{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:02:08Z","timestamp":1788364928299,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fatigue in Parkinson's disease (PD) is a prevalent and debilitating non\u2010motor symptom. Despite its significant impact on quality of life, the underlying neurochemical and network\u2010based mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This observational study applied a multimodal imaging approach to explore potential links between the functional connectivity of neurotransmitter\u2010specific circuits and fatigue in a sample of patients with PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We acquired resting\u2010state functional magnetic resonance imaging data in 35 patients with PD including 18 with clinically significant fatigue and 17 without. We applied the receptor\u2010enriched analysis of functional connectivity by targets (REACT) pipeline to derive patients' specific molecularly enriched networks informed by the spatial distribution of the dopamine, noradrenaline, serotonin transporters, and metabotropic glutamate 5 receptors as assessed using molecular imaging data in independent samples of healthy controls. We then conducted whole\u2010brain analyses inspecting both categorical differences between groups of patients with and without clinically significant fatigue, and associations exploring the full within\u2010sample variation in symptom ratings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found a significant decrease in noradrenaline\u2010enriched and glutamate\u2010enriched functional connectivity in key regions, belonging to the sensorimotor, salience, and default mode network, with increasing fatigue severity. Notably, noradrenaline\u2010enriched functional connectivity reductions were widespread, while glutamate\u2010enriched functional connectivity reductions were more restricted to the supplementary motor area. No significant relationships between fatigue and dopamine or serotonin\u2010enriched functional connectivity were found.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings offer supportive evidence for the putative involvement of the noradrenaline and glutamate systems in the genesis of fatigue in PD, opening new directions for treatment development exploring these neurochemical systems. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  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