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How we experience the pain of other people?

A new study from the Netherlands Institute for Neuroscience recorded from neurons of human patients to show that the pain of others is directly mapped onto neurons in the insula – a brain region critical for our own emotions.

Sharing the distress of others is considered key to empathy and our motivation to help others. With people greatly differing in their ability to empathize, and some psychiatric patients lacking the ability to empathize, understanding how our brain makes the pain of others feel painful is key to understanding the origin of these individual differences.

So far, we have had to rely on fMRI studies to identify brain regions that become activated while we perceive the pain of others. Unfortunately, fMRI cannot directly measure the activity of neurons. Instead it measures changes in blood-flow that help pinpoint brain regions that are associated with empathy. To understand where in the brain neurons help us share the distress of others, we would need to insert electrodes into the brain, and directly measure the electrical activity through which neurons process information. For obvious reasons, this is not possible in humans, or is it?

Epilepsy patients

In certain cases of epilepsy that cannot be treated using pharmacological treatments, surgeons implant electrodes directly into the brain of patients, to localize the origin of the epilepsy. The patients then have to stay in the hospital for about a week, while the surgical team records their brain activity and waits for an epileptic event to occur. To add purpose to this waiting, some patients volunteer a unique opportunity to better understand the human mind: they engage in psychological tasks while their brain activity is measured through these medical electrodes.

In a new paper published in the prestigious journal eLife, a collaboration between NIN researchers Efe Soyman, Rune Bruls, Kalliopi Ioumpa under the supervision of professors Christian Keysers and Valeria Gazzola leveraged this unique opportunity to test the notion that neurons in brain regions involved in our own pain, like the insula, contain neurons with activity that directly mirrors the pain of others. They showed patients short video-clips of a woman experiencing various levels of pain, and measured how strongly neurons in the insula – a brain region involved in the patient’s own pain experiences – respond to the pain they observe the woman in the video-clip to experience. Specifically, they could measure intracranial local field potentials, which measure the activity of some hundreds of insula neurons close to the electrode, from 7epilepsy patients. In addition, they could zoom into the activity of individual neurons in the insula of 3 epilepsy patients.

Background: The insula and our own emotions

The insula, a brain region hidden inside of the brain, is known to play a critical role in our own emotions. It can sense the state of our body through input from our inner organs and skin, and integrates this information with what we see, hear and smell, and is thought to give rise to these conscious feelings we call emotions. In particular, it has also been shown to contain many neurons that respond when we experience pain in or on our own body, with the level of its activity scaling with how unpleasant we find this pain.

The novelty: coding the pain of others

The team therefore explored whether neurons in this region would also represent the level of pain experiences by others. Because the movies they showed participants varied in how much pain the actress in the movies was experiencing, the team could explore whether movies in which the patients perceived others to be in more pain would be movies in which the insular neurons would show more activity – serving as a mirror for other people’s pain. This is exactly what they found: throughout the insula, they could record electrical activity that scaled with the pain the people reported perceiving in the movies. This was true in the local field potentials, and even in individual neurons, providing the first evidence, that a brain region involved in our own pain, contains a fine-grained representation of how much pain others experience.

Using advanced data analysis methods, the team could take the level of electrical activity in the insula during each movie, and predict how the patient would respond to the question: “how intense do you think the pain was that the person in the movie experienced”. By offering the unique opportunity to directly record from their brain, the patients thus provided us with a key insight into human empathy: it really looks as though we empathize with the pain of others because our brains are wired to transform their pain into activity in regions involved in our own pain.

How do we perceive the pain of others?

The team provided further insights into how we perceive the pain of others. In half the videos, the camera was focused on the facial expression of the actress, which was seen to unfold from a neutral expression to one of varying degree of pain in a period of about one second. Analyzing the electrical responses in the insula and the muscle movements of the actress in the movies revealed that what the brain appears to use to perceive the pain of others was not the movement per se, but simply how contracted the eyes of the actress ended up being. In the other half, the camera was focusing on the hand of the actress, and showed a belt hitting the hand. In that case, the brain appeared to deduce the amount of pain from processing how much the hand was moving under the action of the belt. Together, this revealed intricate details of how flexibly the human brain transforms what we see others do into a fine-grained perception of their inner states.

