Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy: A preliminary investigation

Kelin M. Brace, Wei Wei Lee, Peter D. Cole, Elyse S. Sussman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalJournal of Clinical and Experimental Neuropsychology
DOIs
StatePublished - Jan 1 2019

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Evoked Potentials
Leukemia
Drug Therapy
Brain
N-Methylaspartate
Short-Term Memory
Aptitude
Task Performance and Analysis
Methotrexate
Cognition
Electroencephalography
Pediatrics
Therapeutics

Keywords

  • Acute lymphoblastic leukemia (ALL)
  • chemotherapy
  • cognition
  • event-related potentials (ERPs)
  • mismatch negativity (MMN)

ASJC Scopus subject areas

  • Clinical Psychology
  • Neurology
  • Clinical Neurology

Cite this

@article{3684978fc21f4b6eaee93d93efe5a8cc,
title = "Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy: A preliminary investigation",
abstract = "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.",
keywords = "Acute lymphoblastic leukemia (ALL), chemotherapy, cognition, event-related potentials (ERPs), mismatch negativity (MMN)",
author = "Brace, {Kelin M.} and Lee, {Wei Wei} and Cole, {Peter D.} and Sussman, {Elyse S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/13803395.2019.1623865",
language = "English (US)",
journal = "Journal of Clinical and Experimental Neuropsychology",
issn = "1380-3395",
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}

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.

PY - 2019/1/1

Y1 - 2019/1/1

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

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