{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:04:51Z","timestamp":1785819891984,"version":"3.56.0"},"reference-count":69,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2024,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine\u2010related changes in large\u2010scale brain network dynamics and its implications in clinical features. We pooled data from two disease\u2010control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting\u2010state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single\u2010photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age\u2010 and sex\u2010matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age\u2010 and sex\u2010matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010DOPA\u2010positron emission tomography (PET) imaging. The striatal synthesis capacity of\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre\u2010processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44\u2009s window) and a subsequent k\u2010means clustering were conducted separately for each cohort to derive dFC states (reemerging intra\u2010 and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L\u2010dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large\u2010scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Practitioner Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD\u2010specific changes in dynamic functional connectivity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Results only in the PPMI cohort suggest striatal dopamine availability influences large\u2010scale network dynamics that are relevant in motor control.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hbm.26776","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:44:12Z","timestamp":1719989052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease"],"prefix":"10.1002","volume":"45","author":[{"given":"Adrian L.","family":"Asendorf","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Theis","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Department of Neurology University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Tittgemeyer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Metabolism Research, Translational Neurocircuitry Group  Cologne Germany"},{"name":"University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD)  Cologne 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Marburg Germany"},{"name":"Department of Neurology University of Duisburg\u2010Essen, Knappschaftskrankenhaus Bottrop  Bottrop Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Ruppert\u2010Junck","sequence":"additional","affiliation":[{"name":"Department of Neurology  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Universities of Marburg and Gie\u00dfen, Center for Mind, Brain, and Behavior\u2010CMBB  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle C.","family":"Hoenig","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine University of Cologne, Faculty of Medicine and University Hospital Cologne  Cologne Germany"},{"name":"Research Center Juelich, Institute of Neuroscience and Medicine II, Molecular Organization of the Brain  Juelich 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