The Type I interferon antiviral gene program is impaired by lockdown and preserved by caregiving.

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic "shelter in place" (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16- classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.

To what extent is psychological resilience protective or ameliorative: Exploring the effects of deployment on the mental health of combat medics.

Exposure to a major traumatic stressor increases the odds of negative mental health and maladaptive behavioral outcomes not only for victims but also for 1st responders and health care professionals who are exposed to the aftermath. This study investigates the extent to which psychological resilience acts as either a Protective (i.e., vaccine-like) or an Ameliorative (i.e., antibiotic-like) factor to reduce the deleterious mental health outcomes associated with exposure to a major stressor. To do so, this pilot study focused on the understudied population of military combat medics, who are exposed to both stressors associated with direct combat and with providing intense battlefield trauma care. Military combat medics who were identified as having deployed to Iraq or Afghanistan shortly after baseline measurements of posttraumatic stress disorder, depression, and aggressive behavioral tendencies and returned from deployment prior to the follow-up assessment (protective model) were compared to those who returned from deployment in Iraq or Afghanistan shortly before the baseline measurements and were not deployed again prior to the follow-up assessments (ameliorative model). Data were collected on combat experiences to equate the stressor for these 2 samples, and a propensity score matching technique was used to ensure that the 2 samples were similar. The findings provide support for both the protective and the ameliorative models of psychological resilience. Results are discussed in terms of the potential benefits of resilience in mental health programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Loneliness in monkeys: Neuroimmune mechanisms.

Loneliness, or perceived social isolation, may be evident in any group-living species, although its assessment in nonhumans provides some measurement challenges. It is well-known that loneliness in humans confers significant risk for morbidity and mortality, although mechanisms remain unclear. The authors describe a naturally-occurring model of loneliness in adult male rhesus monkeys that shows many parallels with the phenomenon in humans. Lonely monkeys (those that display high frequencies of social initiations but low frequencies of complex interaction) show elevated sympathetic nervous system activity and down regulated Type I interferon responses. Analysis of data from simian immunodeficiency virus-infected monkeys indicates that these physiological changes have functional consequences. Use of this animal model can help identify mechanisms by which loneliness impacts health.

Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness.

Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.

Behavioral and cardiovascular consequences of disrupted oxytocin communication in cohabitating pairs of male and female prairie voles.

Negative social experiences may influence psychological and physiological health via altered central oxytocin communication. The prairie vole is valuable for investigating the potential influence of oxytocin on responses to social experiences. Prairie voles are socially monogamous, live in pairs or family groups, and respond negatively to changes in the social environment. This study investigated the hypothesis that disruptions of oxytocin in one prairie vole of a cohabitating male-female pair would alter social behavior in that specific animal; and these behavioral changes in turn would influence the untreated partner's behavior and physiology. Pharmacological antagonism of oxytocin with the receptor antagonist L-368,899 in the male prairie vole disrupted social behaviors between the male and his untreated female partner. This manipulation also negatively influenced the behavior and cardiovascular function in the untreated female partner, including increased: (a) depression-relevant behaviors in two behavioral stressors, (b) basal mean arterial pressure and heart rate, and (c) cardiovascular reactivity to the behavioral stressors. These results suggest that disruptions of oxytocin and social behavior in one animal may produce indicators of social stress in an untreated social partner. This preliminary research provides a foundation for future studies to investigate mechanisms underlying responses to social experiences in humans.

Loneliness predicts a preference for larger interpersonal distance within intimate space.

Loneliness is thought to serve as an adaptive signal indicating the need to repair or replace salutary social connections. Accordingly, loneliness may influence preferences for interpersonal distance. If loneliness simply motivates a desire to socially reconnect, then loneliness may be associated with a preference for smaller interpersonal distances. According to the evolutionary model of loneliness, however, loneliness also signals an inadequacy of mutual aid and protection, augmenting self-preservation motives. If loneliness both increases the motivation to reconnect and increases the motivation for self-protection, then the resulting approach-avoidance conflict should produce a preference for larger interpersonal distance, at least within intimate (i.e., proximal) space. Here, we report two survey-based studies of participants' preferences for interpersonal distance to distinguish between these competing hypotheses. In Study 1 (N = 175), loneliness predicted preferences for larger interpersonal distance within intimate space net gender, objective social isolation, anxiety, depressive symptomatology, and marital status. In Study 2 (N = 405), we replicated these results, and mediation analyses indicated that measures of social closeness could not adequately explain our findings. These studies provide compelling evidence that loneliness predicts preferences for larger interpersonal distance within intimate space, consistent with predictions from the evolutionary model of loneliness.

