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The neuronal mechanisms underlying such co-occurrence of psychopathological symptoms remain yet unclear. Rather than linking and localizing single psychopathological symptoms to specific regions or networks, this perspective proposes a more global and dynamic topographic approach. We first review recent findings on global brain activity changes during both rest and task states in MDD showing topographic reorganization with a shift from unimodal to transmodal regions. Next, we single out two candidate mechanisms that may underlie and mediate such abnormal uni-\/transmodal topography, namely dynamic shifts from shorter to longer timescales and abnormalities in the excitation-inhibition balance. Finally, we show how such topographic shift from unimodal to transmodal regions relates to the various psychopathological symptoms in MDD including their co-occurrence. This amounts to what we describe as \u2018Topographic dynamic reorganization\u2019 which extends our earlier \u2018Resting state hypothesis of depression\u2019 and complements other models of MDD.<\/jats:p>","DOI":"10.1038\/s41398-024-02995-9","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T19:02:00Z","timestamp":1720206120000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Is depression a global brain disorder with topographic dynamic reorganization?"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-0951","authenticated-orcid":false,"given":"Georg","family":"Northoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-9800","authenticated-orcid":false,"given":"Dusan","family":"Hirjak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"2995_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neubiorev.2020.01.006","volume":"111","author":"JA Arias","year":"2020","unstructured":"Arias JA, Williams C, Raghvani R, Aghajani M, Baez S, Belzung C, et al. 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