Neural mechanisms necessary for empathy-related phenomena across species
Open accessAbstract
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.
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Oxytocin has an effect on empathic responses across many species.
“Especially in empathic responses, previous studies suggest that oxytocin has an effect across many species (Panksepp and Panksepp, 2013; Paradiso et al., 2021).”
From Helping behavior in prairie voles: a model of empathy and the importance of oxytocin (2022) · cites this paper as Paradiso et al., 2021
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“Neurobiology While a decade ago many doubted whether rodents show emotional contagion through neural mechanisms relevant to human empathy, recent work has established that regions associated with empathy for pain in humans are activated by, or necessary for, emotional contagion in rodents (Figure 3) [73].”
Neural basis of prosocial behavior
Wu, Y. E., & Hong, W. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.06.008 · Cited by 127 · see citing works
Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice
Scheggia, D., Greca, F. L., Maltese, F., Chiacchierini, G., Italia, M., Molent, C., Bernardi, F., Coccia, G., Carrano, N., Zianni, E., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01179-2 · Cited by 76 · see citing works
Sexually dimorphic control of affective state processing and empathic behaviors
Fang, S., Luo, Z.-Y., Wei, Z., Qin, Y., Zheng, J., Zhang, H., Jin, J., Li, J., Miao, C., Yang, S., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.02.001 · Cited by 45 · see citing works
Vicarious Emotions of Fear and Pain in Rodents
Keysers, C., & Gazzola, V. (2023) · Affective Science · doi:10.1007/s42761-023-00198-x · Cited by 37 · see citing works
“…one may be more inclined to suspect that witnessing the distress of others may trigger feelings similar to our own, given the significant similarities in neural activity while witnessing the distress of others across rats, mice, and humans (Keysers et al., 2022; Paradiso et al., 2021; Fig.”
BackgroundHelping behavior in prairie voles: a model of empathy and the importance of oxytocin
Kitano, K., Yamagishi, A., Horie, K., Nishimori, K., & Sato, N. (2022) · iScience · doi:10.1016/j.isci.2022.103991 · Cited by 31 · see citing works
“Especially in empathic responses, previous studies suggest that oxytocin has an effect across many species (Panksepp and Panksepp, 2013; Paradiso et al., 2021).”
A distinct cortical code for socially learned threat
Silverstein, S. E., O’Sullivan, R., Bukalo, O., Pati, D., Schaffer, J. A., Limoges, A., Zsembik, L. C. P., Yoshida, T., O’Malley, J. J., Paletzki, R. F., et al. (2024) · Nature · doi:10.1038/s41586-023-07008-1 · Cited by 34 · see citing works
Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia
Phillips, H. L., Dai, H., Choi, S. Y., Jansen‐West, K. R., Zajicek, A. S., Daly, L., Petrucelli, L., Gao, F., & Yao, W. (2023) · Neuron · doi:10.1016/j.neuron.2022.12.027 · Cited by 29 · see citing works
Neural mechanisms of comforting: Prosocial touch and stress buffering
Lim, K. Y., & Hong, W. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2023.105391 · Cited by 29 · see citing works
“…of the process of empathy, including the perception and social transfer of negative states, we recommend referring to other reviews (de Waal and Preston, 2017; Ferretti and Papaleo, 2019; Meyza et al., 2017; Panksepp and Lahvis, 2011; Paradiso et al., 2021; Sivaselvachandran et al., 2018).”
ResultSoyman, E., Bruls, R., Ioumpa, K., Müller‐Pinzler, L., Gallo, S., Qin, C., van Straaten, E. C. W., Self, M. W., Peters, J. C., Possel, J. K., et al. (2022) · eLife · doi:10.7554/elife.75197 · Cited by 25 · see citing works
“Across humans, primates, and rodents, lesions in these regions impair the perception 67 and the sharing of others’ emotions (Paradiso et al., 2021), providing evidence for their 68 causal contribution to the perception or sharing of the emotions of others.”