While this study focused on a single brain region, the insula, that fMRI studies had suggested to be important for empathy, future research of the team will aim to combine the data from all recorded electrodes. They can then develop a map of where in the brain, the pain of others is transformed into the nuanced empathy we can have for other people’s emotions, and pinpoint the locations in which differences across individuals could account for the striking differences in empathy we can observe around us.

Acknowledgements:

This work was made possible through a tight collaboration between the members of the social brain lab that designed the tasks and analysed the data (Efe Soyman, Rune Bruls, Kalliopi Ioumpa, Laura Müller-Pinzler, Selene Gallo, Chaoyi Qin, Christian Keysers and Valeria Gazzola), clinicians at the VUmc in Amsterdam that performed the surgeries and helped in data acquisition (Elisabeth CW van Straaten, Johannes C Baayen, Sander Idema), and the team of Prof. Pieter Roelfsema and Matt Self (Matthew W Self, Judith C Peters, Jessy K Possel) that have established the link between the fundamental research at the NIN and the clinicians at the VUmc, and also helped acquire the data. We extend our warmhearted gratitude to the patients that participate and thereby made these scientific insights possible.

Source: eLife

Quotes:

Christian Keysers: “As a neuroscientist, our dream is to understand how neurons make us who we are. What these patients do, by allowing us to record from these electrodes, is to make that dream come true: we could see in real time, how the pain of someone else is mirrored in the neurons of an observer. After decades of working on empathy, we could see empathy unfold in the human insula”.

Efe Soyman: “Other people’s suffering can be inferred from a variety of indicators: a painful expression, the intensity of the event that inflicts pain in them, etc. With this incredibly valuable data we collected from the patients, we see how the human insula might tune into whichever is available among these various cues when we experience the pain of other people.”

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Keysers Group

While we watch a movie, we share the experiences of the actors we observe: our heart for instance starts beating faster while we see an actor slip from the roof of a tall building. Why?

Specific brain areas are involved when we perform certain actions or have certain emotions or sensations. Interestingly, some of these areas are also recruited when we simply observe someone else performing similar actions, having similar sensations or having similar emotions. These areas called ‘shared circuits’ transform what we see into what we would have done or felt in the same situation. With such brain areas, understanding other people is not an effort of explicit thought but becomes an intuitive sharing of their emotions, sensations and actions.

Christian Keysers‘ lab focuses on providing increasingly detailed insights into how exactly the brain achieves this remarkable feat of empathy. For this aim, the lab combines powerful methods to non-invasively image brain activity in humans, with an unprecedented ability to record and influence brain activity at neural levels in rodents. You can get an impression for the labs spirit in these short movies:

 

In addition, the lab explores why some people seem to show very reduced empathy, for instance in patient groups that suffer from impairments in social cognition, including autism and psychopathy. You can get an impression for that work from the following episode with Morgan Freeman:

Cover The Empathic Brain

 

Read more about our research in Christian Keysers’s book The Empathic Brain.

Available at Amazon US, EU, UK in English, or as translations into Dutch (Het empathische brein), German (Unser Empathisches Gehirn), Turkish or Japanese.

 

Or what Christian Keysers present the lab at the Marie Curie Action’s 20th Anniversary in Brussels

 

Social Brain Lab

Befitting our interest in social cognition, my lab and that of Valeria Gazzola create a joint, strongly collaborative cluster of expertise on the neural basis of social cognition that we call the Social Brain Lab.

Student projects

If you are interested in applying for an internship in the Social Brain Lab please follow the instructions in this document. This also applies to literature thesis projects.

