Altered reward network responses to social touch in major depression.

BACKGROUND: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. METHODS: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. RESULTS: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. CONCLUSIONS: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation.

Do dogs preferentially encode the identity of the target object or the location of others' actions?

The ability to make sense of and predict others' actions is foundational for many socio-cognitive abilities. Dogs (Canis familiaris) constitute interesting comparative models for the study of action perception due to their marked sensitivity to human actions. We tested companion dogs (N = 21) in two screen-based eye-tracking experiments, adopting a task previously used with human infants and apes, to assess which aspects of an agent's action dogs consider relevant to the agent's underlying intentions. An agent was shown repeatedly acting upon the same one of two objects, positioned in the same location. We then presented the objects in swapped locations and the agent approached the objects centrally (Experiment 1) or the old object in the new location or the new object in the old location (Experiment 2). Dogs' anticipatory fixations and looking times did not reflect an expectation that agents should have continued approaching the same object nor the same location as witnessed during the brief familiarization phase; this contrasts with some findings with infants and apes, but aligns with findings in younger infants before they have sufficient motor experience with the observed action. However, dogs' pupil dilation and latency to make an anticipatory fixation suggested that, if anything, dogs expected the agents to keep approaching the same location rather than the same object, and their looking times showed sensitivity to the animacy of the agents. We conclude that dogs, lacking motor experience with the observed actions of grasping or kicking performed by a human or inanimate agent, might interpret such actions as directed toward a specific location rather than a specific object. Future research will need to further probe the suitability of anticipatory looking as measure of dogs' socio-cognitive abilities given differences between the visual systems of dogs and primates.

Investigating belief understanding in children in a nonverbal ambiguous displacement and communication setting.

Finding ways to investigate false belief understanding nonverbally is not just important for preverbal children but also is the only way to assess theory of mind (ToM)-like abilities in nonhuman animals. In this preregistered study, we adapted the design from a previous study on pet dogs to investigate false belief understanding in children and to compare it with belief understanding of those previously tested dogs. A total of 32 preschool children (aged 5-6 years) saw the displacement of a reward and obtained nonverbal cueing of the empty container from an adult communicator holding either a true or false belief. In the false belief condition, when the communicator did not know the location of the reward, children picked the baited container, but not the cued container, more often than the empty one. In the true belief condition, when the communicator witnessed the displacement yet still cued the wrong container, children performed randomly. The children's behavior pattern was at odds with that of the dogs tested in a previous study, which picked the cued container more often when the human communicator held a false belief. In addition to species comparisons, because our task does not require verbal responses or relational sentence understanding, it can also be used in preverbal children. The children in our study behaved in line with the existing ToM literature, whereas most (but not all) dogs from the previously collected sample, although sensitive to differences between the belief conditions, deviated from the children. This difference suggests that using closely matched paradigms and experimental procedures can reveal decisive differences in belief processing between species. It also demonstrates the need for a more comprehensive exploration and direct comparison of the various aspects of false belief processing and ToM in different species to understand the evolution of social cognition.

Aberrant uncertainty processing is linked to psychotic-like experiences, autistic traits, and is reflected in pupil dilation during probabilistic learning.

Aberrant belief updating due to misestimation of uncertainty and an increased perception of the world as volatile (i.e., unstable) has been found in autism and psychotic disorders. Pupil dilation tracks events that warrant belief updating, likely reflecting the adjustment of neural gain. However, whether subclinical autistic or psychotic symptoms affect this adjustment and how they relate to learning in volatile environments remains to be unraveled. We investigated the relationship between behavioral and pupillometric markers of subjective volatility (i.e., experience of the world as unstable), autistic traits, and psychotic-like experiences in 52 neurotypical adults with a probabilistic reversal learning task. Computational modeling revealed that participants with higher psychotic-like experience scores overestimated volatility in low-volatile task periods. This was not the case for participants scoring high on autistic-like traits, who instead showed a diminished adaptation of choice-switching behavior in response to risk. Pupillometric data indicated that individuals with higher autistic- or psychotic-like trait and experience scores differentiated less between events that warrant belief updating and those that do not when volatility was high. These findings are in line with misestimation of uncertainty accounts of psychosis and autism spectrum disorders and indicate that aberrancies are already present at the subclinical level.

