; 47.2% female) and their parents. At baseline, youth and their parents completed a lab-based conflict discussion during which parasympathetic and sympathetic nervous system response were measured and indices of sympathetic-parasympathetic balance and coactivation/coinhibition were calculated. Youth also reported on supportive and non-supportive parental responses. At baseline and after 9 months, youth self-reported on their BPD features. Results demonstrated that shifting toward sympathetic dominance independently predicted exacerbation of BPD across 9 months. Additionally, fewer experiences of supportive parental responses and more non-supportive parental responses were associated with greater severity of BPD features in youth. This study highlights the role of autonomic response to parent-child conflict as well as the significance of parental responses to youth emotion for the development of BPD during this developmental window.

Autonomic nervous system reactivity to emotion and childhood trajectories of relational and physical aggression.

This study investigated the role of autonomic nervous system (ANS) coordination in response to emotion in girls' and boys' development of relational (e.g., ignoring, excluding) and physical (e.g., hitting, kicking) aggression. Caregivers reported on children's relational and physical aggression at ages 6, 7, 8, and 10 years (N = 232, 50.4% girls, 46.6% Latinx). Sympathetic nervous system (assessed via pre-ejection period) and parasympathetic nervous system (assessed via respiratory sinus arrhythmia) reactivity were measured in response to video clips depicting fear, happiness, and sadness at age 7. Growth curve models indicated that ANS reactivity to sadness, but not to fear or happiness, was related to trajectories of relational aggression. In contrast, ANS reactivity to all three emotions was associated with trajectories of physical aggression. Effects differed across genders, indicating that distinct patterns of ANS reactivity to emotion may be involved in girls' and boys' development of aggression. Overall, these findings contribute to a growing literature documenting the role of ANS reactivity to emotion in aggressive behavior. Moreover, this study considers ANS reactivity to specific emotions, as related to both relational and physical aggression, and as differentially expressed among girls versus boys.

Electrodermal Activity Implicating a Sympathetic Nervous System Response under the Perception of Sensing a Divine Presence—A Psychophysiological Analysis

Previous studies have suggested that religious worship experiences may recruit the autonomic nervous system (ANS) in an activating fashion. For this reason, we hypothesized that measurements of the electrodermal activity (EDA) would concur with the notion that the subjective experience of sensing the presence of God recruits a sympathetic nervous system response. We analyzed the EDA of 37 evangelical participants and calculated classic galvanic skin response (GSR) measures. Our experimental design included six conditions with and without music consisting of religious and non-religious songs plus a resting-state condition, which were used to induce a variance in the religious experience suitable for statistical analyses. Results showed that both tonic and phasic signals as well as the overall electrical skin conductance (SC) were positively associated with the religious experience, defined as sensing the presence of God. This implicates that we can accept the hypothesis that such a religious experience under the influence of worship seems to recruit the sympathetic nervous system.

Watching with Argus eyes: Characterization of emotional and physiological responding in adults exposed to childhood maltreatment and/or recent adversity.

Exposure to adverse experiences is a well-established major risk factor for affective psychopathology. The vulnerability of deleterious sequelae is assumed in maladaptive processes of the defensive system, particularly in emotional processing. More specifically, childhood maltreatment has been suggested to be associated with the recruitment of specific and distinct defensive response profiles. To date, it remains unclear whether these are specific or generalizable to recent adversity in adulthood. This pre-registered study aimed to investigate the impact of exposure to childhood and recent adversity on emotional processing in 685 healthy adults with the "Affective Startle Modulation" Paradigm (ASM). First, we replicated higher trait anxiety and depression levels in individuals exposed to both types of adversity. Second, we observed increased general skin conductance reactivity in individuals exposed to recent adversity. Third, individuals exposed to childhood maltreatment showed reduced, while individuals exposed to recent adversity showed increased discrimination between pictures of negative and neutral valence, compared with non-exposed individuals in SCR. No association between exposure to adversity and fear potentiated startle was observed. Furthermore, explorative analyses revealed moderate dimensional and categorical agreement between two childhood maltreatment questionnaires and provide insight into potential adversity-type specific effects. Our results support experience-dependent plasticity in sympathetic nervous system reactivity and suggest distinct response profiles in affective modulation in individuals exposed to early versus recent adversity. We emphasize the need to further explore distinct adversity profiles to further our understanding on specific psychophysiological profiles and their potential implication for prevention and intervention.

Methods for eliciting and measuring behavioral and physiological consequences of stress and uncertainty in virtual reality

Military operations are characterized by high levels of stress and uncertainty, and these states can influence cognitive and physical performance outcomes. These states, however, can be difficult to reliably induce in laboratory contexts, making it challenging to quantify and model their influences on perceptual and cognitive processes underlying performance on applied tasks. Herein we describe the development and validation of a novel scenario-based virtual reality methodology, the decision making under uncertainty and stress (DeMUS) scenario, that accomplishes four primary goals. First, it induces physiological and biochemical stress responses through a threat of shock manipulation. Second, it induces transient states of uncertainty by manipulating stimulus clarity in a perceptual decision-making task. Third, it generates several performance metrics regarding recognition memory, spatial orienting, threat classification, and marksmanship decision making. Finally, the task combines behavioral, physiological, and biochemical measures to provide a more comprehensive understanding of how stress and uncertainty influence applied task performance. To provide an initial validation of the scenario and its associated tasks and measures, we conducted a pilot study (n= 18) involving stress induction and cognitive performance assessment. Analyses revealed that: 1) the DeMUS scenario elicited tonic and phasic biochemical (salivary alpha amylase and cortisol) and physiological (heart rate, pupil diameter) stress responses, 2) the scenario elicited variable sympathetic autonomic nervous system and hypothalamic-pituitary adrenal (HPA) axis responses, and 3) stress influenced some measures of memory and decision-making in both negative and positive directions. Continuing research will assess individual- and group-level predictors of performance on these virtual reality tasks, and emerging performance enhancement techniques that can help military personnel sustain performance during stressful operations.

