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Cited by 509Functional Brain Connectivity StudiesDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

Resting state functional connectivity in preclinical Alzheimer’s disease

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Sheline, Yvette I., Raichle, Marcus E.·2013·Biological Psychiatry
DOI 10.1016/j.biopsych.2012.11.028PMC PMC3537262
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Abstract

There has been a dramatic increase in the number of studies using resting state functional magnetic resonance imaging (rs-fMRI), a recent addition to imaging analysis techniques. The technique analyzes ongoing low-frequency fluctuations in the blood oxygen level-dependent signal. Through patterns of spatial coherence, these fluctuations can be used to identify the networks within the brain. Multiple brain networks are present simultaneously, and the relationships within and between networks are in constant dynamic flux. Resting state fMRI functional connectivity analysis is increasingly used to detect subtle brain network differences and, in the case of pathophysiology, subtle abnormalities in illnesses such as Alzheimer's disease (AD). The sequence of events leading up to dementia has been hypothesized to begin many years or decades before any clinical symptoms occur. Here we review the findings across rs-fMRI studies in the spectrum of preclinical AD to clinical AD. In addition, we discuss evidence for underlying preclinical AD mechanisms, including an important relationship between resting state functional connectivity and brain metabolism and how this results in a distinctive pattern of amyloid plaque deposition in default mode network regions.

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  1. [1]Christoff K Gordon AM Smallwood J Smith R Schooler JW 2009 Experience sampling during fMRI reveals default network and executive system contributions to mind wandering Proc Natl Acad Sci U S A 106 8719 8724 19433790 PMC2689035
  2. [2]Mason MF Norton MI Van Horn JD Wegner DM Grafton ST Macrae CN 2007 Wandering minds: the default network and stimulus-independent thought Science 315 393 395 17234951 PMC1821121
  3. [3]Gruberger M Ben-Simon E Levkovitz Y Zangen A Hendler T 2011 Towards a neuroscience of mind-wandering Front Hum Neurosci 5 56 21713118 PMC3112331
  4. [4]Hasenkamp W Wilson-Mendenhall CD Duncan E Barsalou LW 2012 Mind wandering and attention during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states Neuroimage 59 750 760 21782031
  5. [5]Morcom AM Fletcher PC 2007 Does the brain have a baseline? Why we should be resisting a rest Neuroimage 37 1073 1082 17681817
  6. [6]Larson-Prior LJ Zempel JM Nolan TS Prior FW Snyder AZ Raichle ME 2009 Cortical network functional connectivity in the descent to sleep Proc Natl Acad Sci U S A 106 4489 4494 19255447 PMC2657465
  7. [7]Vincent JL Patel GH Fox MD Snyder AZ Baker JT Van Essen DC 2007 Intrinsic functional architecture in the anaesthetized monkey brain Nature 447 83 86 17476267
  8. [9]Li SJ Biswal B Li Z Risinger R Rainey C Cho JK 2000 Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI Magn Reson Med 43 45 51 10642730
  9. [10]Damoiseaux JS Rombouts SA Barkhof F Scheltens P Stam CJ Smith SM 2006 Consistent resting-state networks across healthy subjects Proc Natl Acad Sci U S A 103 13848 13853 16945915 PMC1564249
  10. [11]Damoiseaux JS Greicius MD 2009 Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity Brain Struct Funct 213 525 533 19565262
  11. [12]Fox MD Raichle ME 2007 Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging Nat Rev Neurosci 8 700 711 17704812
  12. [13]Wig GS Schlaggar BL Petersen SE 2011 Concepts and principles in the analysis of brain networks Ann N Y Acad Sci 1224 126 146 21486299
  13. [14]D’Esposito M Deouell LY Gazzaley A 2003 Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging Nat Rev Neurosci 4 863 872 14595398
  14. [15]Fox MD Snyder AZ Vincent JL Corbetta M Van Essen DC Raichle ME 2005 The human brain is intrinsically organized into dynamic, anticorrelated functional networks P Natl Acad Sci USA 102 9673 9678 PMC1157105 15976020
  15. [16]Birn RM Diamond JB Smith MA Bandettini PA 2006 Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI Neuroimage 31 1536 1548 16632379
