title: Lag threads organize the brain's intrinsic activity.
abstract: It has been widely reported that intrinsic brain activity, in a variety of animals including humans, is spatiotemporally structured. Specifically, propagated slow activity has been repeatedly demonstrated in animals. In human resting-state fMRI, spontaneous activity has been understood predominantly in terms of zero-lag temporal synchrony within widely distributed functional systems (resting-state networks). Here, we use resting-state fMRI from 1,376 normal, young adults to demonstrate that multiple, highly reproducible, temporal sequences of propagated activity, which we term "lag threads," are present in the brain. Moreover, this propagated activity is largely unidirectional within conventionally understood resting-state networks. Modeling experiments show that resting-state networks naturally emerge as a consequence of shared patterns of propagation. An implication of these results is that common physiologic mechanisms may underlie spontaneous activity as imaged with fMRI in humans and slowly propagated activity as studied in animals.
authors.affiliation: Departments of Radiology and marc@npg.wustl.edu anishmitra@wustl.edu.
authors.forename: Anish
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Departments of Radiology and Neurology, Washington University, St. Louis, MO 63110.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: Departments of Radiology and.
authors.forename: Tyler
authors.initials: T
authors.lastname: Blazey
authors.affiliation: Departments of Radiology and Neurology, Washington University, St. Louis, MO 63110 marc@npg.wustl.edu anishmitra@wustl.edu.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Raichle
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology; D003344:Cortical Synchronization; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000502:physiology; D011859:Radiography
keywords: dynamics; fMRI; intrinsic activity; resting state
references.citation: Nat Rev Neurosci. 2004 Nov;5(11):874-85
references.pmid: 15496865
references.citation: Neuron. 2014 Sep 3;83(5):1185-99
references.pmid: 25132467
references.citation: Nat Neurosci. 2005 Aug;8(8):988-90
references.pmid: 16007081
references.citation: Electroencephalogr Clin Neurophysiol. 1969;:Suppl 28:75+
references.pmid: 4188919
references.citation: Nat Rev Neurosci. 2001 Oct;2(10):685-94
references.pmid: 11584306
references.citation: Brain Connect. 2011;1(1):3-12
references.pmid: 22432951
references.citation: J Neurosci. 1998 Jan 1;18(1):266-83
references.pmid: 9412506
references.citation: J Neurosci. 2012 Jun 27;32(26):8890-9
references.pmid: 22745490
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):347-52
references.pmid: 17185420
references.citation: Neuroimage. 2005 Mar;25(1):141-58
references.pmid: 15734351
references.citation: Neuroimage. 2008 Jan 1;39(1):279-89
references.pmid: 17919927
references.citation: Semin Cell Dev Biol. 1997 Feb;8(1):1-4
references.pmid: 15001098
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2065-9
references.pmid: 12576550
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16039-44
references.pmid: 18843113
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9
references.pmid: 20176931
references.citation: J Neurophysiol. 2012 Oct;108(8):2242-63
references.pmid: 22832566
references.citation: Neuron. 2003 Feb 20;37(4):563-76
references.pmid: 12597855
references.citation: Brain. 2013 Mar;136(Pt 3):710-25
references.pmid: 23423673
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):15037-42
references.pmid: 19706442
references.citation: Nat Rev Neurosci. 2007 Sep;8(9):700-11
references.pmid: 17704812
references.citation: Curr Opin Neurobiol. 2013 Apr;23(2):172-8
references.pmid: 23265964
references.citation: Neuron. 2013 Mar 20;77(6):1136-50
references.pmid: 23522048
references.citation: Pediatr Res. 1999 Apr;45(4 Pt 1):447-58
references.pmid: 10203134
references.citation: J Neurosci. 2004 Aug 4;24(31):6862-70
