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Keysers, C.

Publications and source records attributed to Keysers, C..

At least 19 recordsLinked to original sources

Modeling behavior to disentangle motion-related effects in functional ultrasound imaging in awake, head-fixed mice

Functional ultrasound imaging (fUSI) enables brain-wide mapping of hemodynamic activity in awake rodents, offering a powerful bridge between systems neuroscience in animals and human neuroimaging. However, extending fUSI beyond tightly controlled sensory paradigms to more naturalistic behaviors is limited by motion-related confounds arising from locomotion, physiological arousal, and movement-linked neural activity. Here, we introduce a behavior-informed modeling framework that explicitly incorporates continuous measurements of running speed and head motion into a general linear model to account for motion-related variance while preserving interpretable task-related signals. We validate this approach in two head-fixed paradigms with distinct motion profiles: a visual stimulation task with minimal stimulus-driven movement, and a noxious stimulation task in which locomotion and arousal are intrinsic to the behavioral response. In both cases, explicit behavioral modeling recovers neural response patterns that more closely resemble low-motion reference conditions than blind, model-free denoising approaches. Critically, during noxious stimulation, behavior-informed modeling preserves shock-intensity-dependent activity in the primary somatosensory cortex that is attenuated by global component removal. These findings demonstrate that explicit modeling of behavior enables reliable interpretation of brain-wide fUSI signals during naturalistic, high-motion conditions, opening the door to studying affective and cognitive processes that were previously difficult to access with functional ultrasound imaging.

neuroscience↗

Dissociable Effects of Early and Adolescent Adversity on Emotional Contagion

BackgroundEarly-life adversity can alter emotional and social development and increase vulnerability to later life stress. We investigated how early adverse experiences (EAE) and later adverse experiences (LAE) shape adult emotional contagion (EC) responses in female and male rats. MethodsEAE was induced using the limited bedding and nesting model during the first postnatal week. LAE was induced via footshocks during adolescence. In adulthood, male and female rats underwent an EC test in which observers witnessed a conspecific receiving footshocks. ResultsAdolescence-footshock exposed observers showed cingulate cortex-associated increased immobility, proximity, and attention toward distressed conspecifics during adulthood, compared to adult-exposed and sham animals, both in male and female animals. While EAE did alter maternal care, pup stress physiology, and pup weight, we found evidence that it did not alter immobility during EC. However, female demonstrators paired with EAE observers showed increased immobility, linked to a reduced rate and lower frequency of the observers 50-kHz vocalizations. Mediation analysis revealed that a shift toward lower-frequency 50-kHz vocalizations specifically mediated this effect, suggesting a sex-specific pathway by which early adversity shapes social behavior. ConclusionsEarly and adolescent adversity influenced distinct aspects of emotional contagion: EAE mediated an observer-to-demonstrator emotional transfer during EC, while LAE impacted a demonstrator-to-observer transfer, with no evidence of additive effects. Our results highlight developmentally specific and sex-dependent mechanisms by which early and later adversity alter social-affective responses in adulthood.

neuroscience↗

The Intermediate Hippocampus Integrates Shock-Observation and Spatial Information during Observational Fear Memory

Learning where danger lurks by observing others requires linking another individual's distress to one's own representation of space. How the hippocampus implements this mapping is unknown. We recorded Neuropixels activity across the dorsal, intermediate and ventral hippocampus of male rats during contextual fear learning by observation, subsequent rest and recall. Observers showed increased immobility in the context where they had witnessed a conspecific receive footshocks, with substantial inter-individual variability. Pyramidal neurons were recruited by shock observation, with enriched shock-excited cells in the intermediate hippocampus. In the dorsal and intermediate hippocampus, shock-observation responses scaled with baseline place-field firing, revealing a gain-like conjunctive code between observed distress and observer's position. Following learning, shock-context spatial representations were selectively stabilized in the intermediate hippocampus, and post-learning sharp-wave ripples preferentially reactivated shock-context ensembles, especially in animals expressing contextual freezing. These findings identify candidate hippocampal mechanisms by which socially acquired threat information are mapped onto the observer's spatial representation and consolidated into memory.

