{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:41:39Z","timestamp":1784245299010,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008358","name":"Hersenstichting","doi-asserted-by":"publisher","award":["F2013(10\u201015)"],"award-info":[{"award-number":["F2013(10\u201015)"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["09150172010044"],"award-info":[{"award-number":["09150172010044"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008717","name":"Sylvia and Charles Viertel Charitable Foundation","doi-asserted-by":"publisher","award":["NHMRC GNT1193857"],"award-info":[{"award-number":["NHMRC GNT1193857"]}],"id":[{"id":"10.13039\/100008717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parkinson's disease (PD) rest tremor emerges from pathological activity in the basal ganglia and cerebello\u2010thalamo\u2010cortical circuits. A well\u2010known clinical feature is the waxing and waning of PD tremor amplitude, but the mechanisms that drive this variability are unclear. Previous work has shown that arousal amplifies PD tremor by increasing between\u2010network connectivity. Furthermore, brain states in PD are biased toward integration rather than segregation, a pattern that is also associated with increased arousal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim was to test the hypothesis that fluctuations in integrative brain states and\/or arousal drive spontaneous fluctuations in PD rest tremor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the temporal relationship between cerebral integration, the ascending arousal system, and tremor, both during cognitive load and in the resting state. In 40 tremor\u2010dominant PD patients, we performed functional magnetic resonance imaging using concurrent tremor recordings and proxy measures of the ascending arousal system (pupil diameter, heart rate). We calculated whole\u2010brain dynamic functional connectivity and used graph theory to determine a scan\u2010by\u2010scan measure of cerebral integration, which we related to the onset of tremor episodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fluctuations in cerebral integration were time locked to spontaneous changes in tremor amplitude: cerebral integration increased 13\u2009seconds before tremor onset and predicted the amplitude of subsequent increases in tremor amplitude. During but not before tremor episodes, pupil diameter and heart rate increased and correlated with tremor amplitude.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Integrative brain states are an important cerebral environment in which tremor\u2010related activity emerges, which is then amplified by the ascending arousal system. New treatments focused on attenuating enhanced cerebral integration in PD may reduce tremor. \u00a9 2023 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29506","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T12:28:39Z","timestamp":1687782519000},"page":"1615-1624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Integrative Brain States Facilitate the Expression of Parkinson's Tremor"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8763-8071","authenticated-orcid":false,"given":"Michiel F.","family":"Dirkx","sequence":"first","affiliation":[{"name":"Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour Radboud University  Nijmegen The Netherlands"},{"name":"Department of Neurology, Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Shine","sequence":"additional","affiliation":[{"name":"Brain and Mind Center The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-6573","authenticated-orcid":false,"given":"Rick C.","family":"Helmich","sequence":"additional","affiliation":[{"name":"Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour Radboud University  Nijmegen The Netherlands"},{"name":"Department of Neurology, Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27115"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww331"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3634-15.2016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00145"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0854-21.2021"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx233"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz034"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01151-X"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28461"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz192"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28999"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa083"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1162\/netn_a_00042"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2019.04.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.11.1621"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3744\/snak.2003.40.2.021"},{"key":"e_1_2_9_19_1","unstructured":"DirkxMF ZachH vanNulandA BloemBR ToniI HelmichRC.Cognitive load amplifies Parkinson's tremor through excitatory network influences onto the thalamus Journal: Published;2020. 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