Electrophysiological Biomarkers of Chemotherapy-related Cognitive Impairment and Recovery

The broad goal of this research project is to develop a core set of biomarkers for chemotherapy-related cognitive impairment (or chemobrain). Clinical studies have documented mild cognitive impairment in chemotherapy patients most frequently within the domains of attention and memory, though impairments have been observed across a broad range of cognitive abilities. In addition, neuroimaging studies have demonstrated chemotherapy-related structural and functional changes in distributed cortical areas, including regions of the fronto-parietal attention network. While these studies suggest chemotherapy treatment negatively impacts patient health and cognitive function, it remains unclear how chemotherapy affects neural mechanisms of cognitive abilities. Current literature is limited in four major ways: (1) most research has focused on breast cancer populations, providing little insight into impact of tumor type, (2) few studies have examined the parametric effects of chemotherapy toxicity, (3) neuropsychological exams provide weak resolution of specific cognitive functions, and (4) neural factors associated with cognitive impairment are difficult to dissociate from non-neural (e.g. psychosocial) factors. To overcome these central limitations, the investigators propose a one-year longitudinal study that aims to systematically examine the influence of cancer stage and treatment toxicity on mild cognitive impairment observed in hematological malignancy (HM) patients by implementing a core battery of behavioral and neural measures of attention. Our specific aims (SA) are to: SA1: Quantify chemotherapy-related impairments of attention-specific processes in HM patients. H1a: No difference in behavioral measures of attention will be observed across HM groups prior to treatment, and HM groups will perform worse than healthy controls. H1b: Exposure to chemotherapy will predict behavioral impairments of attention, and the magnitude of impairment will be linked with treatment toxicity. SA2: Quantify electrophysiological measures of attention-specific processes and determine the link between chemotherapy-related impairments in neural activity and cognitive ability. H2a: No difference in electrophysiological measures of attention will be observed across HM and healthy control groups prior to treatment. H2b: Exposure to chemotherapy will predict functional impairments in electrophysiological measures of attention, and the magnitude of impairment will be linked with treatment toxicity. H2c: Chemotherapy-related impairment in neural measures of attention will be predicted by concurrent impairments in behavioral measures of attention (as in H1b). SA3: Implement controlled simulations of on-road driving scenarios that probe specific attention processes to determine the impact of chemotherapy on complex real-world behavior. H3a: No difference in driving performance will be observed across HM groups prior to treatment, and driving performance will be better in healthy controls compared to HM patients. H3b: Exposure to chemotherapy will predict greater impairment in simulated driving performance, and the magnitude of impairment will be linked with treatment toxicity. H3c: Impairments in behavioral (as in H1a) and neural measures (as in H2a) of attention will predict greater impairment in simulated on-road driving performance. Our empirical approach will allow us to more rigorously study the neural mechanisms of chemotherapy-related cognitive impairment. The current proposal aims to extend previous research by longitudinally investigating an understudied cancer population whose constituents are assigned to a treatment group at diagnosis, thus providing sufficient experimental control for examining parametric effects of cancer burden and treatment toxicity on specific mechanisms of attention. Results obtained from this study will be critical to understanding risk factors associated with chemotherapy, which will allow clinicians to make informed treatment recommendations in order to reduce the likelihood of cognitive impairment and maintain the highest quality of life possible for the ever-increasing cancer survivor population.