title: Functional alterations of large-scale brain networks related to cognitive control in obsessive-compulsive disorder.
abstract: OBJECTIVE
  Neuroimaging studies have consistently implicated alterations of the basal ganglia and orbitofrontal cortex in the pathophysiology of OCD, however, recent work also emphasizes more diffuse patterns of brain alteration as occurring in this disorder. The goal of this study was to extend such observations by investigating large-scale brain functional network correlates of cognitive-control performance in OCD patients.
  
  
  METHODS
  We combined fMRI with a validated task of cognitive control and a multivariate statistical method to assess multiple functional networks encompassing broad task-relevant cortical regions in OCD patients and matched controls. Functional networks of interest were targeted a priori and the groups were compared in terms of the spatiotemporal profile of network responses (functional connectivity) during the task performance in a data-driven manner.
  
  
  RESULTS
  Task performance was equivalent in both groups and each distinct network demonstrated strong overlap in its general response during task. However, significant differences in functional connectivity were also observed between groups that appeared driven by specific phases of task performance. Such differences were most pronounced during rest-task transitions and mainly involved dorsal anterior cingulate and insular cortices within the paralimbic network. Relative heightened functional connectivity of insula in patients during task correlated with a measure of patients' state anxiety.
  
  
  CONCLUSIONS
  Our findings provide a novel functional imaging characterization of brain network alterations associated with cognitive-control in OCD. Additionally, these findings raise questions about the role of patients' arousal states on the performance of cognitive imaging tasks that are otherwise assumed to be emotionally neutral.
authors: Melbourne Neuropsychiatry Centre, The University of Melbourne, Australia. lcocchi@unimelb.edu.au
authors: Luca
authors: L
authors: Cocchi
authors: Ben J
authors: BJ
authors: Harrison
authors: Jesus
authors: J
authors: Pujol
authors: Ian H
authors: IH
authors: Harding
authors: Alex
authors: A
authors: Fornito
authors: Christos
authors: C
authors: Pantelis
authors: Murat
authors: M
authors: Yücel
references: Neuroimage. 2003 Dec;20(4):2271-80
references: 14683728
references: Nat Rev Neurosci. 2009 Jan;10(1):59-70
references: 19096369
references: Lancet. 1998 Sep 12;352(9131):881-2
references: 9742988
references: Arch Gen Psychiatry. 2004 Jul;61(7):720-30
references: 15237084
references: Neuroimage. 2005 Dec;28(4):956-66
references: 16043368
references: Neuroimage. 2009 Oct 1;47(4):1678-90
references: 19539034
references: Curr Opin Neurobiol. 2003 Oct;13(5):620-9
references: 14630228
references: Int J Neuropsychopharmacol. 2006 Feb;9(1):95-100
references: 15982444
references: Neurosci Biobehav Rev. 2008;32(3):525-49
references: 18061263
references: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11073-8
references: 17576922
references: Hum Brain Mapp. 2009 Jul;30(7):2146-56
references: 18819107
references: Neuroimage. 2007 Apr 15;35(3):1028-37
references: 17321758
references: J Cereb Blood Flow Metab. 1993 Jan;13(1):5-14
references: 8417010
references: Cereb Cortex. 2008 Nov;18(11):2553-9
references: 18296434
references: Neuron. 2006 Jun 1;50(5):799-812
references: 16731517
references: Neuron. 2000 Nov;28(2):343-7
references: 11144344
references: Am J Psychiatry. 2006 Jul;163(7):1282-4
references: 16816237
references: Biol Psychiatry. 2005 Apr 15;57(8):901-10
references: 15820711
references: Neuroimage. 2005 Apr 15;25(3):771-82
references: 15808978
references: Hum Brain Mapp. 2007 Nov;28(11):1251-66
references: 17274023
references: Mol Psychiatry. 2007 Jul;12(7):611, 691-702
references: 17245325
references: Nat Neurosci. 2006 Jul;9(7):971-8
references: 16767087
references: J Neurosci. 2007 Feb 28;27(9):2349-56
references: 17329432
references: Nat Protoc. 2006;1(1):308-13
references: 17406250
references: Psychiatry Res. 2004 Dec 30;132(3):225-37
references: 15664794
references: Neuroimage. 2006 Feb 15;29(4):1359-67
references: 16260155
references: Nat Neurosci. 2004 Feb;7(2):189-95
references: 14730305
references: Mol Psychiatry. 2010 Aug;15(8):823-30
references: 20065955
references: Biol Psychiatry. 1999 Apr 1;45(7):891-7
references: 10202577
references: Am J Psychiatry. 2004 Apr;161(4):707-15
references: 15056518
references: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12569-74
references: 18723676
references: Hum Brain Mapp. 2011 Oct;32(10):1544-56
references: 20814961
references: Arch Gen Psychiatry. 1989 Nov;46(11):1006-11
references: 2684084
references: Arch Gen Psychiatry. 1994 Jan;51(1):62-70
references: 8279930
references: J Neuropsychiatry Clin Neurosci. 1989 Winter;1(1):27-36
references: 2535426
references: Psychiatry Res. 2004 Nov 15;132(1):69-79
references: 15546704
references: Trends Cogn Sci. 2008 Mar;12(3):99-105
references: 18262825
references: J Psychiatr Res. 2000 Jul-Oct;34(4-5):317-24
references: 11104844
references: Neuroimage. 2003 Aug;19(4):1273-302
references: 12948688
references: Psychol Sci. 2003 Jul;14(4):347-53
references: 12807408
references: Int J Psychophysiol. 2009 Aug;73(2):88-94
references: 19414044
references: Arch Gen Psychiatry. 2008 Jan;65(1):102-14
references: 18180434
references: Biol Psychiatry. 2005 Jan 1;57(1):16-20
references: 15607295
references: Neuroimage. 1997 Oct;6(3):218-29
references: 9344826
references: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
references: 19620724
references: Proc Natl Acad Sci U S A. 2009 May 26;106(21):8719-24
references: 19433790
references: Neuron. 2008 May 8;58(3):306-24
references: 18466742
references: Science. 1996 Nov 1;274(5288):740-3
references: 8966556
references: J Chem Neuroanat. 2003 Dec;26(4):317-30
references: 14729134
references: Neurology. 2000 Jan 11;54(1):142-7
references: 10636140
references: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):683-7
references: 11209065
references: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
references: 11209064
references: Arch Gen Psychiatry. 2009 Nov;66(11):1189-200
references: 19884607
references: Brain. 2009 Apr;132(Pt 4):853-68
references: 18952675
references: J Psychiatr Res. 2008 Oct;42(13):1051-9
references: 18261744
references: Brain. 2007 Dec;130(Pt 12):3223-36
references: 17855376
references: Br J Psychiatry. 1994 Apr;164(4):459-68
references: 8038933
references: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13848-53
references: 16945915
references: Neuroimage. 2006 Feb 15;29(4):1185-91
references: 16269249
references: Magn Reson Med. 1995 Oct;34(4):537-41
references: 8524021
references: Magn Reson Imaging. 2004 Nov;22(9):1181-91
references: 15607089
references: Biol Psychiatry. 2007 May 1;61(9):1072-80
references: 17097073
references: Schizophr Res. 2007 Mar;91(1-3):82-6
references: 17307337
references: Neuropsychopharmacology. 2002 Nov;27(5):782-91
references: 12431852
references: Philos Trans R Soc Lond B Biol Sci. 2005 May 29;360(1457):1001-13
references: 16087444
references: Psychol Med. 2000 Sep;30(5):1037-50
references: 12027041
references: Trends Cogn Sci. 2000 Jun;4(6):215-222
references: 10827444
references: Alzheimer Dis Assoc Disord. 2007 Oct-Dec;21(4):S50-7
references: 18090425
references: Neuroimage. 2009 Mar;45(1 Suppl):S163-72
references: 19059344
references: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9781-6
references: 18621692
references: J Cogn Neurosci. 2003 Apr 1;15(3):394-408
references: 12729491
references: PLoS One. 2009;4(4):e5224
references: 19381292
references: Am J Psychiatry. 2001 Jan;158(1):140-2
references: 11136650
references: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10046-51
references: 16788060
references: Arch Gen Psychiatry. 2007 Aug;64(8):946-55
references: 17679639
references: IEEE Eng Med Biol Mag. 2006 Mar-Apr;25(2):102-11
references: 16568942
references: Hum Brain Mapp. 2008 Jul;29(7):828-38
references: 18438867
references: Arch Gen Psychiatry. 2006 Nov;63(11):1225-36
references: 17088503
references: Neuroimage. 2005 Jan 15;24(2):495-503
references: 15627591
references: Behav Res Ther. 1988;26(2):169-77
references: 3365207
references: Brain. 2008 Jan;131(Pt 1):155-64
references: 18065438
references: Hum Brain Mapp. 2001 Nov;14(3):140-51
references: 11559959
references: Acta Psychiatr Scand. 2007 Oct;116(4):271-9
references: 17803757
references: Psychol Med. 2009 Jul;39(7):1177-87
references: 19154647
references: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8
references: 12506194
references: Hum Brain Mapp. 2009 Jan;30(1):256-66
references: 18041738
references: Neuroimage. 2003 Oct;20(2):962-74
references: 14568466
references: J Cogn Neurosci. 2003 Oct 1;15(7):1028-38
references: 14614813
references: Curr Opin Psychiatry. 2007 May;20(3):255-61
references: 17415079
references: Annu Rev Neurosci. 1986;9:357-81
references: 3085570
references: Psychiatry Res. 2006 Oct 30;147(2-3):227-31
references: 16949800
references: PLoS One. 2008 Mar 19;3(3):e1794
references: 18350136
references: Acta Psychiatr Scand. 2007 Feb;115(2):155-8
references: 17244179
references: Neuroimage. 2005 Mar;25(1):230-42
references: 15734358
references: Biol Psychiatry. 2003 Oct 1;54(7):751-6
references: 14512216
references: Arch Gen Psychiatry. 2004 Jun;61(6):564-76
references: 15184236
references: Int J Psychophysiol. 2005 Jul;57(1):69-77
references: 15935263
references: Arch Gen Psychiatry. 1996 Jul;53(7):595-606
references: 8660126