{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:47:00Z","timestamp":1791733620946,"version":"4.3.4"},"posted":{"date-parts":[[2026,8,27]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["F32 AG058479"],"award-info":[{"award-number":["F32 AG058479"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AG066430"],"award-info":[{"award-number":["R01 AG066430"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Pupillometry is often used as a proxy for locus coeruleus (LC) activity but whether this relationship changes across the lifespan is unknown. We collected simultaneous pupillometry and multi-echo fMRI in 89 adults aged 19-78 during a visual oddball task. Oddball-evoked pupillary responses were present in all age groups and largest in middle age. Oddball-evoked LC BOLD responses were detected only in younger adults and did not predict individual pupillary responses. Pupil size and its first derivative (pupil change) correlated with whole-brain BOLD on distinct timescales and in distinct spatial patterns. Against 19 PET maps, pupil derivative coupling correlated uniquely with norepinephrine transporter (NET) density, and pupil size-unique coupling with \u03bc-opioid, cannabinoid CB1, and glutamatergic mGluR5 density. Only the pupil derivative-NET relationship weakened with age, though it remained significant in every group. Pupil size and pupil change therefore carry different information, and only pupil change correlates with activity in NET-rich regions across the lifespan.<\/jats:p>","DOI":"10.64898\/2026.08.24.746786","type":"posted-content","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:50:26Z","timestamp":1787878226000},"source":"Crossref","is-referenced-by-count":0,"title":["Pupil size and pupil change correlate with distinct cortical neurochemical systems across the adult lifespan"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6049-9101","authenticated-orcid":false,"given":"Elizabeth","family":"Riley","sequence":"first","affiliation":[{"name":"Department of Psychology, Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Psychology, Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-6350","authenticated-orcid":false,"given":"Adam","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Psychology, Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026101108452361000_2026.08.24.746786v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.05.070"},{"key":"2026101108452361000_2026.08.24.746786v3.2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12192"},{"key":"2026101108452361000_2026.08.24.746786v3.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135709"},{"key":"2026101108452361000_2026.08.24.746786v3.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-017-1829-1"},{"key":"2026101108452361000_2026.08.24.746786v3.5","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"2026101108452361000_2026.08.24.746786v3.6","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617722000881"},{"key":"2026101108452361000_2026.08.24.746786v3.7","doi-asserted-by":"publisher","DOI":"10.2307\/2346101"},{"key":"2026101108452361000_2026.08.24.746786v3.8","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"2026101108452361000_2026.08.24.746786v3.9","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00626-y"},{"key":"2026101108452361000_2026.08.24.746786v3.10","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1236335"},{"key":"2026101108452361000_2026.08.24.746786v3.11","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01582-0"},{"key":"2026101108452361000_2026.08.24.746786v3.12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020554"},{"key":"2026101108452361000_2026.08.24.746786v3.13","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.7926293"},{"key":"2026101108452361000_2026.08.24.746786v3.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.04.017"},{"key":"2026101108452361000_2026.08.24.746786v3.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrn755"},{"key":"2026101108452361000_2026.08.24.746786v3.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.12.031"},{"key":"2026101108452361000_2026.08.24.746786v3.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-019-0715-2"},{"key":"2026101108452361000_2026.08.24.746786v3.18","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00965"},{"key":"2026101108452361000_2026.08.24.746786v3.19","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.17.633373"},{"key":"2026101108452361000_2026.08.24.746786v3.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroling.2023.101164"},{"key":"2026101108452361000_2026.08.24.746786v3.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2017.09.025"},{"key":"2026101108452361000_2026.08.24.746786v3.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"2026101108452361000_2026.08.24.746786v3.23","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0193(1999)8:4<272::AID-HBM10>3.0.CO;2-4"},{"key":"2026101108452361000_2026.08.24.746786v3.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2009.01.011"},{"key":"2026101108452361000_2026.08.24.746786v3.25","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7935406"},{"key":"2026101108452361000_2026.08.24.746786v3.26","doi-asserted-by":"publisher","DOI":"10.3758\/CABN.10.2.252"},{"key":"2026101108452361000_2026.08.24.746786v3.27","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2594(200007)44:1<162::AID-MRM23>3.0.CO;2-E"},{"key":"2026101108452361000_2026.08.24.746786v3.28","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161078"},{"key":"2026101108452361000_2026.08.24.746786v3.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.02.007"},{"key":"2026101108452361000_2026.08.24.746786v3.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.05.029"},{"key":"2026101108452361000_2026.08.24.746786v3.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.06.021"},{"key":"2026101108452361000_2026.08.24.746786v3.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01186-3"},{"key":"2026101108452361000_2026.08.24.746786v3.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.02.028"},{"key":"2026101108452361000_2026.08.24.746786v3.