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Abstract Functional neuroimaging studies suggest that a large-scale brain network transforms others’ pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [11C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate’s pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others’ pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain.

With age, adolescents increasingly demonstrate the ability to forgo immediate, smaller rewards in favor of larger delayed rewards, indicating reduced delay discounting. Adolescence is also a time of social reorientation, where decisions not only involve weighing immediate against future outcomes, but also consequences for self versus those for others. In this functional Magnetic Resonance Imaging study, we examined the neural correlates of immediate and delayed reward choices where the delayed outcomes could benefit self, friends, or unknown others. A total of 196 adolescent twins aged 14–17 completed a social delay discounting task, with fMRI data acquired from 174 participants. Out of these, 156 adolescents had valid fMRI data, and 138 adolescents had observations in every condition. Adolescents more often chose the immediate reward when it was larger, and when the delay was longer. Area-under-the-curve (AUC) comparisons revealed that behavior differed across delay-beneficiaries, with AUC being highest for the self, followed by friends, and lowest for unknown others. This suggests that adolescents are more willing to wait for rewards for self. Neuroimaging analyses showed increased activity in the midline areas medial prefrontal cortex (MPFC) and precuneus, as well as bilateral temporal parietal junction (TPJ) when considering delayed reward for unknown others and friends compared to self. A whole-brain interaction with choice showed that the bilateral insula and right dorsolateral prefrontal cortex (DLPFC) were more active for delayed choices for unknown others and for immediate choices for friends and self. This underscores that the neuro-cognitive processing of how delays reduce the value of rewards depends on closeness of the beneficiary.

Abstract It has been argued that experiencing the pain of others motivates helping. Here, we investigate the contribution of somatic feelings while witnessing the pain of others onto costly helping decisions, by contrasting the choices and brain activity of participants that report feeling somatic feelings (self-reported mirror-pain synesthetes) against those that do not. Participants in fMRI witnessed a confederate receiving pain stimulations whose intensity they could reduce by donating money. The pain intensity could be inferred either from the facial expressions of the confederate in pain (Face condition) or from the kinematics of the pain-receiving hand (Hand condition). Our results show that self-reported mirror-pain synesthetes increase their donation more steeply, as the intensity of the observed pain increases, and their somatosensory brain activity (SII and the adjacent IPL) was more tightly associated with donation in the Hand condition. For all participants, activation in insula, SII, TPJ, pSTS, amygdala and MCC correlated with the trial by trial donation made in the Face condition, while SI and MTG activation was correlated with the donation in the Hand condition. These results further inform us about the role of somatic feelings while witnessing the pain of others in situations of costly helping.

Abstract Footshock self-experience enhances rodents’ reactions to the distress of others. Here, we tested one potential mechanism supporting this phenomenon, namely that animals auto-condition to their own pain squeaks during shock pre-exposure. In Experiment 1, shock pre-exposure increased freezing and 22 kHz distress vocalizations while animals listened to the audible pain-squeaks of others. In Experiment 2 and 3, to test the auto-conditioning theory, we weakened the noxious pre-exposure stimulus not to trigger pain squeaks, and compared pre-exposure protocols in which we paired it with squeak playback against unpaired control conditions. Although all animals later showed fear responses to squeak playbacks, these were weaker than following typical pre-exposure (Experiment 1) and not stronger following paired than unpaired pre-exposure. Experiment 1 thus demonstrates the relevance of audible pain squeaks in the transmission of distress but Experiment 2 and 3 highlight the difficulty to test auto-conditioning: stimuli weak enough to decouple pain experience from hearing self-emitted squeaks are too weak to trigger the experience-dependent increase in fear transmission that we aimed to study. Although our results do not contradict the auto-conditioning hypothesis, they fail to disentangle it from sensitization effects. Future studies could temporarily deafen animals during pre-exposure to further test this hypothesis.

