{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:34:55Z","timestamp":1789580095449,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is increasingly conceptualized as a disorder of large\u2010scale brain networks, yet whether and how frequency\u2010specific functional connectivity reorganizes across stages remains poorly understood. In this study, we used high\u2010density electroencephalography (EEG) to characterize cortico\u2010cortical functional connectivity across the clinical spectrum of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed high\u2010density EEG in a cross\u2010sectional cohort of 140 PD patients spanning early, intermediate, and advanced stages and 57 healthy controls. Cortico\u2010cortical functional connectivity was reconstructed in source space across multiple frequency bands and analyzed using network\u2010based statistics combined with machine\u2010learning models to identify stage\u2010dependent network alterations and evaluate their diagnostic and prognostic relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected 3 distinct large\u2010scale networks showing divergent trajectories across disease stages. An \u03b1\u2010band network involving prefrontal and parieto\u2010temporal regions exhibited progressive hypoconnectivity and was associated with cognitive and axial impairment. A \u03b2\u2010band sensorimotor network showed progressive hyperconnectivity, paralleling bradykinesia severity. A high\u2010\u03b3 network demonstrated increased connectivity in early PD, followed by a progressive connectivity breakdown, and was inversely associated with motor complications. Multiband integration achieved near\u2010perfect discrimination between early PD and healthy controls and robust stratification across disease stages. Band\u2010specific networks also predicted clinical milestones of disease progression, with preserved \u03b1 connectivity identifying patients at lower risk for cognitive and axial impairment, and stronger high\u2010\n                      <jats:italic>\u03b3<\/jats:italic>\n                      connectivity indicating reduced vulnerability to motor complications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Together, these results identify frequency\u2010specific cortical networks as markers of disease stage and clinical vulnerability and support high\u2010density EEG connectivity as a scalable systems\u2010level biomarker for diagnosis, staging, and risk stratification in PD. ANN NEUROL 2026;100:319\u2013333<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78262","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:31:11Z","timestamp":1779942671000},"page":"319-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Frequency\u2010 and Network\u2010Specific Changes in Functional Connectivity Reflect Pathophysiological Mechanisms across Parkinson's Disease Stages"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-2209","authenticated-orcid":false,"given":"Matteo","family":"Conti","sequence":"first","affiliation":[{"name":"Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome 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