Instructions and experiential learning have similar impacts on pain and pain-related brain responses but produce dissociations in value-based reversal learning

  1. Lauren Y Atlas  Is a corresponding author
  2. Troy C. Dildine
  3. Esther E Palacios-Barrios
  4. Qingbao Yu
  5. Richard C Reynolds
  6. Lauren A Banker
  7. Shara S Grant
  8. Daniel S Pine
  1. National Center for Complementary and Integrative Health, United States
  2. University of Pittsburgh, United States
  3. National Institute of Mental Health, United States

Abstract

Recent data suggest that interactions between systems involved in higher order knowledge and associative learning drive responses during value-based learning. However, it is unknown how these systems impact subjective responses, such as pain. We tested how instructions and reversal learning influence pain and pain-evoked brain activation. Healthy volunteers (n = 40) were either instructed about contingencies between cues and aversive outcomes or learned through experience in a paradigm where contingencies reversed three times. We measured predictive cue effects on pain and heat-evoked brain responses using functional magnetic resonance imaging. Predictive cues dynamically modulated pain perception as contingencies changed, regardless of whether participants received contingency instructions. Heat-evoked responses in the insula, anterior cingulate, and other regions updated as contingencies changed, and responses in the prefrontal cortex mediated dynamic cue effects on pain, whereas responses in the brainstem's rostroventral medulla (RVM) were shaped by initial contingencies throughout the task. Quantitative modeling revealed that expected value was shaped purely by instructions in the Instructed Group, whereas expected value updated dynamically in the Uninstructed Group as a function of error-based learning. These differences were accompanied by dissociations in the neural correlates of value-based learning in the rostral anterior cingulate, thalamus, and posterior insula, among other regions. These results show how predictions dynamically impact subjective pain. Moreover, imaging data delineate three types of networks involved in pain generation and value-based learning: those that respond to initial contingencies, those that update dynamically during feedback-driven learning as contingencies change, and those that are sensitive to instruction. Together, these findings provide multiple points of entry for therapies designs to impact pain.

Data availability

Pain, SCR, and signature data are available on OSF; neuroimaging data has been uploaded to neurovault.

The following data sets were generated

Article and author information

Author details

  1. Lauren Y Atlas

    National Center for Complementary and Integrative Health, Bethesda, United States
    For correspondence
    lauren.atlas@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5693-4169
  2. Troy C. Dildine

    National Center for Complementary and Integrative Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Esther E Palacios-Barrios

    Department of Psychology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Qingbao Yu

    National Center for Complementary and Integrative Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Richard C Reynolds

    National Institute of Mental Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lauren A Banker

    National Center for Complementary and Integrative Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Shara S Grant

    National Center for Complementary and Integrative Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Daniel S Pine

    Emotion and Development Branch, National Institute of Mental Health, Besthesda, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Center for Complementary and Integrative Health (ZIAAT-000030)

  • Lauren Y Atlas

National Institute of Mental Health (ZIAMH-002782)

  • Daniel S Pine

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

Ethics

Human subjects: Consent was obtained as described in Materials and methods. Data were collected under NIH protocol 15-AT-0132, identifier NCT02446262 at clinicaltrials.gov

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 904
    views
  • 150
    downloads
  • 5
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Lauren Y Atlas
  2. Troy C. Dildine
  3. Esther E Palacios-Barrios
  4. Qingbao Yu
  5. Richard C Reynolds
  6. Lauren A Banker
  7. Shara S Grant
  8. Daniel S Pine
(2022)
Instructions and experiential learning have similar impacts on pain and pain-related brain responses but produce dissociations in value-based reversal learning
eLife 11:e73353.
https://doi.org/10.7554/eLife.73353

Share this article

https://doi.org/10.7554/eLife.73353

Further reading

    1. Neuroscience
    Sven Ohl, Martin Rolfs
    Research Article

    Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.