neuroscience↗

Heightened Play following Play Observation in the Absence of 22KHz Calls in Juvenile Rats

Emotional contagion, the process leading to emotional state matching between individuals is considered a cornerstone for the proper functioning of social groups, via its contribution to group coordination and cohesion, the ability to learn from others and engage in prosocial behaviors. However, to date, most studies of emotional contagion investigate the transfer of negative emotional states thereby bypassing the neurobiology of positive affect sharing. In this study, we aimed to leverage on the innately rewarding and salient nature of play behaviour, to investigate the potential contagiousness of positive affective states in juvenile rats. Observers that had been moderately socially deprived for varying durations first witnessed highly-playful (Play) or non-playful (Control) demonstrator rats prior to being reunited and given the opportunity to freely interact. Surprisingly, we observed the emission of negatively-valenced 22 kHz calls in a subset of sessions which was also associated with heightened play behavior of the demonstrators. We found that the reunited observers showed an increase in play behavior following observation in the Play condition compared to the Control condition, but only after short social isolation and in sessions without 22 kHz calls. In addition, an overall higher number of positively-valenced 50 kHz calls were emitted in the Play condition, again in sessions without 22 kHz emissions. Despite the limitations of the experimental procedure, our results highlight the complex nature of positive emotional sharing and provide encouraging first indications of using social play observation to study positive emotional contagion. Highlights- Social deprivation positively modulates play behavior and USV emission in reunited juvenile rats - Heightened play is associated with 22 kHz USVs following social deprivation - Heightened play was observed following play observation in the absence of 22 kHz USVs - Play observation was associated with an overall increased number of 50 kHz calls emissions - Play observation as an encouraging approach to study positive emotional contagion in rat

animal behavior and cognition↗

Representational geometry of emotional empathy in the ventromedial prefrontal cortex and in the mid-posterior insula.

Facial expressions provide rapid and informative cues about others emotional and mental states, playing a critical role in social interactions. However, whether distinct emotional expressions reflect discrete neural processes or arise from varying combinations of underlying affective dimensions such as arousal and valence remains a subject of investigation. Crucially, these accounts need not be mutually exclusive: different brain regions may encode emotional expressions along both categorical and dimensional axes to varying degrees. To test this hypothesis, we probed different brain systems involved in emotion recognition - the ventral attentional network and the cortical limbic system centered on the ventromedial prefrontal cortex (vmPFC) - to investigate the extent to which these networks and their subregions encode emotional facial expressions in terms of (1) perceived arousal, (2) arousal+valence, or (3) six discrete emotion categories (anger, disgust, fear, happiness, pain, sadness). To this aim, we modelled the fMRI signal from perceiving movies of facial emotional expressions with ratings for either arousal, arousal+valence or emotion category using representational similarity analysis (RSA) - a method that aims at assessing which ratings model better represents how the perception of facial expressions is reflected by the fMRI parameter estimates across all the voxels within a brain region. This analysis showed that regions in the vmPFC network, including the subgenual cingulate and the medial OFC, are sensitive to ratings for distinct emotion category and for arousal+valence - significantly more so for the former - while they fail to show sensitivity for arousal ratings alone. In the ventral attentional network, the mid-posterior insula showed a similar profile, while the most posterior and ventral insular show evidence of encoding arousal+valence, but not for emotion category or arousal alone. Our findings support the idea that the vmPFC and the mid-posterior insula play a role in encoding emotion-specific and valence representations beyond general arousal processing. These results contribute to understanding how integrative brain regions support emotional empathy and social cognition.