The neuroscience of persuasion: A review with an emphasis on issues and opportunities.

Persuasion, a prevalent form of social influence in humans, refers to an active attempt to change a person's attitudes, beliefs, or behavior. There is a growing literature on the neural correlates of persuasion. As is often the case in an emerging literature, however, there are a number of questions, concerns, and alternative interpretations that can be raised about the research and interpretations. We provide a critical review of the research, noting potential problems and issues that warrant attention to move the field forward. Among the recommendations are greater integration of neuroimaging approaches with existing behavioral theories and methods on the information processes (cognitive and affective) underlying persuasion, and moving beyond solely correlative approaches for specifying underlying neural mechanisms. Work in this area has the potential to contribute to our understanding of brain-behavior relationships as well as to advance our understanding of persuasion and social influence more generally.

Trait and State Levels of Loneliness in Early and Late Adolescents: Examining the Differential Reactivity Hypothesis.

According to the differential reactivity hypothesis, lonely individuals respond differently to their environment compared to nonlonely individuals, which may sustain their loneliness levels. However, this interesting hypothesis has not yet been explored in daily life: Do lonely individuals feel lonely all the time, or do they feel more or less lonely in specific social contexts? The main aim of the present study was to test the differential reactivity hypothesis in daily life by examining in three samples whether trait levels of loneliness affected the levels of state loneliness in different social contexts. We used baseline questionnaires to measure trait loneliness and the Experience Sampling Method to collect data on state loneliness, in early adolescents (N = 269, Mage = 14.49, 59% female) and late adolescents (N = 223, Mage = 19.60, 91% female) from the Netherlands and late adolescents from the United States (N = 126, Mage = 19.20, 51% female). Results provided evidence for the differential reactivity hypothesis in the total sample, as high lonely adolescents experienced higher levels of state loneliness in situations in which they were alone than low lonely adolescents, but also benefited more from being with intimate company than low lonely adolescents. In sum, the present study provided evidence for the differential reactivity hypothesis and showed that the experience of loneliness in daily life was remarkably similar across age and culture. Our findings provide important insights into the daily experiences of trait lonely people, which may provide starting points for interventions.

Spatio-temporal dynamics of the mirror neuron system during social intentions.

Previous research has shown that specific goals and intentions influence a person's allocation of social attention. From a neural viewpoint, a growing body of evidence suggests that the inferior fronto-parietal network, including the mirror neuron system, plays a role in the planning and the understanding of motor intentions. However, it is unclear whether and when the mirror neuron system plays a role in social intentions. Combining a behavioral task with electrical neuroimaging in 22 healthy male participants, the current study investigates whether the temporal brain dynamic of the mirror neuron system differs during two types of social intentions i.e., lust vs. romantic intentions. Our results showed that 62% of the stimuli evoking lustful intentions also evoked romantic intentions, and both intentions were sustained by similar activations of the inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the first 432 ms after stimulus onset. Intentions to not love or not lust, on the other hand, were characterized by earlier differential activations of the inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset. These results suggest that the mirror neuron system may not only code for the motor correlates of intentions, but also for the social meaning of intentions and its valence at both early/automatic and later/more elaborative stages of information processing.

Predicting Intentions of a Familiar Significant Other Beyond the Mirror Neuron System.

Inferring intentions of others is one of the most intriguing issues in interpersonal interaction. Theories of embodied cognition and simulation suggest that this mechanism takes place through a direct and automatic matching process that occurs between an observed action and past actions. This process occurs via the reactivation of past self-related sensorimotor experiences within the inferior frontoparietal network (including the mirror neuron system, MNS). The working model is that the anticipatory representations of others' behaviors require internal predictive models of actions formed from pre-established, shared representations between the observer and the actor. This model suggests that observers should be better at predicting intentions performed by a familiar actor, rather than a stranger. However, little is known about the modulations of the intention brain network as a function of the familiarity between the observer and the actor. Here, we combined functional magnetic resonance imaging (fMRI) with a behavioral intention inference task, in which participants were asked to predict intentions from three types of actors: A familiar actor (their significant other), themselves (another familiar actor), and a non-familiar actor (a stranger). Our results showed that the participants were better at inferring intentions performed by familiar actors than non-familiar actors and that this better performance was associated with greater activation within and beyond the inferior frontoparietal network i.e., in brain areas related to familiarity (e.g., precuneus). In addition, and in line with Hebbian principles of neural modulations, the more the participants reported being cognitively close to their partner, the less the brain areas associated with action self-other comparison (e.g., inferior parietal lobule), attention (e.g., superior parietal lobule), recollection (hippocampus), and pair bond (ventral tegmental area, VTA) were recruited, suggesting that the more a shared mental representation has been pre-established, the more neurons show suppression in their response to the presentation of information to which they are sensitive. These results suggest that the relation of performance to the extent of neural activation during intention understanding may display differential relationships based on the cognitive domain, brain region, and the cognitive interdependence between the observer and the actor.