  16. [17]Shmueli K van Gelderen P de Zwart JA Horovitz SG Fukunaga M Jansma JM 2007 Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal Neuroimage 38 306 320 17869543 PMC2128785
  17. [18]Power JD Barnes KA Snyder AZ Schlaggar BL Petersen SE 2012 Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion Neuroimage 59 2142 2154 22019881 PMC3254728
  18. [19]Beckmann CF DeLuca M Devlin JT Smith SM 2005 Investigations into resting-state connectivity using independent component analysis Philos T Roy Soc B 360 1001 1013 PMC1854918 16087444
  19. [21]He BJ Snyder AZ Vincent JL Epstein A Shulman GL Corbetta M 2007 Breakdown of functional connectivity in frontoparietal networks underlies behavioral deficits in spatial neglect Neuron 53 905 918 17359924
  20. [22]Fair DA Schlaggar BL Cohen AL Miezin FM Dosenbach NUF Wenger KK 2007 A method for using blocked and event-related fMRI data to study “resting state” functional connectivity Neuroimage 35 396 405 17239622 PMC2563954
  21. [23]Brier M Thomas JB Snyder AZ Benzinger TL Zhang D ERM 2012 Loss of Intranetwork and Internetwork Resting State Functional Connections with Alzheimer’s Disease Progression Neurobiology of Disease In Press PMC3458508 22745490
  22. [24]Raichle ME MacLeod AM Snyder AZ Powers WJ Gusnard DA Shulman GL 2001 A default mode of brain function Proc Natl Acad Sci U S A 98 676 682 11209064 PMC14647
  23. [25]Mintun MA Larossa GN Sheline YI Dence CS Lee SY Mach RH 2006 [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease Neurology 67 446 452 16894106
  24. [26]Allen G Barnard H McColl R Hester AL Fields JA Weiner MF 2007 Reduced hippocampal functional connectivity in Alzheimer disease Arch Neurol 64 1482 1487 17923631
  25. [27]Greicius MD Srivastava G Reiss AL Menon V 2004 Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI Proc Natl Acad Sci U S A 101 4637 4642 15070770 PMC384799
  26. [28]Li SJ Li Z Wu G Zhang MJ Franczak M Antuono PG 2002 Alzheimer Disease: evaluation of a functional MR imaging index as a marker Radiology 225 253 259 12355013
  27. [29]Minoshima S Giordani B Berent S Frey KA Foster NL Kuhl DE 1997 Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease Ann Neurol 42 85 94 9225689
  28. [30]Caroli A Prestia A Chen K Ayutyanont N Landau SM Madison CM 2012 Summary metrics to assess Alzheimer disease-related hypometabolic pattern with 18F-FDG PET: head-to-head comparison J Nucl Med 53 592 600 22343502 PMC3640308
  29. [32]Bischkopf J Busse A Angermeyer MC 2002 Mild cognitive impairment--a review of prevalence, incidence and outcome according to current approaches Acta Psychiatr Scand 106 403 414 12392483
  30. [33]Wee CY Yap PT Zhang D Denny K Browndyke JN Potter GG 2012 Identification of MCI individuals using structural and functional connectivity networks Neuroimage 59 2045 2056 22019883 PMC3254811
  31. [34]Sperling RA Dickerson BC Pihlajamaki M Vannini P LaViolette PS Vitolo OV 2010 Functional alterations in memory networks in early Alzheimer’s disease Neuromolecular Med 12 27 43 20069392 PMC3036844
  32. [35]Bai F Zhang Z Yu H Shi Y Yuan Y Zhu W 2008 Default-mode network activity distinguishes amnestic type mild cognitive impairment from healthy aging: a combined structural and resting-state functional MRI study Neurosci Lett 438 111 115 18455308
  33. [36]Bero AW Bauer AQ Stewart FR White BR Cirrito JR Raichle ME 2012 Bidirectional relationship between functional connectivity and amyloid-beta deposition in mouse brain J Neurosci 32 4334 4340 22457485 PMC3326343
  34. [37]Agosta F Pievani M Geroldi C Copetti M Frisoni GB Filippi M 2011 Resting state fMRI in Alzheimer’s disease: beyond the default mode network Neurobiol Aging 21813210
  35. [38]Zhou J Greicius MD Gennatas ED Growdon ME Jang JY Rabinovici GD 2010 Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease Brain 133 1352 1367 20410145 PMC2912696
  36. [39]Drzezga A Grimmer T Peller M Wermke M Siebner H Rauschecker JP 2005 Impaired cross-modal inhibition in Alzheimer disease PLoS Med 2 e288 16159306 PMC1216331
  37. [40]Lustig C Snyder AZ Bhakta M O’Brien KC McAvoy M Raichle ME 2003 Functional deactivations: change with age and dementia of the Alzheimer type Proc Natl Acad Sci U S A 100 14504 14509 14608034 PMC283621
