{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:01:40Z","timestamp":1785402100562,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,2]]},"group-title":"Neuroscience","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["K99EY035362"],"award-info":[{"award-number":["K99EY035362"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY022930"],"award-info":[{"award-number":["R01EY022930"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY034723"],"award-info":[{"award-number":["R01EY034723"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["RF1NS121913"],"award-info":[{"award-number":["RF1NS121913"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R24AG073138"],"award-info":[{"award-number":["R24AG073138"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["F31NS134290"],"award-info":[{"award-number":["F31NS134290"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"crossref","award":["SFI-AN-NC-GB-Culmination-00002794-01"],"award-info":[{"award-number":["SFI-AN-NC-GB-Culmination-00002794-01"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/006wxqw41","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Circle of Service Foundation"},{"name":"Office of the Director","award":["P51-OD011107"],"award-info":[{"award-number":["P51-OD011107"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Intelligent behavior depends on the brain\u2019s ability to represent multiple features of the environment simultaneously while keeping those representations independent\n                  <jats:sup>1,2<\/jats:sup>\n                  . Patients with Alzheimer\u2019s disease often mix up objects, people, and events\n                  <jats:sup>3\u20137<\/jats:sup>\n                  , raising the possibility that disease mixes up the way that information is represented in the brain. Here we show that the independence of visual representations progressively breaks down during early stages of disease progression in a rhesus macaque model of Alzheimer\u2019s disease and related dementias\n                  <jats:sup>8\u201310<\/jats:sup>\n                  . In visual area V4, representations of different visual features become progressively less independent, such that the representation of one feature is increasingly influenced by the value of another. We term this loss of independence neuronal feature confusion. This neuronal change predicts a specific behavioral consequence: because feature representations become less independent, preferences associated with one visual feature increasingly influence visually guided choices associated with other, independent features. Using an analogous image-selection task, we found the same behavioral signature in people with mild cognitive impairment, distinguishing them from age-matched controls. These results identify a specific and measurable alteration in neuronal population representations that predicts a behavioral change observed across species. More broadly, these findings demonstrate that neuronal population representations can guide the development of sensitive, non-invasive behavioral methods for early detection of functional changes associated with Alzheimer\u2019s disease.\n                <\/jats:p>","DOI":"10.64898\/2026.06.28.734833","type":"posted-content","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:10:18Z","timestamp":1783059018000},"source":"Crossref","is-referenced-by-count":0,"title":["Progressive loss of independence in neuronal representations predicts cognitive decline"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-4619","authenticated-orcid":false,"given":"Drew E.G.","family":"Sheets","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Neuroscience Institute, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-8822","authenticated-orcid":false,"given":"Douglas A.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Neuroscience Institute, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-7250","authenticated-orcid":false,"given":"Ramanujan","family":"Srinath","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Neuroscience Institute, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0959-5471","authenticated-orcid":false,"given":"Keon S.