title: Reduced cognitive control of response inhibition by the anterior cingulate cortex in autism spectrum disorders.
abstract: Response inhibition, or the suppression of prepotent, but contextually inappropriate behaviors, is essential to adaptive, flexible responding. In autism spectrum disorders (ASD), difficulty inhibiting prepotent behaviors may contribute to restricted, repetitive behavior (RRB). Individuals with ASD consistently show deficient response inhibition while performing antisaccades, which require one to inhibit the prepotent response of looking towards a suddenly appearing stimulus (i.e., a prosaccade), and to substitute a gaze in the opposite direction. Here, we used fMRI to identify the neural correlates of this deficit. We focused on two regions that are critical for saccadic inhibition: the frontal eye field (FEF), the key cortical region for generating volitional saccades, and the dorsal anterior cingulate cortex (dACC), which is thought to exert top-down control on the FEF. We also compared ASD and control groups on the functional connectivity of the dACC and FEF during saccadic performance. In the context of an increased antisaccade error rate, ASD participants showed decreased functional connectivity of the FEF and dACC and decreased inhibition-related activation (based on the contrast of antisaccades and prosaccades) in both regions. Decreased dACC activation correlated with a higher error rate in both groups, consistent with a role in top-down control. Within the ASD group, increased FEF activation and dACC/FEF functional connectivity were associated with more severe RRB. These findings demonstrate functional abnormalities in a circuit critical for volitional ocular motor control in ASD that may contribute to deficient response inhibition and to RRB. More generally, our findings suggest reduced cognitive control over behavior by the dACC in ASD.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Agam
authors.forename: Robert M
authors.initials: RM
authors.lastname: Joseph
authors.forename: Jason J S
authors.initials: JJ
authors.lastname: Barton
authors.forename: Dara S
authors.initials: DS
authors.lastname: Manoach
mesh_terms: D000328:Adult; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D056344:Executive Function / Q000502:physiology*; D053483:Eye Movement Measurements; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D012438:Saccades / Q000502:physiology; D013997:Time Factors
references.citation: Exp Brain Res. 1998 May;120(2):173-83
references.pmid: 9629959
references.citation: Neuroimage. 2009 Apr 1;45(2):470-6
references.pmid: 19138749
references.citation: Neuropsychologia. 1976;14(2):261-4
references.pmid: 934460
references.citation: Exp Brain Res. 1981;42(3-4):319-30
references.pmid: 6165607
references.citation: Brain. 2000 Sep;123 ( Pt 9):1838-44
references.pmid: 10960047
references.citation: Am J Psychiatry. 2006 Aug;163(8):1440-3
references.pmid: 16877661
references.citation: Neuron. 2003 Nov 13;40(4):671-83
references.pmid: 14622573
references.citation: Brain. 1999 Jun;122 ( Pt 6):1093-106
references.pmid: 10356062
references.citation: Autism. 2005 Feb;9(1):29-43
references.pmid: 15618261
references.citation: Psychophysiology. 2001 Mar;38(2):179-89
references.pmid: 11347863
references.citation: Neuroimage. 2007 Aug 15;37(2):579-88
references.pmid: 17604651
references.citation: Ann Neurol. 1995 May;37(5):557-67
references.pmid: 7755349
references.citation: Psychol Med. 2009 Sep;39(9):1559-66
references.pmid: 19154646
references.citation: Nat Rev Neurosci. 2004 Mar;5(3):218-28