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.02.025"},{"key":"2026101108452361000_2026.08.24.746786v3.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.10.041"},{"key":"2026101108452361000_2026.08.24.746786v3.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.028"},{"key":"2026101108452361000_2026.08.24.746786v3.37","doi-asserted-by":"publisher","DOI":"10.1126\/science.154.3756.1583"},{"key":"2026101108452361000_2026.08.24.746786v3.38","doi-asserted-by":"publisher","DOI":"10.1111\/psyp.12816"},{"key":"2026101108452361000_2026.08.24.746786v3.39","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0803-z"},{"key":"2026101108452361000_2026.08.24.746786v3.40","doi-asserted-by":"publisher","DOI":"10.3758\/s13428-018-1075-y"},{"key":"2026101108452361000_2026.08.24.746786v3.41","doi-asserted-by":"publisher","DOI":"10.1186\/s12576-022-00849-x"},{"key":"2026101108452361000_2026.08.24.746786v3.42","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2018.00021"},{"key":"2026101108452361000_2026.08.24.746786v3.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1943.tb06325.x"},{"key":"2026101108452361000_2026.08.24.746786v3.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.06.056"},{"key":"2026101108452361000_2026.08.24.746786v3.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.10.014"},{"key":"2026101108452361000_2026.08.24.746786v3.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608282113"},{"key":"2026101108452361000_2026.08.24.746786v3.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01625-w"},{"key":"2026101108452361000_2026.08.24.746786v3.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2016.01.001"},{"key":"2026101108452361000_2026.08.24.746786v3.49","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22466"},{"key":"2026101108452361000_2026.08.24.746786v3.50","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(83)90123-6"},{"key":"2026101108452361000_2026.08.24.746786v3.51","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.1058"},{"key":"2026101108452361000_2026.08.24.746786v3.52","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0657-0"},{"key":"2026101108452361000_2026.08.24.746786v3.53","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-026-09776-8"},{"key":"2026101108452361000_2026.08.24.746786v3.54","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.26.24314117"},{"key":"2026101108452361000_2026.08.24.746786v3.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-0360-9"},{"key":"2026101108452361000_2026.08.24.746786v3.56","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13289"},{"key":"2026101108452361000_2026.08.24.746786v3.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2025.03.005"},{"key":"2026101108452361000_2026.08.24.746786v3.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2025.07.010"},{"key":"2026101108452361000_2026.08.24.746786v3.59","doi-asserted-by":"crossref","unstructured":"Riley, E. , Turker, H. , Wang, D. , Swallow, K. M. , Anderson, A. K. , & De Rosa, E. (2023). Nonlinear changes in pupillary attentional orienting responses across the lifespan. GeroScience, 1\u201317.","DOI":"10.1007\/s11357-023-00834-1"},{"key":"2026101108452361000_2026.08.24.746786v3.60","doi-asserted-by":"crossref","unstructured":"Ross, J. A. , & Van Bockstaele, E. J. (2021). The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives. Frontiers in Psychiatry, 11. https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2020.601519","DOI":"10.3389\/fpsyt.2020.601519"},{"key":"2026101108452361000_2026.08.24.746786v3.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.011"},{"key":"2026101108452361000_2026.08.24.746786v3.62","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhx179"},{"key":"2026101108452361000_2026.08.24.746786v3.63","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13839"},{"key":"2026101108452361000_2026.08.24.746786v3.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.09.039"},{"key":"2026101108452361000_2026.08.24.746786v3.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118865"},{"key":"2026101108452361000_2026.08.24.746786v3.66","doi-asserted-by":"publisher","DOI":"10.3389\/FPSYG.2022.892416"},{"key":"2026101108452361000_2026.08.24.746786v3.67","doi-asserted-by":"publisher","DOI":"10.1101\/308643"},{"key":"2026101108452361000_2026.08.24.746786v3.68","unstructured":"Taylor, P. , Reynolds, R. , & Glen, D . (2024). Improving skullstripping and nonlinear warping in AFNI: sswarper2. 30th Annual Meeting of the Organization for Human Brain Mapping."},{"key":"2026101108452361000_2026.08.24.746786v3.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118047"},{"key":"2026101108452361000_2026.08.24.746786v3.70","doi-asserted-by":"crossref","unstructured":"Unsworth, N. , & Robison, M. K. (2016). Pupillary correlates of lapses of sustained attention.","DOI":"10.3758\/s13415-016-0417-4"},{"key":"2026101108452361000_2026.08.24.746786v3.71","doi-asserted-by":"publisher","DOI":"10.3758\/s13415-016-0417-4"},{"key":"2026101108452361000_2026.08.24.746786v3.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2015.03.018"},{"issue":"3","key":"2026101108452361000_2026.08.24.746786v3.73","first-page":"1132","article-title":"Factors affecting light-adapted pupil size in normal human subjects","volume":"35","year":"1994","journal-title":"Investigative Ophthalmology and Visual Science"},{"key":"2026101108452361000_2026.08.24.746786v3.74","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00338.2011"},{"key":"2026101108452361000_2026.08.24.746786v3.75","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.1.141"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.24.746786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:45:32Z","timestamp":1791733532000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.08.24.746786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":75,"URL":"https:\/\/doi.org\/10.64898\/2026.08.24.746786","relation":{},"subject":[],"published":{"date-parts":[[2026,8,27]]},"subtype":"preprint"}}