Our society faces a great diversity of opportunities for youth. The 10-year Growing Up Together in Society (GUTS) program has the long-term goal to understand which combination of measures best predict societal trajectories, such as school success, mental health, well-being, and developing a sense of belonging in society. Our leading hypothesis is that self-regulation is key to how adolescents successfully navigate the demands of contemporary society. We aim to test these questions using socio-economic, questionnaire (including experience sampling methods), behavioral, brain (fMRI, sMRI, EEG), hormonal, and genetic measures in four large cohorts including adolescents and young adults. Two cohorts are designed as test and replication cohorts to test the developmental trajectory of self-regulation, including adolescents of different socioeconomic status thereby bridging individual, family, and societal perspectives. The third cohort consists of an entire social network to examine how neural and self-regulatory development influences and is influenced by whom adolescents and young adults choose to interact with. The fourth cohort includes youth with early signs of antisocial and delinquent behavior to understand patterns of societal development in individuals at the extreme ends of self-regulation and societal participation, and examines pathways into and out of delinquency. We will complement the newly collected cohorts with data from existing large-scale population-based and case-control cohorts. The study is embedded in a transdisciplinary approach that engages stakeholders throughout the design stage, with a strong focus on citizen science and youth participation in study design, data collection, and interpretation of results, to ensure optimal translation to youth in society.

How we juggle morally conflicting outcomes during learning remains unknown. Here, by comparing variants of reinforcement learning models, the authors show that participants differ substantially in their preference, with some choosing actions that benefit themselves while others choose actions that prevent harm.

Summary: The action observation network (AON) has been extensively studied using short, isolated motor acts. How activity in the network is altered when these isolated acts are embedded in meaningful sequences of actions remains poorly understood. Here we utilized intracranial electrocorticography to characterize how the exchange of information across key nodes of the AON—the precentral, supramarginal, and visual cortices—is affected by such embedding and the resulting predictability. We found more top-down beta oscillation from precentral to supramarginal contacts during the observation of predictable actions in meaningful sequences compared to the same actions in randomized, and hence less predictable, order. In addition, we find that expectations enabled by the embedding lead to a suppression of bottom-up visual responses in the high-gamma range in visual areas. These results, in line with predictive coding, inform how nodes of the AON integrate information to process the actions of others.

The processing of reinforcers and punishers is crucial to adapt to an ever changing environment and its dysregulation is prevalent in mental health and substance use disorders. While many human brain measures related to reward have been based on activity in individual brain regions, recent studies indicate that many affective and motivational processes are encoded in distributed systems that span multiple regions. Consequently, decoding these processes using individual regions yields small effect sizes and limited reliability, whereas predictive models based on distributed patterns yield larger effect sizes and excellent reliability. To create such a predictive model for the processes of rewards and losses, termed the Brain Reward Signature (BRS), we trained a model to predict the signed magnitude of monetary rewards on the Monetary Incentive Delay task (MID; N = 39) and achieved a highly significant decoding performance (92% for decoding rewards versus losses). We subsequently demonstrate the generalizability of our signature on another version of the MID in a different sample (92% decoding accuracy; N = 12) and on a gambling task from a large sample (73% decoding accuracy, N = 1084). We further provided preliminary data to characterize the specificity of the signature by illustrating that the signature map generates estimates that significantly differ between rewarding and negative feedback (92% decoding accuracy) but do not differ for conditions that differ in disgust rather than reward in a novel Disgust-Delay Task (N = 39). Finally, we show that passively viewing positive and negatively valenced facial expressions loads positively on our signature, in line with previous studies on morbid curiosity. We thus created a BRS that can accurately predict brain responses to rewards and losses in active decision making tasks, and that possibly relates to information seeking in passive observational tasks.

