Cancer ‘survivor-care’: II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment)

Abstract

Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation.