Distinguishing pain from nociception, salience, and arousal: How autonomic nervous system activity can improve neuroimaging tests of specificity.

Pain is a subjective, multidimensional experience that is distinct from nociception. A large body of work has focused on whether pain processing is supported by specific, dedicated brain circuits. Despite advances in human neuroscience and neuroimaging analysis, dissociating acute pain from other sensations has been challenging since both pain and non-pain stimuli evoke salience and arousal responses throughout the body and in overlapping brain circuits. In this review, we discuss these challenges and propose that brain-body interactions in pain can be leveraged in order to improve tests for pain specificity. We review brain and bodily responses to pain and nociception and extant efforts toward identifying pain-specific brain networks. We propose that autonomic nervous system activity should be used as a surrogate measure of salience and arousal to improve these efforts and enable researchers to parse out pain-specific responses in the brain, and demonstrate the feasibility of this approach using example fMRI data from a thermal pain paradigm. This new approach will improve the accuracy and specificity of functional neuroimaging analyses and help to overcome current difficulties in assessing pain specific responses in the human brain.

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.

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.

Does anxiety explain why math-anxious people underperform in math?

Math-anxious people consistently underperform in math. The most widely accepted explanation for why this underperformance occurs is that math-anxious people experience heightened anxiety when faced with math, and this in-the-moment anxiety interferes with performance. Surprisingly, this explanation has not been tested directly. Here, using both self-report and physiological indices of anxiety, we directly test how much in-the-moment anxiety explains math-anxious underperformance. Results indicate that in-the-moment anxiety indeed explains why math-anxious people underperform-but only partially, suggesting a need to seriously consider alternative mechanisms. Results also showed that while some highly math-anxious individuals-those with high levels of heart rate variability-experienced less in-the-moment anxiety, they nevertheless performed no better at math. For these individuals, math-anxious underperformance must occur for reasons unrelated to in-the-moment anxiety. More broadly, our findings point to substantial individual heterogeneity in the mechanisms underlying math-anxious underperformance. Accounting for this mechanistic heterogeneity may prove vital for optimally boosting math performance in math-anxious individuals.

Why Definitional Clarity Matters: Implications for the Operationalization of Emotional Well-Being.

The National Institutes of Health (NIH) is increasingly prioritizing research on health-promoting processes. Park et al. (this issue) respond to a call made by NIH to advance the study of emotional well-being (EWB) and to increase understanding of the fundamental constituents of EWB across the lifespan and among diverse subgroups. They propose a definition of EWB that provides an organizing framework for research on 'psychological aspects of well-being' and health. We commend this important first step and urge consideration of three important issues related to operationalization - the process by which an abstract concept is transformed into variables that can be measured - in future research on EWB. We expect that an iterative process of construct refinement and empirical validation will advance the study of EWB, producing scientific discoveries that can be leveraged to enhance health across the lifespan.

Test-Retest Reliability of an Adaptive Thermal Pain Calibration Procedure in Healthy Volunteers.

Quantitative sensory testing (QST) allows researchers to evaluate associations between noxious stimuli and acute pain in clinical populations and healthy participants. Despite its widespread use, our understanding of QST's reliability is limited, as reliability studies have used small samples and restricted time windows. We examined the reliability of pain ratings in response to noxious thermal stimulation in 171 healthy volunteers (n = 99 female, n = 72 male) who completed QST on multiple visits ranging from 1 day to 952 days between visits. On each visit, participants underwent an adaptive pain calibration in which they experienced 24 heat trials and rated pain intensity after stimulus offset on a 0 to 10 Visual Analog Scale. We used linear regression to determine pain threshold, pain tolerance, and the correlation between temperature and pain for each session and examined the reliability of these measures. Threshold and tolerance were moderately reliable (Intra-class correlation = .66 and .67, respectively; P < .001), whereas temperature-pain correlations had low reliability (Intra-class correlation = .23). In addition, pain tolerance was significantly more reliable in female participants than male participants, and we observed similar trends for other pain sensitive measures. Our findings indicate that threshold and tolerance are largely consistent across visits, whereas sensitivity to changes in temperature vary over time and may be influenced by contextual factors. PERSPECTIVE: This article assesses the reliability of an adaptive thermal pain calibration procedure. We find that pain threshold and tolerance are moderately reliable whereas the correlation between pain rating and stimulus temperature has low reliability. Female participants were more reliable than male participants on all pain sensitivity measures.

Expectations about pain and analgesic treatment are shaped by medical providers' facial appearances: Evidence from five online clinical simulation experiments.

