Characterization of resting state activity in MCI individuals

Roberto Esposito, Alessandra Mosca, Valentina Pieramico, Filippo Cieri, Nicoletta Cera, Stefano L Sensi, Roberto Esposito, Alessandra Mosca, Valentina Pieramico, Filippo Cieri, Nicoletta Cera, Stefano L Sensi

Abstract

Objectives. Aging is the major risk factor for Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). The aim of this study was to identify novel modifications of brain functional connectivity in MCI patients. MCI individuals were compared to healthy elderly subjects. Methods. We enrolled 37 subjects (age range 60-80 y.o.). Of these, 13 subjects were affected by MCI and 24 were age-matched healthy elderly control (HC). Subjects were evaluated with Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and prose memory (Babcock story) tests. In addition, with functional Magnetic Resonance Imaging (fMRI), we investigated resting state network (RSN) activities. Resting state (Rs) fMRI data were analyzed by means of Independent Component Analysis (ICA). Subjects were followed-up with neuropsychological evaluations for three years. Results. Rs-fMRI of MCI subjects showed increased intrinsic connectivity in the Default Mode Network (DMN) and in the Somatomotor Network (SMN). Analysis of the DMN showed statistically significant increased activation in the posterior cingulate cortex (PCC) and left inferior parietal lobule (lIPL). During the three years follow-up, 4 MCI subjects converted to AD. The subset of MCI AD-converted patients showed increased connectivity in the right Inferior Parietal Lobule (rIPL). As for SMN activity, MCI and MCI-AD converted groups showed increased level of connectivity in correspondence of the right Supramarginal Gyrus (rSG). Conclusions. Our findings indicate alterations of DMN and SMN activity in MCI subjects, thereby providing potential imaging-based markers that can be helpful for the early diagnosis and monitoring of these patients.

Keywords: AD; Aging; Alzheimer; MCI; rs-fMRI.

Figures

Figure 1. rs-fMRI processing.
Figure 1. rs-fMRI processing.
Selection of two Resting State Networks among the independent components (ICs) were obtained by means of the Fast-ICA algorithm implemented in Brain Voyager QX. In Step 1, individual single subject IC maps were obtained (only three components are depicted). In Step 2, the map of each component (only three components depicted) is spatially correlated with a network template (only for SMN and DMN). Finally, in Step 3, the component with the largest spatial correlation coefficient is selected. SMN and DMN are from a previous study (Mantini et al., 2007).
Figure 2. Cortical representation of two group…
Figure 2. Cortical representation of two group level RSNs (DMN and SMN) in MCI patients and HC.
Figure depicts transverse views of the brain for each group. RSN maps are overimposed on a Talairach template. Color scale represents T values.
Figure 3. Between group differences in DMN…
Figure 3. Between group differences in DMN for MCI patients and Healthy controls (HC).
Panel (A) shows t-maps obtained when comparing MCI and HC. T-test comparisons reveal statistically significant increased levels of intrinsic connectivity in the Posterior Cingulated Cortex (PCC) and left Inferior Parietal Lobe (left IPL) in the MCI group. Panel (B) shows t-maps obtained when comparing MCI-AD converted and HC. Between group comparisons show significant increased values of intrinsic connectivity in the right Inferior Parietal Lobe (right IPL) in MCI-AD converted group. Functional maps shown in A and B are Bonferroni corrected (p < 0.05) and overimposed on a Talairach template.
Figure 4. Between group differences in SMN…
Figure 4. Between group differences in SMN for MCI patients and Healthy controls (HC).
Figure depicts t-maps obtained when comparing MCI and HC (A), MCI-AD converted and HC (B) or MCI-AD converted and MCI (C). T-test comparisons reveal statistically significant increased levels of intrinsic connectivity in the right supramarginal gyrus for the contrast MCI > HC, MCI-AD > HC and MCI-AD > MCI. Functional maps are Bonferroni corrected (p < 0.05) and overimposed on a Talairach template.

