title: Standardizing the intrinsic brain: towards robust measurement of inter-individual variation in 1000 functional connectomes.
abstract: As researchers increase their efforts to characterize variations in the functional connectome across studies and individuals, concerns about the many sources of nuisance variation present and their impact on resting state fMRI (R-fMRI) measures continue to grow. Although substantial within-site variation can exist, efforts to aggregate data across multiple sites such as the 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) datasets amplify these concerns. The present work draws upon standardization approaches commonly used in the microarray gene expression literature, and to a lesser extent recent imaging studies, and compares them with respect to their impact on relationships between common R-fMRI measures and nuisance variables (e.g., imaging site, motion), as well as phenotypic variables of interest (age, sex). Standardization approaches differed with regard to whether they were applied post-hoc vs. during pre-processing, and at the individual vs. group level; additionally they varied in whether they addressed additive effects vs. additive+multiplicative effects, and were parametric vs. non-parametric. While all standardization approaches were effective at reducing undesirable relationships with nuisance variables, post-hoc approaches were generally more effective than global signal regression (GSR). Across approaches, correction for additive effects (global mean) appeared to be more important than for multiplicative effects (global SD) for all R-fMRI measures, with the exception of amplitude of low frequency fluctuations (ALFF). Group-level post-hoc standardizations for mean-centering and variance-standardization were found to be advantageous in their ability to avoid the introduction of artifactual relationships with standardization parameters; though results between individual and group-level post-hoc approaches were highly similar overall. While post-hoc standardization procedures drastically increased test-retest (TRT) reliability for ALFF, modest reductions were observed for other measures after post-hoc standardizations-a phenomena likely attributable to the separation of voxel-wise from global differences among subjects (global mean and SD demonstrated moderate TRT reliability for these measures). Finally, the present work calls into question previous observations of increased anatomical specificity for GSR over mean centering, and draws attention to the near equivalence of global and gray matter signal regression.
authors: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors: Chao-Gan
authors: CG
authors: Yan
authors: R Cameron
authors: RC
authors: Craddock
authors: Xi-Nian
authors: XN
authors: Zuo
authors: Yu-Feng
authors: YF
authors: Zang
authors: Michael P
authors: MP
authors: Milham
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D063132:Connectome / Q000592:standards* / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000592:standards* / Q000706:statistics & numerical data*; D008953:Models, Anatomic; D008959:Models, Neurological; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: Data aggregation; Functional connectomics; Resting-state fMRI; Standardization; Test–retest reliability
references: Neuroimage. 2004 May;22(1):394-400
references: 15110032
references: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9
references: 20176931
references: Front Syst Neurosci. 2013 Feb 04;6:80
references: 23382713
references: Brain Connect. 2012;2(1):25-32
references: 22432927
references: J Neurosci. 2009 Feb 11;29(6):1860-73
references: 19211893
references: Psychol Bull. 1979 Mar;86(2):420-8
references: 18839484
references: Neuroimage. 2006 Nov 1;33(2):471-81
references: 16952468
references: Philos Trans R Soc Lond B Biol Sci. 2005 May 29;360(1457):1001-13
references: 16087444
references: Neuroimage. 2007 Oct 15;38(1):95-113
references: 17761438
references: Neuroimage. 2009 Oct 1;47(4):1408-16
references: 19442749
references: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9885-90
references: 20457896
references: Magn Reson Med. 2005 Aug;54(2):343-53
references: 16032694
references: Neuroimage. 2009 Feb 1;44(3):893-905
references: 18976716
references: J Biopharm Stat. 2004 Aug;14(3):575-89
references: 15468753
references: J Neurosci Methods. 2008 Jul 15;172(1):137-41
references: 18501969
references: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16060-5
references: 16247013
references: PLoS One. 2010 Dec 20;5(12):e15710
references: 21187930
references: J Neurosci. 2010 Nov 10;30(45):15034-43
references: 21068309
references: Neuroimage. 2007 May 15;36(1):144-52
references: 17434757
references: Psychopharmacology (Berl). 2011 Jul;216(2):287-95
references: 21331518
references: Hum Brain Mapp. 2008 Jun;29(6):671-82
references: 17598166
references: Brain Connect. 2011;1(5):401-10
references: 22432454
references: Cereb Cortex. 2012 Aug;22(8):1862-75
references: 21968567
references: PLoS One. 2009 May 29;4(5):e5743
references: 19492040
references: Magn Reson Med. 1999 Jun;41(6):1230-5
references: 10371456
references: Neuroimage. 2013 Aug 1;76:439-41
references: 22440651
references: Brain Dev. 2007 Mar;29(2):83-91
references: 16919409
references: Front Syst Neurosci. 2010 May 14;4:13
references: 20577591
references: Hum Brain Mapp. 2011 Nov;32(11):1811-24
references: 21140434
references: Cereb Cortex. 2011 May;21(5):1134-46
references: 20943668
references: Magn Reson Imaging. 2002 May;20(4):359-64
references: 12165355
references: J Neurophysiol. 2013 Mar;109(5):1444-56
references: 23197455
references: Neuroimage. 2002 Oct;17(2):825-41
references: 12377157
references: Neuroimage. 2013 Jan 15;65:374-86
references: 23085497
references: Hum Brain Mapp. 2000 Nov;11(3):207-13
references: 11098798
references: Neuroimage. 2010 Jan 15;49(2):1432-45
references: 19782143
references: MAGMA. 2010 Dec;23(5-6):375-89
references: 20473549
references: Neuroimage. 1998 Feb;7(2):119-32
references: 9558644
references: Eur J Pediatr. 2010 Sep;169(9):1079-85
references: 20225122
references: Neuroimage. 2013 Jan 1;64:240-56
references: 22926292
references: Trends Cogn Sci. 2012 Mar;16(3):181-8
references: 22341211
references: J Neurophysiol. 2010 Jan;103(1):297-321
references: 19889849
references: Magn Reson Med. 1998 Feb;39(2):331-5
references: 9469720
references: Magn Reson Med. 2006 May;55(5):1006-12
references: 16598718
references: Neurosci Lett. 2009 Sep 4;460(3):227-31
references: 19446602
references: Neuroimage. 2012 Mar;60(1):623-32
references: 22233733
references: Cereb Cortex. 2007 Jun;17(6):1402-11
references: 16905593
references: Neuroimage. 2012 Jan 2;59(1):431-8
references: 21810475
references: Hum Brain Mapp. 2001 Nov;14(3):140-51
references: 11559959
references: Neuroimage. 2009 Feb 1;44(3):1008-21
references: 19007893
references: Neuroimage. 2005 Jul 1;26(3):839-51
references: 15955494
references: Neuroimage. 2009 May 15;46(1):56-63
references: 19457356
references: J Neurophysiol. 2009 Jun;101(6):3270-83
references: 19339462
references: Nat Genet. 2002 Dec;32 Suppl:496-501
references: 12454644
references: Front Syst Neurosci. 2010 Apr 06;4:8
references: 20407579
references: Neuroimage. 2012 Feb 1;59(3):2142-54
references: 22019881
references: J Magn Reson Imaging. 2006 Jun;23(6):827-39
references: 16649196
references: PLoS One. 2011;6(9):e25031
references: 21949842
references: Neuroimage. 2013 Aug 1;76:183-201
references: 23499792
references: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10238-43
references: 20439733
references: Magn Reson Med. 1996 Mar;35(3):346-55
references: 8699946
references: Cereb Cortex. 2009 Oct;19(10):2209-29
references: 19221144
references: Neuroimage. 2009 Oct 1;47(4):1448-59
references: 19446646