title: Anterior cingulate cortex and insula response during indirect and direct processing of emotional faces in generalized social anxiety disorder.
abstract: BACKGROUND
  Generalized social anxiety disorder (gSAD) is associated with a heightened neural sensitivity to signals that convey threat, as evidenced by exaggerated amygdala and/or insula activation when processing face stimuli that express negative emotions. Less clear in the brain pathophysiology of gSAD are cortical top down control mechanisms that moderate reactivity in these subcortical emotion processing regions. This study evaluated amygdala, insula, and anterior cingulate cortex (ACC) activity in gSAD with a novel "Emotional Faces Shifting Attention Task" (EFSAT), an adaptation of perceptual assessment tasks well-known to elicit amygdala response. In healthy volunteers, the task has been shown to engage the amygdala when attention is directed to emotional faces and the ACC when attention is directed to shapes, away from emotional faces.
  
  
  METHODS
  During functional MRI, 29 participants with gSAD and 27 healthy controls viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio of geometric shapes (circles, rectangles, or triangles) within the same field of view. Participants were instructed to match faces or match shapes, effectively directing attention towards or away from emotional information, respectively.
  
  
  RESULTS
  Participants with gSAD exhibited greater insula, but not amygdala, activation compared to controls when attending to emotional faces. In contrast, when attention was directed away from faces, controls exhibited ACC recruitment, which was not evident in gSAD. Across participants, greater ACC activation was associated with less insula activation.
  