references.pmid: 14976521
references.citation: Ann Neurol. 1981 Oct;10(4):309-25
references.pmid: 7032417
references.citation: Biol Psychiatry. 2007 Feb 15;61(4):474-81
references.pmid: 16650833
references.citation: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8275-80
references.pmid: 16702548
references.citation: Neuroimage. 2006 Jan 15;29(2):475-84
references.pmid: 16115783
references.citation: Nat Rev Neurosci. 2002 Mar;3(3):201-15
references.pmid: 11994752
references.citation: Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):925-9
references.pmid: 7846080
references.citation: Exp Brain Res. 2000 Jul;133(1):55-65
references.pmid: 10933210
references.citation: Brain Res Cogn Brain Res. 2003 Dec;18(1):102-5
references.pmid: 14659502
references.citation: J Autism Dev Disord. 2005 Jun;35(3):279-93
references.pmid: 16119469
references.citation: J Autism Dev Disord. 2005 Aug;35(4):445-60
references.pmid: 16134030
references.citation: Biol Psychiatry. 2002 May 15;51(10):816-26
references.pmid: 12007456
references.citation: Hum Brain Mapp. 1999;8(4):272-84
references.pmid: 10619420
references.citation: Biol Psychiatry. 2008 May 15;63(10):974-80
references.pmid: 17916328
references.citation: J Neurophysiol. 1993 Aug;70(2):453-69
references.pmid: 8410148
references.citation: Ann Neurol. 1990 Nov;28(5):597-613
references.pmid: 2260847
references.citation: J Int Neuropsychol Soc. 2006 Sep;12(5):622-31
references.pmid: 16961943
references.citation: Neuroimage. 2007 Apr 15;35(3):1219-30
references.pmid: 17321151
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15700-5
references.pmid: 16227444
references.citation: Biol Psychiatry. 2004 Feb 1;55(3):323-6
references.pmid: 14744477
references.citation: Arch Neurol. 1993 Mar;50(3):279-84
references.pmid: 8442707
references.citation: Neuropsychologia. 2002;40(12):2039-49
references.pmid: 12208001
references.citation: Neuropsychologia. 1987;25(1A):73-83
references.pmid: 3574652
references.citation: Brain. 2008 Sep;131(Pt 9):2464-78
references.pmid: 18550622
references.citation: Nat Neurosci. 2006 Oct;9(10):1218-20
references.pmid: 17001340
references.citation: Brain. 2008 Apr;131(Pt 4):1000-12
references.pmid: 18234695
references.citation: Nat Neurosci. 2002 Dec;5(12):1345-52
references.pmid: 12411958
references.citation: J Child Psychol Psychiatry. 2004 May;45(4):836-54
references.pmid: 15056314
references.citation: Magn Reson Med. 2000 Sep;44(3):457-65
references.pmid: 10975899
references.citation: Annu Rev Med. 2009;60:367-80
references.pmid: 19630577
references.citation: Brain Pathol. 2007 Oct;17(4):408-11
references.pmid: 17919126
references.citation: J Child Psychol Psychiatry. 2003 Sep;44(6):793-809
references.pmid: 12959489
references.citation: Neuroimage. 1999 Feb;9(2):179-94
references.pmid: 9931268
references.citation: Magn Reson Med. 1999 Dec;42(6):1014-8
references.pmid: 10571921
references.citation: Brain. 2004 Aug;127(Pt 8):1811-21
references.pmid: 15215213
references.citation: Hum Brain Mapp. 1998;6(4):270-82
references.pmid: 9704265
references.citation: Neuroimage. 2008 Feb 15;39(4):1877-85
references.pmid: 18083565
references.citation: J Clin Exp Neuropsychol. 2004 Feb;26(1):74-82
references.pmid: 14972695
references.citation: Neuroreport. 1997 Mar 3;8(4):901-5
references.pmid: 9141061
references.citation: J Neurosci. 2000 Jan 1;20(1):387-400
references.pmid: 10627615
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8
references.pmid: 15976020
references.citation: Neuroreport. 2004 Jul 19;15(10):1559-63
references.pmid: 15232283
references.citation: J Neurophysiol. 2003 Feb;89(2):1016-23
