Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also later responses. Namely, touch from a male to his female romantic partner enhanced her subsequent OT release for touch from an unfamiliar stranger, yet females OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial social interaction. In the subsequent interaction, precuneus and parietal-temporal cortex pathways tracked time- and context-dependent variables in an OT-dependent manner. This OT-dependent cortical modulation included a region of the medial prefrontal cortex that also covaried with plasma cortisol, suggesting an influence on stress responses. These findings demonstrate that modulation between hormones and the brain during human social interactions can flexibly adapt to features of social context over time.

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-a-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insulas responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior.

Human touch has an enormous power to engender and mediate meaning in the human mind, from the emotional to the pragmatic, and from the linguistic to the symbolic. Can a functional-neuroanatomical perspective on social touch contribute to a general understanding of the biological workings of such meaning-making? I argue here that it can, and that the ways the brain accomplishes this are manifold. I identify and explore three main neural subsystems which operate in concert to generate the emotional and semantic complexion of social touch. These subsystems underlie how humans: 1) touch to connect with others; 2) explore the physical and social worlds; and 3) explain the significance of a touch within our own knowledge and experience, especially with regard to the way we interpret the world through language and culture. I therefore propose that what makes social touch meaningful has much to do with the functional and evolutionary roots of these brain subsystems. Although they can be distinguished and analyzed, in the "wild" human brain these subsystems are functionally intertwined, and their processes are integrated to generate a unified subjective experience of social touch. This view also acknowledges the intertwined nature of the embodied individual within society, thus carrying potential implications for theoretical analysis in such terms.

The role of CT afferents in affective touch is often viewed in contrast with the more well-established neural and functional systems supporting discriminative touch. However, a recent groundswell of evidence suggests that a categorical affective versus-discriminative contrast may not bear scrutiny at all levels of the nervous system, especially when applied to finer grained anatomical and functional relationships. Discrepancies in this evidence can be addressed by taking the layered phylogenetic history of specialized afferent systems into account, and how this history may have influenced functional integration within complex spinal circuits and brain networks in generating bodily states and behavior. This perspective inspires four proposed body-behavior reference frames, within which somatosensory-behavior relationships can be schematized in the nervous system of the behaving human: (1) proximal-distal (regarding the body axis and limbs, (2) somaticskeletomotor (regarding efferent effectors) (3) reactive predictive (regarding responses to external events); and (4) passive/receptive-active/motivated (with particular application to socially interactive behavior). Affective and discriminative functions can be dissociated at the extremes of these frame spaces without necessarily existing as discrete categories.

Middleton, Perini et al. show that the role of Na(v)1.7 extends beyond pain perception. Using a multidisciplinary, cross-species approach, they show that Na(v)1.7 is also essential for C-low threshold mechanoreceptor function in mice and humans, regulating pleasant touch, punctate discrimination and sensitivity to cooling. Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial electromyography (n = 3 CIP participants and n = 8 healthy controls), we found that these patients also have abnormalities in the encoding of affective touch, which is mediated by the specialized afferents C-low threshold mechanoreceptors (C-LTMRs). In the mouse, we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.

Touch is a powerful communication tool, but we have a limited understanding of the role played by particular physical features of interpersonal touch communication. In this study, adults living in Sweden performed a task in which messages (attention, love, happiness, calming, sadness, and gratitude) were conveyed by a sender touching the forearm of a receiver, who interpreted the messages. Two experiments (N = 32, N = 20) showed that within close relationships, receivers could identify the intuitive touch expressions of the senders, and we characterized the physical features of the touches associated with successful communication. Facial expressions measured with electromyography varied by message but were uncorrelated with communication performance. We developed standardized touch expressions and quantified the physical features with 3D hand tracking. In two further experiments (N = 20, N = 16), these standardized expressions were conveyed by trained senders and were readily understood by strangers unacquainted with the senders. Thus, the possibility emerges of a standardized, intuitively understood language of social touch.

& nbsp;Previous research has shown that a specific type of C fiber, the C tactile afferents, are involved in detecting gentle, dynamic tactile stimuli on the skin, giving rise to affective responses in the central nervous system. Despite building on such bottom-up information flow, the hedonic perception and the physiological consequences of affective touch are influenced by various sources of top-down information. In the present study we investigated how perception of affective touch is influenced by the attractiveness of hypothetical caressers. Participants were stroked on the arm and the palm while looking at photos of high attractive and low attractive opposite-gender faces, and were instructed to imagine those people as the caressers. In a control condition no photo was paired with the touch. The stroking stimulation was delivered with a soft brush either on the forearm or on the palm, and either with a slower or faster speed. Participants rated the pleasantness of each stimulation, while electrocardiographic recordings were made to extract heart rate variability data. Results showed that participants preferred touch stimuli paired with high attractive faces; they also preferred palm stroking and slower stroking speed. Like subjective pleasantness ratings, heart rate variability responses to affective touch (slow) were higher for high attractive than for low attractive caressers, but were not selective for arm or palm stroking. Overall, the present study confirms that contextual social information plays a major role in affective touch experiences, influencing not only the hedonic quality of the experience but also the physiological state of the body. This article is part of a Special Issue entitled: The Neurobiology of Social and Affective Touch.& nbsp; (c) 2020 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

Humans use touch to maintain their social relationships, and the emotional qualities of touch depend on who touches whom. However, it is not known how affective and social dimensions of touch are processed in the brain. We measured haemodynamic brain activity with functional magnetic resonance imaging (fMRI) from 19 subjects (10 males), while they were touched on their upper thigh by either their romantic partner, or an unfamiliar female or male confederate or saw the hand of one of these individuals near their upper thigh but were not touched. We used multi-voxel pattern analysis on pre-defined regions of interest to reveal areas that encode social touch in a relationship-specific manner. The accuracy of the machine learning classifier to identify actor for both feeling touch and seeing hand exceeded the chance level in the primary somatosensory cortex, while in the insular cortex accuracy was above chance level only for the touch condition. When classifying the relationship (partner or stranger), while keeping the toucher sex fixed, amygdala (AMYG), orbitofrontal cortex (OFC), and primary and secondary somatosensory cortices were able to discriminate toucher significantly above chance level. These results suggest that information on the social relationship of the toucher is processed consistently across several regions. More complex information about toucher identity is processed in the primary somatosensory and insular cortices, both of which can be considered early sensory areas. This article is part of a Special Issue entitled: The Neurobiology of Social and Affective Touch. (c) 2020 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/).

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Background Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals. Methods DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in theNR3C1gene, rs1360780 in theFKBP5gene, rs53576 in theOXTRgene, 5-HTTLPR inSLC6A4gene and rs6295 in theHTR1Agene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire. Results Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p = 0.030 andp = 0.036, respectively). For SNP rs41423247 in theNR3C1gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p < 0.01). For the SNP rs53576 in theOXTRgene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p < 0.01). Conclusion This study shows that SNP rs41423247 in theNR3C1gene and SNP rs53576 in theOXTRgene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.

The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain-action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers subjective pain thresholds did not differ from controls, but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain-action integration with increased responses for task-relevant painful stimulation ("signal," requiring button-press execution) over task-irrelevant stimulation ("noise," requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices-but not the AI and mid-ACC regions-during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI-mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.

Bodily states are fundamental to emotions emergence and are believed to constitute the first step in the chain of events that culminate in emotional awareness. Recent works have shown that distinct topographical maps can be derived to describe how basic and more complex emotions are represented in the body. However, it is still unclear whether these bodily maps can also extend to emotions experienced specifically within social interactions and how these representations relate to basic emotions. To address this issue, we used the emBODY tool to obtain high-resolution bodily maps that describe the body activation and deactivation experienced by healthy participants when presented with social scenarios depicting establishment or loss of social bonds. We observed patterns of activation/deactivation for each single social scenario depending on the valence, but also a common activation of head, chest and deactivation of limbs for positive and negative social scenarios, respectively. Furthermore, we show that these maps are comparable to those obtained when taking the perspective of a third person, suggesting the existence of common body representation of social emotions for the self and other person evaluation. Finally, we showed that maps related to complex social scenarios are strongly correlated with bodily states experienced in basic emotions, suggesting that the patterns of body activation/ deactivation observed for social scenarios might arise from a complex interaction of the basic emotions that these experiences elicit.

Affective

Costly altruism entails helping others at a cost to the self and prior work shows that empathic concern (EC) for the well-being of distressed and vulnerable individuals is one of the primary motivators of such behavior. However, extant work has investigated costly altruism with paradigms that did not feature self-relevant and severe costs for the altruist and have solely focused on neurofunctional, and not neuroanatomical, correlates. In the current study, we used a contextually-rich virtual reality environment to study costly altruism and found that individuals who risked their own lives in the virtual world to try to save someone in danger had enlarged right anterior insula and exhibited greater empathic concern than those who did not. These findings add to the growing literature showing the role of caring motivation in promoting altruism and prosociality and its neural correlates in the right anterior insula.

Touch plays a central role in interpersonal behavior, especially in its capacity to convey-and induce- changes in affect. Previous research has established that slow, caress-like stroking over the skin elicits positive subjective affective responses, with higher ratings of "pleasantness" compared to a faster-moving touch stimulus. Ratings of pleasantness are associated with increased activity of a distinct class of nerve fibers: C-tactile (CT) afferents. Here, we used facial electromyography (EMG) to determine if touch that optimally activates CT afferents also influences facial muscle activity believed to reflect changes in affect. We found that less pleasant, fast-moving stroking (30 cm/s) elicited robustly negative facial EMG responses, as indexed by stronger contraction of the corrugator muscle. In contrast, pleasant, slow-moving stroking (3 cm/s) that optimally activates CT afferents resulted in decreased negative facial affective responses, manifested as significant corrugator relaxation compared to fast stroking. Moreover, the facial tracking of affective valence during touch was supra-modal, with similar effects during both directly-experienced touch and viewing of touch videos. The results of this EMG study imply that touch that fails to optimally activate CT afferent produces a negative affective response, whereas pleasant, caress-like touch has not only subjective but expressive correlates, reflected in net positive affective changes in facial expression.