BackgroundEmotional contagion: Improving survival by preparing for socially sensed threats
Keysers, C., & Gazzola, V. (2021) · Current Biology · doi:10.1016/j.cub.2021.03.100 · Cited by 23 · see citing works
Ebisch, S. J. H., Scalabrini, A., Northoff, G., Mucci, C., Sergi, M. R., Saggino, A., Aquino, A., Alparone, F. R., Perrucci, M. G., D, V. G. M., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12040477 · Cited by 18 · see citing works
Tickle contagion in the rat somatosensory cortex
Kaufmann, L. V., Brecht, M., & Ishiyama, S. (2022) · iScience · doi:10.1016/j.isci.2022.105718 · Cited by 21 · see citing works
Liao, C.-H. (2025) · Humanities and Social Sciences Communications · doi:10.1057/s41599-025-05334-5 · Cited by 19 · see citing works
“Decety and Holvoet (2021) argued that cognitive empathy depends signi fi cantly on the maturation of executive functions in the brain, particularly emphasizing the medial prefrontal cortex ’ s centrality during tasks requiring perspective-taking (Decety & Michalska, 2020, Paradiso et al., 2021).”
Environmental factors and their impact on chronic pain development and maintenance
Sant’Anna, M. B., Kimura, L. F., Vieira, W. F., Zambelli, V. O., Novaes, L. S., Hösch, N. G., & Picolo, G. (2024) · Physics of Life Reviews · doi:10.1016/j.plrev.2024.01.007 · Cited by 19 · see citing works
Negative energy balance hinders prosocial helping behavior
Pozo, M., Milà‐Guasch, M., Haddad-Tóvolli, R., Boudjadja, M. B., Chivite, Í., Toledo, M., Gómez-Valadés, A. G., Eyre, E., Ramírez, S., Obri, A., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2218142120 · Cited by 18 · see citing works
“Oxytocin neurons of the PVN have been associated with empathy, emotion recognition, and social engagement (26).”
Parental brain through time: The origin and development of the neural circuit of mammalian parenting
Kuroda, K. O., Fukumitsu, K., Kurachi, T., Ohmura, N., Shiraishi, Y., & Yoshihara, C. (2024) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15111 · Cited by 18 · see citing works
“262 Wu et al. 263 reported that the GABAergic projections from the MeA to the MPOA mediateconsolatoryallogroomingbehavior,tothesameextentinmale and female mice.”
BackgroundIntracranial EEG signals disentangle multi-areal neural dynamics of vicarious pain perception
Tan, H., Zeng, X., Ni, J., Liang, K., Xu, C., Zhang, Y., Wang, J., Li, Z., Yang, J., Han, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49541-1 · Cited by 19 · see citing works
“…imaging (fMRI) studies have identi fi ed a core pain empathy network, including the anterior insula (AI), anterior cingulate cortex (ACC), amygdala, and inferior frontal gyrus (IFG) 9,10 . fMRI fi ndings have linked these regions to distinct processes involved in vicarious pain experiences 9 – 12 .”
BackgroundDoing good well (Karma Yoga, the path of selfless action): Psychotherapeutic lessons from the East
Keshavan, M. S., Hegde, S., & Bhargav, H. (2024) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2024.104201 · Cited by 17 · see citing works
Watch and Learn: Vicarious Threat Learning across Human Development
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Evolutionary origin and the development of consciousness
Александрович, К. И. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.034 · Cited by 15 · see citing works
“Recent evidence from neuroimaging and neuromodulation reveals that in the neural systems of rodents, macaques, and humans, the anterior cingulate and the amygdala are necessary to facilitate empathy and prosocial behaviour (Paradiso et al., 2021; Smith et al., 2021).”
BackgroundAn opinion on the interpretation of social release in rats
Blystad, M. H. (2021) · Biology Letters · doi:10.1098/rsbl.2021.0355 · Cited by 13 · see citing works
Protocols for the social transfer of pain and analgesia in mice
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“Historically, empathy has been considered a high-level cognitive process experienced exclusively by humans, but it is now accepted that many mammals display endophenotypes of empathy (de Waal, 2008; Panksepp and Lahvis, 2011; Martin et al., 2015; Decety et al., 2016; Keum et al., 2016; Sivaselvachandran et al., 2018;…”
BackgroundGenzer, S., Adiva, Y. B., & Perry, A. (2023) · Cambridge University Press eBooks · doi:10.1017/9781009281072 · Cited by 14 · see citing works
Virtual social grooming in macaques and its psychophysiological effects
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“…interaction, one could suggest that vicarious processes could be at play, and engage similar mechanisms and brain circuits that have been found to support empathic responses to both painful and rewarding stimuli 26,27 , and the still poorly understood mechanisms involved in giving grooming 28 .”
