{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:05:21Z","timestamp":1784819121500,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,21]]},"group-title":"Neuroscience","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5R01 AG-056535"],"award-info":[{"award-number":["5R01 AG-056535"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Functional activity in response to increasing task difficulty (BOLD-modulation) in regions of the default mode network (DMN\/task-negative) and multiple demand network (MDN\/task-positive) shows age-related decline, which is associated with reduced cognitive performance. While BOLD-modulation in the DMN begins to decline in middle-age, white matter structural connectivity declines earlier in MDN regions. We conjecture that to maintain executive function (EF) performance with aging, altered BOLD-modulation in DMN during task engagement serves as a compensatory reaction to structural decline in MDN. To test this possibility, functionally-guided tractography was applied in 160 healthy adults aged 20-94 to locate white matter connecting MDN and\/or DMN regions that were active during a distance judgement paradigm. Specifically, analyses examined the effects of 1) age on white matter tracts (fractional anisotropy; FA); 2) structure-function association between FA and BOLD-modulation; and 3) age, positive\/negative BOLD-modulation, and quadratic FA on EF. Age-related decline was found in one MDN tract (U-shaped tract) and a significant structure-function association was found in inferior fronto-occipital fasciculus (IFOF). Additionally, an interaction effect between quadratic frontal-insular (U-shaped) tract FA, age, and positive\/negative BOLD-modulation was found for inhibition performance, supporting the hypothesis of compensatory functional activity effects on executive function for older adults with altered white matter microstructure.<\/jats:p>","DOI":"10.64898\/2026.07.16.739039","type":"posted-content","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:30:46Z","timestamp":1784694646000},"source":"Crossref","is-referenced-by-count":0,"title":["Brain Structure-Function Association as a Compensatory Factor in Cognitive Aging"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9418-3195","authenticated-orcid":false,"given":"Tzu-Chen","family":"Lung","sequence":"first","affiliation":[{"name":"Center for Vital Longevity; Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, 75235 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3442-383X","authenticated-orcid":false,"given":"David A.","family":"Hoagey","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO 63110 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-7961","authenticated-orcid":false,"given":"Karen M.","family":"Rodrigue","sequence":"additional","affiliation":[{"name":"Center for Vital Longevity; Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, 75235 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Rugg","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO 63110 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-9026","authenticated-orcid":false,"given":"Kristen M.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Center for Vital Longevity; Department of Psychology, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, 75235 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072307350612000_2026.07.16.739039v1.1","doi-asserted-by":"crossref","unstructured":"Andrews-Hanna, J. R. , Grilli, M. D. , & Irish, M . (2019). A Review and Reappraisal of the Default Network in Normal Aging and Dementia. In: Oxford University Press.","DOI":"10.1093\/acrefore\/9780190236557.013.384"},{"key":"2026072307350612000_2026.07.16.739039v1.2","doi-asserted-by":"publisher","DOI":"10.54294\/uvnhin"},{"key":"2026072307350612000_2026.07.16.739039v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199904260-00040"},{"key":"2026072307350612000_2026.07.16.739039v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2018.05.059"},{"key":"2026072307350612000_2026.07.16.739039v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2026072307350612000_2026.07.16.739039v1.6","unstructured":"Brett, M. , Anton, J. L. , Valabregue, R. , & Poline, J.-B . (2002). Region of interest analysis using the MarsBar toolbox for SPM 99. Neuroimage, 16."},{"key":"2026072307350612000_2026.07.16.739039v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00194"},{"key":"2026072307350612000_2026.07.16.739039v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2018.04.006"},{"key":"2026072307350612000_2026.07.16.739039v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.03.073"},{"key":"2026072307350612000_2026.07.16.739039v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2575"},{"key":"2026072307350612000_2026.07.16.739039v1.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1426-13.2013"},{"key":"2026072307350612000_2026.07.16.739039v1.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1426-13.2013"},{"key":"2026072307350612000_2026.07.16.739039v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2008.05.004"},{"key":"2026072307350612000_2026.07.16.739039v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311772110"},{"key":"2026072307350612000_2026.07.16.739039v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt066"},{"key":"2026072307350612000_2026.07.16.739039v1.16","doi-asserted-by":"publisher","DOI":"10.4135\/9781412952644.n116"},{"key":"2026072307350612000_2026.07.16.739039v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bht289"},{"key":"2026072307350612000_2026.07.16.739039v1.18","doi-asserted-by":"crossref","unstructured":"Delis, D. C. , Kaplan, E. , & Kramer, J. H . (2001). Delis-Kaplan executive function system (D-KEFS) [[Database record]]. APA