Based on neuroimaging data, the insula is considered important for people to empathize with the pain of others. Here, we present intracranial electroencephalographic (iEEG) recordings and single-cell recordings from the human insula while seven epilepsy patients rated the intensity of a woman’s painful experiences seen in short movie clips. Pain had to be deduced from seeing facial expressions or a hand being slapped by a belt. We found activity in the broadband 20–190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Within the insula, some locations had activity correlating with perceived intensity for our facial expressions but not for our hand stimuli, others only for our hand but not our face stimuli, and others for both. The timing of responses to the sight of the hand being hit is best explained by kinematic information; that for our facial expressions, by shape information. Comparing the broadband activity in the iEEG signal with spiking activity from a small number of neurons and an fMRI experiment with similar stimuli revealed a consistent spatial organization, with stronger associations with intensity more anteriorly, while viewing the hand being slapped.

Past historical events and experimental research have shown complying with the orders from an authority has a strong impact on people's behaviour. However, the mechanisms underlying how obeying orders influences moral behaviours remain largely unknown. Here, we test the hypothesis that when male and female humans inflict a painful stimulation to another individual, their empathic response is reduced when this action complied with the order of an experimenter (coerced condition) in comparison with being free to decide to inflict that pain (free condition). We observed that even if participants knew that the shock intensity delivered to the ‘victim’ was exactly the same during coerced and free conditions, they rated the shocks as less painful in the coerced condition. MRI results further indicated that obeying orders reduced activity associated with witnessing the shocks to the victim in the ACC, insula/IFG, TPJ, MTG and dorsal striatum (including the caudate and the putamen) as well as neural signatures of vicarious pain in comparison with being free to decide. We also observed that participants felt less responsible and showed reduced activity in a multivariate neural guilt signature in the coerced than in the free condition, suggesting that this reduction of neural response associated with empathy could be linked to a reduction of felt responsibility and guilt. These results highlight that obeying orders has a measurable influence on how people perceive and process others’ pain. This may help explain how people's willingness to perform moral transgressions is altered in coerced situations.

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3 ​T scanner using five sequences, up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movie blocks showing complex actions with hand object interactions and (ii) control movie blocks without hand object interaction. Data were processed using a widely used analysis pipeline implemented in SPM12 including the unified segmentation and canonical HRF modelling. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7 ​mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.

Social transmission of freezing behavior has been conceived of as a one-way phenomenon in which an observer "catches" the fear of another. Here, we use a paradigm in which an observer rat witnesses another rat receiving electroshocks. Bayesian model comparison and Granger causality show that rats exchange information about danger in both directions: how the observer reacts to the demonstrator's distress also influences how the demonstrator responds to the danger. This was true to a similar extent across highly familiar and entirely unfamiliar rats but is stronger in animals preexposed to shocks. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. Using simulations, we support the notion that the coupling of freezing across rats could be selected for to more efficiently detect dangers in a group, in a way similar to cross-species eavesdropping.

Exposure to stress during the early postnatal period (i.e., early life stress, ES) can impact brain physiology and modify individual variability in adult social behavior. Arginine vasopressin (AVP) and oxytocin (OXT) are two centrally released neuropeptides that are involved in shaping essential social behaviors, like aggression, social recognition, and social motivation. AVP and OXT modulate activity in brain regions important for the establishment of social behavior, and may be particularly sensitive to ES. In this review, we discuss whether ES alters the characteristics of the AVP- and OXT- systems in rodents, and whether these changes are associated with later alterations in aggression, social recognition, and social motivation. We have integrated causal studies indicating that (1) ES affects AVP/OXT, and (2) that changing AVP/OXT in affected regions alters social behavior. Although there is encouraging evidence that ES causes AVP- and OXT-system changes, and that these may mediate social behavior, a comprehensive understanding of the exact nature of AVP- and OXT changes and whether they are causal in establishing these behavioral disturbances needs further investigation. As there are indications that ES alters AVP- and OXT characteristics in humans as well, and that these may interact with adult predisposition to psychopathology with social dysfunction, future rodent studies may lay ground for a better understanding of such changes in humans. Ultimately, this may assist in developing therapeutic strategies to target ES effects on social behavior.