BackgroundDissecting shared pain representations to understand their behavioral and clinical relevance
Rütgen, M., & Lamm, C. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105769 · Cited by 11 · see citing works
“Animal models of empathy, and in particular lesion studies allow to move beyond some of the limitations of research in humans (see (Paradiso et al., 2021) for a recent in-depth review of rodent and non-human primate models of empathy).”
BackgroundThe neuroscience of human empathy for pleasure: protocol for a scoping review
Mello, M., Fusaro, M., & Aglioti, S. M. (2024) · Systematic Reviews · doi:10.1186/s13643-024-02481-9 · Cited by 8 · see citing works
“However, most of the neuroscience literature has hitherto focused on the behavioral and neural correlates of empathizing with others’ negative emotions, and in particular pain [7, 13–15].”
BackgroundBrain organoids: a new paradigm for studying human neuropsychiatric disorders
Sun, Y. E., & Pan, W. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1699814 · Cited by 8 · see citing works
ARNT2 controls prefrontal somatostatin interneurons mediating affective empathy
Choi, J., Jung, S., Kim, J., So, D., Kim, A., Kim, S., Choi, S., Yoo, E., Kim, J. Y., Jang, Y. C., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114659 · Cited by 8 · see citing works
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“Those brain areas include the insula, inferior frontal gyrus and medial frontal regions around the cingulate cortex, as well as the amygdala, thalamus, putamen, caudate and primary somatosensory area [80,81].”
BackgroundWhy help others? Insights from rodent to human early childhood research
Chen, Y., Han, S., & Yin, B. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1058352 · Cited by 6 · see citing works
“This role seems to be conservative in rodents, macaques and humans, consistent with their evolutionary homology (van Heukelum et al., 2020; Paradiso et al., 2021).”
BackgroundHe, J., Bore, M. C., Jiang, H., Gan, X., Wang, J., Li, J., Xu, X., Wang, L., Fu, K., Li, L., et al. (2024) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.08.019 · Cited by 7 · see citing works
Empathic pain: Underlying neural mechanism
Zhang, M.-M., & Chen, T. (2024) · The Neuroscientist · doi:10.1177/10738584241283435 · Cited by 6 · see citing works
Reading the Mind through the Nose: Mentalizing Skills Predict Olfactory Performance
Lübke, K. T., Blum, T. C., & Pause, B. M. (2022) · Brain Sciences · doi:10.3390/brainsci12050644 · Cited by 6 · see citing works
Aggression: The dark side of mirror neurons sheds light on their functions
Ferrari, P. F., Méndez, C. A., & Coudé, G. (2023) · Current Biology · doi:10.1016/j.cub.2023.03.028 · Cited by 6 · see citing works
Ketterer-Sykes, E. B., Saraceno, E., Hough, F., Wyse, M., Restifo-Bernstein, G., Blais, A. Y., Khondokar, M., Hoen, P., & López, H. H. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173846 · Cited by 5 · see citing works
Neural control of sex differences in affiliative and prosocial behaviors
Mikulovic, S., & Lenschow, C. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106039 · Cited by 5 · see citing works
“In contrast, empathy is characterized as the cognitive and emotional capacity to comprehend and resonate with the emotional and cognitive conditions of others (Paradiso et al., 2021).”
The neurostructural bases of empathy: morphometric evidence for a multicomponential approach
Arioli, M., Baghi, L. R., Cattaneo, Z., & Canessa, N. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1544632 · Cited by 5 · see citing works
Exploring rodent prosociality: A conceptual framework
Charron, V., Talbot, J., & Plamondon, H. (2025) · Translational Neuroscience · doi:10.1515/tnsci-2025-0375 · Cited by 4 · see citing works
“Additionally, the basolateral amygdala (BLA) appears to be implicated in both rodents [67,122] and humans [123].”
