Neural correlates of chemotherapy-related cognitive impairment

Cancer survivors frequently experience cognitive deficits following chemotherapy. The most commonly affected functions include memory, attention and executive control. The present paper reviews animal research and clinical studies including event-related potential (ERP) and neuroimaging investigations of chemotherapy-related changes of brain structure and function. In rodents, chemotherapeutic substances have been shown to damage neural precursor cells and white matter tracts and are associated with impairments of learning and memory. Structural and functional changes associated with chemotherapy have also been observed in humans. Structural imaging has revealed gray and white matter volume reductions and altered white matter microstructure. Functional studies using either ERPs or hemodynamic imaging have shown that chemotherapy alters the activation patterns of cortical networks involved in higher cognitive functions. Collectively, these findings support the existence of the "chemobrain" phenomenon beyond the patients' subjective reports. However, the rather small number of studies and methodological limitations of some of the pioneering investigations call for further research of high methodological quality, including larger numbers of subjects with appropriate controls to delineate the temporal and spatial pattern of chemotherapy-associated central nervous system (CNS) toxicity. Brain activation studies in humans might systematically vary task difficulty levels to distinguish between compensatory hyper-activations on the one hand and deficient recruitment of resources on the other hand. Integrative functions could be tested by connectivity analyses using both electrophysiological and hemodynamic measures. The ultimate goal should be the development of cognitive-behavioral and pharmacological interventions to reduce the cognitive side effects of the medically indispensable but neurotoxic chemotherapeutic treatments.