title: Diagnosis of Autism Spectrum Disorders Using Temporally Distinct Resting-State Functional Connectivity Networks.
abstract: BACKGROUND
  Resting-state functional magnetic resonance imaging (R-fMRI) is dynamic in nature as neural activities constantly change over the time and are dominated by repeating brief activations and deactivations involving many brain regions. Each region participates in multiple brain functions and is part of various functionally distinct but spatially overlapping networks. Functional connectivity computed as correlations over the entire time series always overlooks interregion interactions that often occur repeatedly and dynamically in time, limiting its application to disease diagnosis.
  
  
  OBJECTIVE
  We develop a novel framework that uses short-time activation patterns of brain connectivity to better detect subtle disease-induced disruptions of brain connectivity. A clustering algorithm is first used to temporally decompose R-fMRI time series into distinct clusters with similar spatial distribution of neural activity based on the assumption that functionally distinct networks should be largely temporally distinct as brain states do not simultaneously coexist in general. A Pearson correlation-based functional connectivity network is then constructed for each cluster to allow for better exploration of spatiotemporal dynamics of individual neural activity. To reduce significant intersubject variability and to remove possible spurious connections, we use a group-constrained sparse regression model to construct a backbone sparse network for each cluster and use it to weight the corresponding Pearson correlation network.
  
  
  RESULTS
  The proposed method outperforms the conventional static, temporally dependent fully connected correlation-based networks by at least 7% on a publicly available autism dataset. We were able to reproduce similar results using data from other centers.
  
  
  CONCLUSIONS
  By combining the advantages of temporal independence and group-constrained sparse regression, our method improves autism diagnosis.
authors.affiliation: Image Display, Enhancement, and Analysis (IDEA) Laboratory, Biomedical Research Imaging Center (BRIC) and Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina USA.|Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
authors.forename: Chong-Yaw
authors.initials: CY
authors.lastname: Wee
authors.affiliation: Image Display, Enhancement, and Analysis (IDEA) Laboratory, Biomedical Research Imaging Center (BRIC) and Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina USA.
authors.forename: Pew-Thian
authors.initials: PT
authors.lastname: Yap
authors.affiliation: Image Display, Enhancement, and Analysis (IDEA) Laboratory, Biomedical Research Imaging Center (BRIC) and Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina USA.|Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea.
authors.forename: Dinggang
authors.initials: D
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000175:diagnosis*; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009434:Neural Pathways / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D012146:Rest; D013997:Time Factors
chemical_list: D010100:Oxygen
keywords: Brain Activation Patterns; Resting-State Functional Connectivity; Sparse Representation; Spatiotemporal Dynamics; Temporal Decomposition
references.citation: Neuroimage. 2002 Jan;15(1):273-89
references.pmid: 11771995
references.citation: Am J Psychiatry. 2003 Feb;160(2):262-73
references.pmid: 12562572
references.citation: Brain Res Bull. 2003 Oct 15;61(6):557-69
references.pmid: 14519452
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42
references.pmid: 15070770
references.citation: Neuroimage. 2004 Sep;23(1):364-9
references.pmid: 15325384
references.citation: Brain. 2005 Feb;128(Pt 2):268-76
references.pmid: 15548557
references.citation: Hum Brain Mapp. 2005 Dec;26(4):231-9
references.pmid: 15954139
references.citation: J Neurosci. 2006 Jan 4;26(1):63-72
references.pmid: 16399673
references.citation: Am J Psychiatry. 2006 Jul;163(7):1290-2
references.pmid: 16816240
references.citation: Neuroscientist. 2006 Dec;12(6):512-23
references.pmid: 17079517
references.citation: Cereb Cortex. 2007 Oct;17(10):2407-19
references.pmid: 17204824
references.citation: Science. 2007 Feb 16;315(5814):972-6
references.pmid: 17218491
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11073-8
references.pmid: 17576922
references.citation: J Neurosci. 2007 Oct 24;27(43):11725-35
references.pmid: 17959814
references.citation: Trends Neurosci. 2008 Mar;31(3):137-45
references.pmid: 18258309
references.citation: PLoS Comput Biol. 2008 Jun 27;4(6):e1000100
references.pmid: 18584043
references.citation: Biol Psychiatry. 2008 Oct 1;64(7):589-98
references.pmid: 18672231
references.citation: Nat Rev Neurosci. 2009 Mar;10(3):186-98
references.pmid: 19190637
references.citation: PLoS One. 2009;4(4):e5226
references.pmid: 19381298
references.citation: Neuroimage. 2010 Jan 1;49(1):44-56
references.pmid: 19683584
references.citation: Neuroimage. 2010 Sep;52(3):1059-69
references.pmid: 19819337
references.citation: J Neurophysiol. 2010 Jan;103(1):297-321
references.pmid: 19889849
references.citation: Neuroimage. 2010 Mar;50(1):81-98
references.pmid: 20006716
references.citation: Neuroimage. 2010 Apr 15;50(3):935-49
references.pmid: 20079441
references.citation: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9885-90
references.pmid: 20457896
references.citation: Curr Opin Neurol. 2010 Aug;23(4):341-50
references.pmid: 20581686
references.citation: Front Syst Neurosci. 2010 Jun 07;4:16
references.pmid: 20589099
references.citation: J Neurosci. 2010 Aug 11;30(32):10612-23
references.pmid: 20702694
references.citation: Cereb Cortex. 2011 May;21(5):1134-46
references.pmid: 20943668
references.citation: PLoS One. 2011 Feb 16;6(2):e17191
references.pmid: 21359184
references.citation: Psychiatry Res. 2011 Apr 30;192(1):60-6
references.pmid: 21377337
references.citation: IEEE Trans Med Imaging. 2011 May;30(5):1154-65
references.pmid: 21478072
references.citation: PLoS One. 2011;6(7):e21976
references.pmid: 21818285
references.citation: Biol Psychiatry. 2011 Nov 1;70(9):833-41
references.pmid: 21890111
references.citation: Brain. 2011 Dec;134(Pt 12):3742-54
references.pmid: 22006979
references.citation: Neuroimage. 2012 Feb 1;59(3):2045-56
references.pmid: 22019883
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3131-6
references.pmid: 22323591
references.citation: Front Physiol. 2012 Feb 08;3:15
references.pmid: 22347863
references.citation: PLoS One. 2012;7(3):e33182
references.pmid: 22457741
references.citation: J Child Psychol Psychiatry. 2012 May;53(5):490-509
references.pmid: 22486486
references.citation: PLoS One. 2012;7(5):e37828
references.pmid: 22666397
references.citation: Neuroimage. 2012 Nov 15;63(3):1712-9
references.pmid: 22796990
references.citation: PLoS One. 2012;7(10):e45502
references.pmid: 23056205
references.citation: J Am Acad Child Adolesc Psychiatry. 2012 Nov;51(11):1150-9
references.pmid: 23101741
references.citation: Cereb Cortex. 2014 Mar;24(3):663-76
references.pmid: 23146964
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4392-7
references.pmid: 23440216
references.citation: Brain Struct Funct. 2014 Mar;219(2):641-56
references.pmid: 23468090
references.citation: Neuroimage. 2013 Oct 15;80:360-78
references.pmid: 23707587
references.citation: Brain. 2013 Sep;136(Pt 9):2799-815
references.pmid: 23935125
references.citation: Front Hum Neurosci. 2013 Aug 06;7:430
references.pmid: 23964221
references.citation: Hum Brain Mapp. 2014 Jul;35(7):2876-97
references.pmid: 24038749
references.citation: Front Hum Neurosci. 2013 Sep 25;7:599
references.pmid: 24093016
references.citation: IEEE Trans Biomed Eng. 2014 Feb;61(2):576-89
references.pmid: 24108708
references.citation: MMWR Surveill Summ. 2014 Mar 28;63(2):1-21
references.pmid: 24670961
references.citation: Hum Brain Mapp. 2014 Jul;35(7):3414-30
references.pmid: 25050428
references.citation: Neuroimage Clin. 2014 Jul 24;5:298-308
references.pmid: 25161896
references.citation: Neuroinformatics. 2015 Jul;13(3):277-95
references.pmid: 25501275
references.citation: Hum Brain Mapp. 2015 Dec;36(12):4880-96
references.pmid: 26368659
references.citation: J Intellect Disabil Res. 1993 Aug;37 ( Pt 4):343-72
references.pmid: 8400719
references.citation: Magn Reson Med. 1996 Mar;35(3):346-55
references.pmid: 8699946