References

    1. Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW. Patterns of brain activation in people at risk for Alzheimer’s disease. New England Journal of Medicine. 2000;343:450–456. doi: 10.1056/NEJM200008173430701.
    1. Boyke J, Driemeyer J, Gaser C, Buchel C, May A. Training-induced brain structure changes in the elderly. Journal of Neuroscience. 2008;28:7031–7035. doi: 10.1523/JNEUROSCI.0742-08.2008.
    1. Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJ. Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews. 2009;33:279–296. doi: 10.1016/j.neubiorev.2008.09.002.
    1. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences. 2008;1124:1–38. doi: 10.1196/annals.1440.011.
    1. Calhoun VD, Adali T, Pearlson GD, Pekar JJ. A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping. 2001;14:140–151. doi: 10.1002/hbm.1048.
    1. Chetelat G, Desgranges B, de la Sayette V, Viader F, Berkouk K, Landeau B, Lalevee C, Le Doze F, Dupuy B, Hannequin D, Baron J-C, Eustache F. Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain. 2003;126:1955–1967. doi: 10.1093/brain/awg196.
    1. Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF. Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America. 2006;103:13848–13853. doi: 10.1073/pnas.0601417103.
    1. De Martino F, Gentile F, Esposito F, Balsi M, Di Salle F, Goebel R, Formisano E. Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers. Neuroimage. 2007;34(1):177–194. doi: 10.1016/j.neuroimage.2006.08.041.
    1. De Vogelaere F, Santens P, Achten E, Boon P, Vingerhoets G. Altered default-mode network activation in mild cognitive impairment compared with healthy aging. Neuroradiology. 2012;54:1195–1206. doi: 10.1007/s00234-012-1036-6.
    1. Deco G, Jirsa VK, McIntosh AR. Emerging concepts for the dynamical organization of resting-state activity in the brain. Nature Reviews: Neuroscience. 2011;12:43–56. doi: 10.1038/nrn2961.
    1. Ding SL, Van Hoesen G, Rockland KS. Inferior parietal lobule projections to the presubiculum and neighboring ventromedial temporal cortical areas. Journal of Comparative Neurology. 2000;425:510–530. doi: 10.1002/1096-9861(20001002)425:4<510::AID-CNE4>;2-R.
    1. Esposito F, Scarabino T, Hyvarinen A, Himberg J, Formisano E, Comani S, Tedeschi G, Goebel R, Seifritz E, Di Salle F. Independent component analysis of fMRI group studies by self-organizing clustering. Neuroimage. 2005;25:193–205. doi: 10.1016/j.neuroimage.2004.10.042.
    1. Ferreira LK, Busatto GF. Resting-state functional connectivity in normal brain aging. Neuroscience and Biobehavioral Reviews. 2013;37(3):384–400. doi: 10.1016/j.neubiorev.2013.01.017.
    1. Fleisher AS, Sherzai A, Taylor C, Langbaum JB, Chen K, Buxton RB. Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer’s disease risk groups. Neuroimage. 2009;47:1678–1690. doi: 10.1016/j.neuroimage.2009.06.021.
    1. Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews: Neuroscience. 2007;8:700–711. doi: 10.1038/nrn2201.
    1. Frautschy SA, Cole GM. Why pleiotropic interventions are needed for Alzheimer’s disease. Molecular Neurobiology. 2010;41:392–409. doi: 10.1007/s12035-010-8137-1.
    1. Friston KJ, Williams S, Howard R, Frackowiak RS, Turner R. Movement-related effects in fMRI time-series. Magnetic Resonance in Medicine. 1996;35:346–355. doi: 10.1002/mrm.1910350312.
    1. Greene SJ, Killiany RJ, Alzheimer’s Disease Neuroimaging Initiative Subregions of the inferior parietal lobule are affected in the progression to Alzheimer’s disease. Neurobiology of Aging. 2010;31:1304–1311. doi: 10.1016/j.neurobiolaging.2010.04.026.
    1. Hajnal JV, Myers R, Oatridge A, Schwieso JE, Young IR, Bydder GM. Artifacts due to stimulus correlated motion in functional imaging of the brain. Magnetic Resonance in Medicine. 1994;31:283–291. doi: 10.1002/mrm.1910310307.
    1. Hartwigsen G, Bestmann S, Ward NS, Woerbel S, Mastroeni C, Granert O, Siebner HR. Left dorsal premotor cortex and supramarginal gyrus complement each other during rapid action reprogramming. Journal of Neuroscience. 2012;32:16162–16171. doi: 10.1523/JNEUROSCI.1010-12.2012.
