Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls

Abstract

Background: Patients who receive adjuvant chemotherapy have reported cognitive impairments that may last for years after the completion of treatment. Working memory-related and long-term memory-related changes in this population are not well understood. The objective of this study was to demonstrate that cancer-related cognitive impairments are associated with the under recruitment of brain regions involved in working and recognition memory compared with controls.

Methods: Oncology patients (n = 15) who were receiving adjuvant chemotherapy and had evidence of cognitive impairment according to neuropsychological testing and self-report and a group of age-matched, education group-matched, cognitively normal control participants (n = 14) underwent functional magnetic resonance imaging. During functional magnetic resonance imaging, participants performed a nonverbal n-back working memory task and a visual recognition task.

Results: On the working memory task, when 1-back and 2-back data were averaged and contrasted with 0-back data, significantly reduced activation was observed in the right dorsolateral prefrontal cortex for oncology patients versus controls. On the recognition task, oncology patients displayed decreased activity of the left-middle hippocampus compared with controls. Neuroimaging results were not associated with patient-reported cognition.

Conclusions: Decreased recruitment of brain regions associated with the encoding of working memory and recognition memory was observed in the oncology patients compared with the control group. These results suggest that there is a reduction in neural functioning postchemotherapy and corroborate patient-reported cognitive difficulties after cancer treatment, although a direct association was not observed. Cancer 2016;122:258-268. © 2015 American Cancer Society.

Keywords: cancer-related cognitive impairment (CRCI); functional magnetic resonance imaging (fMRI); patient-reported outcomes (PRO); recognition memory; working memory.

Figure 1. N-back working memory task

In the 0-back condition participants respond whenever the indicated figure appeared, regardless of any figures that preceded it. In the 1-back condition participants respond whenever the figure is the same as in the previous trial. Subjects respond in the 2-back condition whenever the figure matches the stimulus that came 2 trials before it. Arrows indicate correct responses for all conditions. Stimuli courtesy of J. Daniel Ragland (University of Pennsylvania).

Figure 2. Between-groups behavioral results for the n-back task

Left panel demonstrates mean accuracy and right panel demonstrates mean d-prime. While there were no statistically significant differences between groups for each n-back condition, the differences for the 0- and 1-back conditions showed moderate effects sizes.

Figure 3. Between-groups functional differences in the right dorsolateral prefrontal cortex for the n-back working memory task

Oncology patients show significantly decreased BOLD activation in right dorsolateral prefrontal cortex as compared with controls.

Figure 4. Between-group behavioral and functional differences in recognition task

A. Proportion of hits, misses, false alarms and correct rejections for the visual recognition task. B. Controls show increased activation when contrasting hits to correct rejections in the middle hippocampus. Regions of increased activation not displayed also include left lateral parietal cortex, left fusiform gyrus, and left lateral occipital cortex. Conversely, oncology patients showed decreased activation than controls in the left hippocampus.