{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:08:09Z","timestamp":1790687289479,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Previous studies have established the role of the cortico\u2010mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated for prediction. In this study, we set out to study whether functional connectivity (FC) of the nucleus accumbens (NAc) and the periaqueductal gray matter (PAG) is predictive of pain chronification in early\u2010acute mTBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To estimate FC, resting\u2010state functional magnetic resonance imaging (fMRI) of 105 participants with mTBI following a motor vehicle collision was acquired within 72\u2009hours post\u2010accident. Participants were classified according to pain ratings provided at 12\u2010months post\u2010collision into chronic pain (head\/neck pain \u226530\/100, n\u00a0=\u00a044) and recovery (n\u00a0=\u00a061) groups, and their FC maps were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The chronic pain group exhibited reduced negative FC between NAc and a region within the primary motor cortex corresponding with the expected representation of the area of injury. A complementary pattern was also demonstrated between PAG and the primary somatosensory cortex. PAG and NAc also shared increased FC to the rostral anterior cingulate cortex (rACC) within the recovery group. Brain connectivity further shows high classification accuracy (area under the curve [AUC]\u00a0=\u00a0.86) for future chronic pain, when combined with an acute pain intensity report.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>FC features obtained shortly after mTBI predict its transition to long\u2010term chronic pain, and may reflect an underlying interaction of injury\u2010related primary sensorimotor cortical areas with the mesolimbic and pain modulation systems. Our findings indicate a potential predictive biomarker and highlight targets for future early preventive interventions. 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