{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:27:19Z","timestamp":1776954439437,"version":"3.51.4"},"posted":{"date-parts":[[2025,12,11]]},"group-title":"Neuroscience","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006528","name":"Goizueta Alzheimer\u2019s Disease Research Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006528","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Health","award":["1R01AG062581"],"award-info":[{"award-number":["1R01AG062581"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Alzheimer\u2019s disease (AD) is characterized by progressive disruptions in large-scale brain networks that precede cognitive decline, yet conventional functional connectivity analyses often fail to detect disruptions in coordination among large-scale brain networks that may be critical for early detection. This study leverages quasi periodic patterns (QPPs) and complex principal component analysis (cPCA) to characterize spatiotemporal network alterations across longitudinally stable (normal cognitive, mild cognitive impairment, dementia of Alzheimer\u2019s type) and transitioning (normal cognitive to mild cognitive impairment, mild cognitive impairment to dementia of Alzheimer\u2019s type) cohorts from the Alzheimer\u2019s Disease Neuroimaging Initiative using resting state fMRI. QPPs were used to derive recurrent spatiotemporal templates and network integrity measures at the intrinsic connectivity network level, while cPCA decomposed Hilbert transformed time series into complex valued patterns that capture amplitude and phase relationships. Nonparametric group comparisons revealed a structured trajectory in which limbic, subcortical, and higher cognition networks, including triple network components, are affected early, followed by progressive disruption in visual, cerebellar, sensorimotor, and additional triple network systems. Transitioning cohorts showed many of these alterations before formal diagnostic conversion, indicating that spatiotemporal signatures carry preclinical information. QPP based metrics were particularly sensitive to limbic and subcortical degradation, whereas cPCA emphasized changes in higher order, visual, and cerebellar patterns, revealing complementary aspects of the same underlying pathology. These findings extend prior QPP only work and highlight the utility of combining QPP and cPCA based measures as a dynamic, network-level biomarker framework for AD progression. with potential applications in early detection, characterizing disease trajectories, and treatment monitoring.<\/jats:p>","DOI":"10.64898\/2025.12.09.692653","type":"posted-content","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T23:55:11Z","timestamp":1765497311000},"source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal Network Dynamics Reveal Alzheimer\u2019s Disease Progression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2680-7385","authenticated-orcid":false,"given":"Theodore J.","family":"LaGrow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-9844","authenticated-orcid":false,"given":"Vaibhavi","family":"Itkyal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8765-2233","authenticated-orcid":false,"given":"Harrison","family":"Watters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-2232","authenticated-orcid":false,"given":"Kyle M.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0217-3163","authenticated-orcid":false,"given":"Ram","family":"Ballem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-5439","authenticated-orcid":false,"given":"Wen-ju","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Iraji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9058-0747","authenticated-orcid":false,"given":"Vince D.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5737-1660","authenticated-orcid":false,"given":"Shella","family":"Keilholz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025121311102695000_2025.12.09.692653v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"issue":"6","key":"2025121311102695000_2025.12.09.692653v1.2","first-page":"797","article-title":"Functional connectivity and cognitive decline: A review of rs-fmri, eeg, meg, and graph theory approaches in aging and dementia","volume":"5","year":"2024","journal-title":"Exploration of Medicine"},{"key":"2025121311102695000_2025.12.09.692653v1.3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neurobiolaging.2021.09.001","article-title":"Dissemination in time and space in presymptomatic granulin mutation carriers: a genfi spatial chronnectome study","volume":"108","year":"2021","journal-title":"Neurobiology of Aging"},{"key":"2025121311102695000_2025.12.09.692653v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2019.12.004"},{"issue":"1","key":"2025121311102695000_2025.12.09.692653v1.5","doi-asserted-by":"crossref","first-page":"10024","DOI":"10.1038\/s41598-018-28237-9","article-title":"Quasi-periodic patterns of neural activity improve classification of alzheimer\u2019s disease in mice","volume":"8","year":"2018","journal-title":"Scientific reports"},{"key":"2025121311102695000_2025.12.09.692653v1.6","first-page":"1","article-title":"Widespread spatiotemporal patterns of functional brain networks in longitudinal progression of alzheimer\u2019s disease","volume":"2025","year":"2025","journal-title":"in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 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