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Neuroscience Institute, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-0964","authenticated-orcid":false,"given":"John H.","family":"Morrison","sequence":"additional","affiliation":[{"name":"California National Primate Research Center, University of California Davis, Davis, California, USA"},{"name":"Department of Neurology, School of Medicine, University of California Davis, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-4300","authenticated-orcid":false,"given":"Marlene R.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Neuroscience Institute, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070601100693000_2026.06.28.734833v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.05.010"},{"key":"2026070601100693000_2026.06.28.734833v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.03.04.583375"},{"key":"2026070601100693000_2026.06.28.734833v1.3","first-page":"5284504","article-title":"False Memory in Alzheimer\u2019s Disease","volume":"2020","year":"2020","journal-title":"Behav. Neurol"},{"key":"2026070601100693000_2026.06.28.734833v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn241"},{"key":"2026070601100693000_2026.06.28.734833v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2006.08.001"},{"key":"2026070601100693000_2026.06.28.734833v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/0278-2626(92)90043-L"},{"key":"2026070601100693000_2026.06.28.734833v1.7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1017\/S1355617708080193","article-title":"Error detection and correction patterns in dementia: a breakdown of error monitoring processes and their neuropsychological correlates","volume":"14","year":"2008","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"2026070601100693000_2026.06.28.734833v1.8","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/alz.12318","article-title":"A novel tau-based rhesus monkey model of Alzheimer\u2019s pathogenesis","volume":"17","year":"2021","journal-title":"Alzheimers Dement"},{"key":"2026070601100693000_2026.06.28.734833v1.9","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1002\/alz.13868","article-title":"Temporal progression of tau pathology and neuroinflammation in a rhesus monkey model of Alzheimer\u2019s disease","volume":"20","year":"2024","journal-title":"Alzheimers Dement. J. Alzheimers Assoc"},{"key":"2026070601100693000_2026.06.28.734833v1.10","doi-asserted-by":"publisher","DOI":"10.64898\/2026.03.18.712735"},{"key":"2026070601100693000_2026.06.28.734833v1.11","doi-asserted-by":"crossref","first-page":"371","DOI":"10.14283\/jpad.2021.23","article-title":"Diagnosis of Early Alzheimer\u2019s Disease: Clinical Practice in 2021","volume":"8","year":"2021","journal-title":"J. Prev. Alzheimers Dis"},{"key":"2026070601100693000_2026.06.28.734833v1.12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","year":"2018","journal-title":"Alzheimers Dement. J. Alzheimers Assoc"},{"key":"2026070601100693000_2026.06.28.734833v1.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"2026070601100693000_2026.06.28.734833v1.14","doi-asserted-by":"crossref","first-page":"e71345","DOI":"10.1002\/alz.71345","article-title":"2026 Alzheimer\u2019s disease facts and figures","volume":"22","year":"2026","journal-title":"Alzheimers Dement"},{"key":"2026070601100693000_2026.06.28.734833v1.15","doi-asserted-by":"crossref","unstructured":"Riverol, M. & L\u00f3pez, O. L . Biomarkers in Alzheimer\u2019s disease. Front. Neurol. 2, 46 (2011).","DOI":"10.3389\/fneur.2011.00046"},{"issue":"Suppl 1","key":"2026070601100693000_2026.06.28.734833v1.16","first-page":"S237","article-title":"Alzheimer\u2019s disease and the quest for its biological measures","volume":"33","year":"2013","journal-title":"J. Alzheimers Dis. JAD"},{"key":"2026070601100693000_2026.06.28.734833v1.17","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000147470.58328.50"},{"key":"2026070601100693000_2026.06.28.734833v1.18","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3233\/JAD-140843","article-title":"Biomarkers for preclinical Alzheimer\u2019s disease","volume":"42","year":"2014","journal-title":"J. Alzheimers Dis. JAD"},{"key":"2026070601100693000_2026.06.28.734833v1.19","first-page":"1149","article-title":"Biomarkers for Alzheimer\u2019s Disease Diagnosis","volume":"14","year":"2017","journal-title":"Curr. Alzheimer Res"},{"key":"2026070601100693000_2026.06.28.734833v1.20","doi-asserted-by":"crossref","unstructured":"Villa, C. , Lavitrano, M. , Salvatore, E. & Combi, R . Molecular and Imaging Biomarkers in Alzheimer\u2019s Disease: A Focus on Recent Insights. J. Pers. Med. 10, 61 (2020).","DOI":"10.3390\/jpm10030061"},{"key":"2026070601100693000_2026.06.28.734833v1.21","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.3390\/ijms23094962","article-title":"Biomarkers for Alzheimer\u2019s Disease in the Current State: A Narrative Review","volume":"23","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"2026070601100693000_2026.06.28.734833v1.22","unstructured":"World Health Organization. Global Action Plan on the Public Health Response to Dementia 2017\u20132025. (World Health Organization, Geneva, 2017)."