references.pmid: 15295020
references.citation: Neuroimage. 2013 Jul 1;74:288-97
references.pmid: 23481462
references.citation: PLoS Biol. 2009 Feb 17;7(2):e33
references.pmid: 19226186
references.citation: Science. 1996 Nov 15;274(5290):1133-8
references.pmid: 8895456
references.citation: Neuroimage. 2010 Sep;52(3):752-65
references.pmid: 20036335
references.citation: Nat Rev Neurosci. 2005 Nov;6(11):877-88
references.pmid: 16261181
references.citation: Cereb Cortex. 2016 Jan;26(1):288-303
references.pmid: 25316338
references.citation: Neuroimage. 2012 Aug 15;62(2):720-5
references.pmid: 22281677
references.citation: Neuron. 2011 Nov 17;72(4):665-78
references.pmid: 22099467
references.citation: Front Syst Neurosci. 2014 Jun 25;8:122
references.pmid: 25009476
references.citation: Neuron. 2007 Dec 6;56(5):907-23
references.pmid: 18054865
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13638-43
references.pmid: 14595013
references.citation: Nat Neurosci. 2006 Nov;9(11):1359-61
references.pmid: 17041594
references.citation: Nat Rev Neurosci. 2005 Jun;6(6):477-83
references.pmid: 15928717
references.citation: Neuron. 2011 Apr 14;70(1):153-69
references.pmid: 21482364
references.citation: Nature. 2003 May 15;423(6937):283-8
references.pmid: 12748641
references.citation: J Neurosci. 2010 Mar 10;30(10):3745-51
references.pmid: 20220008
references.citation: Cell. 1993 Jan;72 Suppl:77-98
references.pmid: 8428376
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11372-7
references.pmid: 22711833
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18453-8
references.pmid: 22027012
references.citation: J Neurophysiol. 2014 Jun 1;111(11):2374-91
references.pmid: 24598530
references.citation: Nature. 2003 Oct 30;425(6961):954-6
references.pmid: 14586468
references.citation: Nat Neurosci. 2013 Oct;16(10):1426-35
references.pmid: 23974708
references.citation: Neuron. 2014 Feb 19;81(4):728-39
references.pmid: 24559669
references.citation: J Neurosci. 2007 Feb 28;27(9):2349-56
references.pmid: 17329432
references.citation: J Neurophysiol. 2011 Dec;106(6):3035-44
references.pmid: 21849616
references.citation: Science. 2004 Apr 23;304(5670):559-64
references.pmid: 15105494
references.citation: Curr Opin Neurobiol. 2009 Aug;19(4):439-44
references.pmid: 19647992
references.citation: Hum Brain Mapp. 1999;8(4):194-208
references.pmid: 10619414
references.citation: Neuroimage. 2011 Sep 15;58(2):303-5; author reply 310-1
references.pmid: 19770049
references.citation: Neuroimage. 2004 Apr;21(4):1639-51
references.pmid: 15050587
references.citation: J Neurosci. 2014 Jun 25;34(26):8875-93
references.pmid: 24966387
references.citation: J Neurophysiol. 2011 Sep;106(3):1125-65
references.pmid: 21653723
references.citation: Biopolymers. 2003 Mar;68(3):422-36
references.pmid: 12601800
references.citation: J Comput Neurosci. 2007 Feb;22(1):5-19
references.pmid: 16998643
references.citation: Neuroimage. 2013 Nov 15;82:616-33
references.pmid: 23735260
references.citation: Science. 2004 Jun 25;304(5679):1926-9
references.pmid: 15218136
references.citation: Neuron. 2010 May 13;66(3):353-69
references.pmid: 20471349
references.citation: Nature. 2006 Dec 7;444(7120):707-12
references.pmid: 17151658
references.citation: Nature. 2001 Jul 12;412(6843):150-7
references.pmid: 11449264
references.citation: J Neurophysiol. 1995 Jan;73(1):20-38
references.pmid: 7714565
references.citation: J Neurosci. 1993 Aug;13(8):3284-99
references.pmid: 8340808
references.citation: Philos Trans R Soc Lond B Biol Sci. 2005 May 29;360(1457):1001-13
references.pmid: 16087444
references.citation: J Neurosci. 1993 Aug;13(8):3252-65
references.pmid: 8340806
references.citation: Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):E4053-61
references.pmid: 25201983
references.citation: J Neurophysiol. 2011 Nov;106(5):2322-45
references.pmid: 21795627
references.citation: Magn Reson Med. 1995 Oct;34(4):537-41
references.pmid: 8524021