neuroscience↗

Endogenous opioid receptor system mediates costly altruism in the human brain

Functional neuroimaging studies suggest that a large-scale brain network transforms others pain into its vicarious representation in the observer, potentially modulating helping behaviour. The neuromolecular basis of individual differences in vicarious pain and helping, however, have remain poorly understood. Here we investigated the role of the endogenous -opioid receptor (MOR) system - known for its role in analgesia and sociability - in altruistic costly helping. MOR density was measured with high-affinity agonist radioligand [11C]carfentanil. In a separate fMRI experiment, participants could choose to donate money to reduce the pain of the confederate who was subjected to electric shocks of varying intensity. We found that subjects were in general willing to engage in costly helping, and haemodynamic activity in amydala, anterior insula, anterior cingulate cortex, striatum, primary motor cortex, primary somatosensory cortex, and thalamus increased when participants witnessed the pain of others. These haemodynamic responses were negatively associated with MORs availability in the striatolimbic and cortical emotion circuits. In turn, haemodynamic responses during helping were positively associated with MOR availability in the anterior cingulate cortex and hippocampus. Altogether these data suggest that the endogenous MOR system modulates the processing of altruistic behaviour and costly helping in the human brain.

neuroscience↗

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

Helping others often comes with a cost to ourselves. It has been argued that experiencing the pain of others motivates helping. Here we investigate how individuals that report somatically feeling the pain of others (mirror-pain synesthetes) differ from those that do not, when deciding to help and reduce someones pain conveyed through different modalities. Mirror-pain synesthetes and participants who do not report such everyday life experiences witnessed a confederate expressing pain and could decide to reduce the intensity by donating money. Measuring brain activity using fMRI confirmed our initial hypothesis: self-reported mirror-pain synesthetes increased their donation more steeply, as the intensity of the observed pain increased, and their somatosensory brain activity (in SII and the adjacent IPL) activity was more tightly associated with donation when the pain of other was conveyed by the reactions of the pain-receiving hand. For all participants, in a condition where the pain was conveyed by facial expressions, activation in insula, SII and MCC correlated with the trial by trial donation made, while SI and MTG activation was correlated with the donation in the Hand condition. These results further inform us about the role of empathy in costly helping, the underlying neural mechanism, and individual variability.

neuroscience↗

Predictive coding during action observation - an Electrocorticographic study

Predictive coding is a theoretical framework that has received much attention for its ability to generate testable hypotheses on how multiple brain regions integrate information during cognitive functions. Given relatively large sensorimotor delays, during social interactions, predicting the behavior of others is crucial to enable joint actions or provide competitive advantages. The action observation network (AON) has been extensively studied, but how information is integrated across its main nodes remains poorly understood. Here we leverage the high spatial and temporal resolution of intracranial Electrocorticography (ECoG), to characterize how the key nodes of the AON - including precentral, supramarginal and visual areas - exchange information. We found more top-down beta oscillation from precentral to supramarginal contacts during the observation of predictable actions while more bottom-up gamma oscillation from visual to supramarginal contacts were measured for unpredictable actions. These results, in line with predictive coding, provide critical evidence towards an understanding of how nodes of the AON integrate information to process the actions of others.

neuroscience↗

Investigating the mechanistic role of painful self-experience in emotional contagion: an effect of auto-conditioning?

Emotional contagion refers to the transmission of emotions from one conspecific to another. Previous research in rodents has demonstrated that the self-experience of footshocks enhances how much an observer is affected by the emotional state of a conspecific in pain or distress. We hypothesized auditory auto-conditioning to contribute to this enhancement: during the observers own experience of shocks, the animal associates its own audible nocifensive responses, i.e. its pain squeaks, with the negative affective state induced by the shock. When the animal later witnesses a cage mate receive shocks and hears it squeak, the previously strengthened connection between fear and squeaks could be a mechanism eliciting the enhanced fearful response in the observer. As hypothesized, in a first study, we found pre-exposure to shocks to increase freezing and 22 kHz vocalizations associated with distress upon the playback of pain squeaks. Freezing was also increased during the playbacks of phase-scrambled squeaks, but 22 kHz calls were more frequent during the playback of regular squeaks. Core to the notion of auto-conditioning is that the effect of pre-exposure is due to the pairing of a pain-state with hearing ones own pain squeaks. In a second study, we therefore compared the response to squeak playbacks after animals had been pre-exposed to pairings of a CO2 laser with a squeak playback against three control groups that were pre-exposed to the CO2 laser alone, to squeak playbacks alone or to neither of these conditions. We however could not find any differences in freezing or 22 kHz calls among all experimental groups. In summary, we demonstrate the sufficiency of pain squeaks to trigger fear in a way that critically depends on the nature of an animals prior experience and discuss why the pairing of a CO2 laser with pain squeaks cannot substitute footshock pre-exposure.

animal behavior and cognition↗

A multivariate brain signature for reward

The processing of rewards and losses are crucial for learning to adapt to an ever changing environment. Dysregulated reward processes are 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 much larger effect sizes and excellent reliability. To create such a predictive model for the processes of rewards and losses, from now on termed the Brain Reward Signature (BRS), we trained a LASSO-PCR model to predict the signed magnitude of monetary rewards and losses on the Monetary Incentive Delay task (MID; N = 39) and achieved a high 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 for rewards versus losses; N = 12) and on a gambling task from a large sample (73% decoding accuracy for rewards versus losses, N = 1084) from the Human Connectome Project. Lastly, we also provided preliminary evidence for specificity to rewarding outcomes 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). We thus created a BRS that can be used to make specific, generalizable and reproducible predictions about brain responses to rewards and losses.

neuroscience↗

Depth-resolved intersubject functional correlation of 7T BOLD signals reveals increased stimulus related information sharing across deep layers in premotor and parietal nodes for predictable actions

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 observers 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.

neuroscience↗

Intracortical human recordings reveal intensity coding 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, whether that pain is perceived through facial expressions or the sight of limbs in painful situations. Here we present the first report of intracranial electroencephalographic (iEEG) recordings from the insulae collected while 7 presurgical epilepsy patients rated the intensity of a womans painful experiences viewed in movies. In two separate conditions, pain was deduced from seeing facial expressions or a hand being slapped by a belt. We found that broadband activity in the 20-190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Using microwires at the tip of a selection of the electrodes, we additionally isolated 8 insular neurons with spiking that correlated with perceived intensity. Within the insula, we found a patchwork of locations with differing selectivities within our stimulus set, some representing intensity only for facial expressions, others only for the hand being hit, and others for both. That we found some locations with intensity coding only for faces, and others only for hand across simultaneously recorded locations suggests that insular activity while witnessing the pain of others cannot be entirely reduced to a univariate salience representation. Psychophysics and the temporal properties of our signals indicate that the timing of responses encoding intensity for the sight of the hand being hit are best explained by kinematic information; the timing of those encoding intensity for facial expressions are best explained by shape information in the face. In particular, the furrowing of the eyebrows and the narrowing of the eyes of the protagonist in the movies suffice to predict both the rating of and the timing of the neuronal response to the facial expressions. Comparing the broadband activity in the iEEG signal with spiking activity and an fMRI experiment with similar stimuli revealed a consistent spatial organization for the representation of intensity from our hand stimuli, with stronger intensity representation more anteriorly and around neurons with intensity coding. In contrast, for the facial expressions, we found that the activity at the three levels of measurement do not coincide, suggesting a more disorganized representation. Together, our intracranial recordings indicate that the insula encodes, in a partially intermixed layout, both static and dynamic cues from different body parts that reflect the intensity of pain experienced by others.

