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

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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.

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References

  • Abraham WC, Williams JM (2003) Properties and mechanisms of LTP maintenance. Neuroscientist 9:463–474

    Article  CAS  PubMed  Google Scholar 

  • Beal MF, Ferrante RJ (2004) Experimental therapeutics in transgenic mouse models of Huntington’s disease. Nat Rev Neurosci 5:373–384

    Article  CAS  PubMed  Google Scholar 

  • Beste C, Dinse HR (2013) Learning without training. Curr Biol 23:R489–R499

    Article  CAS  PubMed  Google Scholar 

  • Beste C, Saft C, Güntürkün O, Falkenstein M (2008a) Increased cognitive functioning in symptomatic Huntington’s disease as revealed by behavioral and event-related potential indices of auditory sensory memory and attention. J Neurosci 28:11695–11702

    Article  CAS  PubMed  Google Scholar 

  • Beste C, Saft C, Andrich J, Gold R, Falkenstein M (2008b) Stimulus-response compatibility in Huntington’s disease: a cognitive-neurophysiological analysis. J Neurophysiol 99:1213–1223

    Article  PubMed  Google Scholar 

  • Beste C, Wascher E, Güntürkün O, Dinse HR (2011) Improvement and impairment of # visually guided behavior through LTP- and LTD-like exposure-based visual learning. Curr Biol 21:876–882

    Article  CAS  PubMed  Google Scholar 

  • Beste C, Wascher E, Dinse HR, Saft C (2012) Faster perceptual learning through excitotoxic neurodegeneration. Curr Biol 22:1914–1917

    Article  CAS  PubMed  Google Scholar 

  • Bi G, Poo M (2001) Synaptic modification by correlated activity: Hebb’s postulate revisited. Annu Rev Neurosci 24:139–166

    Article  CAS  PubMed  Google Scholar 

  • Cardoso-Leite P, Ascher P, Bavelier D (2012) Brain plasticity: paradoxical case of a neurodegenerative disease? Curr Biol 22:R884–R886

    Article  CAS  PubMed  Google Scholar 

  • Cooke SF, Bear MF (2011) Stimulus-selective response plasticity in the visual cortex: an # assay for the assessment of pathophysiology and treatment of cognitive impairment associated with psychiatric disorders. Biol Psychiatry 71:487–495

    Article  PubMed  Google Scholar 

  • Dinse HR, Ragert P, Pleger B, Schwenkreis P, Tegenthoff M (2003) Pharmacological modulation of perceptual learning and associated cortical reorganization. Science 301:91–94

    Article  CAS  PubMed  Google Scholar 

  • Eimer M, Kiss M (2008) Involuntary attentional capture is determined by task set: evidence from event-related brain potentials. J Cogn Neurosci 20:1423–1433

    Article  PubMed Central  PubMed  Google Scholar 

  • Farrow M, Churchyard A, Chua P, Bradshaw JL, Chiu E, Georgiou-Karistianis N (2006) Attention, inhibition, and proximity to clinical onset in preclinical mutation carriers for Huntington’s disease. J Clin Exp Neuropsychol 29:235–246

    Article  Google Scholar 

  • Finke K, Bublak P, Dose M, Müller HJ, Schneider WX (2006) Parameter-based assessment of spatial and non-spatial attentional deficits in Huntington’s disease. Brain 129:1137–1151

    Article  PubMed  Google Scholar 

  • Folstein JR, Van Petten C (2008) Influence of cognitive control and mismatch on the N2 component of the ERP: a review. Psychophysiology 45:152–170

    Article  PubMed Central  PubMed  Google Scholar 

  • Frenkel MY, Sawtell NB, Diogo AC, Yoon RL, Neven RL, Bear MF (2006) Instructive effect of visual experience in mouse visual cortex. Neuron 51:339–349

    Article  CAS  PubMed  Google Scholar 

  • Georgiou-Karistianis N, Churchyard A, Chiu E, Bradshaw JL (2002) Reorientation of attention in Huntington’s disease. Neuropsychiatry Neuropsychol Behav Neurol 15:225–231

