Working memory in survivors of childhood acute lymphocytic leukemia: functional neuroimaging analyses

Abstract

Background: Research on the physical and psychological late effects of treatment of childhood cancer has led to the identification of significant long-term neurocognitive deficits experienced by some survivors, particularly in the areas of memory and executive functioning. Despite indications of deficits based on cognitive assessment, the identification of specific mechanisms of neurocognitive deficits using neuroimaging techniques has yet to be adequately considered.

Procedure: This study used functional neuroimaging techniques to examine working memory and executive functioning deficits of survivors of childhood acute lymphocytic leukemia (ALL), as compared to age- and gender-matched healthy controls.

Results: There was a trend for ALL survivors to perform more poorly on a working memory task in terms of overall accuracy. Additionally, survivors displayed significantly greater activation in areas underlying working memory (dorsolateral and ventrolateral prefrontal cortex) and error monitoring (dorsal and ventral anterior cingulate cortex).

Conclusions: These results support the theory of compensatory activation in necessary brain regions in order to complete tasks in pediatric ALL survivors, similar to that observed in multiple sclerosis patients. Concurrent examination of testing and brain imaging enables the connection of behavioral observations with underlying neurological characteristics of deficits in survivors and may help provide insight into mechanisms through which deficits appear.

Figure 1

Between Group Differences in DLPFC Activation on the 2 vs. 0 N-back Contrast During Neuroimaging. Differences in activation in the 2-back versus 0-back conditions for survivors of ALL (left column) and control subjects (right column). Yellow-to-orange clusters indicate areas of significantly greater activation in the 2-back condition relative to the 0-back conditions. Red circles identify the bilateral region of interest (right and left DLPFC).

Figure 2

Between Group Differences in D-ACC Activation on the 3 vs. 1 N-back Contrast During Neuroimaging. Differences in activation in the 3-back versus 1-back conditions for survivors of ALL (left column) and control subjects (right column). Yellow-to-orange clusters indicate areas of significantly greater activation in the 3-back condition relative to the 1-back conditions. Red circles identify the region of interest (D-ACC).