RATIONALE: There is a robust link between patients' expectations and clinical outcomes, as evidenced by the placebo effect. Expectations depend in large part on the context surrounding treatment, including the patient-provider interaction. Prior work indicates that providers' behavior and characteristics, including warmth and competence, can shape patient outcomes. Yet humans rapidly form trait impressions of others before any in-person interaction. It is unknown whether these first impressions influence subsequent health care choices and expectations. OBJECTIVE: Our goal was to test whether trait impressions of hypothetical medical providers, based exclusively on facial images, influence the choice of medical providers and expectations about pain and analgesia following hypothetical painful medical procedures. METHOD: Across five online experiments, participants (total N = 1108) viewed and made judgments about hypothetical healthcare providers. Experiments 1-4 included computer-generated faces that varied in features associated with competence, while experiment 5 included real faces. We measured how apparent competence affected expectations about pain and anticipated analgesic use in all studies. We also measured warmth and similarity. RESULTS: Across five online studies, participants selected providers who appeared more competent, based on facial visual information alone. Further, providers' apparent competence predicted participants' expectations about post-procedural pain and medication use. Participants' perception of their similarity to providers also shaped expectations about pain and treatment outcomes. CONCLUSIONS: Results from our experimental simulations suggest that humans develop expectations about pain and health outcomes before even setting foot in the clinic, based exclusively on first impressions. These findings have strong implications for health care, as individuals increasingly rely on digital services to select healthcare providers and even receive treatment, a trend that is exacerbated as the world embraces telemedicine.

Confidence in subjective pain is predicted by reaction time during decision making.

Self-report is the gold standard for measuring pain. However, decisions about pain can vary substantially within and between individuals. We measured whether self-reported pain is accompanied by metacognition and variations in confidence, similar to perceptual decision-making in other modalities. Eighty healthy volunteers underwent acute thermal pain and provided pain ratings followed by confidence judgments on continuous visual analogue scales. We investigated whether eye fixations and reaction time during pain rating might serve as implicit markers of confidence. Confidence varied across trials and increased confidence was associated with faster pain rating reaction times. The association between confidence and fixations varied across individuals as a function of the reliability of individuals' association between temperature and pain. Taken together, this work indicates that individuals can provide metacognitive judgments of pain and extends research on confidence in perceptual decision-making to pain.

Applications of dynamic functional connectivity to pain and its modulation.

Since early work attempting to characterize the brain's role in pain, it has been clear that pain is not generated by a specific brain region, but rather by coordinated activity across a network of brain regions, the "neuromatrix." The advent of noninvasive whole-brain neuroimaging, including functional magnetic resonance imaging, has provided insight on coordinated activity in the pain neuromatrix and how correlations in activity between regions, referred to as "functional connectivity," contribute to pain and its modulation. Initial functional connectivity investigations assumed interregion connectivity remained stable over time, and measured variability across individuals. However, new dynamic functional connectivity (dFC) methods allow researchers to measure how connectivity changes over time within individuals, permitting insights on the dynamic reorganization of the pain neuromatrix in humans. We review how dFC methods have been applied to pain, and insights afforded on how brain connectivity varies across time, either spontaneously or as a function of psychological states, cognitive demands, or the external environment. Specifically, we review psychophysiological interaction, dynamic causal modeling, state-based dynamic community structure, and sliding-window analyses and their use in human functional neuroimaging of acute pain, chronic pain, and pain modulation. We also discuss promising uses of dFC analyses for the investigation of chronic pain conditions and predicting pain treatment efficacy and the relationship between state- and trait-based pain measures. Throughout this review, we provide information regarding the advantages and shortcomings of each approach, and highlight potential future applications of these methodologies for better understanding the brain processes associated with pain.

The Role of Social and Interpersonal Factors in Placebo Analgesia.

Placebo effects are beneficial clinical outcomes that emerge as a result of nonspecific contextual factors, transmitted primarily by the treating physician and the social, physical, and behavioral cues he or she displays. The patient-provider therapeutic alliance is critical for determining placebo effects and health outcomes. In this chapter, we review the recent literature, suggesting that provider social characteristics modulate placebo and clinical outcomes. We highlight the importance of studying not only the provider but also the patient's perception of the provider, which is subject to the influence of the patient's psychosocial orientation, such as their psychosocial motivations and perceptions of their interpersonal relationships broadly. We argue that psychosocial orientation can exaggerate the influence of the patient-provider relationship on placebo effects and can directly affect the likelihood of placebo effects emerging by modulating the underlying biological systems that support them. Here, we examine patient loneliness, or perceived social isolation, as a case example for understanding how patients' psychosocial orientation may affect placebo effects across diseases. We propose psychosocial mechanisms by which loneliness might modulate placebo effects across medical outcomes, and focus in particular on how loneliness might specifically alter behaviorally conditioned immune responses and placebo analgesia. Future studies should directly measure social factors to formally test the effects of social isolation on placebo effects and better elucidate the role of psychosocial and interpersonal factors in placebo effects and clinical outcomes.

Loneliness and Social Internet Use: Pathways to Reconnection in a Digital World?