PsycTests. https:\/\/psycnet.apa.org\/doi\/10.1037\/t15082-000","DOI":"10.1037\/t15082-000"},{"key":"2026072307350612000_2026.07.16.739039v1.19","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00111"},{"key":"2026072307350612000_2026.07.16.739039v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2015.00585"},{"key":"2026072307350612000_2026.07.16.739039v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"2026072307350612000_2026.07.16.739039v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.10.068"},{"key":"2026072307350612000_2026.07.16.739039v1.23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090307"},{"key":"2026072307350612000_2026.07.16.739039v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.116809"},{"key":"2026072307350612000_2026.07.16.739039v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nn1205-1791c"},{"key":"2026072307350612000_2026.07.16.739039v1.26","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp207"},{"key":"2026072307350612000_2026.07.16.739039v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2015.04.008"},{"key":"2026072307350612000_2026.07.16.739039v1.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219562110"},{"key":"2026072307350612000_2026.07.16.739039v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24774"},{"key":"2026072307350612000_2026.07.16.739039v1.30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0518-14.2014"},{"key":"2026072307350612000_2026.07.16.739039v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.08.027"},{"key":"2026072307350612000_2026.07.16.739039v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.11.094"},{"key":"2026072307350612000_2026.07.16.739039v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.01.030"},{"key":"2026072307350612000_2026.07.16.739039v1.34","first-page":"1","article-title":"Contributions to the theory of testing statistical hypotheses","volume":"1","year":"1936","journal-title":"Statistical Research Memoirs"},{"key":"2026072307350612000_2026.07.16.739039v1.35","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.09.075.2009"},{"key":"2026072307350612000_2026.07.16.739039v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1238411"},{"key":"2026072307350612000_2026.07.16.739039v1.37","doi-asserted-by":"publisher","DOI":"10.1162\/jocn.2007.19.6.1021"},{"key":"2026072307350612000_2026.07.16.739039v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.01.058"},{"key":"2026072307350612000_2026.07.16.739039v1.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089581"},{"key":"2026072307350612000_2026.07.16.739039v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2020.107335"},{"key":"2026072307350612000_2026.07.16.739039v1.41","doi-asserted-by":"publisher","DOI":"10.1177\/014662167700100306"},{"key":"2026072307350612000_2026.07.16.739039v1.42","unstructured":"Raz, N . (2000). Aging of the brain and its impact on cognitive performance: Integration of structural and functional findings. In F. I. M. Craik & T. A. Salthouse (Eds.), The handbook of aging and cognition (pp. 1\u201390). Lawrence Erlbaum Associates."},{"key":"2026072307350612000_2026.07.16.739039v1.43","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23514"},{"key":"2026072307350612000_2026.07.16.739039v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.12.022"},{"key":"2026072307350612000_2026.07.16.739039v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbas.2023.100067"},{"key":"2026072307350612000_2026.07.16.739039v1.46","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2014.00772"},{"key":"2026072307350612000_2026.07.16.739039v1.47","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24522"},{"key":"2026072307350612000_2026.07.16.739039v1.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2815-14.2014"},{"key":"2026072307350612000_2026.07.16.739039v1.49","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr339"},{"key":"2026072307350612000_2026.07.16.739039v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.06.016"},{"key":"2026072307350612000_2026.07.16.739039v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.05.020"},{"key":"2026072307350612000_2026.07.16.739039v1.52","doi-asserted-by":"publisher","DOI":"10.1177\/1745691619827511"},{"key":"2026072307350612000_2026.07.16.739039v1.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800005105"},{"key":"2026072307350612000_2026.07.16.739039v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.08.025"},{"key":"2026072307350612000_2026.07.16.739039v1.55","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00358"},{"key":"2026072307350612000_2026.07.16.739039v1.56","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_00869"},{"key":"2026072307350612000_2026.07.16.739039v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.12.075"},{"key":"2026072307350612000_2026.07.16.739039v1.58","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz193"},{"key":"2026072307350612000_2026.07.16.739039v1.59","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz193"},{"key":"2026072307350612000_2026.07.16.739039v1.60","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22368"},{"key":"2026072307350612000_2026.07.16.739039v1.61","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.1038756"},{"key":"2026072307350612000_2026.07.16.739039v1.62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084518"},{"key":"2026072307350612000_2026.07.16.739039v1.63","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bht212"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.16.739039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:35:16Z","timestamp":1784817316000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.16.739039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":63,"URL":"https:\/\/doi.org\/10.64898\/2026.07.16.739039","relation":{},"subject":[],"published":{"date-parts":[[2026,7,21]]},"subtype":"preprint"}}