Witnessing another person’s suffering elicits vicarious brain activity in areas that are active when we ourselves are in pain. Whether this activity influences prosocial behavior remains the subject of debate. Here participants witnessed a confederate express pain through a reaction of the swatted hand or through a facial expression, and could decide to reduce that pain by donating money. Participants donate more money on trials in which the confederate expressed more pain. Electroencephalography shows that activity of the somatosensory cortex I (SI) hand region explains variance in donation. Transcranial magnetic stimulation (TMS) shows that altering this activity interferes with the pain–donation coupling only when pain is expressed by the hand. High-definition transcranial direct current stimulation (HD-tDCS) shows that altering SI activity also interferes with pain perception. These experiments show that vicarious somatosensory activations contribute to prosocial decision-making and suggest that they do so by helping to transform observed reactions of affected body-parts into accurate perceptions of pain that are necessary for decision-making.

Perceiving other people's actions triggers activity in premotor and parietal areas, brain areas also involved in executing and sensing our own actions. Paralleling this phenomenon, observing emotional states (including pain) in others is associated with activity in the same brain areas as activated when experiencing similar emotions directly. This emotion perception associated activity has been shown to be affected by the perceived fairness of the actor, and in-group membership more generally. Here, we examine whether action observation associated brain activity is also affected by the perceived social fairness of the actors. Perceived fairness was manipulated using an alternating iterated Prisoner's Dilemma game between the participant and two confederates, one of whom played fairly and the other unfairly. During fMRI scanning the participants watched movies of the confederates performing object-directed hand actions, and then performed hand actions themselves. Mass-univariate analysis showed that observing the actions triggered robust activation in regions associated with action execution, but failed to identify a strong modulation of this activation based on perceived fairness. Multivariate pattern analysis, however, identified clusters potentially carrying information about the perceived fairness of the actor in the middle temporal gyrus, left postcentral gyrus, right inferior parietal lobule, right middle cingulate cortex, right angular gyrus, and right superioroccipital gyrus. Despite being identified by a whole-brain searchlight analysis (and so without anatomical restriction), these clusters fall into areas frequently associated with action observation. We conclude that brain activity during action observation may be modulated by perceived fairness, but such modulation is subtle; robust activity is associated with observing the actions of both fair and unfair individuals.

Many daily life activities demand precise integration of spatial and temporal information of sensory inputs followed by appropriate motor actions. This type of integration is carried out in part by the cerebellum, which has been postulated to play a central role in learning and timing of movements. Cerebellar damage due to atrophy or lesions may compromise forward-model processing, in which both spatial and temporal cues are used to achieve prediction for future motor states. In the present study we sought to further investigate the cerebellar contribution to predictive and reactive motor timing, as well as to learning of sequential order and temporal intervals in these tasks. We tested patients with spinocerebellar ataxia type 6 (SCA6) and healthy controls for two related motor tasks; one requiring spatio-temporal prediction of dynamic visual stimuli and another one requiring reactive timing only. We found that healthy controls established spatio-temporal prediction in their responses with high temporal precision, which was absent in the cerebellar patients. SCA6 patients showed lower predictive motor timing, coinciding with a reduced number of correct responses during the 'anticipatory' period on the task. Moreover, on the task utilizing reactive motor timing functions, control participants showed both sequence order and temporal interval learning, whereas patients only showed sequence order learning. These results suggest that SCA6 affects predictive motor timing and temporal interval learning. Our results support and highlight cerebellar contribution to timing and argue for cerebellar engagement during spatio-temporal prediction of upcoming events.

Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar Demonstrators receive painful footshocks (six sessions). Results confirm that Observers freeze during the first testing session. The occurrence of this behaviour however gradually diminished as the experimental sessions progressed, reaching minimal freezing levels by the end of the experiments. In contrast, the appearance and continuous increase in the frequency of yawning, a behavior that was inhibited by metyrapone (i.e,. a glucocorticoid synthesis blocker), might represent an alternative coping strategy, suggesting that the observer's reduced freezing does not necessarily indicate a disappearance in the affective response to the Demonstrator's distress.

