Abstract
Growing evidence of attention related failures in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) has already been proposed by previous studies. However, previous studies lacked of systematic investigation on the functional and structural substrates for attention function for patients with AD and aMCI. In this work, we investigated the functional connectivity and gray matter density in dorsal and ventral attention networks (DAN, VAN) of normal participants (n = 15) and patients with aMCI (n = 12) and AD (n = 16) by applying group independent component analysis (ICA) and voxel-based morphometry (VBM) analysis. Using ICA, we extracted the functional patterns of DAN and VAN which are respectively responsible for the “top-down” attention process and “bottom-up” process. One-way analysis of variance (ANOVA) revealed significant group-differed functional connectivity in bilateral frontal eye fields (FEF) area and intraparietal sulcus (IPS) area, as well as posterior cingulate cortex and precuneus in the dorsal system. With regard to the ventral system, group-effects were significantly focused in right orbital superior/middle frontal gyrus, right inferior parietal lobule, angular gyrus, and supramarginal gyrus around the temporal-parietal junction area. Post hoc cluster-level comparisons revealed totally impaired functional substrates for both attentional networks for patients with AD, whereas selectively impaired attention systems for patients with aMCI with impaired functional patent of DAN but preserved functional pattern of VAN. Correspondingly, VBM analysis revealed gray matter loss in right ventral and dorsal frontal cortex was in the AD group, whereas preserved gray matter density was in aMCI, even a little extent of expansion of gray matter density in several participants. Using multivariate regression analysis we found discrepant couplings of functional-structural degenerations between both patient groups. Specifically, positive coupling of structural-functional degeneration was found in right dorsal and ventral frontal cortex in the AD group, whereas inverse coupling in dorsal frontal cortex was found in the aMCI group. These findings suggested discrepant functional-structural degenerations in both attention systems between both patient groups, widening avenues to better understanding the attentional deficits in patients with aMCI and AD.
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References
Astafiev, S. V., Shulman, G. L., Stanley, C. M., Snyder, A. Z., Van Essen, D. C., & Corbetta, M. (2003). Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 23(11), 4689–4699.
Bai, F., Watson, D. R., Yu, H., Shi, Y., Yuan, Y., & Zhang, Z. (2009). Abnormal resting-state functional connectivity of posterior cingulate cortex in amnestic type mild cognitive impairment. Brain Research, 1302, 167–174.
Berardi, A. M., Parasuraman, R., & Haxby, J. V. (2005). Sustained attention in mild Alzheimer’s disease. Developmental Neuropsychology, 28(1), 507–537.
Bonekamp, D., Yassa, M. A., Munro, C. A., Geckle, R. J., Yousem, D. M., Barker, P. B., Schretlen, D. J., Brandt, J., & Horska, A. (2010). Gray matter in amnestic mild cognitive impairment: voxel-based morphometry. Neuroreport, 21(4), 259–263.
Corbetta, M., & Shulman, G. L. (2002). Control of goal-directed and stimulus-driven attention in the brain. Nature Reviews Neuroscience, 3(3), 201–215.
Dai, W., Lopez, O. L., Carmichael, O. T., Becker, J. T., Kuller, L. H., & Gach, H. M. (2009). Mild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging. Radiology, 250(3), 856–866.
Damoiseaux, J. S., & Greicius, M. D. (2009). Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity. Brain Structure & Function, 213(6), 525–533.
Dannhauser, T. M., Walker, Z., Stevens, T., Lee, L., Seal, M., & Shergill, S. S. (2005). The functional anatomy of divided attention in amnestic mild cognitive impairment. Brain: A Journal of Neurology, 128(Pt 6), 1418–1427.
Derflinger, S., Sorg, C., Gaser, C., Myers, N., Arsic, M., Kurz, A., Zimmer, C., Wohlschlager, A., & Muhlau, M. (2011). Grey-matter atrophy in Alzheimer’s disease is asymmetric but not lateralized. Journal of Alzheimer’s Disease: JAD, 25(2), 347–357.
Duarte, A., Hayasaka, S., Du, A., Schuff, N., Jahng, G. H., Kramer, J., Miller, B., & Weiner, M. (2006). Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer’s disease. Neuroscience Letters, 406(1–2), 60–65.
Fernandes, M. A., & Moscovitch, M. (2000). Divided attention and memory: evidence of substantial interference effects at retrieval and encoding. Journal of Experimental Psychology: General, 129(2), 155–176.
Fernandez-Duque, D., & Black, S. E. (2006). Attentional networks in normal aging and Alzheimer’s disease. Neuropsychology, 20(2), 133–143.
Finke, K., Myers, N., Bublak, P., & Sorg, C. (2013). A biased competition account of attention and memory in Alzheimer’s disease. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 368(1628), 20130062.