Exposure to a Virtual Reality Mass-Casualty Simulation Elicits a Differential Sympathetic Response in Medical Trainees and Attending Physicians.

Previous studies have demonstrated the use of virtual reality (VR) in mass-casualty incident (MCI) simulation; however, it is uncertain if VR simulations can be a substitute for in-person disaster training. Demonstrating that VR MCI scenarios can elicit the same desired stress response achieved in live-action exercises is a first step in showing non-inferiority. The primary objective of this study was to measure changes in sympathetic nervous system (SNS) response via a decrease in heart rate variability (HRV) in subjects participating in a VR MCI scenario. An MCI simulation was filmed with a 360º camera and shown to participants on a VR headset while simultaneously recording electrocardiography (EKG) and HRV activity. Baseline HRV was measured during a calm VR scenario immediately prior to exposure to the MCI scenarios, and SNS activation was captured as a decrease in HRV compared to baseline. Cognitive stress was measured using a validated questionnaire. Wilcoxon matched pairs signed rank analysis, Welch's t-test, and multivariate logistic regression were performed with statistical significance established at P <.05. Thirty-five subjects were enrolled: eight attending physicians (two surgeons, six Emergency Medicine [EM] specialists); 13 residents (five Surgery, eight EM); and 14 medical students (six pre-clinical, eight clinical-year students). Sympathetic nervous system activation was observed in all groups during the MCI compared to baseline (P <.0001) and occurred independent of age, sex, years of experience, or prior MCI response experience. Overall, 23/35 subjects (65.7%) reported increased cognitive stress in the MCI (11/14 medical students, 9/13 residents, and 3/8 attendings). Resident and attending physicians had higher odds of discordance between SNS activation and cognitive stress compared to medical students (OR = 8.297; 95% CI, 1.408-64.60; P = .030). Live-actor VR MCI simulation elicited a strong sympathetic response across all groups. Thus, VR MCI training has the potential to guide acquisition of confidence in disaster response.

PS-B05-8: AGTR1A RECEPTORS IN NEURONS OF THE SUBFORNICAL ORGAN AND THE PARAVENTRICULAR NUCLEUS OF HYPOTHALAMUS ACTIVATE SPLENIC IMMUNITY TO HYPERTENSIVE STIMULI

Angiotensin II (AngII) is an important modulator of the sympathetic nervous system (SNS), activating type 1a AT receptors (AT1aRs), densely expressed in brain regions controlling cardiovascular function. Circumventricular organs (CVOs) locating in proximity of the ventricles are characterized by a leaky blood brain barrier, with the subfornical organ (SFO) particularly, exposed to circulating substances like AngII. Interestingly, the SFO is structurally and functionally connected to the paraventricular nucleus of the hypothalamus (PVN), a key regulator of the SNS. In our previous works, we demonstrated that AngII is capable to increase blood pressure by recruiting the splenic sympathetic nervous system (SSNA) and adaptive immune response in mice. Whether the splenic SNS and immune response are under brain control in hypertension is still unknown. To investigate the role of SFO, we exploited the stereotaxic injection of a recombinant adenovirus, encoding a Cre-recombinase and a GFP-reporter (AT1aR-KO-SFO), or GFP alone as control (AT1aR-WT-SFO), in the SFO of AT1aRflox mice. To selectively target AT1aRs in the PVN, we crossed AT1aRflox with mice expressing a Cre recombinase under Sim1 promoter, which typically characterize PVN neurons (AT1aR KO-PVN and AT1aR WT-PVN mice). Efficacy of gene deletion was evaluated by RT-PCR in brain samples obtained by laser microdissection (Figure 1) and AngII or vehicle were infused for 28 days through osmotic minipumps. First, we evaluated SSNA by microneurography, finding a significant reduction in firing frequency of mice with AT1aR KO in SFO. Then we analyzed whether the SSNA inhibition also hampered immune activation in the spleen and by immunofluorescence analysis of splenic white pulp area containing CD3 T cell, we observed that AT1aR KO-SFO mice displayed a reduced egression of T cells after chronic AngII infusion from the spleen towards target organs of hypertension. Further supporting the observation that AT1aR signaling in the brain SFO are necessary to prime T cell egression from the spleen, we found a significantly reduced infiltration of CD8 and CD4 T cells, and less renal damage, typical hallmarks of hypertension. More important, we also observed that AT1aR KO-PVN mice were significantly protected from AngII-induced hypertension, when compared to their respective controls showing a protection from T cells egression and infiltration in kidneys. Our data demonstrate the existence of a SFO-PVN-splenic axis as the main neural regulator of AngII-induced immune response and blood pressure increase. JOURNAL/jhype/04.03/00004872-202301001-00918/figure1/v/2023-10-24T163949Z/r/image-jpeg