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While localized representations have traditionally dominated, evidence suggests information is also encoded in distributed, hierarchical networks. Recent research indicates that the hierarchy of causal influences shaping functional patterns serves as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first explore how whole\u2010brain models, guided by the thermodynamics of mind framework, estimate brain hierarchy and how perturbing such models enables the study of in\u2010silico transitions represented by static functional connectivity. We then apply this to major depressive disorder, where different brain hierarchical reconfigurations emerge following psilocybin and escitalopram treatments. We build resting\u2010state whole\u2010brain models of depressed patients before and after interventions and conduct a dynamic sensitivity analysis to explore brain states\u2019 susceptibility\u2014measuring their capacity to change\u2014and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments promote healthier transitions. These results align with the post\u2010treatment window of plasticity opened by serotonergic psychedelics and the similar clinical efficacy of both drugs in trials. Overall, this work demonstrates how whole\u2010brain models of brain hierarchy can inform in\u2010silico neurostimulation protocols for neuropsychiatric disorders.<\/jats:p>","DOI":"10.1111\/nyas.15391","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T14:43:33Z","timestamp":1753109013000},"page":"255-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Perturbing whole\u2010brain models of brain hierarchy: An application for depression following pharmacological treatment"],"prefix":"10.1111","volume":"1550","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7430-1460","authenticated-orcid":false,"given":"Marcel","family":"Socor\u00f3\u2010Garrigosa","sequence":"first","affiliation":[{"name":"Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies Universitat Pompeu Fabra  Barcelona 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