{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:45:14Z","timestamp":1775976314636,"version":"3.50.1"},"posted":{"date-parts":[[2026,4,11]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging","award":["NIA K23 AG063900"],"award-info":[{"award-number":["NIA K23 AG063900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,11]]},"abstract":"<jats:p>BACKGROUND: Neurodegenerative diseases share selective vulnerability patterns suggesting common physical mechanisms. We apply unified mechanics theory to neural systems, predicting that brain regions accumulate structural damage proportional to computational workload.\nMETHODS: We simulated a hierarchical neural network implementing relationships between mechanical work (W = F * D), proportional thermodynamic entropy accumulation, and structural failure thresholds. Neural architectures at three hierarchical levels employed Hebbian learning across 2000 simulation sets, tracking entropy generation and dynamic stability. A coupled \"siphon\" model simulated cortical and subcortical support populations under constant cognitive demand. RESULTS: Heteromodal integration nodes consistently exhibited elevated work, accelerated entropy accumulation, and dynamic instability across architectures. Support systems reached 50% population loss before cortical systems despite lower absolute work, demonstrating accelerated compensatory failure. DISCUSSION: These thermodynamic-informational entropic relationships (TIER) reveal physical mechanisms underlying selective vulnerability across neurodegenerative diseases, reframing neurodegeneration as inevitable consequence of evolutionary trade-offs optimizing cognition over longevity.<\/jats:p>","DOI":"10.64898\/2026.04.08.714596","type":"posted-content","created":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:00:11Z","timestamp":1775973611000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic thermodynamic-informational entropic relationship (TIER) models of selective vulnerability to neurodegeneration"],"prefix":"10.64898","author":[{"given":"Peter S","family":"Pressman","sequence":"first","affiliation":[{"name":"Layton Healthy Aging and Alzheimer's Disease Research Center, Oregon Health & Science University;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cemal","family":"Basaran","sequence":"additional","affiliation":[{"name":"University at Buffalo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Foltz","sequence":"additional","affiliation":[{"name":"University of Colorado, Boulder;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Tai","family":"Au-Yeung","sequence":"additional","affiliation":[{"name":"Layton Healthy Aging and Alzheimer's Disease Research Center, Oregon Health & Science University;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Steele","sequence":"additional","affiliation":[{"name":"University of North Dakota, Indigenous Health Department;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Silbert","sequence":"additional","affiliation":[{"name":"Layton Healthy Aging and Alzheimer's Disease Research Center, Oregon Health & Science University;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence E","family":"Hunter","sequence":"additional","affiliation":[{"name":"University of Chicago"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.08.714596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:00:11Z","timestamp":1775973611000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.08.714596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.04.08.714596","relation":{},"subject":[],"published":{"date-parts":[[2026,4,11]]},"subtype":"preprint"}}