  
  CONCLUSIONS
  Evidence that individuals with gSAD exhibited exaggerated insula reactivity when attending to emotional faces in EFSAT is consistent with other studies suggesting that the neural basis of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in controls than gSAD when sustained goal-directed attention is required to shift attention away from social signals, together with a negative relationship between ACC and bilateral insula activity, indicate the ACC may have served a regulatory role when the focus of attention was directed to shapes amidst emotional faces.
authors.affiliation: Mood and Anxiety Disorders Research Program, Department of Psychiatry (HK, DP, DAF, KLP), University of Illinois at Chicago, 1747 W. Roosevelt Rd, Chicago, IL, 60608, USA.
authors.forename: Heide
authors.initials: H
authors.lastname: Klumpp
authors.affiliation: Mood and Anxiety Disorders Research Program, Department of Psychiatry (HK, DP, DAF, KLP), University of Illinois at Chicago, 1747 W. Roosevelt Rd, Chicago, IL, 60608, USA.
authors.forename: David
authors.initials: D
authors.lastname: Post
authors.affiliation: Department of Psychiatry (MA, KLP), University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Angstadt
authors.affiliation: Mood and Anxiety Disorders Research Program, Department of Psychiatry (HK, DP, DAF, KLP), University of Illinois at Chicago, 1747 W. Roosevelt Rd, Chicago, IL, 60608, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fitzgerald
authors.affiliation: Mood and Anxiety Disorders Research Program, Department of Psychiatry (HK, DP, DAF, KLP), University of Illinois at Chicago, 1747 W. Roosevelt Rd, Chicago, IL, 60608, USA ; Department of Psychiatry (MA, KLP), University of Michigan, Ann Arbor, MI, USA ; Neuropsychiatric Research Program (KLP), Mental Health Service, Jesse Brown VA Medical Center, Chicago, IL, USA.
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
keywords: Brain imaging; Emotional faces; Social anxiety; Threat processing; fMRI
references.citation: Biol Psychiatry. 2009 Mar 1;65(5):374-82
references.pmid: 18996510
references.citation: Neuron. 2006 Sep 21;51(6):871-82
references.pmid: 16982430
references.citation: Am Psychol. 2000 Nov;55(11):1196-214
references.pmid: 11280935
references.citation: Biol Psychiatry. 2006 Apr 1;59(7):664-6
references.pmid: 16325155
references.citation: Depress Anxiety. 2009;26(5):419-24
references.pmid: 19242987
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):617-27
references.pmid: 15939839
references.citation: Biol Psychiatry. 2006 Aug 15;60(4):383-7
references.pmid: 16780813
references.citation: Biol Psychiatry. 2012 Sep 15;72(6):476-82
references.pmid: 22592057
references.citation: J Comp Neurol. 1984 Dec 20;230(4):465-96
references.pmid: 6520247
references.citation: Nat Rev Neurosci. 2009 Jan;10(1):59-70
references.pmid: 19096369
references.citation: Nat Neurosci. 2004 Feb;7(2):184-8
references.pmid: 14703573
references.citation: Am J Psychiatry. 2007 Oct;164(10):1476-88
references.pmid: 17898336
references.citation: Mol Psychiatry. 2001 Jan;6(1):13-34
references.pmid: 11244481
references.citation: Brain Res Cogn Brain Res. 2002 Dec;15(1):31-45
references.pmid: 12433381
references.citation: J Neurosci. 2007 Feb 28;27(9):2349-56
references.pmid: 17329432
references.citation: Nat Protoc. 2006;1(1):293-6
references.pmid: 17406247
references.citation: Neuropsychologia. 2009 Apr;47(5):1386-9
references.pmid: 19428403
references.citation: Biol Psychol. 2012 Jan;89(1):273-6
references.pmid: 22027088
references.citation: Neuropsychobiology. 2005;52(3):163-8
references.pmid: 16137995
references.citation: Brain Struct Funct. 2010 Jun;214(5-6):451-63
references.pmid: 20490545
references.citation: Cereb Cortex. 2011 Apr;21(4):911-9
references.pmid: 20732901
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):565-80
references.pmid: 20206659
references.citation: Science. 2000 Jun 9;288(5472):1835-8
references.pmid: 10846167
references.citation: Biol Psychiatry. 2001 Dec 15;50(12):932-42
references.pmid: 11750889
references.citation: F1000 Biol Rep. 2011 Jan 14;3:2
references.pmid: 21399763
references.citation: Biol Psychiatry. 2005 May 1;57(9):975-81
references.pmid: 15860337
references.citation: J Comp Neurol. 1982 Nov 20;212(1):38-52
references.pmid: 7174907
references.citation: J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):611-8
references.pmid: 20522870
references.citation: Brain Struct Funct. 2010 Jun;214(5-6):669-80
references.pmid: 20512372
references.citation: Neuroscience. 2002;115(4):1261-79
references.pmid: 12453496
references.citation: Trends Cogn Sci. 2011 Feb;15(2):85-93
references.pmid: 21167765
references.citation: Neuroimage. 2006 Jun;31(2):920-33
references.pmid: 16487729
references.citation: Science. 1998 May 1;280(5364):747-9
references.pmid: 9563953
references.citation: Neuroimage. 2002 Jul;16(3 Pt 1):651-62
references.pmid: 12169250
references.citation: Cereb Cortex. 2007 Jul;17(7):1595-603
references.pmid: 16956980
references.citation: J Neurosci. 1995 Sep;15(9):5879-91
references.pmid: 7666173
references.citation: Biol Psychol. 2010 May;84(2):304-12
references.pmid: 20227458
references.citation: Neuroimage. 2002 Sep;17(1):317-23
references.pmid: 12482086
references.citation: Trends Cogn Sci. 2000 Jun;4(6):215-222
references.pmid: 10827444
references.citation: Psychol Med. 2008 Jan;38(1):15-28
references.pmid: 17976249
references.citation: Arch Gen Psychiatry. 1994 Jan;51(1):8-19
references.pmid: 8279933
references.citation: Emotion. 2008 Apr;8(2):250-5
references.pmid: 18410198
references.citation: Trends Neurosci. 2000 Oct;23(10):475-83
references.pmid: 11006464
references.citation: Transl Psychiatry. 2011 Oct 04;1:e46
references.pmid: 22833192
references.citation: J Psychiatry Neurosci. 2009 Jul;34(4):296-302
references.pmid: 19568481
references.citation: Biol Psychiatry. 2006 Mar 1;59(5):424-9
references.pmid: 16256956
references.citation: Clin Psychol Rev. 2004 Nov;24(7):827-56
references.pmid: 15501558
references.citation: Neurosci Biobehav Rev. 2008;32(4):811-30
references.pmid: 18316124
references.citation: Neuroimage. 2007 Feb 1;34(3):905-23
references.pmid: 17126037
references.citation: Mod Probl Pharmacopsychiatry. 1987;22:141-73
references.pmid: 2885745
references.citation: Cogn Affect Behav Neurosci. 2010 Sep;10(3):357-71
references.pmid: 20805537
references.citation: Behav Res Ther. 1994 Feb;32(2):269-80
references.pmid: 8155066
references.citation: Lancet. 2008 Mar 29;371(9618):1115-25
references.pmid: 18374843
references.citation: Neuroimage. 2002 Jun;16(2):331-48
references.pmid: 12030820
references.citation: Psychol Rev. 2001 Jul;108(3):624-52
references.pmid: 11488380
references.citation: Brain Res Brain Res Rev. 1996 Oct;22(3):229-44
references.pmid: 8957561
references.citation: Neuroimage. 2012 Jan 16;59(2):1879-87
references.pmid: 21920442
references.citation: Arch Gen Psychiatry. 2005 Feb;62(2):146-52
references.pmid: 15699291
references.citation: Depress Anxiety. 2011 Mar;28(3):194-201
references.pmid: 21394852
references.citation: Nat Rev Neurosci. 2002 Aug;3(8):655-66
references.pmid: 12154366
references.citation: Neuron. 2001 Jun;30(3):829-41
references.pmid: 11430815
references.citation: Biol Psychiatry. 2004 Dec 15;56(12):921-30
references.pmid: 15601601
references.citation: Depress Anxiety. 2008;25(6):496-505
references.pmid: 17595018
references.citation: Neurosci Lett. 2012 Apr 18;514(2):210-3
references.pmid: 22425719