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Children with SCD have reduced\/restricted cerebral blood flow, resulting in neurocognitive deficits. Hydroxyurea is the standard treatment for SCD; however, whether hydroxyurea influences such effects is unclear. A key area of SCD-associated neurocognitive impairment is working memory, which is implicated in other cognitive and academic skills. The neural correlates of working memory can be tested using n-back tasks. We analyzed functional magnetic resonance imaging (fMRI) data of patients with SCD (20 hydroxyurea-treated patients and 11 controls, aged 7\u201318 years) while they performed n-back tasks. Blood-oxygenation level\u2013dependent (BOLD) signals were assessed during working memory processing at 2 time points: before hydroxyurea treatment and ~1 year after treatment was initiated. Neurocognitive measures were also assessed at both time points. Our results suggested that working memory was stable in the treated group. We observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- &gt;0-back contrast. Searchlight-pattern classification of the 2 time points of the 2-back tasks identified greater changes in the pattern and magnitude of BOLD signals, especially in the posterior regions of the brain, in the control group than in the treated group. In the control group at 1-year follow-up, 2-back BOLD signals increased across time points in several clusters (e.g., right inferior temporal lobe, right angular gyrus). We hypothesize that these changes resulted from increased cognitive effort during working memory processing in the absence of hydroxyurea. In the treated group, 0- to 2-back BOLD signals in the right angular gyrus and left cuneus increased continuously with increasing working memory load, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. These findings suggest that hydroxyurea treatment helps maintain working memory function in SCD.<\/jats:p>","DOI":"10.1371\/journal.pone.0296196","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T16:59:45Z","timestamp":1719507585000},"page":"e0296196","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hydroxyurea maintains working memory function in pediatric sickle cell disease"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-7675","authenticated-orcid":true,"given":"Jesyin","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josue L.","family":"Dalboni da Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Heitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Patni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Scoggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-2081","authenticated-orcid":true,"given":"Akshay","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfred C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J.","family":"Helton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranganatha","family":"Sitaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"pone.0296196.ref001","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1207\/S15326942DN2401_01","article-title":"Patterns of Verbal Long-Term and Working Memory Performance Reveal Deficits in Strategic Processing in Children With Frontal Infarcts Related to Sickle Cell Disease","volume":"24","author":"EM Brandling-Bennett","year":"2003","journal-title":"Dev Neuropsychol"},{"key":"pone.0296196.ref002","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0065-3101(24)00141-5","article-title":"Neurologic Complications of Sickle Cell Disease","volume":"36","author":"SG Pavlakis","year":"1989","journal-title":"Adv Pediatr"},{"key":"pone.0296196.ref003","first-page":"288","article-title":"Cerebrovascular Accidents in Sickle Cell Disease: Rates and Risk Factors","volume":"91","author":"K Ohene-Frempong","year":"1998","journal-title":"Blood"},{"key":"pone.0296196.ref004","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1067\/mpd.2001.117580","article-title":"Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease","volume":"139","author":"ST Miller","year":"2001","journal-title":"J Pediatr"},{"key":"pone.0296196.ref005","first-page":"965","article-title":"The spectrum of brain MR abnormalities in sickle-cell disease: a report from the Cooperative Study of Sickle Cell Disease","volume":"17","author":"FG Moser","year":"1996","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0296196.ref006","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1182\/blood.V99.8.3014","article-title":"Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease","volume":"99","author":"CH Pegelow","year":"2002","journal-title":"Blood"},{"key":"pone.0296196.ref007","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/ajh.23604","article-title":"Parent education and biologic factors influence on cognition in sickle cell anemia","volume":"89","author":"AA King","year":"2014","journal-title":"Am J Hematol"},{"key":"pone.0296196.ref008","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nrn2897","article-title":"Socioeconomic status and the brain: mechanistic insights from human and animal research","volume":"11","author":"DA Hackman","year":"2010","journal-title":"Nat Rev Neurosci"},{"key":"pone.0296196.ref009","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/jpepsy\/jsz031","article-title":"Cognitive Function in Sickle Cell Disease Across Domains, Cerebral Infarct Status, and the Lifespan: A Meta-Analysis","volume":"44","author":"K V. 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