Some theories of motor control suggest efference-copies of motor commands reach somatosensory cortices. Here we used functional magnetic resonance imaging to test these models. We varied the amount of efference-copy signal by making participants squeeze a soft material either actively or passively. We found electromyographical recordings, an efference-copy proxy, to predict activity in primary somatosensory regions, in particular Brodmann Area (BA) 2. Partial correlation analyses confirmed that brain activity in cortical structures associated with motor control (premotor and supplementary motor cortices, the parietal area PF and the cerebellum) predicts brain activity in BA2 without being entirely mediated by activity in early somatosensory (BA3b) cortex. Our study therefore provides valuable empirical evidence for efference-copy models of motor control, and shows that signals in BA2 can indeed reflect an input from motor cortices and suggests that we should interpret activations in BA2 as evidence for somatosensory-motor rather than somatosensory coding alone.

Learning what behaviour is appropriate in a specific context by observing the actions of others and their outcomes is a key constituent of human cognition, because it saves time and energy and reduces exposure to potentially dangerous situations. Observational learning of associative rules relies on the ability to map the actions of others onto our own, process outcomes, and combine these sources of information. Here, we combined newly developed experimental tasks and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms that govern such observational learning. Results show that the neural systems involved in individual trial-and-error learning and in action observation and execution both participate in observational learning. In addition, we identified brain areas that specifically activate for others' incorrect outcomes during learning in the posterior medial frontal cortex (pMFC), the anterior insula and the posterior superior temporal sulcus (pSTS).

The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs) when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm to study empathy as a social loop.

Communication is an important aspect of human life, allowing us to powerfully coordinate our behaviour with that of others. Boiled down to its mere essentials, communication entails transferring a mental content from one brain to another. Spoken language obviously plays an important role in communication between human individuals. Manual gestures however often aid the semantic interpretation of the spoken message, and gestures may have played a central role in the earlier evolution of communication. Here we used the social game of charades to investigate the neural basis of gestural communication by having participants produce and interpret meaningful gestures while their brain activity was measured using functional magnetic resonance imaging. While participants decoded observed gestures, the putative mirror neuron system (pMNS: premotor, parietal and posterior mid-temporal cortex), associated with motor simulation, and the temporo-parietal junction (TPJ), associated with mentalizing and agency attribution, were significantly recruited. Of these areas only the pMNS was recruited during the production of gestures. This suggests that gestural communication relies on a combination of simulation and, during decoding, mentalizing/agency attribution brain areas. Comparing the decoding of gestures with a condition in which participants viewed the same gestures with an instruction not to interpret the gestures showed that although parts of the pMNS responded more strongly during active decoding, most of the pMNS and the TPJ did not show such significant task effects. This suggests that the mere observation of gestures recruits most of the system involved in voluntary interpretation.

The discovery of mirror neurons has suggested a potential neural basis for simulation and common coding theories of action perception, theories which propose that we understand other people's actions because perceiving their actions activates some of our neurons in much the same way as when we perform the actions. We propose testing this model directly in humans with functional magnetic resonance imaging (fMRI) by means of cross-modal classification. Cross-modal classification evaluates whether a classifier that has learned to separate stimuli in the sensory domain can also separate the stimuli in the motor domain. Successful classification provides support for simulation theories because it means that the fMRI signal, and presumably brain activity, is similar when perceiving and performing actions. In this paper we demonstrate the feasibility of the technique by showing that classifiers which have learned to discriminate whether a participant heard a hand or a mouth action, based on the activity patterns in the premotor cortex, can also determine, without additional training, whether the participant executed a hand or mouth action. This provides direct evidence that, while perceiving others' actions, (1) the pattern of activity in premotor voxels with sensory properties is a significant source of information regarding the nature of these actions, and (2) that this information shares a common code with motor execution.