    1. Hayes SM, Salat DH, Verfaellie M. Default network connectivity in medial temporal lobe amnesia. Journal of Neuroscience. 2012;32:14622–14629. doi: 10.1523/JNEUROSCI.0700-12.2012.
    1. Holtzman DM, Mandelkow E, Selkoe DJ. Alzheimer disease in 2020. Cold Spring Harbor Perspectives in Medicine. 2012;2(11):a011585. doi: 10.1101/cshperspect.a011585.
    1. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. New England Journal of Medicine. 2013;368:1326–1334. doi: 10.1056/NEJMsa1204629.
    1. Hyvarinen A. Fast and robust fixed-point algorithms for independent component analysis. IEEE Transactions on Neural Networks. 1999;10:626–634. doi: 10.1109/72.761722.
    1. Jack CR, Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurology. 2013;12:207–216. doi: 10.1016/S1474-4422(12)70291-0.
    1. Jessen F, Wolfsgruber S, Wiese B, Bickel H, Mösch E, Kaduszkiewicz H, Pentzek M, Riedel-Heller SG, Luck T, Fuchs A, Weyerer S, Werle J, van den Bussche H, Scherer M, Maier W, Wagner M. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimer’s & Dementia. doi: 10.1016/j.jalz.2012.09.017. In Press .
    1. Koch W, Teipel S, Mueller S, Buerger K, Bokde AL, Hampel H, Coates U, Reiser M, Meindl T. Effects of aging on default mode network activity in resting state fMRI: does the method of analysis matter? Neuroimage. 2010;51:280–287. doi: 10.1016/j.neuroimage.2009.12.008.
    1. Kovacs T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer’s disease. Neuropathology and Applied Neurobiology. 1999;25:481–491. doi: 10.1046/j.1365-2990.1999.00208.x.
    1. Laczo J, Andel R, Vlcek K, Macoska V, Vyhnalek M, Tolar M, Bojar M, Hort J. Spatial navigation and APOE in amnestic mild cognitive impairment. Neuro-Degenerative Diseases. 2011;8:169–177. doi: 10.1159/000321581.
    1. Larocque KF, Smith ME, Carr VA, Witthoft N, Grill-Spector K, Wagner AD. Global similarity and pattern separation in the human medial temporal lobe predict subsequent memory. Journal of Neuroscience. 2013;33:5466–5474. doi: 10.1523/JNEUROSCI.4293-12.2013.
    1. Lewis CM, Baldassarre A, Committeri G, Romani GL, Corbetta M. Learning sculpts the spontaneous activity of the resting human brain. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:17558–17563. doi: 10.1073/pnas.0902455106.
    1. Liang F, Jia J, Wang S, Qin W, Liu G. Decreased plasma levels of soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer’s disease. Journal of Clinical Neuroscience. 2013;20:357–361. doi: 10.1016/j.jocn.2012.06.005.
    1. Liao W, Chen H, Feng Y, Mantini D, Gentili C, Pan Z, Ding J, Duan X, Qiu C, Lui S, Gong Q, Zhang W. Selective aberrant functional connectivity of resting state networks in social anxiety disorder. Neuroimage. 2010;52:1549–1558. doi: 10.1016/j.neuroimage.2010.05.010.
    1. Iliffe S, Booroff A, Gallivan S, Goldenberg E, Morgan P, Haines A. Screening for cognitive impairment in the elderly using the mini-mental state examination. British Journal of General Practice. 1990;40(336):277–279.
    1. Mantini D, Caulo M, Ferretti A, Romani GL, Tartaro A. Noxious somatosensory stimulation affects the default mode of brain function: evidence from functional MR imaging. Radiology. 2009;253:797–804. doi: 10.1148/radiol.2533090602.
    1. Mantini D, Perrucci MG, Del Gratta C, Romani GL, Corbetta M. [Electrophysiological signatures of resting state networks in the human brain]. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:13170–13175. doi: 10.1073/pnas.0700668104.
    1. McKeown MJ, Makeig S, Brown GG, Jung TP, Kindermann SS, Bell AJ, Sejnowski TJ. Analysis of fMRI data by blind separation into independent spatial components. Human Brain Mapping. 1998;6:160–188. doi: 10.1002/(SICI)1097-0193(1998)6:3<160::AID-HBM5>;2-1.
    1. Medina J, Kannan V, Pawlak MA, Kleinman JT, Newhart M, Davis C, Heidler-Gary JE, Herskovits EH, Hillis AE. Neural substrates of visuospatial processing in distinct reference frames: evidence from unilateral spatial neglect. Journal of Cognitive Neuroscience. 2009;21:2073–2084. doi: 10.1162/jocn.2008.21160.
