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From these, the mesocircuit hypothesis has emerged as a leading model, proposing that consciousness depends on a distributed network of brainstem arousal systems, central thalamic hubs and cortico\u2013subcortical loops. However, rare and underrecognized causes of coma and prolonged disorders of consciousness offer a unique opportunity to test, refine and expand these models. In this review, we analyse a wide array of rare aetiologies\u2014including genetic syndromes, parasitic and fungal infections, autoimmune encephalitides, amyloid and tau pathologies, toxic-metabolic states and haematological disorders\u2014that are often excluded from mainstream consciousness research. Despite their diverse mechanisms, these conditions converge on a consistent set of anatomical targets: the central thalamus, brainstem reticular activating system, deep white matter \u2018bridging zones\u2019, basal ganglia and distributed cortical networks. This convergence not only provides powerful external validation of network-based frameworks such as the mesocircuit hypothesis but also underscores the clinical need for therapeutic approaches that address both aetiology-specific pathology and distributed circuit-level dysfunction. However, evidence quality varies considerably across these rare conditions, with many findings based on limited case reports or small series, necessitating cautious interpretation of proposed anatomical frameworks.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf439","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:04:46Z","timestamp":1762520686000},"source":"Crossref","is-referenced-by-count":1,"title":["Different diseases, same circuits: lessons from rare and overlooked causes of disorders of consciousness"],"prefix":"10.1093","volume":"7","author":[{"given":"Daniel","family":"Toker","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California , Los Angeles, CA 90095 ,","place":["USA"]},{"name":"Department of Psychology, University of California , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-3780","authenticated-orcid":false,"given":"Martin M","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of California , Los Angeles, CA 90095 ,","place":["USA"]},{"name":"Brain Injury Research Center, Department of Neurosurgery, University of California , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"issue":"Suppl 1","key":"2025112901530642900_fcaf439-B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s12028-021-01281-6","article-title":"Mechanisms underlying disorders of consciousness: Bridging gaps to move toward an integrated translational science","volume":"35","author":"Luppi","year":"2021","journal-title":"Neurocrit Care."},{"issue":"12","key":"2025112901530642900_fcaf439-B2","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.tics.2005.10.010","article-title":"The neural correlate of (un)awareness: Lessons from the vegetative state","volume":"9","author":"Laureys","year":"2005","journal-title":"Trends Cogn Sci."},{"issue":"9","key":"2025112901530642900_fcaf439-B3","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1474-4422(04)00852-X","article-title":"Brain function in coma, vegetative state, and related disorders","volume":"3","author":"Laureys","year":"2004","journal-title":"Lancet Neurol."},{"key":"2025112901530642900_fcaf439-B4","first-page":"1","volume-title":"Neuroscience in the 21st century","author":"Gosseries","year":"2022"},{"issue":"9517","key":"2025112901530642900_fcaf439-B5","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S0140-6736(06)68508-5","article-title":"Chronic disorders of consciousness","volume":"367","author":"Bernat","year":"2006","journal-title":"Lancet"},{"issue":"3","key":"2025112901530642900_fcaf439-B6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1212\/WNL.58.3.349","article-title":"The minimally conscious state: Definition and diagnostic criteria","volume":"58","author":"Giacino","year":"2002","journal-title":"Neurology"},{"issue":"10","key":"2025112901530642900_fcaf439-B7","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1212\/WNL.0000000000005926","article-title":"Practice guideline update recommendations summary: Disorders of consciousness: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology; 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