What is it about?

Pain perception is a warning signal to protect our body integrity. When pain persists over time, our brain needs to learn to predict its temporal evolution in order to minimize the risk of harm. How can we perform such predictions and how does it affect our brain activity? It is very well known that pain does not only depend on external stimulation intensities; it is also affected by numerous contextual factors. In particular, expectations can affect pain perception and associated brain responses, as exemplified by the powerful placebo and nocebo effects. Hence, our brain does not passively receive external stimuli; it rather interprets them based on the context, based on what we know and expect to feel. Knowing that, we studied how expectations affect brain responses to pain by exposing participants to sequences of stimuli which induced varying levels of expectations along time. We first showed that humans are able to identify and learn the temporal structures contained in sequences of painful stimuli. Participants received sequences of thermal stimuli to the forearm, each stimulus being either cool or warm. Each sequence had some specific structures, such as a majority of cool or warm stimuli, many warm-warm or cool-cool repetitions, many alternations in intensity, etc. These structures were reliably estimated by the participants along the sequences. During the experiments, we recorded the participants' brain activity using an electroencephalogram (EEG). These recordings revealed that the largest brain activities evoked by painful stimuli are modulated by uncertainty: higher uncertainty about the incoming stimulus leads to higher activities of our neurons. In other words, this means that when we are certain about the type of stimulus that we are going to receive, our brain activities are reduced, as our brain relies mainly on our expectations and less on the stimulus that is actually applied.

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Why is it important?

This work sheds light on the functional significance of human brain responses to painful stimuli, and thereby helps understanding how our neurons encode information from the external world.


Pathological pain conditions have been linked to maladaptive predictions in previous studies -- this work therefore opens the path to promising clinical research aiming to alleviate chronic pain.

Dounia Mulders
Massachusetts Institute of Technology

Read the Original

This page is a summary of: Confidence of probabilistic predictions modulates the cortical response to pain, Proceedings of the National Academy of Sciences, January 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2212252120.
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