Implicit Bias Scenario Design: What Can We Learn from Cognitive Science?
Gilbert, M., & Keyser, V. (2022) · Clinical Simulation in Nursing · doi:10.1016/j.ecns.2022.08.003 · Cited by 4 · see citing works
Packheiser, J., Soyman, E., Paradiso, E., Michon, F., Ramaaker, E., Sahin, N., Muralidharan, S., Wöhr, M., Gazzola, V., & Keysers, C. (2023) · Communications Biology · doi:10.1038/s42003-023-05474-x · Cited by 4 · see citing works
“Taking the results from Experiments 2 and 3 together, it seems unlikely that the null effects from the second experiment were due to changes in modality (CO 2 vs. footshocks).”
BackgroundResultNeuronal networks in the dorsal hippocampus causally regulate rescue behavior in mice
Corrêa, M. D. S., Agafonova, A., Braun, A., Omprakash, C., Tafani, E., Lowitsch, M., Marquardt, L., Bauer, P., Albrecht, A., & Mikulovic, S. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.116923 · Cited by 4 · see citing works
The spread of fear in an empathetic fish
DeAngelis, R., & Hofmann, H. A. (2023) · Science · doi:10.1126/science.adh0769 · Cited by 3 · see citing works
The impact of membrane receptors on modulating empathic pain
Teixeira, G. P., Rocha, L., & Faria, R. X. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110471 · Cited by 3 · see citing works
Dapor, C., Sperandio, I., & Meconi, F. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.1028150 · Cited by 3 · see citing works
Endogenous opioid receptor system mediates costly altruism in the human brain
Chen, J., Putkinen, V., Seppälä, K., Hirvonen, J., Ioumpa, K., Gazzola, V., Keysers, C., & Nummenmaa, L. (2024) · Communications Biology · doi:10.1038/s42003-024-07084-7 · Cited by 3 · see citing works
“Accordingly, empathy can be hypothesized to drive prosociality 11 – 14 .”
BackgroundMapping brain-wide activity networks: brainways as a tool for neurobiological discovery
Kantor, B., Ruzal, K., & Bartal, I. B.-A. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02105-3 · Cited by 3 · see citing works
“Notably, as previously reported, these regions include areas that participate in empathy in humans [19, 20] and rodents [21 – 24].”
Tickle contagion in the somatosensory cortexPreprint
Kaufmann, L. V., Brecht, M., & Ishiyama, S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.22.465426 · Cited by 3 · see citing works
“From an evolutionary point of view, emotional contagion, “feeling into” one’s conspecifics, can be a vital ability, not only for humans but for all social species [4-6].”
BackgroundChronic social stress in early life can predispose mice to antisocial maltreating behavior
Jeon, D., Kim, S., Lee, S. K., & Chu, K. (2024) · encephalitis · doi:10.47936/encephalitis.2023.00199 · Cited by 2 · see citing works
“OXY is known to affect social and empathic behavior [50,51], and we previously showed that OXY is involved in the mal-treating behavior in our perpetrator–victim behavioral system [45].”
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Byun, Y., & Noh, J. (2023) · Physiology & Behavior · doi:10.1016/j.physbeh.2023.114379 · Cited by 2 · see citing works
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Scoping Review on Brain Mapping Leadership and Talent Engagement
Thanyawatpornkul, R., SupalakKhemthong, & Chatthong, W. (2022) · Indian Journal of Public Health Research & Development · doi:10.37506/ijphrd.v14i4.18592 · Cited by 2 · see citing works
Galván, K. X. D., Gutiérrez, A. L., González, J. D. J. G., & Shejet, F. O. (2023) · Edupsykhé Revista de Psicología y Educación · doi:10.57087/edupsykhe.v20i1.4533 · Cited by 2 · see citing works
The Evolutionary Pathway to Consciousness and Reason: the Cognitome from a Philosophical Perspective
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“In this regard, studies have shown that, along with the default mode network, the anterior cingulate cortex and the amygdala also make signi fi cant contributions to the nervous system’s own activity [Paradiso et al., 2021; Smith et al., 2021].”
