Growing Up Together in Society (GUTS): A team science effort to predict societal trajectories in adolescence and young adulthood.

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.

Neural mechanisms of costly helping in the general population and mirror-pain synesthetes.

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.

A systematic review and multivariate meta-analysis of the physical and mental health benefits of touch interventions.

Receiving touch is of critical importance, as many studies have shown that touch promotes mental and physical well-being. We conducted a pre-registered (PROSPERO: CRD42022304281) systematic review and multilevel meta-analysis encompassing 137 studies in the meta-analysis and 75 additional studies in the systematic review (n = 12,966 individuals, search via Google Scholar, PubMed and Web of Science until 1 October 2022) to identify critical factors moderating touch intervention efficacy. Included studies always featured a touch versus no touch control intervention with diverse health outcomes as dependent variables. Risk of bias was assessed via small study, randomization, sequencing, performance and attrition bias. Touch interventions were especially effective in regulating cortisol levels (Hedges' g = 0.78, 95% confidence interval (CI) 0.24 to 1.31) and increasing weight (0.65, 95% CI 0.37 to 0.94) in newborns as well as in reducing pain (0.69, 95% CI 0.48 to 0.89), feelings of depression (0.59, 95% CI 0.40 to 0.78) and state (0.64, 95% CI 0.44 to 0.84) or trait anxiety (0.59, 95% CI 0.40 to 0.77) for adults. Comparing touch interventions involving objects or robots resulted in similar physical (0.56, 95% CI 0.24 to 0.88 versus 0.51, 95% CI 0.38 to 0.64) but lower mental health benefits (0.34, 95% CI 0.19 to 0.49 versus 0.58, 95% CI 0.43 to 0.73). Adult clinical cohorts profited more strongly in mental health domains compared with healthy individuals (0.63, 95% CI 0.46 to 0.80 versus 0.37, 95% CI 0.20 to 0.55). We found no difference in health benefits in adults when comparing touch applied by a familiar person or a health care professional (0.51, 95% CI 0.29 to 0.73 versus 0.50, 95% CI 0.38 to 0.61), but parental touch was more beneficial in newborns (0.69, 95% CI 0.50 to 0.88 versus 0.39, 95% CI 0.18 to 0.61). Small but significant small study bias and the impossibility to blind experimental conditions need to be considered. Leveraging factors that influence touch intervention efficacy will help maximize the benefits of future interventions and focus research in this field.

Vicarious Emotions of Fear and Pain in Rodents.

Affective empathy, the ability to share the emotions of others, is an important contributor to the richness of our emotional experiences. Here, we review evidence that rodents show signs of fear and pain when they witness the fear and pain of others. This emotional contagion creates a vicarious emotion in the witness that mirrors some level of detail of the emotion of the demonstrator, including its valence and the vicinity of threats, and depends on brain regions such as the cingulate, amygdala, and insula that are also at the core of human empathy. Although it remains impossible to directly know how witnessing the distress of others feels for rodents, and whether this feeling is similar to the empathy humans experience, the similarity in neural structures suggests some analogies in emotional experience across rodents and humans. These neural homologies also reveal that feeling distress while others are distressed must serve an evolutionary purpose strong enough to warrant its stability across ~ 100 millions of years. We propose that it does so by allowing observers to set in motion the very emotions that have evolved to prepare them to deal with threats - with the benefit of triggering them socially, by harnessing conspecifics as sentinels, before the witness personally faces that threat. Finally, we discuss evidence that rodents can engage in prosocial behaviors that may be motivated by vicarious distress or reward.

Predictability alters information flow during action observation in human electrocorticographic activity.

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.

Audible pain squeaks can mediate emotional contagion across pre-exposed rats with a potential effect of auto-conditioning.

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.

Sharing Positive Affective States Amongst Rodents.

Group living is thought to benefit from the ability to empathize with others. Much attention has been paid to empathy for the pain of others as an inhibitor of aggression. Empathizing with the positive affect of others has received less attention although it could promote helping by making it vicariously rewarding. Here, we review this latter, nascent literature to show that three components of the ability to empathize with positive emotions are already present in rodents, namely, the ability to perceive, share, and prefer actions that promote positive emotional states of conspecifics. While it has often been argued that empathy evolved as a motivation to care for others, we argue that these tendencies may have selfish benefits that could have stabilized their evolution: approaching others in a positive state can provide information about the source of valuable resources; becoming calmer and optimistic around animals in a calm or positive mood can help adapt to the socially sensed safety level in the environment; and preferring actions also benefiting others can optimize foraging, reduce aggression, and trigger reciprocity. Together, these findings illustrate an emerging field shedding light on the emotional world of rodents and on the biology and evolution of our ability to cooperate in groups.

Neuro-computational mechanisms and individual biases in action-outcome learning under moral conflict.

Learning to predict action outcomes in morally conflicting situations is essential for social decision-making but poorly understood. Here we tested which forms of Reinforcement Learning Theory capture how participants learn to choose between self-money and other-shocks, and how they adapt to changes in contingencies. We find choices were better described by a reinforcement learning model based on the current value of separately expected outcomes than by one based on the combined historical values of past outcomes. Participants track expected values of self-money and other-shocks separately, with the substantial individual difference in preference reflected in a valuation parameter balancing their relative weight. This valuation parameter also predicted choices in an independent costly helping task. The expectations of self-money and other-shocks were biased toward the favored outcome but fMRI revealed this bias to be reflected in the ventromedial prefrontal cortex while the pain-observation network represented pain prediction errors independently of individual preferences.

A multivariate brain signature for reward.

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.

