Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands,
Brain Imaging Behav. 2013 Dec;7(4):388-408. doi: 10.1007/s11682-013-9249-9.
With increasing survival, cognitive problems after systemic treatment for non-CNS cancers are a growing concern. Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that has the potential to uncover the neural circuitry underlying cognitive problems after systemic treatment in cancer patients. Here, we provide an in depth review of the 14 fMRI studies that have been published to date on potential neurotoxic side effects of systemic treatment for non-CNS cancers. Cross-sectional studies in breast cancer survivors show a consistent pattern of hypoactivation in prefrontal and parietal brain regions during various executive functioning tasks 5 to 10 years after completion of adjuvant chemotherapy that are sometimes associated with worse cognitive performance compared to cancer-specific or no-cancer controls. These findings suggest reduced neural functioning as a result of chemotherapy in brain regions that support cognitive functioning. With regard to episodic memory, hypoactivation at encoding is followed by hyperactivation at retrieval, suggestive of impairments in memory encoding that are compensated by neural hyperactivation to perform adequate memory retrieval. Prospective studies of executive functioning and episodic memory show a more complex picture of hypo- and hyperactivation that is possibly due to various counteracting mechanisms relatively shortly after chemotherapy. Two small studies in prostate cancer patients, finally, provide preliminary evidence for reduced activation in task-relevant brain regions after androgen deprivation therapy, suggestive of reduction of neural function. Statistical correction for multiple comparisons in the reviewed studies is typically quite lenient. We suggest that future studies should preferably include larger sample sizes to allow proper statistical correction for multiple comparisons and include comprehensive neurocognitive tests and multimodal MRI to facilitate the interpretation of the observed fMRI findings.
随着生存率的提高，非中枢神经系统癌症系统治疗后出现认知问题的情况越来越令人担忧。功能磁共振成像（fMRI）是一种非侵入性的神经影像学技术，具有揭示癌症患者系统治疗后认知问题潜在神经回路的潜力。在这里，我们对迄今为止已发表的关于非中枢神经系统癌症系统治疗潜在神经毒性副作用的 14 项 fMRI 研究进行了深入回顾。乳腺癌幸存者的横断面研究显示，在辅助化疗完成后 5 至 10 年内，各种执行功能任务期间，前额叶和顶叶大脑区域的激活程度持续降低，与癌症特异性或无癌症对照组相比，认知表现有时更差。这些发现表明，由于化疗导致大脑区域的神经功能下降，从而支持认知功能。关于情景记忆，在编码时出现的低激活随后是检索时的高激活，提示记忆编码受损，通过神经超激活来进行适当的记忆检索来补偿。执行功能和情景记忆的前瞻性研究显示，低激活和高激活的情况更为复杂，这可能是由于化疗后不久存在各种相互抵消的机制。最后，两项针对前列腺癌患者的小型研究初步证明，去势治疗后与任务相关的大脑区域的激活减少，提示神经功能下降。在综述研究中，对多重比较进行的统计校正通常相当宽松。我们建议，未来的研究最好包括更大的样本量，以允许对多重比较进行适当的统计校正，并包括全面的神经认知测试和多模态 MRI，以促进对观察到的 fMRI 发现的解释。