Top Publications

  • 2022    Cerliani L, Bhandari R, De Angelis L, vdZwaag W, Bazin PL, Gazzola V, Keysers C. Predictive coding during action observation – a depth-resolved intersubject functional correlation study at 7T. Cortex. https://doi.org/10.1016/j.cortex.2021.12.008.
  • 2021    Paradiso E, Gazzola V, Keysers C. Neural mechanisms necessary for empathy-related phenomena across species. Current Opinions in Neurobiology. https://doi.org/10.1016/j.conb.2021.02.005.
  • 2020    Hernandez-Lallement J, Attah AT, Soyman E, Pinhal C, Gazzola V*, & Keysers C*. Harm to others acts as a cingulate dependent negative reinforcer in rat. Current Biology. [see online] For a video summary click here:
  • 2020    Han Y, Sichterman B, Carrillo M, Gazzola V, Keysers C. Similar levels of emotional contagion in male and female rats. Sci Rep. 2020; 10: 2763. https://doi.org/10.1038/s41598-020-59680-2.
  • 2020    Borja Jimenez KC, Abdelgabar AR, De Angelis L, McKay LS, Keysers C, Gazzola V. Changes in brain activity following the voluntary control of empathy. Neuroimage. 2020 https://doi.org/10.1016/j.neuroimage.2020.116529
  • 2019    Abdelgabar AR*, Suttrup J*, Broersen R*, Bhandari R*, Picard S, Keysers C*, de Zeeuw C* & Gazzola V*. Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia. Brain : A Journal of Neurology [see online]
  • 2019    Han Y*, Bruls R*, Thomas RM, Pentaraki V, Jelinek N, Heinemans M, …, Gazzola V, Carrillo M, Keysers, C. Bidirectional cingulate-dependent danger information transfer across rats. PLoS Biology, e3000524 [see online]
  • 2019    Carrillo M, Han Y, Migliorati F, Liu M, Gazzola V, Keysers C (2019). Emotional Mirror Neurons in the Rat’s Anterior Cingulate Cortex. Current Biology. [see online] see podcast below
  • 2018    Gallo S, Paracampo R, Müller-Pinzler L, Severo MC, Blömer L, Fernandes-Henriques C, Henschel A, Lammes BK, Maskaljunas T, Suttrup J, Avenanti A, Keysers C, Gazzola V. The causal role of the somatosensory cortex in prosocial behaviour. eLife 7 e32740 [see online]
  • 2016    Zaki J, Wager TD*, Singer T*, Keysers C*, Gazzola, V*. The Anatomy of Suffering: Understanding the relationship between nociceptive and empathic pain. Trends in Cognitive Sciences 20, 249-259. [see online]
  • 2015    Cerliani L, Mennes M, Thomas RM, Di Martino A, Thioux M & Keysers C. Increased functional connectivity between subcortical and cortical resting-state networks in autism spectrum disorder. JAMA Psychiatry 72, 767-777. [see online]
  • 2014    Keysers C & Gazzola V. Dissociating the ability and propensity for empathy. Trends Cogn. Sci. 18, 163-166. [see online]
  • 2014    Di Martino A, Yan CG, Li Q, Denio E, Castellanos FX, Alaerts K, Anderson JS, Assaf M, Bookheimer SY, Dapretto M, Deen B, Delmonte S, Dinstein I, Ertl-Wagner B, Fair DA, Gallagher L, Kennedy DP, Keown CL, Keysers C, Lainhart JE, Lord C, Luna B, Menon V, Minshew NJ, Monk CS, Mueller S, Muller RA, Nebel MB, Nigg JT, O’Hearn K, Pelphrey KA, Peltier SJ, Rudie JD, Sunaert S, Thioux M, Tyszka JM, Uddin LQ, Verhoeven JS, Wenderoth N, Wiggins JL, Mostofsky SH & Milham MP. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol. Psychiatr. 19, 659-667. [see online]
  • 2013    Meffert H, Gazzola V, den Boer JA, Bartels AAJ & Keysers C. Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy. Brain 136, 2550-2562. [see online]
  • 2012    Hasson U, Ghazanfar AA, Galantucci B, Garrod S & Keysers C. Brain-to-brain coupling: a mechanism for creating and sharing a social world. Trends Cogn. Sci. 16, 114-121. [see online]