Reciprocal Influences Between Loneliness and Self-Centeredness: A Cross-Lagged Panel Analysis in a Population-Based Sample of African American, Hispanic, and Caucasian Adults.

Loneliness has been posited to increase the motivation to repair or replace deficient social relationships and, seemingly paradoxically, to increase the implicit motivation for self-preservation. In the current research, we report a cross-lagged panel analysis of 10 waves of longitudinal data ( N = 229) on loneliness and self-centeredness (as gauged by Feeney and Collins's measure of chronic self-focus) in a representative sample of middle-aged and older adults. As predicted by the proposition that loneliness increases the implicit motivation for self-preservation, loneliness in the current year predicts self-centeredness in the subsequent year beyond what is explained by current-year demographic variables, self-centeredness, depressive symptomatology, and overall negative mood. Analyses also show that self-centeredness in the current year (net covariates) predicts loneliness in the subsequent year, a reciprocal relationship that could potentially contribute to the maintenance of loneliness. Theoretical and practical implications are discussed.

Neuroimaging of Female Sexual Desire and Hypoactive Sexual Desire Disorder.

INTRODUCTION: Recent advances in neuroimaging offer an unprecedented window into the female sexual brain. The small samples and poor statistical power of individual functional magnetic resonance imaging studies have limited what can be gleaned about the systematic brain network that is involved in female sexual desire and female sexual dysfunction (eg, hypoactive sexual desire disorder [HSDD]). AIM: To quantitatively determine the brain network involved in HSDD. METHODS: Systematic retrospective review and statistical meta-analysis of pertinent neuroimaging literature. MAIN OUTCOME MEASURES: Review of published literature on functional magnetic resonance imaging studies illustrating brain regions associated with female sexual desire and female HSDD. RESULTS: HSDD is associated with a specific fronto-limbic-parietal dysfunction characterized by (i) lower blood oxygen level-dependent responses in the sexual desire brain network and (ii) higher blood oxygen level-dependent responses in the self-referential brain network. CONCLUSION: The meta-analytic results are in line with a top-down neurofunctional model of HSDD in which inspecting, monitoring, and evaluating oneself (rather than sensory experience) before or during sexual activities interfere with sexual desire. These results raise new questions regarding the necessity and sufficiency of dysfunctional activation in the sexual desire and self-referential brain networks, whose answers bear on the development and evaluation of personalized treatments for HSDD. Cacioppo S. Neuroimaging of Female Sexual Desire and Hypoactive Sexual Desire Disorder. Sex Med Rev 2017;5:434-444.

Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.

Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.

Dynamic spatiotemporal brain analyses of the visual checkerboard task: Similarities and differences between passive and active viewing conditions.

We introduce a new analytic technique for the microsegmentation of high-density EEG to identify the discrete brain microstates evoked by the visual reversal checkerboard task. To test the sensitivity of the present analytic approach to differences in evoked brain microstates across experimental conditions, subjects were instructed to (a) passively view the reversals of the checkerboard (passive viewing condition), or (b) actively search for a target stimulus that may appear at the fixation point, and they were offered a monetary reward if they correctly detected the stimulus (active viewing condition). Results revealed that, within the first 168 ms of a checkerboard presentation, the same four brain microstates were evoked in the passive and active viewing conditions, whereas the brain microstates evoked after 168 ms differed between these two conditions, with more brain microstates elicited in the active than in the passive viewing condition. Additionally, distinctions were found in the active condition between a change in a scalp configuration that reflects a change in microstate and a change in scalp configuration that reflects a change in the level of activation of the same microstate. Finally, the bootstrapping procedure identified that two microstates lacked robustness even though statistical significance thresholds were met, suggesting these microstates should be replicated prior to placing weight on their generalizability across individuals. These results illustrate the utility of the analytic approach and provide new information about the spatiotemporal dynamics of the brain states underlying passive and active viewing in the visual checkerboard task.

Measuring the Prevalence of Problematic Respondent Behaviors among MTurk, Campus, and Community Participants.