  38. [41]Celone KA Calhoun VD Dickerson BC Atri A Chua EF Miller SL 2006 Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis J Neurosci 26 10222 10231 17021177 PMC6674636
  39. [42]Hamalainen A Pihlajamaki M Tanila H Hanninen T Niskanen E Tervo S 2007 Increased fMRI responses during encoding in mild cognitive impairment Neurobiol Aging 28 1889 1903 16997428
  40. [43]Heun R Freymann K Erb M Leube DT Jessen F Kircher TT 2007 Mild cognitive impairment (MCI) and actual retrieval performance affect cerebral activation in the elderly Neurobiol Aging 28 404 413 16530885
  41. [44]Dickerson BC Sperling RA 2009 Large-scale functional brain network abnormalities in Alzheimer’s disease: insights from functional neuroimaging Behav Neurol 21 63 75 19847046 PMC2872923
  42. [45]Machulda MM Ward HA Borowski B Gunter JL Cha RH O’Brien PC 2003 Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients Neurology 61 500 506 12939424 PMC2744465
  43. [46]Bakker A Krauss GL Albert MS Speck CL Jones LR Stark CE 2012 Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment Neuron 74 467 474 22578498 PMC3351697
  44. [47]Price JL Morris JC 1999 Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease Ann Neurol 45 358 368 10072051
  45. [50]Klunk WE Engler H Nordberg A Wang Y Blomqvist G Holt DP 2004 Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B Ann Neurol 55 306 319 14991808
  46. [51]Johnson KA Gregas M Becker JA Kinnecom C Salat DH Moran EK 2007 Imaging of amyloid burden and distribution in cerebral amyloid angiopathy Ann Neurol 62 229 234 17683091
  47. [52]Gomperts SN Rentz DM Moran E Becker JA Locascio JJ Klunk WE 2008 Imaging amyloid deposition in Lewy body diseases Neurology 71 903 910 18794492 PMC2637553
  48. [53]Vlassenko AG Mintun MA Xiong C Sheline YI Goate AM Benzinger TL 2011 Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data Ann Neurol 70 857 861 22162065 PMC3243969
  49. [54]Becker JA Hedden T Carmasin J Maye J Rentz DM Putcha D 2011 Amyloid-beta associated cortical thinning in clinically normal elderly Ann Neurol 69 1032 1042 21437929 PMC3117980
  50. [55]Storandt M Mintun MA Head D Morris JC 2009 Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition Arch Neurol 66 1476 1481 20008651 PMC2796577
  51. [58]Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM 2011 Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease Alzheimers Dement 7 280 292 21514248 PMC3220946
  52. [59]Jack CR Jr Knopman DS Jagust WJ Shaw LM Aisen PS Weiner MW 2010 Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade Lancet Neurol 9 119 128 20083042 PMC2819840
  53. [60]Braak H Thal DR Ghebremedhin E DelTredici K 2011 Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years J Neuropathol Exp Neurol 70 960 969 22002422
  54. [61]Liu L Drouet V Wu JW Witter MP Small SA Clelland C 2012 Trans-synaptic spread of tau pathology in vivo PLoS One 7 e31302 22312444 PMC3270029
  55. [62]Jack CR Jr Vemuri P Wiste HJ Weigand SD Aisen PS Trojanowski JQ 2011 Evidence for ordering of Alzheimer disease biomarkers Arch Neurol 68 1526 1535 21825215 PMC3387980
  56. [63]Bateman RJ Xiong C Benzinger TL Fagan AM Goate A Fox NC 2012 Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease N Engl J Med PMC3474597 22784036
  57. [64]Sheline YI Morris JC Snyder AZ Price JL Yan Z D’Angelo G 2010 APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42 J Neurosci 30 17035 17040 21159973 PMC3023180
  58. [65]Reiman EM Chen K Alexander GE Caselli RJ Bandy D Osborne D 2004 Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia Proc Natl Acad Sci U S A 101 284 289 14688411 PMC314177
  59. [66]Filippini N MacIntosh BJ Hough MG Goodwin GM Frisoni GB Smith SM 2009 Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele Proc Natl Acad Sci U S A 106 7209 7214 19357304 PMC2678478
  60. [67]Machulda MM Jones DT Vemuri P McDade E Avula R Przybelski S 2011 Effect of APOE epsilon4 status on intrinsic network connectivity in cognitively normal elderly subjects Arch Neurol 68 1131 1136 21555604 PMC3392960
  61. [68]Sheline YI Raichle ME Snyder AZ Morris JC Head D Wang S 2010 Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly Biol Psychiatry 67 584 587 19833321 PMC2829379
