Kaiser Jochen, Bledowski Christoph, Dietrich Jörg
Institute of Medical Psychology, Medical Faculty, Goethe University, Frankfurt am Main, Germany.
Institute of Medical Psychology, Medical Faculty, Goethe University, Frankfurt am Main, Germany.
Cortex. 2014 May;54:33-50. doi: 10.1016/j.cortex.2014.01.010. Epub 2014 Jan 30.
Cancer survivors frequently experience cognitive deficits following chemotherapy. The most commonly affected functions include memory, attention and executive control. The present paper reviews animal research and clinical studies including event-related potential (ERP) and neuroimaging investigations of chemotherapy-related changes of brain structure and function. In rodents, chemotherapeutic substances have been shown to damage neural precursor cells and white matter tracts and are associated with impairments of learning and memory. Structural and functional changes associated with chemotherapy have also been observed in humans. Structural imaging has revealed gray and white matter volume reductions and altered white matter microstructure. Functional studies using either ERPs or hemodynamic imaging have shown that chemotherapy alters the activation patterns of cortical networks involved in higher cognitive functions. Collectively, these findings support the existence of the "chemobrain" phenomenon beyond the patients' subjective reports. However, the rather small number of studies and methodological limitations of some of the pioneering investigations call for further research of high methodological quality, including larger numbers of subjects with appropriate controls to delineate the temporal and spatial pattern of chemotherapy-associated central nervous system (CNS) toxicity. Brain activation studies in humans might systematically vary task difficulty levels to distinguish between compensatory hyper-activations on the one hand and deficient recruitment of resources on the other hand. Integrative functions could be tested by connectivity analyses using both electrophysiological and hemodynamic measures. The ultimate goal should be the development of cognitive-behavioral and pharmacological interventions to reduce the cognitive side effects of the medically indispensable but neurotoxic chemotherapeutic treatments.
癌症幸存者在化疗后经常出现认知缺陷。最常受影响的功能包括记忆、注意力和执行控制。本文综述了动物研究和临床研究，包括与化疗相关的脑结构和功能变化的事件相关电位（ERP）和神经影像学研究。在啮齿动物中，化疗药物已被证明会损害神经前体细胞和白质束，并与学习和记忆障碍有关。在人类中也观察到了与化疗相关的结构和功能变化。结构成像显示灰质和白质体积减少以及白质微观结构改变。使用ERP或血流动力学成像的功能研究表明，化疗会改变参与高级认知功能的皮质网络的激活模式。总体而言，这些发现支持了“化疗脑”现象的存在，而不仅仅是患者的主观报告。然而，一些开创性研究的数量相对较少以及方法学上的局限性，需要进行更高质量的进一步研究，包括纳入更多有适当对照的受试者，以描绘化疗相关的中枢神经系统（CNS）毒性的时间和空间模式。在人类中的脑激活研究可以系统地改变任务难度水平，以区分一方面的代偿性过度激活和另一方面的资源募集不足。可以通过使用电生理和血流动力学测量的连通性分析来测试整合功能。最终目标应该是开发认知行为和药物干预措施，以减少医学上必不可少但具有神经毒性的化疗治疗的认知副作用。
