{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:25:50Z","timestamp":1791419150808,"version":"4.3.3"},"posted":{"date-parts":[[2025,5,21]]},"group-title":"Neuroscience","reference-count":198,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["K23NS123345"],"award-info":[{"award-number":["K23NS123345"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Prescription stimulants such as methylphenidate are being used by an increasing portion of the population, primarily children. These potent norepinephrine and dopamine reuptake inhibitors promote wakefulness, suppress appetite, enhance physical performance, and are purported to increase attentional abilities. Prior functional magnetic resonance imaging (fMRI) studies have yielded conflicting results about the effects of stimulants on the brain\u2019s attention, action\/motor, and salience regions that are difficult to reconcile with their proposed attentional effects. Here, we utilized resting-state fMRI (rs-fMRI) data from the large Adolescent Brain Cognitive Development (ABCD) Study to understand the effects of stimulants on brain functional connectivity (FC) in children (\n                  <jats:italic>n<\/jats:italic>\n                  = 11,875; 8-11 years old) using network level analysis (NLA). We validated these brain-wide association study (BWAS) findings in a controlled, precision imaging drug trial (PIDT) with highly-sampled (165-210 minutes) healthy adults receiving high-dose methylphenidate (Ritalin, 40 mg). In both studies, stimulants were associated with altered FC in action and motor regions, matching patterns of norepinephrine transporter expression. Connectivity was also changed in the salience (SAL) and parietal memory networks (PMN), which are important for reward-motivated learning and closely linked to dopamine, but not the brain\u2019s attention systems (e.g. dorsal attention network, DAN). Stimulant-related differences in FC closely matched the rs-fMRI pattern of getting enough sleep, as well as EEG- and respiration-derived brain maps of arousal. Taking stimulants rescued the effects of sleep deprivation on brain connectivity and school grades. The combined noradrenergic and dopaminergic effects of stimulants may drive brain organization towards a more wakeful and rewarded configuration, explaining improved task effort and persistence without direct effects on attention networks.\n                <\/jats:p>","DOI":"10.1101\/2025.05.19.654915","type":"posted-content","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T06:35:15Z","timestamp":1747809315000},"source":"Crossref","is-referenced-by-count":4,"title":["Stimulant medications affect arousal and reward, not attention"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3628-8029","authenticated-orcid":false,"given":"Benjamin P.","family":"Kay","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriah D.","family":"Wheelock","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, New York University Langone Center for Psychedelic Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Raut","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Allen Institute, Seattle, WA, USA"},{"name":"Department of Physiology & Biophysics, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-4705","authenticated-orcid":false,"given":"Roselyne J.","family":"Chauvin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Metoki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Rajesh","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Eck","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Pollaro","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahdeta","family":"Suljic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babatunde","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah J.","family":"Baden","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"Scheidter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeshka","family":"Ramirez-Perez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R.","family":"Krimmel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, 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M.","family":"Hermosillo","sequence":"additional","affiliation":[{"name":"Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA"},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA"},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hendrickson","sequence":"additional","affiliation":[{"name":"Masonic Institute for the Developing Brain, University of Minnesota Medical School, Minneapolis, MN, USA"},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN, 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