Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors

Abstract

In this study, we aimed to investigate the intrinsic hippocampal functional connectivity (FC) network and its relationship with prospective memory in patients with breast cancer suffering from chemotherapy-induced cognitive impairment (CICI). Thirty-four breast cancer patients before and after adjuvant chemotherapy (CB and CC, respectively) and 31 age- and education-matched cognitively normal (CN) women were recruited and subjected to a prospective memory task and a resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity analysis was used to compare the hippocampal FC networks between CC and CN groups. Partial correction analysis was used to examine the association between the hippocampal FC network and prospective memory in the CC group. The cancer group that underwent chemotherapy obtained significantly poorer scores than the CN group on mini-mental state examination, verbal fluency test, digit span, and prospective memory examination. Compared to the CN group, CC group showed increased hippocampal connectivity in the frontal and parietal cortex, precuneus, posterior cingulate cortex, and the cerebellum. In addition, the increasing hippocampal FC networks were negatively correlated with prospective memory performance in the CC group. These findings suggest maladaptive hippocampal functioning as a mechanism underlying the impairment of prospective memory in patients experiencing CICI.

Hippocampus—Related Cognitive and Affective Impairments in Patients With Breast Cancer—A Systematic Review

“…Thereby, Chen et al (55) found decreased functional connectivity of the Dorsolateral prefrontal cortex (DLPFC) with the right hippocampus in BCP treated with tamoxifen compared to HC. Additionally, Cheng et al (57) found right hippocampus in BCP treated with tamoxifen compared to HC. Additionally, Cheng et al (57) found chemotherapy compared to HC, including not only the frontal and parietal cortex but also the precuneus, posterior cingulate cortex, and the cerebellum.…”

“…Structure-and Connectivity-Related Hippocampal Changes or Differences in BCP Compared to HC All seven studies illustrated structure-and connectivityrelated hippocampal changes or differences compared to HC, including hippocampal volume loss (52-54, 56, 58), hippocampal deformation (58) as well as changes in bilateral hippocampal (57) and whole-brain functional connectivity (55). Reduced hippocampal volume was reported in most of the studies, referring mainly to the left hippocampus (53,54) and posterior regions (52,54).…”

“…In contrast to hippocampal volume reduction, hippocampal deformation (meaning specific morphological abnormalities and differences in shape compared to healthy controls) in BCP who underwent chemotherapy and endocrine therapy were mainly observed in the right hippocampus after controlling for age compared to HC (58). In addition to structural differences, two studies measured differences in functional connectivity, including whole brain functional connectivity (55) and bilateral hippocampal network connectivity (57). Thereby, Chen et al (55) found decreased functional connectivity of the Dorsolateral prefrontal cortex (DLPFC) with the right hippocampus in BCP treated with tamoxifen compared to HC.…”

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors

“…Previous research suggests that the developing brain is highly sensitive to cranial radiation (CR) and chemotherapy treatments for central nervous system cancers. Both chemotherapy and CR are linked to altered white matter microstructure (de Blank, Berman, & Fisher, ; (Deprez et al, ) Moxon‐Emre et al, ), altered hippocampal function (Cheng et al, ; Monje et al, ), and smaller hippocampal volumes (Kesler et al, ; Nagel et al, ; Riggs et al, ). Smaller hippocampal volumes after CR and chemotherapy are unrelated to smaller overall brain volumes (Riggs et al, ), suggesting that the developing hippocampus may be particularly vulnerable to treatments.…”

Structural and Functional Brain Alterations in Post-Chemotherapy Cognitive Impairment in Gastric Cancer: A Longitudinal Multimodal Neuroimaging Study

“…In various previous rodent researches, evidences proving that chemobrain is related to impaired neurogenesis of hippocampus (14,15), neuroin ammation (16,17), oxidative stress, mitochondrial dysfunction (18,19), and structural damage to neurons have been cumulating. Several recent neuroimaging studies have reported reduced total volume and inward deformities in hippocampal sub elds in breast cancer patients (20,21). Hippocampus is also a key area in cognitive function such as memory formation, learning (22), spatial processing(23), memory recognition, prospective memory processing(24), etc..…”