Adaptive coding of pain prediction error in the anterior insula

Abstract

Background: Understanding the mechanisms behind the influence of expectation and context on pain perception is crucial for improving analgesic treatments. Prediction error (PE) signals how much a noxious stimulus deviates from expectation and is therefore crucial for our understanding of pain perception. It is thought that the brain engages in 'adaptive coding' of pain PE, such that sensitivity to unexpected outcomes is modulated by contextual information. While there is behavioural evidence that pain is coded adaptively, and evidence that reward PE signals are coded adaptively, controversy remains regarding the underlying neural mechanism of adaptively-coded pain PEs.Methods: A cued-pain task was performed by 19 healthy adults while undergoing FMRI scanning. BOLD responses to the task were tested using an axiomatic approach to identify areas that may code pain PE adaptively. Results:The left dorsal anterior insula demonstrated a pattern of response consistent with adaptively-coded pain PE. Signals from this area were sensitive to both predicted pain magnitudes on the instigation of expectation, and the unexpectedness of pain delivery. Crucially however, the response at pain delivery was consistent with the local context of the pain stimulation, rather than the absolute magnitude of delivered pain, a pattern suggestive of an adaptively-coded PE signal. Conclusions:The study advances our understanding of the neural basis of pain prediction. Alongside existing evidence that the periaqueductal grey codes pain PE and the posterior insula codes pain magnitude, the results highlight a distinct contribution of the left dorsal anterior insula in the processing of pain.Significance: Although there is behavioural evidence that pain is coded adaptively, the neural mechanisms serving this process are not well understood. This study used functional MRI to provide the first evidence that the left dorsal anterior insula, an area associated with aversive learning, responds to pain in a manner consistent with the adaptive coding of pain prediction error. This study aids our understanding of the neural basis of subjective pain representation, and thus can contribute to the advancement of analgesic treatments.

Neurofeedback modulation of insula activity via MEG-based brain-machine interface: A double-blind randomized controlled crossover trial

“…First, in emotional processing 34 , the insula is essential for assessing pain's emotional aspects and interpreting the emotional context of pain sensations. Second, regarding cognitive modulation 35 , the insula plays a role in anticipating pain and focusing attention 36 , potentially amplifying or reducing pain perception based on how it modulates related cognitive processes. Third, through its connection to the autonomic nervous system 37 , the insula can regulate physiological responses such as heart rate and blood pressure changes in response to pain.…”

Structural and functional brain changes in people with knee osteoarthritis: a scoping review

“…Other regions, such as the ACC, thalamus, insular cortex, and amygdala are responsible for the sensory-discriminative components of pain given their specific function and reciprocal connections ( Fenton, Shih & Zolton, 2015 ; Kang et al, 2021a ; Hazra et al, 2022 ; Hoskin & Talmi, 2023 ). These three regions are also connected to the thalamus, through the paleospinothalamic nociceptive pathway, which is involved in aspects such as attention and mood related to pain ( Horn et al, 2014 ).…”