    1. Mevel K, Chetelat G, Eustache F, Desgranges B. The default mode network in healthy aging and Alzheimer’s disease. International Journal of Alzheimer’s Disease. 2011;2011:535816. doi: 10.4061/2011/535816.
    1. Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67:446–452. doi: 10.1212/01.wnl.0000228230.26044.a4.
    1. Nedelska Z, Andel R, Laczo J, Vlcek K, Horinek D, Lisy J, Sheardova K, Bures J, Hort J. Spatial navigation impairment is proportional to right hippocampal volume. Proceedings of the National Academy of Sciences of the United States of America. 2012;109:2590–2594. doi: 10.1073/pnas.1121588109.
    1. Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Santacruz K, Smith CD, Patel E, Markesbery WR. Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. Journal of Neuropathology and Experimental Neurology. 2009;68:774–784. doi: 10.1097/NEN.0b013e3181aacbe9.
    1. Pai MC, Jacobs WJ. Topographical disorientation in community-residing patients with Alzheimer’s disease. International Journal of Geriatric Psychiatry. 2004;19:250–255. doi: 10.1002/gps.1081.
    1. Pieramico V, Esposito R, Sensi F, Cilli F, Mantini D, Mattei PA, Frazzini V, Ciavardelli D, Gatta V, Ferretti A, Romani GL, Sensi SL. Combination training in aging individuals modifies functional connectivity and cognition, and is potentially affected by dopamine-related genes. PLoS ONE. 2012;7:e43901. doi: 10.1371/journal.pone.0043901.
    1. Prvulovic D, Hubl D, Sack AT, Melillo L, Maurer K, Frolich L, Lanfermann H, Zanella FE, Goebel R, Linden DEJ, Dierks T. Functional imaging of visuospatial processing in Alzheimer’s disease. Neuroimage. 2002;17:1403–1414. doi: 10.1006/nimg.2002.1271.
    1. Qi Z, Wu X, Wang Z, Zhang N, Dong H, Yao L, Li K. Impairment and compensation coexist in amnestic MCI default mode network. Neuroimage. 2010;50:48–55. doi: 10.1016/j.neuroimage.2009.12.025.
    1. Russ MO, Mack W, Grama CR, Lanfermann H, Knopf M. Enactment effect in memory: evidence concerning the function of the supramarginal gyrus. Experimental Brain Research. 2003;149:497–504.
    1. Sestieri C, Capotosto P, Tosoni A, Luca Romani G, Corbetta M. Interference with episodic memory retrieval following transcranial stimulation of the inferior but not the superior parietal lobule. Neuropsychologia. 2013;51:900–906. doi: 10.1016/j.neuropsychologia.2013.01.023.
    1. Sheline YI, Raichle ME. Resting state functional connectivity in preclinical Alzheimer’s disease. Biological Psychiatry. doi: 10.1016/j.biopsych.2012.11.028. In Press .
    1. Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF. Correspondence of the brain’s functional architecture during activation and rest. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:13040–13045. doi: 10.1073/pnas.0905267106.
    1. Sperling RA, Laviolette PS, O’Keefe K, O’Brien J, Rentz DM, Pihlajamaki M, Marshall G, Hyman BT, Selkoe DJ, Hedden T, Buckner RL, Becker JA, Johnson KA. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron. 2009;63:178–188. doi: 10.1016/j.neuron.2009.07.003.
    1. Sun E, Lim A, Liu X, Snellingen T, Wang N, Liu N. Apolipoprotein E gene and age-related macular degeneration in a Chinese population. Molecular Vision. 2011;17:997–1002.
    1. Turner GR, Spreng RN. Executive functions and neurocognitive aging: dissociable patterns of brain activity. Neurobiology of Aging. 2012;33(826) doi: 10.1016/j.neurobiolaging.2011.06.005. e821–813.
    1. van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. European Neuropsychopharmacology. 2010;20:519–534. doi: 10.1016/j.euroneuro.2010.03.008.
    1. Weissenbacher A, Kasess C, Gerstl F, Lanzenberger R, Moser E, Windischberger C. Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies. Neuroimage. 2009;47:1408–1416. doi: 10.1016/j.neuroimage.2009.05.005.
    1. Zhu DC, Majumdar S, Korolev IO, Berger KL, Bozoki AC. Alzheimer’s disease and amnestic mild cognitive impairment weaken connections within the default-mode network: a multi-modal imaging study. Journal of Alzheimer’s Disease. 2013;34:969–984. doi: 10.3233/JAD-121879.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다