ArticlePLoS biology2022
The human insula processes both modality-independent and pain-selective learning signals.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- No reliable gray matter alterations in idiopathic dystonia.Frontiers in neurology · 2025Pooled it
- Coordinates-based meta-analysis for vestibular migraine and the underlying mechanisms behind it.Frontiers in neurology · 2025Pooled it
- Auditory Hyperresponsivity in Chronic Back Pain: A Randomized Controlled Trial of Pain Reprocessing Therapy.Annals of neurology · 2026Trial
- Kappa opioid receptor availability correlates with depressive symptom burden in chronic migraine: a preliminary investigation.The journal of headache and pain · 2026Article
- Ultrasound neuromodulation reveals distinct roles of the dorsal anterior cingulate cortex and anterior insula in learning.PLoS biology · 2026Article
- Temporal predictions shape somatosensory perception.Nature communications · 2026Article
- Controllability changes pain perception by increasing the precision of expectations.Nature communications · 2025Article
- The Anterior Insula Processes a Time-Resolved Subjective Risk Prediction Error.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Enhanced behavioural and neural sensitivity to punishments in chronic pain and fatigue.Brain : a journal of neurology · 2025Article
- Comparing neural responses to cutaneous heat and pressure pain in healthy participants.Scientific reports · 2025Article
- Neural basis of intensity-dependent brain activity in response to mechanical stimulation and the level of pain sensitivity.Frontiers in human neuroscience · 2025Article
- Exploration of Key Brain Regions Involved in Acupuncture and Moxibustion Analgesia: An Imaging-Based Study.Journal of pain research · 2025Review
- Altered patterns in the prefrontal cortex and limbic system in female patients with neuropathic pain secondary to recurrent median nerve entrapment post carpal tunnel release.Brain communications · 2025Article
- Article
- An externally validated resting-state brain connectivity signature of pain-related learning.Communications biology · 2024Article
- Uncovering Interoceptive Human Insular Lobe Function through Intraoperative Cortical Stimulation-A Review.Brain sciences · 2024Review
- The Role of the Insula in Chronic Pain and Associated Structural Changes: An Integrative Review.Cureus · 2024Review
- A chronometric relationship between circuits underlying learning and error monitoring in the basal ganglia and salience network.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- Editorial: The neurobiological and cognitive underpinnings of appetitive and aversive motivation.Frontiers in behavioral neuroscience · 2024Article
- Pain suffering and the self. An active allostatic inference explanation.Neuroscience of consciousness · 2024Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prediction errors (PEs) are generated when there are differences between an expected and an actual event or sensory input. The insula is a key brain region involved in pain processing, and studies have shown that the insula encodes the magnitude of an unexpected outcome (unsigned PEs). In addition to signaling this general magnitude information, PEs can give specific information on the direction of this deviation-i.e., whether an event is better or worse than expected. It is unclear whether the unsigned PE responses in the insula are selective for pain or reflective of a more general processing of aversive events irrespective of modality. It is also unknown whether the insula can process signed PEs at all. Understanding these specific mechanisms has implications for understanding how pain is processed in the brain in both health and in chronic pain conditions. In this study, 47 participants learned associations between 2 conditioned stimuli (CS) with 4 unconditioned stimuli (US; painful heat or loud sound, of one low and one high intensity each) while undergoing functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. We demonstrate that activation in the anterior insula correlated with unsigned intensity PEs, irrespective of modality, indicating an unspecific aversive surprise signal. Conversely, signed intensity PE signals were modality specific, with signed PEs following pain but not sound located in the dorsal posterior insula, an area implicated in pain intensity processing. Previous studies have identified abnormal insula function and abnormal learning as potential causes of pain chronification. Our findings link these results and suggest that a misrepresentation of learning relevant PEs in the insular cortex may serve as an underlying factor in chronic pain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.