    PubMed  Google Scholar 

  • Georgiou-Karistianis N, Farrow M, Wilson-Ching M, Churchyard A, Bradshaw JL, Seppard DM (2012) Deficits in selective attention in symptomatic Huntington disease: assessment using an attentional blink paradigm. Cogn Behav Neurol 25:1–6

    Article  PubMed  Google Scholar 

  • Hardingham G, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 11:682–696

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huntington Study Group (1996) Unified Huntington’s disease rating scale: reliability and consistency. Mov Disord 11:136–142

    Article  Google Scholar 

  • Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR, International Huntington’s disease collaborative group (2004) A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length. Clin Genet 65:267–277

    Article  CAS  PubMed  Google Scholar 

  • Milnerwood AJ, Galling CM, Pouladi MA, Kaufman AM, Hines RM, Boyd RW, Vasuta OC, Graham RK, Hayden MR, Murphy TH et al (2010) Early increase in extrasynaptic NMDA receptor signalling and expression contributes to phenotype onset in Huntington’s disease mice. Neuron 65:178–190

    Article  CAS  PubMed  Google Scholar 

  • Nguyen L, Bradshaw JL, Stout JC, Croft RJ, Georgiou-Karistianis N (2010) Electrophysiological measures as potential biomarkers in Huntington’s disease: a review and future directions. Brain Res Rev 64:177–194

    Article  PubMed  Google Scholar 

  • Okamoto S, Pouladi MA, Talantova M, Yao D, Xia P, Ehrnhoefer DE, Zaidi R, Clemente A, Kaul M, Graham RK (2009) Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med 15:1407–1413

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rosas HD, Hevelone ND, Zaleta AK, Greve DN, Salat DH, Fischl B (2005) Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 65:745–747

    Article  CAS  PubMed  Google Scholar 

  • Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B, Greve D, Hevelone N, Hersch SM (2008) Cerebral cortex and the clinical expression of Huntington’s disease. Complexity and heterogeneity. Brain 131:1057–1068

    Article  PubMed Central  PubMed  Google Scholar 

  • Seitz AR, Dinse HR (2007) A common network for perceptual learning. Curr Opin Neurobiol 17:148–153

    Article  CAS  PubMed  Google Scholar 

  • Storey E, Kowall NW, Finn SF, Mazurek MF, Beal MF (1992) The cortical lesion of Huntington’s disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. Ann Neurol 32:526–534

    Article  CAS  PubMed  Google Scholar 

  • Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, Kennard C, Hicks SL, Fox NC, Scahill RI (2009) Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 8:791–801

    Article  PubMed Central  PubMed  Google Scholar 

  • Verleger R, Hagenah J, Weiss M, Ewers T, Heberlein I, Pramstaller PP, Siebner HR, Klein C (2010) Responsiveness to distracting stimuli, though increased in Parkinson’s disease, is decreased in asymptomatic PINK1 and Parkin mutation carriers. Neuropsychologia 48:467–476

    Article  PubMed  Google Scholar 

  • Wascher E, Beste C (2010) Tuning perceptual competition. J Neurophysiol 103:1057–1065

    Article  PubMed  Google Scholar 

  • Willemssen R, Falkenstein M, Schwarz M, Müller T, Beste C (2011) Effects of aging, Parkinson’s disease, and dopaminergic medication on response selection and control. Neurobiol Aging 32:327–335

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Kurup P, Zhang Y, Goebel-Goody SM, Wu PH, Hawasli AH, Baum ML, Bibb JA, Lombroso PJ (2009) Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP. J Neurosci 29:9330–9343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by a grant from the CHDI foundation and by a grant from the Deutsche Forschungsgemeinschaft (DFG) BE 4045/10-1.

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Correspondence to Christian Beste.

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Beste, C., Stock, AK., Ness, V. et al. Evidence for divergent effects of neurodegeneration in Huntington’s disease on attentional selection and neural plasticity: implications for excitotoxicity. Brain Struct Funct 220, 1437–1447 (2015). https://doi.org/10.1007/s00429-014-0735-7

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  • DOI: https://doi.org/10.1007/s00429-014-0735-7

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