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Here, we applied a novel supervised machine learning method, combining the strengths of a priori theoretical insights with a data\u2010driven approach, to identify which connectivity changes are most prominently associated with a state of acute stress and individual differences therein. Resting\u2010state functional magnetic resonance imaging scans were taken from 334 healthy participants (79 females) before and after a formal stress induction. For each individual scan, mean time\u2010series were extracted from 46 functional parcels of three major brain networks previously shown to be potentially sensitive to stress effects (default mode network (DMN), salience network (SN), and executive control networks). A data\u2010driven approach was then used to obtain discriminative spatial linear filters that classified the pre\u2010 and post\u2010stress scans. To assess potential relevance for understanding individual differences, probability of classification using the most discriminative filters was linked to individual cortisol stress responses. Our model correctly classified pre\u2010 versus post\u2010stress states with highly significant accuracy (above 75%; leave\u2010one\u2010out validation relative to chance performance). Discrimination between pre\u2010 and post\u2010stress states was mainly based on connectivity changes in regions from the SN and DMN, including the dorsal anterior cingulate cortex, amygdala, posterior cingulate cortex, and precuneus. Interestingly, the probability of classification using these connectivity changes were associated with individual cortisol increases. Our results confirm the involvement of DMN and SN using a data\u2010driven approach, and specifically single out key regions that might receive additional attention in future studies for their relevance also for individual differences.<\/jats:p>","DOI":"10.1002\/hbm.25000","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T10:55:47Z","timestamp":1586948147000},"page":"3089-3099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Discriminating stress from rest based on resting\u2010state connectivity of the human brain: A supervised machine learning study"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6428-2033","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Donders Institute, Centre for Cognitive Neuroimaging Radboud University  Nijmegen The Netherlands"},{"name":"Behavioural Science Institute Radboud University Nijmegen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Llera","sequence":"additional","affiliation":[{"name":"Donders Institute, Centre for Cognitive Neuroimaging Radboud University  Nijmegen The Netherlands"},{"name":"Department of Cognitive Neuroscience Radboud University Medical Centre  Nijmegen The Netherlands"},{"name":"Karakter Child and Adolescent Psychiatry  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahur M.","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Donders Institute, Centre for Cognitive Neuroimaging Radboud University  Nijmegen The Netherlands"},{"name":"Behavioural Science Institute Radboud University Nijmegen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinoud","family":"Kaldewaij","sequence":"additional","affiliation":[{"name":"Donders Institute, Centre for Cognitive Neuroimaging Radboud University  Nijmegen The Netherlands"},{"name":"Behavioural Science Institute Radboud University Nijmegen  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia B. 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