Regional hyperconnectivity in the medial temporal lobes as a maladaptive mechanism for colorectal cancer-related cognitive decline

Colorectal cancer is the third most commonly diagnosed cancer in the world that affects both men and women. Approximately 40% of colorectal cancer patients exhibit cognitive impairment in executive functions including verbal learning, verbal memory, and information processing that is independent of chemotherapy. However, little information is currently available regarding the neural mechanisms underlying colorectal cancer-related cognitive decline (CRCD). In this study, we utilized highly sensitive 7 Tesla magnetic resonance imaging methods combined with standardized cognitive assessments to investigate the changes in brain local functional connectivity in early-stage colorectal cancer survivors compared to healthy controls. We observed that early-stage colorectal cancer survivors exhibited increased regional homogeneity (ReHo) in the left hippocampus, parahippocampal gyrus, and inferior temporal gyrus, along with decreased ReHo in the left inferior frontal gyrus, which were associated with reduced verbal memory performance compared to healthy controls. Furthermore, survivors exhibited significantly weaker inter-regional functional connectivity, suggesting a potential disruption in coordination among regions critical for verbal memory. Collectively, these findings indicate a maladaptive mechanism in the medial temporal lobes that is associated with declines in verbal memory processes among colorectal cancer survivors. ReHo analysis was found to be a valuable tool for characterizing the neurophysiological basis of colorectal CRCD and presents the medial temporal lobe as a promising target for therapeutic interventions.