Postchemotherapy hippocampal functional connectivity patterns in patients with breast cancer: a longitudinal resting state functional MR imaging study

The hippocampus plays a key role in cognitive function and emotion regulation due to its wide connection with the whole brain. This study examined the acute effect of chemotherapy on hippocampal and subfield functional connectivity and neuropsychological status in breast cancer patients (BC). This IRB approved study included 29 BC and 25 age matched healthy controls (HCs) who underwent resting state functional magnetic resonance imaging (Rs-fMRI), neuropsychological tests and blood examinations at baseline and one week after completing chemotherapy or in the same time interval. Within-group comparisons and group-by-time interactions analysis of hippocampus- and subregion- based functional connectivity were performed between the two groups. Functional connectivity changes were correlated with changes of blood examination and neuropsychological test scores in the BC group. The BC group had higher depression and anxiety scores, poorer performance on visual mobility, auditory memory and executive function than HCs ( p < 0.05), and significantly abnormal estrodiol, total cholesterol and triglycerides (p < 0.05). BC survivors showed significant hippocampal functional connectivity changes mainly in the left insula, temporal lobe (Gaussian Random Field theory correction, P < 0.001) and the left inferior frontal gyrus ( P < 0.01). The functional connections from the anterior hippocampus to the left temporal lobe were greater than the posterior hippocampus ( P < 0.05). The hippocampus functional connectivity alterations were closely related to changes in depression scores, estrodiol and triglycerides (all p < 0.05). Chemotherapy induced especially anterior hippocampal functional connectivity abnormality, which is related to depression symptom, estrodiol and triglycerides disorders.