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.
Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L., & Raichle, M. E. (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proceedings of the National Academy of Sciences of the United States of America, 103(26), 10046–10051.
Gorus, E., De Raedt, R., Lambert, M., Lemper, J. C., & Mets, T. (2006). Attentional processes discriminate between patients with mild Alzheimer’s disease and cognitively healthy elderly. International Psychogeriatrics IPA, 18(3), 539–549.
Hagmann, P., Sporns, O., Madan, N., Cammoun, L., Pienaar, R., Wedeen, V. J., Meuli, R., Thiran, J. P., & Grant, P. E. (2010). White matter maturation reshapes structural connectivity in the late developing human brain. Proceedings of the National Academy of Sciences of the United States of America, 107(44), 19067–19072.
Hao, J., Li, K., Zhang, D., Wang, W., Yang, Y., Yan, B., Shan, B., & Zhou, X. (2005). Visual attention deficits in Alzheimer’s disease: an fMRI study. Neuroscience Letters, 385(1), 18–23.
He, Y., Wang, L., Zang, Y., Tian, L., Zhang, X., Li, K., & Jiang, T. (2007). Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. NeuroImage, 35(2), 488–500.
Hedden, T., Van Dijk, K. R., Becker, J. A., Mehta, A., Sperling, R. A., Johnson, K. A., & Buckner, R. L. (2009). Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 29(40), 12686–12694.
Honey, C. J., Thivierge, J. P., & Sporns, O. (2010). Can structure predict function in the human brain? NeuroImage, 52(3), 766–776.
Johannsen, P., Jakobsen, J., Bruhn, P., & Gjedde, A. (1999). Cortical responses to sustained and divided attention in Alzheimer’s disease. NeuroImage, 10(3 Pt 1), 269–281.
Karas, G. B., Scheltens, P., Rombouts, S. A., Visser, P. J., van Schijndel, R. A., Fox, N. C., & Barkhof, F. (2004). Global and local gray matter loss in mild cognitive impairment and Alzheimer’s disease. NeuroImage, 23(2), 708–716.
Killiany, R. J., Gomez-Isla, T., Moss, M., Kikinis, R., Sandor, T., Jolesz, F., Tanzi, R., Jones, K., Hyman, B. T., & Albert, M. S. (2000). Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Annals of Neurology, 47(4), 430–439.
Ko, P. C., Kilduff, P. T., Higgens, J. A., Milberg, W., & McGlinchey, R. (2005). Evidence for intact selective attention in Alzheimer’s disease patients using a location priming task. Neuropsychology, 19(3), 381–389.
Li, C., Wang, J., Gui, L., Zheng, J., Liu, C., & Du, H. (2011). Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer’s disease. Journal of Alzheimer’s Disease: JAD, 27(2), 281–290.
Li, R., Wu, X., Fleisher, A. S., Reiman, E. M., Chen, K., & Yao, L. (2012). Attention-related networks in Alzheimer’s disease: a resting functional MRI study. Human Brain Mapping, 33(5), 1076–1088.
Li, R., Wu, X., Chen, K., Fleisher, A. S., Reiman, E. M., & Yao, L. (2013). Alterations of directional connectivity among resting-state networks in Alzheimer disease. AJNR. American Journal of Neuroradiology, 34(2), 340–345.
Liao, W., Mantini, D., Zhang, Z., Pan, Z., Ding, J., Gong, Q., Yang, Y., & Chen, H. (2010). Evaluating the effective connectivity of resting state networks using conditional Granger causality. Biological Cybernetics, 102(1), 57–69.
Marra, C., Silveri, M. C., & Gainotti, G. (2000). Predictors of cognitive decline in the early stage of probable Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 11(4), 212–218.
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology, 34(7), 939–944.
Morris, J. C. (1993). The clinical dementia rating (CDR): current version and scoring rules. Neurology, 43(11), 2412–2414.
Neufang, S., Akhrif, A., Riedl, V., Forstl, H., Kurz, A., Zimmer, C., Sorg, C., & Wohlschlager, A. M. (2011). Disconnection of frontal and parietal areas contributes to impaired attention in very early Alzheimer’s disease. Journal of Alzheimer’s Disease: JAD, 25(2), 309–321.
Park, M., Hood, M. M., Shah, R. C., Fogg, L. F., & Wyatt, J. K. (2012). Sleepiness, parkinsonian features and sustained attention in mild Alzheimer’s disease. Age and Ageing, 41(6), 765–770.
Perry, R. J., & Hodges, J. R. (1999). Attention and executive deficits in Alzheimer’s disease. Brain: A Journal of Neurology, 122, 383–404.