The reliance on small samples and underpowered studies may undermine the replicability of scientific findings. Large sample sizes may be necessary to achieve adequate statistical power. Crowdsourcing sites such as Amazon's Mechanical Turk (MTurk) have been regarded as an economical means for achieving larger samples. Because MTurk participants may engage in behaviors which adversely affect data quality, much recent research has focused on assessing the quality of data obtained from MTurk samples. However, participants from traditional campus- and community-based samples may also engage in behaviors which adversely affect the quality of the data that they provide. We compare an MTurk, campus, and community sample to measure how frequently participants report engaging in problematic respondent behaviors. We report evidence that suggests that participants from all samples engage in problematic respondent behaviors with comparable rates. Because statistical power is influenced by factors beyond sample size, including data integrity, methodological controls must be refined to better identify and diminish the frequency of participant engagement in problematic respondent behaviors.

Spatiotemporal Brain Dynamics of Empathy for Pain and Happiness in Friendship.

BACKGROUND: Although a large number of functional magnetic resonance imaging (fMRI) studies have investigated the neural bases of empathy, little is known about its spatiotemporal dynamics or its modulation by the level of friendship between the observer and the agent who is being hurt. Moreover, most of the previous studies on empathy have focused on empathy for pain rather than empathy for positive emotions, such as happiness. In the present study, we addressed this question by investigating the spatiotemporal brain dynamics of two different kinds of empathy (empathy for pain, empathy for happiness) with a behavioral priming empathy task involving two different level of primes (a close friend, a stranger). METHOD/PRINCIPAL FINDINGS: Electrical brain activity and behavioral data were analyzed from 30 subjects (12 males and 18 females). Half of the subjects performed a behavioral task on empathy for pain task (EPT), while the other half performed a behavioral task on empathy for happiness task (EHT). In each task, participants viewed prime photographs of either: (1) a stranger; or (2) a close friend (primes) followed by target photographs showing either a hand being hurt (or not; targets in the EPT), or a hand in happy circumstances (or not; targets in the EHT). In each task, participants were asked to judge the target situation and report whether they could feel the pain (in EPT) or the happiness (in the EHT), as a function of the primes i.e., either from the close friend's or from the stranger's perspective. Although our behavioral results didn't reveal any explicit differences among the different types of primes within each task, our electrophysiological results showed variations as a function of the primes. First, a early smaller N110 amplitude for pain was observed in the anterior prefrontal cortex during the friend prime condition compared to the stranger prime condition. No similar early effects were found for happiness. On the other hand, both empathy for happiness (EHT) and empathy for pain (EPT) elicited later differences. In the EPT, the friend prime elicited a larger late positive potential (LPP) than the stranger prime. In the EHT, the friend prime elicited a larger N250, a smaller P300, and a smaller LPP than the stranger prime. CONCLUSIONS: Taking the perspective of a close friend (as a prime stimulus) does have a dual-stage effect on empathy that is characterized by an early modulation for pain and later modulations for both pain and happiness. The early differences between friend and stranger primes for pain (but not for happiness) suggest that empathy for pain is an automatic process that has been socially learned and passed among friends. On the other hand, the later differences observed between stranger and friend prime suggest that additional cognitive appraisal take place for both pain and happiness. Our results suggest that it takes more cognitive attentional efforts to judge a stranger's happiness than a friend's happiness, whereas the opposite is true for pain. These findings open new avenues toward a better understanding of the empathic mind.

Loneliness and implicit attention to social threat: A high-performance electrical neuroimaging study.

Prior research has suggested that loneliness is associated with an implicit hypervigilance to social threats-an assumption in line with the evolutionary model of loneliness that indicates feeling socially isolated (or on the social perimeter) leads to increased attention and surveillance of the social world and an unwitting focus on self-preservation. Little is known, however, about the temporal dynamics for social threat (vs. nonsocial threat) in the lonely brains. We used high-density electrical neuroimaging and a behavioral task including social and nonsocial threat (and neutral) pictures to investigate the brain dynamics of implicit processing for social threat vs. nonsocial threat stimuli in lonely participants (N = 10), compared to nonlonely individuals (N = 9). The present study provides evidence that social threat images are differentiated from nonsocial threat stimuli more quickly in the lonely (~116 ms after stimulus onset) than nonlonely (~252 ms after stimulus onset) brains. That speed of threat processing in lonely individuals is in accord with the evolutionary model of loneliness. Brain source estimates expanded these results by suggesting that lonely (but not nonlonely) individuals showed early recruitment of brain areas involved in attention and self-representation.