},{"key":"2026070601100693000_2026.06.28.734833v1.23","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666200528142429"},{"key":"2026070601100693000_2026.06.28.734833v1.24","first-page":"66","article-title":"Can visuospatial measures improve the diagnosis of Alzheimer\u2019s disease?","volume":"10","year":"2018","journal-title":"Alzheimers Dement. Amst. Neth"},{"key":"2026070601100693000_2026.06.28.734833v1.25","first-page":"e58416","article-title":"A Review of Recent Advances in the Management of Alzheimer\u2019s Disease","volume":"16","year":"2024","journal-title":"Cureus"},{"key":"2026070601100693000_2026.06.28.734833v1.26","doi-asserted-by":"crossref","unstructured":"Sims, J. R. et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA 330, 512 (2023).","DOI":"10.1001\/jama.2023.21109"},{"key":"2026070601100693000_2026.06.28.734833v1.27","doi-asserted-by":"crossref","first-page":"e70905","DOI":"10.1002\/alz.70905","article-title":"Long-term safety and efficacy of lecanemab in early Alzheimer\u2019s disease: Results from the clarity AD open-label extension study","volume":"21","year":"2025","journal-title":"Alzheimers Dement"},{"key":"2026070601100693000_2026.06.28.734833v1.28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/JCMA.0000000000001252","article-title":"2025 update on treatment strategies for the Alzheimer\u2019s disease spectrum","volume":"88","year":"2025","journal-title":"J. Chin. Med. Assoc. JCMA"},{"key":"2026070601100693000_2026.06.28.734833v1.29","doi-asserted-by":"publisher","DOI":"10.2147\/DNND.S228939"},{"key":"2026070601100693000_2026.06.28.734833v1.30","unstructured":"Chu, L. Alzheimer\u2019s disease: early diagnosis and treatment."},{"key":"2026070601100693000_2026.06.28.734833v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.11.033"},{"key":"2026070601100693000_2026.06.28.734833v1.32","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/13803390903540315","article-title":"Diagnosis of Alzheimer\u2019s disease using neuropsychological testing improved by multivariate analyses","volume":"32","year":"2010","journal-title":"J. Clin. Exp. Neuropsychol"},{"key":"2026070601100693000_2026.06.28.734833v1.33","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.19.4.520"},{"key":"2026070601100693000_2026.06.28.734833v1.34","first-page":"e65972","article-title":"Navigating Prevention: A Systematic Review of Strategies for Alzheimer\u2019s Disease in High-Risk and Affected Individuals","volume":"16","year":"2024","journal-title":"Cureus"},{"key":"2026070601100693000_2026.06.28.734833v1.35","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1080\/13803395.2018.1513453","article-title":"False memories in patients with mild cognitive impairment and mild Alzheimer\u2019s disease dementia: Can cognitive strategies help?","volume":"41","year":"2019","journal-title":"J. Clin. Exp. Neuropsychol"},{"key":"2026070601100693000_2026.06.28.734833v1.36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.21.1.227"},{"key":"2026070601100693000_2026.06.28.734833v1.37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-080317-061936"},{"key":"2026070601100693000_2026.06.28.734833v1.38","doi-asserted-by":"publisher","DOI":"10.7551\/mitpress\/9504.003.0041"},{"key":"2026070601100693000_2026.06.28.734833v1.39","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113038"},{"key":"2026070601100693000_2026.06.28.734833v1.40","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-vision-082114-035431"},{"key":"2026070601100693000_2026.06.28.734833v1.41","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1016\/j.neuron.2023.03.022","article-title":"Tasks and their role in visual