Perry, R. J., & Hodges, J. R. (2003). Dissociation between top down attentional control and the time course of visual. The European Journal of Neuroscience, 18, 221–226.
Perry, R. J., Watson, P., & Hodges, J. R. (2000). The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment. Neuropsychologia, 38(3), 252–271.
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56(3), 303–308.
Pinotsis, D. A., Hansen E., Friston K. J., Jirsa V. K. (2012). Anatomical connectivity and the resting state activity of large cortical networks. NeuroImage.
Rapp, M. A., & Reischies, F. M. (2005). Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE). The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry, 13(2), 134–141.
Redel, P., Bublak, P., Sorg, C., Kurz, A., Forstl, H., Muller, H. J., Schneider, W. X., Perneczky, R., & Finke, K. (2012). Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer’s disease. Neurobiology of Aging, 33(1), 195. e127–142.
Romero-Garcia, R., Atienza M., Cantero J. L. (2013). Predictors of coupling between structural and functional cortical networks in normal aging. Human Brain Mapping.
Sanz-Arigita, E. J., Schoonheim, M. M., Damoiseaux, J. S., Rombouts, S. A., Maris, E., Barkhof, F., Scheltens, P., & Stam, C. J. (2010). Loss of ‘small-world’ networks in Alzheimer’s disease: graph analysis of FMRI resting-state functional connectivity. PLoS ONE, 5(11), e13788.
Sheline, Y. I., Morris, J. C., Snyder, A. Z., Price, J. L., Yan, Z., D’Angelo, G., Liu, C., Dixit, S., Benzinger, T., Fagan, A., Goate, A., & Mintun, M. A. (2010a). APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 30(50), 17035–17040.
Sheline, Y. I., Raichle, M. E., Snyder, A. Z., Morris, J. C., Head, D., Wang, S., & Mintun, M. A. (2010b). Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biological Psychiatry, 67(6), 584–587.
Sorg, C., Riedl, V., Muhlau, M., Calhoun, V. D., Eichele, T., Laer, L., Drzezga, A., Forstl, H., Kurz, A., Zimmer, C., & Wohlschlager, A. M. (2007). Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 104(47), 18760–18765.
Storandt, M. (2008). Cognitive deficits in the early stages of Alzheimer’s disease. Current Directions in Psychological Science, 17(3), 198–202.
Sun, Y., Yin, Q., Fang, R., Yan, X., Wang, Y., Bezerianos, A., Tang, H., Miao, F., & Sun, J. (2014). Disrupted functional brain connectivity and its association to structural connectivity in amnestic mild cognitive impairment and Alzheimer’s disease. PLoS ONE, 9(5), e96505.
Visser, P. J., Scheltens, P., Verhey, F. R., Schmand, B., Launer, L. J., Jolles, J., & Jonker, C. (1999). Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. Journal of Neurology, 246(6), 477–485.
Wang, Z., Chen, L. M., Négyessy, L., Friedman, R. M., Mishra, A., Gore, J. C., & Roe, A. W. (2013). The relationship of anatomical and functional connectivity to resting-state connectivity in primate somatosensory cortex. Neuron, 78(6), 1116–1126.
Zhang, Z., Lu, G., Zhong, Y., Tan, Q., Yang, Z., Liao, W., Chen, Z., Shi, J., & Liu, Y. (2009). Impaired attention network in temporal lobe epilepsy: a resting FMRI study. Neuroscience Letters, 458(3), 97–101.
Zhang, Z., Liao, W., Chen, H., Mantini, D., Ding, J. R., Xu, Q., Wang, Z., Yuan, C., Chen, G., Jiao, Q., & Lu, G. (2011). Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain: A Journal of Neurology, 134(Pt 10), 2912–2928.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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Shaowen Qian, Zhaoyan Zhang, Bo Li, and Gang Sun declare that they have no conflicts of interest.
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Figure S1
Both attention systems in the within-group analysis for z-transformed functional connectivity. (a1-c1) Top to bottom: the DAN maps in NC, aMCI and AD group respectively. (a2-c2) Top to bottom: the VAN maps in NC, aMCI, and AD group respectively. (DOC 500 kb)
Table S1
Brain regions in DAN maps in NC, aMCI, and AD groups (DOC 50 kb)
Table S2
Brain regions in VAN maps in NC, aMCI, and AD groups (DOC 44 kb)
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Qian, S., Zhang, Z., Li, B. et al. Functional-structural degeneration in dorsal and ventral attention systems for Alzheimer’s disease, amnestic mild cognitive impairment. Brain Imaging and Behavior 9, 790–800 (2015). https://doi.org/10.1007/s11682-014-9336-6
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DOI: https://doi.org/10.1007/s11682-014-9336-6