Evidence for divergent effects of neurodegeneration in Huntington's disease on attentional selection and neural plasticity: implications for excitotoxicity
Evidence for divergent effects of neurodegeneration in Huntington's disease on attentional selection and neural plasticity: implications for excitotoxicity
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DOI：
10.1007/s00429-014-0735-7
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Saft, Carsten
中科院分区：
文献类型：
--
作者：
Beste, Christian;Stock, Ann-Kathrin;Saft, Carsten
一般认为，神经退行性变会导致认知功能下降。然而，有证据表明，与兴奋性毒性相关的神经退行性过程可能导致有限认知功能的矛盾改善，同时其他过程受到损害。一个悬而未决的问题是，文献中报道的这种矛盾的改善和通常与神经变性相关的衰退是如何相互关联的。矛盾的改善仅仅反映了一种短暂的现象，还是在神经退行性变的过程中加剧了？我们在兴奋性毒性神经变性（即亨廷顿舞蹈病，HD）的人类模型中使用行为和神经生理学（EEG）数据来研究这个问题。结果表明，注意选择过程在前显性疾病进展过程中下降。重要的是，用于诱导注意选择过程中潜在的神经可塑性的方案的有效性也在显前HD的持续神经退行性变过程中增加。这反映在行为数据和与注意力分配相关的过程的电生理相关。总之，我们的研究结果表明，特定认知功能的受限增强与众所周知的有害影响一样，都是神经变性发育过程的结果。这些结果解释了与兴奋毒性密切相关的神经退行性过程对认知功能的不同影响。
It is generally assumed that neurodegeneration leads to declines in cognitive functions. However, there is evidence that neurodegenerative processes related to excitotoxicity can lead to paradoxical improvements in circumscribed cognitive functions, while at the same time other processes are compromised. An open question is how such paradoxical improvements reported in literature and declines usually associated with neurodegeneration relate to each other. Do paradoxical improvements only reflect a transient phenomenon, or do they intensify in the course of neurodegeneration? We examine this question using behavioral and neurophysiological (EEG) data in a human model of excitotoxic neurodegeneration (i.e., Huntington's disease, HD). The results show that attentional selection processes decline during pre-manifest disease progression. Importantly, the efficacy of protocols used to induce neural plasticity in processes underlying attentional selection processes also increases in course of ongoing neurodegeneration in pre-manifest HD. This was reflected in behavioral data and electrophysiological correlates of processes related to the allocation of attention. To conclude, our results suggest that circumscribed enhancements of specific cognitive functions are as much a result of the developmental process of neurodegeneration as the well-known detrimental effects. The results account for the divergent effects of neurodegenerative processes closely related to excitotoxicity on cognitive functions.