Evidence for divergent effects of neurodegeneration in Huntington’s disease on attentional selection and neural plasticity: implications for excitotoxicity

Abstract

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.