Homeostatic Regulation of Energetic Arousal During Acute Social Isolation: Evidence From the Lab and the Field.

Recent evidence suggests that social contact is a basic need governed by a social homeostatic system. Little is known, however, about how conditions of altered social homeostasis affect human psychology and physiology. Here, we investigated the effects of 8 hr of social isolation on psychological and physiological variables and compared this with 8 hr of food deprivation in a lab experiment (N = 30 adult women). Social isolation led to lowered self-reported energetic arousal and heightened fatigue, comparable with food deprivation. To test whether these findings would extend to a real-life setting, we conducted a preregistered field study during a COVID-19 lockdown (N = 87 adults; 47 women). The drop in energetic arousal after social isolation observed in the lab replicated in the field study for participants who lived alone or reported high sociability, suggesting that lowered energy could be part of a homeostatic response to the lack of social contact.

Effective connectivity reveals distinctive patterns in response to others' genuine affective experience of disgust.

Empathy is significantly influenced by the identification of others' emotions. In a recent study, we have found increased activation in the anterior insular cortex (aIns) that could be attributed to affect sharing rather than perceptual saliency, when seeing another person genuinely experiencing pain as opposed to merely acting to be in pain. In that prior study, effective connectivity between aIns and the right supramarginal gyrus (rSMG) was revealed to represent what another person really feels. In the present study, we used a similar paradigm to investigate the corresponding neural signatures in the domain of empathy for disgust - with participants seeing others genuinely sniffing unpleasant odors as compared to pretending to smell something disgusting (in fact the disgust expressions in both conditions were acted for reasons of experimental control). Consistent with the previous findings on pain, we found stronger activations in aIns associated with affect sharing for genuine disgust (inferred) compared with pretended disgust. However, instead of rSMG we found engagement of the olfactory cortex. Using dynamic causal modeling (DCM), we estimated the neural dynamics of aIns and the olfactory cortex between the genuine and pretended conditions. This revealed an increased excitatory modulatory effect for genuine disgust compared to pretended disgust. For genuine disgust only, brain-to-behavior regression analyses highlighted a link between the observed modulatory effect and a few empathic traits. Altogether, the current findings complement and expand our previous work, by showing that perceptual saliency alone does not explain responses in the insular cortex. Moreover, it reveals that different brain networks are implicated in a modality-specific way when sharing the affective experiences associated with pain vs. disgust.

Diurnal dynamics of stress and mood during COVID-19 lockdown: a large multinational ecological momentary assessment study.

The COVID-19 pandemic resulted in severe disruption to people's lives as governments imposed national 'lockdowns'. Several large surveys have underlined the detrimental short- and long-term mental health consequences resulting from this disruption, but survey findings are only informative of individuals' retrospectively reported psychological states. Furthermore, knowledge on psychobiological responses to lockdown restrictions is scarce. We used smartphone-based real-time assessments in 731 participants for 7 days and investigated how individuals' self-reported stress and mood fluctuated diurnally during lockdown in spring 2020. We found that age, gender, financial security, depressive symptoms and trait loneliness modulated the diurnal dynamics of participants' momentary stress and mood. For example, younger and less financially secure individuals showed an attenuated decline in stress as the day progressed, and similarly, more lonely individuals showed a diminished increase in calmness throughout the day. Hair collected from a subsample (n = 140) indicated a decrease in cortisol concentrations following lockdown, but these changes were not related to any of the assessed person-related characteristics. Our findings provide novel insights into the psychobiological impact of lockdown and have implications for how, when and which individuals might benefit most from interventions during psychologically demanding periods.

Placebo Analgesia Reduces Costly Prosocial Helping to Lower Another Person's Pain.

Painkiller administration lowers pain empathy, but whether this also reduces prosocial behavior is unknown. In this preregistered study, we investigated whether inducing analgesia through a placebo painkiller reduced effortful helping. When given the opportunity to reduce the pain of another person, individuals experiencing placebo analgesia (n = 45 adults from Austria; 21 male, 24 female) made fewer prosocial choices at the lowest helping level and exerted less physical effort when helping, compared with controls whose pain sensitivity was unaltered (n = 45; 21 male, 24 female). Self-reported empathic unpleasantness positively correlated with prosocial choices across the whole sample. While not replicating group differences in empathy, a mediation analysis revealed that the level of unpleasantness to other people's pain fully mediated the effect of placebo analgesia on prosocial choices. Given the importance of prosociality for social cohesion, these findings have broad potential implications both for individuals under the influence of painkillers and for society at large.

