Empathic pain evoked by sensory and emotional-communicative cues share common and process-specific neural representation
Abstract
Pain empathy can be evoked by multiple cues, particularly observation of acute pain inflictions or facial expressions of pain. Previous studies suggest that these cues commonly activate the insula and anterior cingulate, yet vicarious pain encompass pain-specific responses as well as unspecific processes (e.g., arousal) and overlapping activations are not sufficient to determine process-specific shared neural representations. We employed multivariate pattern analyses to fMRI data acquired during observation of noxious stimulation of body limbs (NS) and painful facial expressions (FE) and found spatially and functionally similar cross-modality (NS versus FE) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. The vicarious pain patterns were not sensitive to respond to non-painful high-arousal negative stimuli but predicted self-experienced thermal pain. Finally, a domain-general vicarious pain pattern predictive of self-experienced pain but not arousal was developed. Our findings demonstrate shared pain-associated neural representations of vicarious pain.
Data availability
The functional MRI, numerical data as well as the Matlab scripts used to generate the figures have been deposited on the figshare repository under accession code 11994498 (https://figshare.com/articles/Vicarious_pain_dataset/11994498)Statistical and pattern weight maps are available on the Neurovault repository under collection 6332 (https://neurovault.org/collections/6332/). Statistical and pattern weight images are available on Neurovault
-
Vicarious pain datasetFigshare, Vicarious_pain_dataset/11994498.
Article and author information
Author details
Funding
National Natural Science Foundation of China (91632117)
- Benjamin Becker
National Natural Science Foundation of China (31700998)
- Keith M Kendrick
National Natural Science Foundation of China (31530032)
- Shuxia Yao
National Institute of Mental Health (R01 MH116026)
- Tor D Wager
National Institute of Biomedical Imaging and Bioengineering (R01EB026549)
- Tor D Wager
National Key Research and Development Program of China (2018YFA0701400)
- Benjamin Becker
Fundamental Research Funds for Central Universities (ZYGX2015Z002)
- Benjamin Becker
Science, Innovation and Technology Department of the Sichuan Province (2018JY0001)
- Benjamin Becker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alexander Shackman, University of Maryland, United States
Ethics
Human subjects: All participants provided written informed consent for study participation and consent to publish the data. The study and all procedures were approved by the local ethics committee at the University of Electronic Science and Technology of China (Approval ID: 298) and was in accordance with the most recent revision of the Declaration of Helsinki.
Version history
- Received: March 14, 2020
- Accepted: September 5, 2020
- Accepted Manuscript published: September 7, 2020 (version 1)
- Version of Record published: September 21, 2020 (version 2)
Copyright
© 2020, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,392
- Page views
-
- 445
- Downloads
-
- 43
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Developmental Biology
- Neuroscience
The cell-type-specific expression of ligand/receptor and cell-adhesion molecules is a fundamental mechanism through which neurons regulate connectivity. Here, we determine a functional relevance of the long-established mutually exclusive expression of the receptor tyrosine kinase Kit and the trans-membrane protein Kit Ligand by discrete populations of neurons in the mammalian brain. Kit is enriched in molecular layer interneurons (MLIs) of the cerebellar cortex (i.e., stellate and basket cells), while cerebellar Kit Ligand is selectively expressed by a target of their inhibition, Purkinje cells (PCs). By in vivo genetic manipulation spanning embryonic development through adulthood, we demonstrate that PC Kit Ligand and MLI Kit are required for, and capable of driving changes in, the inhibition of PCs. Collectively, these works in mice demonstrate that the Kit Ligand/Kit receptor dyad sustains mammalian central synapse function and suggest a rationale for the affiliation of Kit mutation with neurodevelopmental disorders.
-
- Neuroscience
Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.