TY - JOUR
T1 - Sex-Based Differences in Functional Brain Activity During Working Memory in Survivors of Pediatric Acute Lymphoblastic Leukemia
AU - Gandy, Kellen
AU - Scoggins, Matthew A.
AU - Phillips, Nicholas
AU - Van Der Plas, Ellen
AU - Fellah, Slim
AU - Jacola, Lisa M.
AU - Pui, Ching Hon
AU - Hudson, Melissa M.
AU - Reddick, Wilburn E.
AU - Sitaram, Ranganatha
AU - Krull, Kevin R.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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 gyrus, 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.
AB - 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 gyrus, 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.
UR - http://www.scopus.com/inward/record.url?scp=85134963835&partnerID=8YFLogxK
U2 - 10.1093/jncics/pkac026
DO - 10.1093/jncics/pkac026
M3 - Article
C2 - 35603857
AN - SCOPUS:85134963835
SN - 2515-5091
VL - 6
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 2
M1 - pkac026
ER -