Coping with pain is a complex phenomenon encompassing a variety of behavioral responses and a large network of underlying neural circuits. Whether pain coping is adaptive or maladaptive depends on the type of pain (e.g., escapable or inescapable), personal factors (e.g., individual experiences with coping strategies in the past), and situational circumstances. Keeping these factors in mind, costs and benefits of different strategies have to be appraised and will guide behavioral decisions in the face of pain. In this review we present pain coping as an unconscious decision-making process during which accurately evaluated costs and benefits lead to adaptive pain coping behavior. We emphasize the importance of passive coping as an adaptive strategy when dealing with ongoing pain and thus go beyond the common view of passivity as a default state of helplessness. In combination with passive pain coping, we highlight the role of the reward system in reestablishing affective homeostasis and discuss existing evidence on a behavioral and neural level. We further present neural circuits involved in the decision-making process of pain coping when circumstances are ambiguous and, therefore, costs and benefits are difficult to anticipate. Finally, we address the wider implications of this topic by discussing its relevance for chronic pain patients.

Pain is a highly salient and attention-demanding experience that motivates people to act. We investigated the effect of pain on decision making by delivering acute thermal pain to participants’ forearm while they made risky and intertemporal choices involving money. Participants (n = 107) were more risk seeking under pain than in a no-pain control condition when decisions involved gains but not when they involved equivalent losses. Pain also resulted in greater preference for immediate (smaller) over future (larger) monetary rewards. We interpret these results as a motivation to offset the aversive, pain-induced state, where monetary rewards become more appealing under pain than under no pain and when delivered sooner rather than later. Our findings add to the long-standing debate regarding the role of intuition and reflection in decision making.

Pleasant touch is thought to increase the release of oxytocin. Oxytocin, in turn, has been extensively studied with regards to its effects on trust and prosocial behavior, but results remain inconsistent. The purpose of this study was to investigate the effect of touch on economic decision making. Participants (n = 120) were stroked on their left arm using a soft brush (touch condition) or not at all (control condition; varied within subjects), while they performed a series of decision tasks assessing betrayal aversion (the Betrayal Aversion Elicitation Task), altruism (donating money to a charitable organization), and risk taking (the Balloon Analog Risk Task). We found no significant effect of touch on any of the outcome measures, neither within nor between subjects. Furthermore, effects were not moderated by gender or attachment. However, attachment avoidance had a significant effect on altruism in that those who were high in avoidance donated less money. Our findings contribute to the understanding of affective touch-and, by extension, oxytocin-in social behavior, and decision making by showing that touch does not directly influence performance in tasks involving risk and prosocial decisions. Specifically, our work casts further doubt on the validity of oxytocin research in humans.

Emotionally-laden tactile stimulationsuch as a caress on the skin or the feel of velvetmay represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta-analysis was performed. This meta-analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n=291, 34 experimental contrasts). A separate ALE meta-analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n=1,075, 91 experimental contrasts). These meta-analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta-analytic connectivity (MCAM) analyses investigated network-level co-activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective-related PI and discriminative-related SI regions co-activated with different networks, implicated in dissociable functions, but sharing somatosensory co-activations. Taken together, these meta-analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct pathways.

The rare nerve growth factor-beta (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience.

Affective touch is a dynamic process. In this fMRI study we investigated affective touch by exploring its effects on overt behavior. Arm and palm skin were stroked with a soft brush at five different velocities (0.3, 1, 10, 3, and 30 cm s(-1)), using a novel feedback-based paradigm. Following stimulation in each trial, participants actively chose whether the caress they would receive in the next trial would be the same speed ("repeat") or different ("change"). Since preferred stroking speeds should be sought with greater frequency than non-preferred speeds, this paradigm provided a measure of such preferences in the form of active choices. The stimulation velocities were implemented with respect to the differential subjective pleasantness ratings they elicit in healthy subjects, with intermediate velocities (1, 10, and 3 cm s(-1)) considered more pleasant than very slow or very fast ones. Such pleasantness ratings linearly correlate with changes in mean firing rates of unmyelinated low-threshold C-tactile (CT) afferent nerves in the skin. Here, gentle, dynamic stimulation optimal for activating CT-afferents not only affected behavioral choices, but engaged brain regions involved in reward-related behavior and decision-making. This was the case for both hairy skin of the arm, where CTs are abundant, and glabrous skin of the palm, where CTs are absent. These findings provide insights on central and behavioral mechanisms underlying the perception of affective touch, and indicate that seeking affective touch involves value-based neural processing that is ultimately reflected in behavioral preferences.