With the rise of online social networking, social relationships are increasingly developed and maintained in a digital domain. Drawing conclusions about the impact of the digital world on loneliness is difficult because there are contradictory findings, and cross-sectional studies dominate the literature, making causation difficult to establish. In this review, we present our theoretical model and propose that there is a bidirectional and dynamic relationship between loneliness and social Internet use. When the Internet is used as a way station on the route to enhancing existing relationships and forging new social connections, it is a useful tool for reducing loneliness. But when social technologies are used to escape the social world and withdraw from the "social pain" of interaction, feelings of loneliness are increased. We propose that loneliness is also a determinant of how people interact with the digital world. Lonely people express a preference for using the Internet for social interaction and are more likely to use the Internet in a way that displaces time spent in offline social activities. This suggests that lonely people may need support with their social Internet use so that they employ it in a way that enhances existing friendships and/or to forge new ones.

The influence of social stress on time perception and psychophysiological reactivity.

Time perception is a fundamental component of everyday life. Although time can be measured using standard units, the relationship between an individual's experience of perceived time and a standard unit is highly sensitive to context. Stressful and threatening stimuli have been previously shown to produce time distortion effects, such that individuals perceive the stimuli as lasting for different amounts of time as compared to a standard unit. As a highly social species, humans are acutely sensitive to social stressors; however, time distortion effects have not been studied in the context of social stress. We collected psychophysiological (electrocardiogram and impedance cardiography) and time perception data before, during, and after a modified version of the Trier Social Stress Test for 42 participants. Based on prior theories and evidence from the time perception literature, we hypothesized that experiencing a stressful event would result in time distortion. This hypothesis was supported by the data, with individuals on average reproducing short and long duration negative and positive stimuli as lasting longer after experiencing social stress, t(41) = -3.55, p = .001, and t(41) = -4.12, p < .001 for negative stimuli, and t(41) = -2.43, p = .02, and t(41) = -3.07, p = .004 for positive stimuli. However, changes in time perception were largely unrelated to psychophysiological reactivity to social stress. These findings are in line with some other studies of time distortion, and provide evidence for the interoceptive salience model of time perception. Implications for mechanisms of time distortion are discussed.

Physiological dynamics of stress contagion.

Can viewing others experiencing stress create a "contagious" physiological stress response in the observer? To investigate second-hand stress, we first created a stimulus set of videos, which featured participants speaking under either minimal stress, high stress, or while recovering from stress. We then recruited a second set of participants to watch these videos. All participants (speakers and observers) were monitored via electrocardiogram. Cardiac activity of the observers while watching the videos was then analyzed and compared to that of the speakers. Furthermore, we assessed dispositional levels of empathy in observers to determine how empathy might be related to the degree of stress contagion. Results revealed that depending on the video being viewed, observers experienced differential changes in cardiac activity that were based on the speaker's stress level. Additionally, this is the first demonstration that individuals high in dispositional empathy experience these physiological changes more quickly.

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.

Is Valuing Happiness Associated With Lower Well-Being? A Factor-Level Analysis using the Valuing Happiness Scale.

Recent studies suggest that valuing happiness is negatively associated with well-being. Most of these studies used the Valuing Happiness Scale (Mauss, Tamir, et al., 2011). In the present paper, we examined the factor structure of this scale using data pooled from six independent samples (Ntotal = 938). Exploratory and confirmatory factor analysis showed that the Valuing Happiness Scale is not unidimensional and that only one of its three factors correlates negatively with various indicators of well-being, whereas non-significant or positive correlations were found for the other factors. These findings indicate that valuing happiness may not necessarily be bad for one's well-being, and call for a better definition, theoretical foundation, and operationalization of this construct.

The role of self-math overlap in understanding math anxiety and the relation between math anxiety and performance.

Recent work has demonstrated that math anxiety is more than just the product of poor math skills. Psychosocial factors may play a key role in understanding what it means to be math anxious, and hence may aid in attempts to sever the link between math anxiety and poor math performance. One such factor may be the extent to which individuals integrate math into their sense of self. We adapted a well-established measure of this degree of integration (i.e., self-other overlap) to assess individuals' self-math overlap. This non-verbal single-item measure showed that identifying oneself with math (having higher self-math overlap) was strongly associated with lower math anxiety (r = -0.610). We also expected that having higher self-math overlap would leave one especially susceptible to the threat of poor math performance to the self. We identified two competing hypotheses regarding how this plays out in terms of math anxiety. Those higher in self-math overlap might be more likely to worry about poor math performance, exacerbating the negative relation between math anxiety and math ability. Alternatively, those higher in self-math overlap might exhibit self-serving biases regarding their math ability, which would instead predict a decoupling of the relation between their perceived and actual math ability, and in turn the relation between their math ability and math anxiety. Results clearly favored the latter hypothesis: those higher in self-math overlap exhibited almost no relation between math anxiety and math ability, whereas those lower in self-math overlap showed a strong negative relation between math anxiety and math ability. This was partially explained by greater self-serving biases among those higher in self-math overlap. In sum, these results reveal that the degree to which one integrates math into one's self - self-math overlap - may provide insight into how the pernicious negative relation between math anxiety and math ability may be ameliorated.