The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen.
The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen.
复制标题
他莫昔芬治疗长期存活乳腺癌患者的工作记忆和背外侧前额叶-海马功能连接的变化
DOI：
10.1093/ijnp/pyx008
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发表时间：
2017-05-01
期刊：
影响因子：
--
通讯作者：
Wang K
中科院分区：
文献类型：
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作者：
Chen X;He X;Tao L;Li J;Wu J;Zhu C;Yu F;Zhang L;Zhang J;Qiu B;Yu Y;Wang K
摘要背景：他莫昔芬是目前应用最广泛的治疗雌激素受体敏感型乳腺癌的药物。有证据表明，接受他莫昔芬治疗的乳腺癌患者表现出认知功能障碍。然而，其潜在的神经机制仍不清楚。本研究旨在研究长期接受三苯氧胺治疗的绝经前乳腺癌妇女工作记忆缺陷和功能连接改变的神经机制。方法：31例接受三苯氧胺治疗的绝经前乳腺癌妇女和32例匹配的健康对照受试者。参与者完成了n-back任务，并接受了静息状态的功能磁共振成像，分别测量工作记忆表现和大脑功能连接。以背外侧前额叶皮质为种子区域，进行了基于SEED的全脑功能连通性分析。结果：与健康对照组相比，他莫昔芬治疗组在工作记忆和一般执行功能表现方面存在显着缺陷，右侧前额叶背外侧皮质与右侧海马区的功能连接性显著降低。在他莫昔芬组和健康对照组之间，全脑内左侧背外侧前额叶皮质的功能连接没有显著变化。此外，在他莫昔芬组中，发现背外侧前额叶皮质与右侧海马区的功能连接强度与工作记忆成绩下降之间存在显著的相关性。结论：三苯氧胺治疗可影响前额叶皮质和海马区，支持三苯氧胺在乳腺癌患者长期治疗中的拮抗作用。
Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients.