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Sex-Based Differences in Functional Brain Activity During Working Memory in Survivors of Pediatric Acute Lymphoblastic Leukemia
Journal article   Open access   Peer reviewed

Sex-Based Differences in Functional Brain Activity During Working Memory in Survivors of Pediatric Acute Lymphoblastic Leukemia

Kellen Gandy, Matthew A. Scoggins, Nicholas Phillips, Ellen van der Plas, Slim Fellah, Lisa M. Jacola, Ching-Hon Pui, Melissa M. Hudson, Wilburn E. Reddick, Ranganatha Sitaram, …
JNCI cancer spectrum, Vol.6(2), pkac026
03/02/2022
DOI: 10.1093/jncics/pkac026
PMCID: PMC9041337
PMID: 35603857
url
https://doi.org/10.1093/jncics/pkac026View
Published (Version of record) Open Access

Abstract

Background: Long-term survivors of pediatric acute lymphoblastic leukemia are at elevated risk for neurocognitive deficits and corresponding brain dysfunction. This study examined sex-based differences in functional neuroimaging outcomes in acute lymphoblastic leukemia survivors treated with chemotherapy alone. Methods: Functional magnetic resonance imaging (fMRI) and neurocognitive testing were obtained in 123 survivors (46% male; median [min-max] age = 14.2 years [8.3-26.5 years]; time since diagnosis = 7.7 years [5.1-12.5 years]) treated on the St. Jude Total XV treatment protocol. Participants performed the n-back working memory task in a 3 T scanner. Functional neuroimaging data were processed (realigned, slice time corrected, normalized, smoothed) and analyzed using statistical parametric mapping with contrasts for 1-back and 2-back conditions, which reflect varying degrees of working memory and task load. Group-level fMRI contrasts were stratified by sex and adjusted for age and methotrexate exposure. Statistical tests were 2-sided (P < .05 statistical significance threshold). Results: Relative to males, female survivors exhibited less activation (ie, reduced blood oxygen dependent-level signals) in the right parietal operculum, supramarginal gyrus and inferior occipital gyms, and bilateral superior frontal medial gyrus during increased working memory load (family-wise error-corrected P = .004 to .008, adjusting for age and methotrexate dose). Female survivors were slower to correctly respond to the 2-back condition than males (P < .05), though there were no differences in overall accuracy. Performance accuracy was negatively correlated with fMRI activity in female survivors (Pearson's r = -0.39 to -0.29, P = .001 to .02), but not in males. Conclusions: These results suggest the working memory network is more impaired in female survivors than male survivors, which may contribute to ongoing functional deficits.
Oncology Life Sciences & Biomedicine Science & Technology

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