{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:40:41Z","timestamp":1790520041039,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["VR 2010-2120"],"award-info":[{"award-number":["VR 2010-2120"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain\u2013action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers\u2019 subjective pain thresholds did not differ from controls\u2019, but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain\u2013action integration with increased responses for task-relevant painful stimulation (\u201csignal,\u201d requiring button-press execution) over task-irrelevant stimulation (\u201cnoise,\u201d requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices\u2014but not the AI and mid-ACC regions\u2014during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI\u2013mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.<\/jats:p>","DOI":"10.1093\/cercor\/bhaa078","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T16:21:15Z","timestamp":1583770875000},"page":"4858-4870","source":"Crossref","is-referenced-by-count":14,"title":["Mutation Carriers with Reduced C-Afferent Density Reveal Cortical Dynamics of Pain\u2013Action Relationship during Acute Pain"],"prefix":"10.1093","volume":"30","author":[{"given":"I","family":"Perini","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience, Link\u00f6ping University, Link\u00f6ping 581 83, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ceko","sequence":"additional","affiliation":[{"name":"Institute 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