  62. [69]Hedden T Van Dijk KR Becker JA Mehta A Sperling RA Johnson KA 2009 Disruption of functional connectivity in clinically normal older adults harboring amyloid burden J Neurosci 29 12686 12694 19812343 PMC2808119
  63. [70]Oh H Mormino EC Madison C Hayenga A Smiljic A Jagust WJ 2011 beta-Amyloid affects frontal and posterior brain networks in normal aging Neuroimage 54 1887 1895 20965254 PMC3038633
  64. [71]Kobayashi Y Amaral DG 2003 Macaque monkey retrosplenial cortex: II. Cortical afferents The Journal of Comparative Neurology 466 48 79 14515240
  65. [72]Parvizi J Van Hoesen GW Buckwalter J Damasio A 2006 Neural connections of the posteromedial cortex in the macaque Proc Natl Acad Sci U S A 103 1563 1568 16432221 PMC1345704
  66. [73]Drzezga A Becker JA Van Dijk KR Sreenivasan A Talukdar T Sullivan C 2011 Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden Brain 134 1635 1646 21490054 PMC3102239
  67. [74]Mormino EC Smiljic A Hayenga AO Onami SH Greicius MD Rabinovici GD 2011 Relationships between Beta-Amyloid and Functional Connectivity in Different Components of the Default Mode Network in Aging Cerebral Cortex 21 2399 2407 21383234 PMC3169663
  68. [75]Sibson NR Dhankhar A Mason GF Behar KL Rothman DL Shulman RG 1997 In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling Proc Natl Acad Sci U S A 94 2699 2704 9122259 PMC20152
  69. [77]Cirrito JR Yamada KA Finn MB Sloviter RS Bales KR May PC 2005 Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo Neuron 48 913 922 16364896
  70. [80]Newington JT Rappon T Albers S Wong DY Rylett RJ Cumming RC 2012 Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid beta and other toxins by decreasing mitochondrial respiration and ROS production J Biol Chem PMC3481323 22948140
  71. [82]Vaughn AE Deshmukh M 2008 Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c Nat Cell Biol 10 1477 1483 19029908 PMC2626347
  72. [84]Olney JW 2003 Excitotoxicity, apoptosis and neuropsychiatric disorders Curr Opin Pharmacol 3 101 109 12550750
  73. [85]Zhang D Hou Q Wang M Lin A Jarzylo L Navis A 2009 Na, K-ATPase activity regulates AMPA receptor turnover through proteasome-mediated proteolysis J Neurosci 29 4498 4511 19357275 PMC2680442
  74. [86]Hsieh H Boehm J Sato C Iwatsubo T Tomita T Sisodia S 2006 AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss Neuron 52 831 843 17145504 PMC1850952
  75. [87]Brand KA Hermfisse U 1997 Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species FASEB J 11 388 395 9141507
  76. [88]Mattson MP Magnus T 2006 Ageing and neuronal vulnerability Nat Rev Neurosci 7 278 294 16552414 PMC3710114
  77. [89]Fukui H Moraes CT 2008 The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 31 251 256 18403030 PMC2731695
  78. [90]Magistretti PJ 2006 Neuron-glia metabolic coupling and plasticity J Exp Biol 209 2304 2311 16731806
  79. [91]Allaman I Gavillet M Belanger M Laroche T Viertl D Lashuel HA 2010 Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability J Neurosci 30 3326 3338 20203192 PMC6634099
  80. [92]Galvin JE Price JL Yan Z Morris JC Sheline YI 2011 Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease Neurology 76 1797 1803 21525427 PMC3100121
  81. [94]Zhang D Raichle ME 2010 Disease and the brain’s dark energy Nat Rev Neurol 6 15 28 20057496

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Authors
Sheline, Y. I., & Raichle, M. E.
Affiliations
Washington University in St. Louis (US)
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2013-09
Volume
74
Issue
5
Pages
340-347
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2012.11.028
PMC
PMC3537262
OpenAlex
W2010216178
Cited by
509
References
14
Citations by year
2026: 26 · 2025: 35 · 2024: 34 · 2023: 43 · 2022: 45 · 2021: 40 · 2020: 37 · 2019: 46 · 2018: 38 · 2017: 39 · 2016: 41 · 2015: 42 · 2014: 28 · 2013: 15
FWCI
3.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NeoSync
  • National Institute of Mental Health (K24 MH79510)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
preclinical Alzheimer's disease, resting-state functional connectivity, default mode network, brain metabolism, brain network dynamics, dementia pathophysiology, BOLD signal, spatial coherence
MeSH terms
Alzheimer Disease, Brain, Humans, Magnetic Resonance Imaging, Nerve Net, Cognitive Dysfunction, Prodromal Symptoms

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