neuroscience","volume":"111","year":"2023","journal-title":"Neuron"},{"key":"2026070601100693000_2026.06.28.734833v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-06-01799.1987"},{"key":"2026070601100693000_2026.06.28.734833v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01774-5"},{"key":"2026070601100693000_2026.06.28.734833v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0223792"},{"key":"2026070601100693000_2026.06.28.734833v1.45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.82580"},{"key":"2026070601100693000_2026.06.28.734833v1.46","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1177\/1533317509332093","article-title":"Eye Tracking During a Visual Paired Comparison Task as a Predictor of Early Dementia","volume":"24","year":"2009","journal-title":"Am. J. Alzheimers Dis. Dementiasr"},{"key":"2026070601100693000_2026.06.28.734833v1.47","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1177\/1533317512470484","article-title":"A Behavioral Task Predicts Conversion to Mild Cognitive Impairment and Alzheimer\u2019s Disease","volume":"28","year":"2013","journal-title":"Am. J. Alzheimers Dis. Dementias\u00ae"},{"key":"2026070601100693000_2026.06.28.734833v1.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-01-00451.2000"},{"key":"2026070601100693000_2026.06.28.734833v1.49","doi-asserted-by":"crossref","unstructured":"Bott, N. T. et al. Web Camera Based Eye Tracking to Assess Visual Memory on a Visual Paired Comparison Task. Front. Neurosci. 11, 370 (2017).","DOI":"10.3389\/fnins.2017.00370"},{"key":"2026070601100693000_2026.06.28.734833v1.50","unstructured":"Simonyan, K. & Zisserman, A . Very Deep Convolutional Networks for Large-Scale Image Recognition. Preprint at http:\/\/arxiv.org\/abs\/1409.1556 (2015)."},{"key":"2026070601100693000_2026.06.28.734833v1.51","doi-asserted-by":"crossref","unstructured":"Kramer, M. A. , Hebart, M. N. , Baker, C. I. & Bainbridge, W. A . The features underlying the memorability of objects. Sci. Adv. (2023).","DOI":"10.1101\/2022.04.29.490104"},{"key":"2026070601100693000_2026.06.28.734833v1.52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2171-10.2010"},{"key":"2026070601100693000_2026.06.28.734833v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3476"},{"key":"2026070601100693000_2026.06.28.734833v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.09.035"},{"key":"2026070601100693000_2026.06.28.734833v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.11.006"},{"key":"2026070601100693000_2026.06.28.734833v1.56","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1159\/000442383","article-title":"Exploring Visual Selective Attention towards Novel Stimuli in Alzheimer\u2019s Disease Patients","volume":"5","year":"2015","journal-title":"Dement. Geriatr. Cogn. Disord. EXTRA"},{"key":"2026070601100693000_2026.06.28.734833v1.57","doi-asserted-by":"crossref","unstructured":"Stonebarger, G. A. , Bimonte-Nelson, H. A. & Urbanski, H. F . The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer\u2019s Disease. Front. Aging Neurosci. 13, 734173 (2021).","DOI":"10.3389\/fnagi.2021.734173"},{"key":"2026070601100693000_2026.06.28.734833v1.58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1919895116"},{"key":"2026070601100693000_2026.06.28.734833v1.59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902279116"},{"key":"2026070601100693000_2026.06.28.734833v1.60","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz151"},{"key":"2026070601100693000_2026.06.28.734833v1.61","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1152\/jn.1998.79.6.3272","article-title":"Signal timing across the macaque visual system","volume":"79","year":"1998","journal-title":"J. Neurophysiol"},{"key":"2026070601100693000_2026.06.28.734833v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2439"},{"key":"2026070601100693000_2026.06.28.734833v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.003"},{"key":"2026070601100693000_2026.06.28.734833v1.64","doi-asserted-by":"publisher","DOI":"10.1109\/ICCV48922.2021.01268"},{"key":"2026070601100693000_2026.06.28.734833v1.65","first-page":"1583","article-title":"THINGSplus: New norms and metadata for the THINGS database of 1854 object concepts and 26,107 natural object images","volume":"56","year":"2024","journal-title":"Behav. Res. Methods"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.28.734833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:10:43Z","timestamp":1783325443000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.28.734833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":65,"URL":"https:\/\/doi.org\/10.64898\/2026.06.28.734833","relation":{},"subject":[],"published":{"date-parts":[[2026,7,2]]},"subtype":"preprint"}}