neuroscience↗

Significance tests for Leave-One-Out Inter-Subject Correlations in fMRI

The inter-subject correlation (ISC) of fMRI data of different subjects performing the same task is a powerful way to localize and differentiate neural processes caused by a stimulus from those that spontaneously or idiosyncratically take place in each subject. The wider adoption of this method has however been impeded by the lack of widely available tools to assess the significance of the observed correlations. Several non-parametric approaches have been proposed, but these approaches are computationally intensive, challenging to implement, and sensitive methods to correct for multiple comparison across voxels are not yet well established. More widely available, and computationally simple, parametric methods have been criticized theoretically on the basis that dependencies in the data could inflate false positives. Here, we therefore endeavored to assess the actual performance of parametric tests on leave-one-out ISC values in two ways. First, we assess whether parametric tests protect against Type I error by assessing how often they find significant clusters of synchronized activity in publicly available datasets, in which such synchronization should not occur. This includes three resting state datasets, and one dataset in which participants did view movies, but where we randomly select segments that were not taken at the same time in the same movie. Contrary to what has been suspected, we find that parametric tests with corrections for multiple comparisons do protect appropriately against Type I error in that data. This was true for FDR correction at the voxel level at q < 0.05, with a minimum cluster-size of k = 20 voxels, FWE correction at the voxel level at < 0.05, with a minimum cluster-size of k = 5, and for correction at the cluster-level with punc < 0.001 with k = max(20, FWEc). Second, we assessed how these parametric tests compare with non-parametric methods when it comes to detecting ISC when participants actually did watch the same movies. We used a dataset including 150 participants viewing two movies, and used a bootstrapping thresholding of the ISC in the entire dataset to outline our best guess of the network of brain regions that truly synchronize while viewing the movies. We then drew subsamples of between 10 and 50 participants from the entire dataset, calculated the ISC, and thresholded it using our candidate methods. We find that FDR thresholding with k = 20 in particular, was substantially more sensitive than bootstrapping methods in detecting this network even in smallish samples of N = 20 participants typical of cognitive neuroscience studies, while at the same time retaining appropriate specificity. Because the parametric tests we show to perform well are more readily available to the neuroscience community than the non-parametric tests previously championed, we trust that this finding paves the way to a wider adoption of ISC, and empowers a wider range of neuroimagers to use ISC to tackle the challenges of naturalistic neuroscience. In particular in the context of often limited sample sizes and modest effect sizes in cognitive neuroscience, we trust that using FDR correction in particular will help neuroimagers identify the contribution of higher brain regions that process stimuli in more loosely timed fashions, more effectively than non-parametric alternatives.

neuroscience↗

Obeying orders reduces vicarious brain activation towards victim's pain

Past historical events and experimental research have shown complying with the orders from an authority has a strong impact on peoples 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, the 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 peoples willingness to perform moral transgressions is altered in coerced situations.

neuroscience↗

Neuro-computational mechanisms of action-outcome learning under moral conflict

Predicting how actions result in conflicting outcomes for self and others is essential for social functioning. We tested whether Reinforcement Learning Theory captures how participants learn to choose between symbols that define a moral conflict between financial self-gain and other-pain. We tested whether choices are better explained by model-free learning (decisions based on combined historical values of past outcomes), or model-based learning (decisions based on the current value of separately expected outcomes) by including trials in which participants know that either self-gain or other-pain will not be delivered. Some participants favored options benefiting themselves, others, preventing other-pain. When removing the favored outcome, participants instantly altered their choices, suggesting model-based learning. Computational modelling confirmed choices were best described by model-based learning in which participants track expected values of self-gain and other-pain separately, with an individual valuation parameter capturing their relative weight. This valuation parameter predicted costly helping in an independent task. The expectations of self-gain and other-pain were also biased: the favoured outcome was associated with more differentiated symbol-outcome probability reports than the less favoured outcome. FMRI helped localize this bias: signals in the pain-observation network covaried with pain prediction errors without linear dependency on individual preferences, while the ventromedial prefrontal cortex contained separable signals covarying with pain prediction errors in ways that did and did not reflected individual preferences.

