TY - JOUR
T1 - Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy
T2 - A preliminary investigation
AU - Brace, Kelin M.
AU - Lee, Wei Wei
AU - Cole, Peter D.
AU - Sussman, Elyse S.
N1 - Funding Information:
This work was funded by the National Institutes of Health: the National Cancer Institute [CA187226]; National Institute of General Medical Sciences [T32GM007288]; and the National Institute on Deafness and Other Communication Disorders [DC004263].
Funding Information:
This work was supported by the NIDCD and the NCI of the NIH (grants # R01 DC004263, R01 CA187226) and by the NIGMS Medical Scientist Training Program grant (T32GM007288). The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH. We thank Jean DeMarco and Sufen Chen for assistance with data collection. We thank the children and families for participating in this study.
PY - 2019/9/14
Y1 - 2019/9/14
N2 - Objective: The purpose of this study was to characterize post-chemotherapy sensory, memory, and attention abilities in childhood survivors of acute lymphoblastic leukemia (ALL) to better understand how treatment affects cognitive functioning. Methods: Eight ALL survivors and eight age-matched, healthy children between the ages of 5-11 years participated in the study. Among the ALL survivors, a median of 63 days (range 22-267 days) elapsed between completion of chemotherapy and this assessment. Sounds were presented in an oddball paradigm while recording the electroencephalogram in separate conditions of passive listening and active task performance. To assess different domains of cognition, we measured event-related brain potentials (ERPs) reflecting sensory processing (P1 component), working memory (mismatch negativity [MMN] component), attentional orienting (P3a), and target detection (P3b component) in response to the sounds. We also measured sound discrimination and response speed performance. Results: Relative to control subjects, ALL survivors had poorer performance on auditory tasks, as well as decreased amplitude of the P1, MMN, P3a, and P3b components. ALL survivors also did not exhibit the amplitude gain typically observed in the sensory P1 component when attending to the sound input compared to when passively listening. Conclusions: Atypical responses were observed in brain processes associated with sensory discrimination, auditory working memory, and attentional control in pediatric ALL survivors indicating deficiencies in all cognitive domains compared to age-matched controls. Significance: ERPs differentiated aspects of cognitive functioning, which may provide a useful tool for assessing recovery and risk of post-chemotherapy cognitive deficiencies in young children. The decreased MMN amplitude in ALL survivors may indicate (N-methyl D-aspartate) NMDA dysfunction induced by methotrexate, and thus provides a potential therapeutic target for chemotherapy-associated cognitive impairments.
AB - Objective: The purpose of this study was to characterize post-chemotherapy sensory, memory, and attention abilities in childhood survivors of acute lymphoblastic leukemia (ALL) to better understand how treatment affects cognitive functioning. Methods: Eight ALL survivors and eight age-matched, healthy children between the ages of 5-11 years participated in the study. Among the ALL survivors, a median of 63 days (range 22-267 days) elapsed between completion of chemotherapy and this assessment. Sounds were presented in an oddball paradigm while recording the electroencephalogram in separate conditions of passive listening and active task performance. To assess different domains of cognition, we measured event-related brain potentials (ERPs) reflecting sensory processing (P1 component), working memory (mismatch negativity [MMN] component), attentional orienting (P3a), and target detection (P3b component) in response to the sounds. We also measured sound discrimination and response speed performance. Results: Relative to control subjects, ALL survivors had poorer performance on auditory tasks, as well as decreased amplitude of the P1, MMN, P3a, and P3b components. ALL survivors also did not exhibit the amplitude gain typically observed in the sensory P1 component when attending to the sound input compared to when passively listening. Conclusions: Atypical responses were observed in brain processes associated with sensory discrimination, auditory working memory, and attentional control in pediatric ALL survivors indicating deficiencies in all cognitive domains compared to age-matched controls. Significance: ERPs differentiated aspects of cognitive functioning, which may provide a useful tool for assessing recovery and risk of post-chemotherapy cognitive deficiencies in young children. The decreased MMN amplitude in ALL survivors may indicate (N-methyl D-aspartate) NMDA dysfunction induced by methotrexate, and thus provides a potential therapeutic target for chemotherapy-associated cognitive impairments.
KW - Acute lymphoblastic leukemia (ALL)
KW - chemotherapy
KW - cognition
KW - event-related potentials (ERPs)
KW - mismatch negativity (MMN)
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U2 - 10.1080/13803395.2019.1623865
DO - 10.1080/13803395.2019.1623865
M3 - Article
C2 - 31156064
AN - SCOPUS:85066987031
VL - 41
SP - 814
EP - 831
JO - Journal of Clinical and Experimental Neuropsychology
JF - Journal of Clinical and Experimental Neuropsychology
SN - 1380-3395
IS - 8
ER -