Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula

  1. Stephan Geuter  Is a corresponding author
  2. Sabrina Boll
  3. Falk Eippert
  4. Christian Büchel
  1. University Medical Center Hamburg Eppendorf, Germany
  2. University of Oxford, United Kingdom

Abstract

The computational principles by which the brain creates a painful experience from nociception are still unknown. Classic theories suggest that cortical regions either reflect stimulus intensity or additive effects of intensity and expectations, respectively. By contrast, predictive coding theories provide a unified framework explaining how perception is shaped by the integration of beliefs about the world with mismatches resulting from the comparison of these believes against sensory input. Using functional magnetic resonance imaging during a probabilistic heat pain paradigm, we investigated which computations underlie pain perception. Skin conductance, pupil dilation, and anterior insula responses to cued pain stimuli strictly followed the response patterns hypothesized by the predictive coding model, whereas posterior insula encoded stimulus intensity. This novel functional dissociation of pain processing within the insula together with previously observed alterations in chronic pain offer a novel interpretation of aberrant pain processing as disturbed weighting of predictions and prediction errors.

Article and author information

Author details

  1. Stephan Geuter

    Department of Systems Neuroscience, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    For correspondence
    stephan.geuter@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4935-5692
  2. Sabrina Boll

    Department of Systems Neuroscience, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Falk Eippert

    Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3986-1719
  4. Christian Büchel

    Department of Systems Neuroscience, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (SFB 936 A06)

  • Christian Büchel

European Commission (ERC Advanced Investigator Grant 2010-AdG_20100407)

  • Christian Büchel

Deutsche Forschungsgemeinschaft (Fellowship GE 2774/1-1)

  • Stephan Geuter

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was approved by and conducted in accordance with the ethics guidelines of the Medical Chamber Hamburg (PV4745). All participants provided informed consent to participate and to publish.

Reviewing Editor

  1. Heidi Johansen-Berg, University of Oxford, United Kingdom

Publication history

  1. Received: January 2, 2017
  2. Accepted: May 18, 2017
  3. Accepted Manuscript published: May 19, 2017 (version 1)
  4. Version of Record published: June 14, 2017 (version 2)

Copyright

© 2017, Geuter 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

  • 3,179
    Page views
  • 656
    Downloads
  • 63
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Stephan Geuter
  2. Sabrina Boll
  3. Falk Eippert
  4. Christian Büchel
(2017)
Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula
eLife 6:e24770.
https://doi.org/10.7554/eLife.24770

Further reading

    1. Neuroscience
    Hussein Ghareh et al.
    Research Article Updated

    Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the critical barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce craving and contribute to relapse. The insular cortex (IC) is thought to be a critical substrate of nicotine addiction and relapse. However, its specific role in context-induced relapse of nicotine-seeking is not fully known. In this study, we report a novel rodent model of context-induced relapse to nicotine-seeking after punishment-imposed abstinence, which models self-imposed abstinence through increasing negative consequences of excessive drug use. Using the neuronal activity marker Fos we find that the anterior (aIC), but not the middle or posterior IC, shows increased activity during context-induced relapse. Combining Fos with retrograde labeling of aIC inputs, we show projections to aIC from contralateral aIC and basolateral amygdala exhibit increased activity during context-induced relapse. Next, we used fiber photometry in aIC and observed phasic increases in aIC activity around nicotine-seeking responses during self-administration, punishment, and the context-induced relapse tests. Next, we used chemogenetic inhibition in both male and female rats to determine whether activity in aIC is necessary for context-induced relapse. We found that chemogenetic inhibition of aIC decreased context-induced nicotine-seeking after either punishment- or extinction-imposed abstinence. These findings highlight the critical role nicotine-associated contexts play in promoting relapse, and they show that aIC activity is critical for this context-induced relapse following both punishment and extinction-imposed abstinence.

    1. Neuroscience
    Jessica H Kim et al.
    Research Article Updated

    Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here, we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.