Altered spatial patterns of intrinsic brain activity and cognitive decline in colorectal cancer survivors

Cancer-related cognitive impairment (CRCI) is a common and debilitating complication among colorectal cancer survivors, even in those without chemotherapy exposure. To identify cancer-related neural changes, we investigated spontaneous brain activity and cognition in colorectal cancer survivors using cognitive assessments and resting-state functional magnetic resonance imaging (rsfMRI).

Nineteen survivors (stages I-II, cancer diagnosis < 12 months, chemotherapy-naïve) and 18 healthy controls underwent a battery of objective/subjective cognitive tests and MRI. RsfMRI data was analyzed with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity (FC). Statistical analysis was controlled for age, sex, education, depression, and anxiety, with multiple comparison correction.

Compared to controls, survivors performed significantly worse on the Hopkins Verbal Learning Test (HVLT-R) Recognition Discrimination Index (RDI) (p = 0.03) and showed slower psychomotor speed on the Trail Making Test (TMT-A) (p = 0.02). RsfMRI analysis revealed increased fALFF in the right hippocampus and bilateral inferior/middle temporal, parahippocampal, and fusiform gyri, with decreased fALFF in the bilateral superior/middle frontal gyri and left inferior frontal gyrus. RDI was negatively correlated with fALFF in right temporal regions. Survivors also exhibited reduced FC within the default mode network (DMN) (p < 0.05).

This cross-sectional study shows that colorectal cancer survivors display hyperactivity in the temporal regions and disrupted DMN connectivity associated with cognitive decline, suggesting a maladaptive neural response.

Our study identified the functionally altered brain regions and networks associated with colorectal CRCI using MRI. This would provide potential biological targets for developing interventions such as neuromodulation for mitigating the adverse effects of colorectal CRCI.