Beyond Sharing Unpleasant Affect-Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain.

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.

Variability in Brain Structure and Function Reflects Lack of Peer Support.

Humans are a highly social species. Complex interactions for mutual support range from helping neighbors to building social welfare institutions. During times of distress or crisis, sharing life experiences within one's social circle is critical for well-being. By translating pattern-learning algorithms to the UK Biobank imaging-genetics cohort (n = ~40 000 participants), we have delineated manifestations of regular social support in multimodal whole-brain measurements. In structural brain variation, we identified characteristic volumetric signatures in the salience and limbic networks for high- versus low-social support individuals. In patterns derived from functional coupling, we also located interindividual differences in social support in action-perception circuits related to binding sensory cues and initiating behavioral responses. In line with our demographic profiling analysis, the uncovered neural substrates have potential implications for loneliness, substance misuse, and resilience to stress.

Negative emotional contagion and cognitive bias in common ravens (Corvus corax).

Emotional contagion is described as an emotional state matching between subjects, and has been suggested to facilitate communication and coordination in complex social groups. Empirical studies typically focus on the measurement of behavioral contagion and emotional arousal, yet, while highly important, such an approach often disregards an additional evaluation of the underlying emotional valence. Here, we studied emotional contagion in ravens by applying a judgment bias paradigm to assess emotional valence. We experimentally manipulated positive and negative affective states in demonstrator ravens, to which they responded with increased attention and interest in the positive condition, as well as increased redirected behavior and a left-eye lateralization in the negative condition. During this emotion manipulation, another raven observed the demonstrator's behavior, and we used a bias paradigm to assess the emotional valence of the observer to determine whether emotional contagion had occurred. Observers showed a pessimism bias toward the presented ambiguous stimuli after perceiving demonstrators in a negative state, indicating emotional state matching based on the demonstrators' behavioral cues and confirming our prediction of negative emotional contagion. We did not find any judgment bias in the positive condition. This result critically expands upon observational studies of contagious play in ravens, providing experimental evidence that emotional contagion is present not only in mammalian but also in avian species. Importantly, this finding also acts as a stepping stone toward understanding the evolution of empathy, as this essential social skill may have emerged across these taxa in response to similar socioecological challenges.

A neuroscientific perspective on the computational theory of social groups.

We welcome a computational theory on social groups, yet we argue it would benefit from a broader scope. A neuroscientific perspective offers the possibility to disentangle which computations employed in a group context are genuinely social in nature. Concurrently, we emphasize that a unifying theory of social groups needs to additionally consider higher-level processes like motivations and emotions.

When Implicit Prosociality Trumps Selfishness: The Neural Valuation System Underpins More Optimal Choices When Learning to Avoid Harm to Others Than to Oneself.

Humans learn quickly which actions cause them harm. As social beings, we also need to learn to avoid actions that hurt others. It is currently unknown whether humans are as good at learning to avoid others' harm (prosocial learning) as they are at learning to avoid self-harm (self-relevant learning). Moreover, it remains unclear how the neural mechanisms of prosocial learning differ from those of self-relevant learning. In this fMRI study, 96 male human participants learned to avoid painful stimuli either for themselves or for another individual. We found that participants performed more optimally when learning for the other than for themselves. Computational modeling revealed that this could be explained by an increased sensitivity to subjective values of choice alternatives during prosocial learning. Increased value sensitivity was further associated with empathic traits. On the neural level, higher value sensitivity during prosocial learning was associated with stronger engagement of the ventromedial PFC during valuation. Moreover, the ventromedial PFC exhibited higher connectivity with the right temporoparietal junction during prosocial, compared with self-relevant, choices. Our results suggest that humans are particularly adept at learning to protect others from harm. This ability appears implemented by neural mechanisms overlapping with those supporting self-relevant learning, but with the additional recruitment of structures associated to the social brain. Our findings contrast with recent proposals that humans are egocentrically biased when learning to obtain monetary rewards for self or others. Prosocial tendencies may thus trump egocentric biases in learning when another person's physical integrity is at stake.SIGNIFICANCE STATEMENT We quickly learn to avoid actions that cause us harm. As "social animals," we also need to learn and consider the harmful consequences our actions might have for others. Here, we investigated how learning to protect others from pain (prosocial learning) differs from learning to protect oneself (self-relevant learning). We found that human participants performed better during prosocial learning than during self-relevant learning, as they were more sensitive toward the information they collected when making choices for the other. Prosocial learning recruited similar brain areas as self-relevant learning, but additionally involved parts of the "social brain" that underpin perspective-taking and self-other distinction. Our findings suggest that people show an inherent tendency toward "intuitive" prosociality.

Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain.

The shared representations account of empathy suggests that sharing other people's emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia induced for first-hand pain resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models.

Effects of non-invasive brain stimulation on visual perspective taking: A meta-analytic study.

Visual perspective taking (VPT) is a critical ability required by complex social interaction. Non-invasive brain stimulation (NIBS) has been increasingly used to examine the causal relationship between brain activity and VPT, yet with heterogeneous results. In the current study, we conducted two meta-analyses to examine the effects of NIBS of the right temporoparietal junction (rTPJ) or dorsomedial prefrontal cortex (dmPFC) on VPT, respectively. We performed a comprehensive literature search to identify qualified studies and computed the standardized effect size (ES) for each combination of VPT level (Level-1: visibility judgment; Level-2: mental rotation) and perspective (self and other). Thirteen studies (rTPJ: 12 studies, 23 ESs; dmPFC: 4 studies, 14 ESs) were included in the meta-analyses. Random-effects models were used to generate the overall effects. Subgroup analyses for distinct VPT conditions were also performed. We found that rTPJ stimulation significantly improved participants' visibility judgment from the allocentric perspective, whereas its effects on other VPT conditions are negligible. Stimulation of dmPFC appeared to influence Level-1 performance from the egocentric perspective, although this finding was only based on a small number of studies. Notably, contrary to some theoretical models, we did not find strong evidence that these regions are involved in Level-2 VPT with a higher requirement of mental rotation. These findings not only advance our understanding of the causal roles of the rTPJ and dmPFC in VPT, but also reveal that the efficacy of NIBS on VPT is relatively small. Additionally, researchers should also be cautious about the potential publication bias and selective reporting.

Tailored haemodynamic response function increases detection power of fMRI in awake dogs (Canis familiaris).

Functional magnetic resonance imaging (fMRI) of awake and unrestrained dogs (Canis familiaris) has been established as a novel opportunity for comparative neuroimaging, promising important insights into the evolutionary roots of human brain function and cognition. However, data processing and analysis pipelines are often derivatives of methodological standards developed for human neuroimaging, which may be problematic due to profound neurophysiological and anatomical differences between humans and dogs. Here, we explore whether dog fMRI studies would benefit from a tailored dog haemodynamic response function (HRF). In two independent experiments, dogs were presented with different visual stimuli. BOLD signal changes in the visual cortex during these experiments were used for (a) the identification and estimation of a tailored dog HRF, and (b) the independent validation of the resulting dog HRF estimate. Time course analyses revealed that the BOLD signal in the primary visual cortex peaked significantly earlier in dogs compared to humans, while being comparable in shape. Deriving a tailored dog HRF significantly improved the model fit in both experiments, compared to the canonical HRF used in human fMRI. Using the dog HRF yielded significantly increased activation during visual stimulation, extending from the occipital lobe to the caudal parietal cortex, the bilateral temporal cortex, into bilateral hippocampal and thalamic regions. In sum, our findings provide robust evidence for an earlier onset of the dog HRF in two visual stimulation paradigms, and suggest that using such an HRF will be important to increase fMRI detection power in canine neuroimaging. By providing the parameters of the tailored dog HRF and related code, we encourage and enable other researchers to validate whether our findings generalize to other sensory modalities and experimental paradigms.

Dogs follow human misleading suggestions more often when the informant has a false belief.

We investigated whether dogs (Canis familiaris) distinguish between human true (TB) and false beliefs (FB). In three experiments with a pre-registered change of location task, dogs (n = 260) could retrieve food from one of two opaque buckets after witnessing a misleading suggestion by a human informant (the 'communicator') who held either a TB or a FB about the location of food. Dogs in both the TB and FB group witnessed the initial hiding of food, its subsequent displacement by a second experimenter, and finally, the misleading suggestion to the empty bucket by the communicator. On average, dogs chose the suggested container significantly more often in the FB group than in the TB group and hence were sensitive to the experimental manipulation. Terriers were the only group of breeds that behaved like human infants and apes tested in previous studies with a similar paradigm, by following the communicator's suggestion more often in the TB than in the FB group. We discuss the results in terms of processing of goals and beliefs. Overall, we provide evidence that pet dogs distinguish between TB and FB scenarios, suggesting that the mechanisms underlying sensitivity to others' beliefs have not evolved uniquely in the primate lineage.

A causal role of estradiol in human reinforcement learning.

The sex hormone estradiol is hypothesized to play a key role in human cognition, and reward processing specifically, via increased dopamine D1-receptor signalling. However, the effect of estradiol on reward processing in men has never been established. To fill this gap, we performed a double-blind placebo-controlled study in which men (N = 100) received either a single dose of estradiol (2 mg) or a placebo. Subjects performed a probabilistic reinforcement learning task where they had to choose between two options with varying reward probabilities to maximize monetary reward. Results showed that estradiol administration increased reward sensitivity compared to placebo. This effect was observed in subjects' choices, how much weight they assigned to their previous choices, and subjective reports about the reward probabilities. Furthermore, effects of estradiol were moderated by reward sensitivity, as measured through the BIS/BAS questionnaire. Using reinforcement learning models, we found that behavioral effects of estradiol were reflected in increased learning rates. These results demonstrate a causal role of estradiol within the framework of reinforcement learning, by enhancing reward sensitivity and learning. Furthermore, they provide preliminary evidence for dopamine-related genetic variants moderating the effect of estradiol on reward processing.

Placebo-induced pain reduction is associated with negative coupling between brain networks at rest.

Placebos can reduce pain by inducing beliefs in the effectiveness of an actually inert treatment. Such top-down effects on pain typically engage lateral and medial prefrontal regions, the insula, somatosensory cortex, as well as the thalamus and brainstem during pain anticipation or perception. Considering the level of large-scale brain networks, these regions spatially align with fronto-parietal/executive control, salience, and sensory-motor networks, but it is unclear if and how placebos alter interactions between them during rest. Here, we investigated how placebo analgesia affected intrinsic network coupling. Ninety-nine human participants were randomly assigned to a placebo or control group and underwent resting-state fMRI after pain processing. Results revealed inverse coupling between two resting-state networks in placebo but not control participants. Specifically, networks comprised the bilateral somatosensory cortex and posterior insula, as well as the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the anterior insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, and there was no significant relation with expectations of medication effectiveness in the placebo group. Altogether, these findings provide initial evidence that placebo analgesia affects the intrinsic communication between large-scale brain networks, even in the absence of pain. We suggest a theoretical model where placebo analgesia might affect processing within a descending pain-modulatory network, potentially segregating it from somatosensory regions that may code for painful experiences.

Increasing self-other bodily overlap increases sensorimotor resonance to others' pain.

Empathy for another person's pain and feeling pain oneself seem to be accompanied by similar or shared neural responses. Such shared responses could be achieved by mapping the bodily states of others onto our own bodily representations. We investigated whether sensorimotor neural responses to the pain of others are increased when experimentally reducing perceived bodily distinction between the self and the other. Healthy adult participants watched video clips of the hands of ethnic ingroup or outgroup members being painfully penetrated by a needle syringe or touched by a cotton swab. Manipulating the video presentation to create a visuospatial overlap between the observer's and the target's hand increased the perceived bodily self-attribution of the target's hand. For both ingroup and outgroup targets, this resulted in increased neural responses to the painful injections (compared with nonpainful contacts), as indexed by desynchronizations of central mu and beta scalp rhythms recorded using electroencephalography. Furthermore, these empathy-related neural activations were stronger in participants who reported stronger bodily self-attribution of the other person's hand. Our findings provide further evidence that empathy for pain engages sensorimotor resonance mechanisms. They also indicate that reducing bodily self-other distinction may increase such resonance for ingroup as well as outgroup targets.