Intracranial human recordings reveal association between neural activity and perceived intensity for the pain of others in the insula.

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.

Commanding or Being a Simple Intermediary: How Does It Affect Moral Behavior and Related Brain Mechanisms?

Psychology and neuroscience research have shown that fractioning operations among several individuals along a hierarchical chain allows diffusing responsibility between components of the chain, which has the potential to disinhibit antisocial actions. Here, we present two studies, one using fMRI (Study 1) and one using EEG (Study 2), designed to help understand how commanding or being in an intermediary position impacts the sense of agency and empathy for pain. In the age of military drones, we also explored whether commanding a human or robot agent influences these measures. This was done within a single behavioral paradigm in which participants could freely decide whether or not to send painful shocks to another participant in exchange for money. In Study 1, fMRI reveals that activation in social cognition-related and empathy-related brain regions was equally low when witnessing a victim receive a painful shock while participants were either commander or simple intermediary transmitting an order, compared with being the agent directly delivering the shock. In Study 2, results indicated that the sense of agency did not differ between commanders and intermediary, no matter whether the executing agent was a robot or a human. However, we observed that the neural response over P3 event-related potential was higher when the executing agent was a robot compared with a human. Source reconstruction of the EEG signal revealed that this effect was mediated by areas including the insula and ACC. Results are discussed regarding the interplay between the sense of agency and empathy for pain for decision-making.

Emotional contagion and prosocial behavior in rodents.

Empathy is critical to adjusting our behavior to the state of others. The past decade dramatically deepened our understanding of the biological origin of this capacity. We now understand that rodents robustly show emotional contagion for the distress of others via neural structures homologous to those involved in human empathy. Their propensity to approach others in distress strengthens this effect. Although rodents can also learn to favor behaviors that benefit others via structures overlapping with those of emotional contagion, they do so less reliably and more selectively. Together, this suggests evolution selected mechanisms for emotional contagion to prepare animals for dangers by using others as sentinels. Such shared emotions additionally can, under certain circumstances, promote prosocial behavior.

Predictive coding during action observation - A depth-resolved intersubject functional correlation study at 7T.

While the brain regions involved in action observation are relatively well documented in humans and primates, how these regions communicate to help understand and predict actions remains poorly understood. Traditional views emphasized a feed-forward architecture in which visual features are organized into increasingly complex representations that feed onto motor programs in parietal and then premotor cortices where the matching of observed actions upon the observer's own motor programs contributes to action understanding. Predictive coding models place less emphasis on feed-forward connections and propose that feed-back connections from premotor regions back to parietal and visual neurons represent predictions about upcoming actions that can supersede visual inputs when actions become predictable, with visual input then merely representing prediction errors. Here we leverage the notion that feed-back connections target specific cortical layers to help adjudicate across these views. Specifically, we test whether observing sequences of hand actions in their natural order, which permits participants to predict upcoming actions, triggers more feed-back input to parietal regions than seeing the same actions in a scrambled sequence that hinders making predictions. Using submillimeter fMRI acquisition at 7T, we find that watching predictable sequences triggers more action-related activity (as measured using intersubject functional correlation) in the parietal cortical area PFt at depths receiving feed-back connections (layers III and V/VI) than watching the exact same actions in scrambled and hence unpredictable sequence. In addition, functional connectivity analysis performed using intersubject functional connectivity confirms that these increased action-related signals in PFt could originate from ventral premotor region BA44. This data showcases the utility of intersubject functional correlation in combination with 7T MRI to explore the architecture of social cognition under more naturalistic conditions, and provides evidence for models that emphasize the importance of feed-back connections in action prediction.

Emotional contagion: Improving survival by preparing for socially sensed threats.

Rats respond to the emotions of others. A new study reveals how their central amygdala uses such social information to selfishly trigger defences that adapt to the nature of the danger with all the hallmarks of true emotional contagion.

Neural mechanisms necessary for empathy-related phenomena across species.

The neural basis of empathy and prosociality has received much interest over the past decades. Neuroimaging studies localized a network of brain regions with activity that correlates with empathy. Here, we review how the emergence of rodent and nonhuman primate models of empathy-related phenomena supplements human lesion and neuromodulation studies providing evidence that activity in several nodes is necessary for these phenomena to occur. We review proof that (i) affective states triggered by the emotions of others, (ii) motivations to act in ways that benefit others, and (iii) emotion recognition can be altered by perturbing brain activity in many nodes identified by human neuroimaging, with strongest evidence for the cingulate and the amygdala. We also include evidence that manipulations of the oxytocin system and analgesics can have such effects, the latter providing causal evidence for the recruitment of an individual's own nociceptive system to feel with the pain of others.

Author Correction: Using Bayes factor hypothesis testing in neuroscience to establish evidence of absence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Obeying orders reduces vicarious brain activation towards victims' pain.

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.

Author Correction: Similar levels of emotional contagion in male and female rats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Using Bayes factor hypothesis testing in neuroscience to establish evidence of absence.

Most neuroscientists would agree that for brain research to progress, we have to know which experimental manipulations have no effect as much as we must identify those that do have an effect. The dominant statistical approaches used in neuroscience rely on P values and can establish the latter but not the former. This makes non-significant findings difficult to interpret: do they support the null hypothesis or are they simply not informative? Here we show how Bayesian hypothesis testing can be used in neuroscience studies to establish both whether there is evidence of absence and whether there is absence of evidence. Through simple tutorial-style examples of Bayesian t-tests and ANOVA using the open-source project JASP, this article aims to empower neuroscientists to use this approach to provide compelling and rigorous evidence for the absence of an effect.