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Unlike the conventional linear approach, cross-sample entropy (CSE) analysis shows the nonlinear property in fMRI signals between brain regions. Moreover, recent advances in deep learning, such as convolutional neural networks (CNNs), provide a timely application for understanding LLD. Accurate and prompt diagnosis is essential in LLD; hence, this study aimed to combine CNN and CSE analysis to discriminate LLD patients and non-depressed comparison older adults based on brain resting-state fMRI signals. Seventy-seven older adults, including 49 patients and 28 comparison older adults, were included for fMRI scans. Three-dimensional CSEs with volumes corresponding to 90 seed regions of interest of each participant were developed and fed into models for disease classification and depression severity prediction. We obtained a diagnostic accuracy\u2009&gt;\u200985% in the superior frontal gyrus (left dorsolateral and right orbital parts), left insula, and right middle occipital gyrus. With a mean root-mean-square error (RMSE) of 2.41, three separate models were required to predict depressive symptoms in the severe, moderate, and mild depression groups. The CSE volumes in the left inferior parietal lobule, left parahippocampal gyrus, and left postcentral gyrus performed best in each respective model. Combined complexity analysis and deep learning algorithms can classify patients with LLD from comparison older adults and predict symptom severity based on fMRI data. Such application can be utilized in precision medicine for disease detection and symptom monitoring in LLD.<\/jats:p>","DOI":"10.1007\/s11682-022-00748-0","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T17:18:26Z","timestamp":1669310306000},"page":"125-135","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Automatic diagnosis of late-life depression by 3D convolutional neural networks and cross-sample Entropy analysis from resting-state fMRI"],"prefix":"10.1007","volume":"17","author":[{"given":"Chemin","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shwu-Hua","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Mao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Yen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hang","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatia Mei-Chun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Chi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"issue":"12","key":"748_CR1","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1093\/brain\/aww194","volume":"139","author":"H Aerts","year":"2016","unstructured":"Aerts, H., Fias, W., Caeyenberghs, K., & Marinazzo, D. 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