  • 2012    Gazzola V, Spezio ML, Etzel JA, Castelli F, Adolphs R & Keysers C. Primary somatosensory cortex discriminates affective significance in social touch. Proc. Natl. Acad. Sci. U. S. A. 109, E1657-E1666. [see online]
  • 2012    Cerliani L, Thomas RM, Jbabdi S, Siero JCW, Nanetti L, Crippa A, Gazzola V, D’Arceuil H & Keysers C. Probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex. Hum. Brain Mapp. 33, 2005-2034. [see online]
  • 2011    Atsak P, Orre M, Bakker P, Cerliani L, Roozendaal B, Gazzola V, Moita M & Keysers C. Experience Modulates Vicarious Freezing in Rats: A Model for Empathy. PLoS One 6 [see online]
  • 2011    Arnstein D, Cui F, Keysers C, Maurits NM & Gazzola V. mu-Suppression during Action Observation and Execution Correlates with BOLD in Dorsal Premotor, Inferior Parietal, and SI Cortices. J. Neurosci. 31, 14243-14249. [see online]
  • 2010    Schippers MB, Roebroeck A, Renken R, Nanetti L & Keysers C. Mapping the information flow from one brain to another during gestural communication. Proc. Natl. Acad. Sci. U. S. A. 107, 9388-9393. [see online]
  • 2010    Keysers C, Kaas JH & Gazzola V. Somatosensation in social perception. Nat. Rev. Neurosci. 11, 417-428. [see online]
  • 2009    Keysers C & Gazzola V. Expanding the mirror: vicarious activity for actions, emotions, and sensations. Curr. Opin. Neurobiol. 19, 666-671. [see online]
  • 2009    Keysers C. Mirror neurons. Curr. Biol.19, R971-R973
  • 2009    Gazzola V & Keysers C. The Observation and Execution of Actions Share Motor and Somatosensory Voxels in all Tested Subjects: Single-Subject Analyses of Unsmoothed fMRI Data. Cereb. Cortex 19, 1239-1255
  • 2009    Bastiaansen J, Thioux M & Keysers C. Evidence for mirror systems in emotions. Philos. Trans. R. Soc. B-Biol. Sci. 364, 2391-2404
  • 2007    Jabbi M, Swart M & Keysers C. Empathy for positive and negative emotions in the gustatory cortex. Neuroimage34 1744-1753
  • 2007    Gazzola V, van der Worp H, Mulder T, Wicker B, Rizzolatti G & Keysers C. Aplasics born without hands mirror the goal of hand actions with their feet. Curr. Biol. 17, 1235-1240
  • 2007    Gazzola V, Rizzolatti G, Wicker B & Keysers C. The anthropomorphic brain: The mirror neuron system responds to human and robotic actions. Neuroimage 35, 1674-1684
  • 2006    Keysers C & Gazzola V Towards a unifying neural theory of social cognition. Understanding Emotions 379-401
  • 2006    Gazzola V, Aziz-Zadeh L & Keysers C. Empathy and the somatotopic auditory mirror system in humans. Curr. Biol. 16, 1824-1829
  • 2004    Keysers C, Wicker B, Gazzola V, Anton JL, Fogassi L & Gallese V. A touching sight: SII/PV activation during the observation and experience of touch. Neuron 42, 335-346
  • 2004    Keysers C & Perrett DI. Demystifying social cognition: a Hebbian perspective. Trends Cogn. Sci. 8, 501-507
  • 2004    Gallese V, Keysers C & Rizzolatti G. A unifying view of the basis of social cognition. Trends Cogn. Sci. 8, 396-403
  • 2003    Wicker B, Keysers C, Plailly J, Royet JP, Gallese V & Rizzolatti G. Both of us disgusted in My Insula: The common neural basis of seeing and feeling disgust. Neuron 40, 655-664
  • 2002    Kohler E, Keysers C, Umilta MA, Fogassi L, Gallese V & Rizzolatti G. Hearing sounds, understanding actions: Action representation in mirror neurons. Science 297, 846-848
  • 2001    Umilta MA, Kohler E, Gallese V, Fogassi L, Fadiga L, Keysers C & Rizzolatti G. I know what you are doing: A neurophysiological study. Neuron 31, 155-165