neuroscience↗

Similar levels of emotional contagion in male and female rats

Emotional contagion, the ability to feel what other individuals feel, is thought to be an important element of social life. In humans, emotional contagion has been shown to be stronger in women than men. Emotional contagion has been shown to exist also in rodents, and a growing number of studies explore the neural basis of emotional contagion in male rats and mice. These studies promise to shed light on the mechanisms that might go astray in psychiatric disorders characterized by dysfunctions of emotional contagion and empathy. Here we explore whether there are sex differences in emotional contagion in rats. We use an established paradigm in which a demonstrator rat receives footshocks while freezing is measured in both the demonstrator and an observer rat, which can hear, smell and see each other. By comparing pairs of male rats with pairs of female rats, we find (i) that female demonstrators freeze less when submitted to footshocks, but that (ii) the emotional contagion response, i.e. the degree of influence across the rats, does not depend on the sex of the rats. This was true whether emotional contagion was quantified based on the slope of a regression linking demonstrator and observer average freezing, or on Granger causality estimates of moment-to-moment freezing. The lack of sex differences in emotional contagion is compatible with an interpretation of emotional contagion as serving selfish danger detection.

animal behavior and cognition↗

Bayesian statistics show a lack of change in excitability following bi-hemispheric HD-TDCS over the primary somatosensory cortices

BackgroundHigh Definition transcranial Direct Current Stimulation (HD-tDCS) is a method meant to explore the causal structure-function relationship of brain areas, developed to improve the spatial resolution of tDCS, but the validity of tDCS results is currently under intense debate\n\nObjectiveThe goal of this study is to validate a new HD-tDCS protocol for bilateral modulation of the Somatosensory Cortex (SI). The new montage is meant to increase the focus of the stimulation while limiting the area of the scalp covered by electrodes. We aim to characterize the effect of the stimulation in terms of directionality, consistency and reproducibility.\n\nMethodsWe aim to leverage a 1 x 1 montage to most focally stimulate the primary somatosensory cortex (SI) and measure modulation via Somatosensory Evoked Potentials (SEP) triggered by median nerve stimulation.\n\nResultsThe results of Experiment1 suggest that our montage increases the amplitude of the SEP component N30. In Experiment2, we aim to replicate our finding and to assess the duration of the modulatory effect on N30 over time. Data from Experiment2 fails to replicate N30 modulation. A sequential Bayesian analysis performed on N30 data from both experiments indicates that the effect fluctuates across participants, without a clear homogenous directionality.\n\nConclusionThis study sets boundaries on the effect size that can be expected for this montage and illustrates the need to include replication samples or larger sample sizes to avoid overestimating effect sizes. We conclude that our montage has insufficient effect size for use in moderately sample-sized experimental studies and clinical applications.

neuroscience↗

Harm to others acts as a cingulate dependent negative reinforcer in rat

Empathy, the ability to share another individuals emotional state and/or experience, has been suggested to be a source of prosocial motivation by making actions that harm others aversive. The neural underpinnings and evolution of such harm aversion remain poorly understood. Here, we characterize an animal model of harm aversion in which a rat can choose between two levers providing equal amounts of food, but one additionally delivering a footshock to a neighboring rat. We find that independently of sex and familiarity, rats reduce their usage of the preferred lever when it causes harm to a conspecific, displaying an individually varying degree of harm aversion. Prior experience with pain increases this effect. In additional experiments, we show that rats reduce the usage of the harm-inducing lever when it delivers twice, but not thrice the number of pellets than the non-preferred lever, setting boundaries on the magnitude of harm aversion. Finally, we show that pharmacological deactivation of the anterior cingulate cortex, a region we have shown to be essential for emotional contagion, reduces harm aversion, while leaving behavioral flexibility unaffected. This model of harm aversion might help shed light onto the neural basis of psychiatric disorders characterized by reduced harm aversion, including psychopathy and conduct disorders with reduced empathy, and provide an assay for the development of pharmacological treatments of such disorders.

neuroscience↗