BackgroundScheggia, D., Greca, F. L., Maltese, F., Carrano, N., Luca, M. D., & Papaleo, F. (2021) · Research Square · doi:10.21203/rs.3.rs-404701/v1 · Cited by 2 · see citing works
Kantor, B., & Bartal, I. B.-A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.25.542252 · Cited by 2 · see citing works
“Notably, as previously reported, these regions include areas that have been shown to participate in empathy in humans (Shamay-Tsoory and Lamm, 2018; De-cety et al., 2016) and rodents (Meyza and Knapska, 2018; Wu and Hong, 2022; Walsh et al., 2023; Paradiso et al., 2021).”
BackgroundMin, J., Zhu, T., Liu, M., Zhang, J., Yan, T., Zhu, S., Yang, Y., Zhu, X., Yu, R., Huang, Y., et al. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116845 · Cited by 1 · see citing works
Dissociating neural circuits of social and prosocial reward in rat helping behavior
Ruzal, K., Trachtenberg, E., Kantor, B., Flumin, H., Roemer, A., Crespo, A., Kohl, J., & Bartal, I. B.-A. (2026) · iScience · doi:10.1016/j.isci.2026.114694 · Cited by 2 · see citing works
EVOLUTIONARY PATH OF CONSCIOUSNESS AND REASON: COGNITOME FROM A PHILOSOPHICAL PERSPECTIVE
Александрович, К. И., & Dryaeva, E. D. (2023) · Журнал высшей нервной деятельности им И П Павлова · doi:10.31857/s0044467723010082 · Cited by 1 · see citing works
Khodagholi, F., Dezfouli, M. A., Yazdanfar, N., Rashidi, S. K., Zeinaddini-Meymand, A., Javadpour, P., Mirbehbahani, S. H., & Zare, N. (2024) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10410 · Cited by 1 · see citing works
“In rodents, damage to the amygdala has been associated with deficits in empathic behaviours (Paradiso, Gazzola, and Keysers 2021; Deming, Heilicher, and Koenigs 2022).”
Packheiser, J., Soyman, E., Paradiso, E., Ramaaker, E., Sahin, N., Muralidharan, S., Wöhr, M., Gazzola, V., & Keysers, C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.27.497737 · Cited by 1 · see citing works
“Empathy refers to the ability to understand and share the feelings of other individuals (Baron-Cohen & Wheelwright, 2004; Keysers & Gazzola, 2014a; Paradiso et al., 2021).”
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A Neuropsychological Exploration of a Society’s Ongoing Descent Into a Moral and Factual AbyssPreprint
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“Furthermore, across mammal species and in humans, empathetic behavior depends on activation of similar brain regions, including the amygdala and cingulate cortices (Paradiso et al., 2021).”
Harnessing the Neurobiology of Empathy and Compassion to Alleviate Burnout in Neurology
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Additional file 1 of The neuroscience of human empathy for pleasure: protocol for a scoping review
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“The ability to perceive other people’s facial emotions and the ability to experience emotions are closely related, as they rely on overlapping neural circuits that enable empathic and socially adequate behaviour [5, 41, 42].”
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“27,28 The difficulty to respond appropriately to another’s emotions can compromise interpersonal relationships, thereby contributing to the onset and/or the sustainment of alcohol-related problems but also interfere with recovery.”
- Authors
- Paradiso, E., Gazzola, V., & Keysers, C.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Gazzola, Valeria
- Keysers, Christian
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 68
- Pages
- 107-115
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W3138164693
- Cited by
- 78
- References
- 93
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 18 · 2023: 18 · 2022: 11 · 2021: 9
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Neurobiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, cc-by)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- European Research Council (758703)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (452-14-015, 453-15-009)
- Topics
- Social Sciences › Psychology › Social Psychology › Action Observation and Synchronization
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
- Keywords
- empathy, prosocial behavior, neural basis of empathy, affective empathy, cognitive empathy, emotion recognition, cingulate cortex, amygdala, oxytocin, analgesics, rodent models, nonhuman primate model, lesion studies, neuromodulation, interoception
- MeSH terms
- Brain, Emotions, Empathy, Magnetic Resonance Imaging, Neuroimaging
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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