 

Funding

ERC European Commission FP7

NWOMarieCurie

The Keysers lab studies fundamental issues in social neuroscience. To do so, we are entirely dependent on public funding. We are enormously thankful to the Dutch Science Foundation (NWO) and the European Commission for being dedicated patrons of such frontier science. Without the Talent Scheme of NWO that has supported our work through VENI, VIDI and VICI grants, and without the European Commission that has supported us through the ERC and several Marie Skłodowska-Curie actions, we would have been unable to tackle the mysteries of our social nature. In addition, the Dutch Government has helped us deeply through the  National Initiative for Brain and Cognition.

FACILITIES

The social brain lab is equipped to integrate research in humans and rodents. For this purpose it has the following equipment.

HUMAN RESEARCH:

Human Equipment at SBL
Human Equipment at SBL
  • 3T philips scanner at the Spinoza Center (10m away, click here for details)
  • 7T philips scanner at the Spinoza Center (10m away, click here for details)
  • 130Ch ActiChamp EEG system (that can be split in two 64Ch systems for hyperscanning)
  • Magstim Rapid TMS system with neuronavigation
  • 8Ch Soterix tDCS system

RODENT RESEARCH

  • housing facilities for mice and rats
  • 64Ch Neuralynx Electrophysiology system for freely moving rodents with silicon probes or tetrodes
  • Dual Neuropixel recording
  • Neurolabware two-photon laser scanning microscope
  • DM2 fascilities for viral transfections
  • Ethovision system for behavioral analysis

DATA ANALYSIS

  • 40 Core, 2TB RAM shared ram supercomputer

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Gazzola Group

When we see a little girl falling from her bike, why do most of us instinctively run to help and comfort her?

Years of research show that one of the reasons why we help other people is because their suffering activates brain regions that are also active when we ourselves are hurt. The pain of the child with her bleeding knee becomes our own pain. Helping the girl now becomes a way to sooth what is now our pain. A similar contagion happens for other emotions as well: we rejoice with our friend when we watch her crossing the finish line of her first marathon.
In some circumstances the decision to help is less readily made, but requires a detailed analysis of the pros and cons of the action we decide to take. For instance, if you are late for an important job interview, and you see the mother also running toward the child, you might decide to keep on going instead. This is because you have quickly calculated the benefits for the other against the costs for yourself, and found that the costs of helping (high probability of not getting the coveted new job) in this case are higher than the benefits to the other (comforting a child you do not know while her mom will soon arrive).

Some of the core questions my lab currently investigates are: What areas of the brain cause us to act prosocially? How does the brain weigh the benefits to self and the cost to others? How do we learn the consequences our actions have on others? When we hit someone he will likely be in pain. How does this make us learn that hitting people is bad? Why do psychopathic individuals fail to acquire these moral sentiments? Does the activation of our own pain brain regions while witnessing the other wince in pain play a critical role in that learning?

In order to answer these questions, we synergize brain imaging tools such as 3T and 7T fMRI and EEG, and neuro-modulation tools, such as TMS and tDCS.

 

 

Social Brain Lab

Befitting our interest in social cognition, my lab and that of Christian Keysers create a joint, strongly collaborative cluster of expertise on the neural basis of social cognition that we call the Social Brain Lab.

STUDENT PROJECTS

If you are interested in applying for an internship in the Social Brain Lab please follow the instructions in this document. This also applies to literature thesis projects.

Funding

The Gazzola lab is generously financed by the Dutch Science Foundation’s Innovational Research Incentives Scheme (VIDI), the Brain & Behavior Research Foundation, the European Research Council Start Up Grant, the European Commission’s Marie Skłodowska-Curie actions, and the Consejo Nacional de Ciencia y Tecnología of Mexico.

 

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