references.pmid: 12574477
references.citation: J Comput Assist Tomogr. 1994 Mar-Apr;18(2):192-205
references.pmid: 8126267
references.citation: Magn Reson Med. 1995 Oct;34(4):537-41
references.pmid: 8524021
references.citation: J Neurophysiol. 2006 Dec;96(6):3517-31
references.pmid: 16899645
references.citation: Biol Psychiatry. 2003 Sep 1;54(5):504-14
references.pmid: 12946879
references.citation: J Neurophysiol. 2005 Jul;94(1):429-40
references.pmid: 15728770
references.citation: Am J Psychiatry. 1997 Aug;154(8):1047-50
references.pmid: 9247387
references.citation: J Neurophysiol. 1996 Jan;75(1):454-68
references.pmid: 8822570
references.citation: Trends Cogn Sci. 2004 Jan;8(1):26-32
references.pmid: 14697400
references.citation: Cereb Cortex. 2004 Jan;14(1):11-22
references.pmid: 14654453
references.citation: Neuron. 1998 Feb;20(2):285-96
references.pmid: 9491989
references.citation: Neuroimage. 2006 Nov 1;33(2):644-59
references.pmid: 16949303
references.citation: Trends Cogn Sci. 2000 Jun;4(6):215-222
references.pmid: 10827444
references.citation: Neuropsychologia. 2007 Jan 7;45(1):2-14
references.pmid: 16806312
references.citation: Psychiatry Res. 2004 Jul 30;131(2):147-55
references.pmid: 15313521
references.citation: Autism. 2007 Sep;11(5):437-51
references.pmid: 17942457
references.citation: Acta Psychol (Amst). 1989 May;70(3):235-50
references.pmid: 2750553
references.citation: Neuron. 2007 Feb 1;53(3):453-62
references.pmid: 17270740
references.citation: J Autism Dev Disord. 1997 Feb;27(1):59-77
references.pmid: 9018582
references.citation: Annu Rev Neurosci. 2001;24:167-202
references.pmid: 11283309
references.citation: Neuroreport. 2003 Feb 10;14(2):283-7
references.pmid: 12598747
references.citation: J Neurosci. 2007 Feb 14;27(7):1791-8
references.pmid: 17301186
references.citation: Neurosci Lett. 1989 Nov 20;106(1-2):157-62
references.pmid: 2586821
references.citation: Brain Cogn. 2006 Jun;61(1):96-109
references.pmid: 16458401
references.citation: Vision Res. 1978;18(10):1279-96
references.pmid: 726270
references.citation: Hum Brain Mapp. 1999;8(2-3):109-14
references.pmid: 10524601
references.citation: Biol Psychiatry. 2006 Jan 1;59(1):7-16
references.pmid: 16140278
references.citation: Neurology. 1999 Mar 23;52(5):917-22
references.pmid: 10102406
references.citation: J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1719-26
references.pmid: 15548490
references.citation: Neuropsychologia. 1971 Mar;9(1):97-113
references.pmid: 5146491
references.citation: Biol Psychiatry. 1998 Dec 15;44(12):1219-28
references.pmid: 9861465
references.citation: Neuron. 2004 Mar 4;41(5):795-807
references.pmid: 15003178
references.citation: Brain. 1995 Feb;118 ( Pt 1):279-306
references.pmid: 7895011
references.citation: Am J Psychiatry. 2003 Aug;160(8):1439-41
references.pmid: 12900306
references.citation: Curr Opin Neurol. 2004 Feb;17(1):17-25
references.pmid: 15090873
references.citation: J Neurophysiol. 2010 Jan;103(1):297-321
references.pmid: 19889849
references.citation: Biol Psychiatry. 2007 Aug 1;62(3):198-206
references.pmid: 17137558
references.citation: Dev Neuropsychol. 2005;27(3):379-401
references.pmid: 15843103
references.citation: Ann N Y Acad Sci. 2008 Mar;1124:1-38
references.pmid: 18400922
references.citation: J Comp Neurol. 1987 Nov 15;265(3):332-61
references.pmid: 2447132
references.citation: Hum Brain Mapp. 2000 Dec;11(4):249-60
references.pmid: 11144754
references.citation: Neuropsychologia. 2009 Oct;47(12):2515-26
references.pmid: 19410583
references.citation: Am J Psychiatry. 2000 Dec;157(12):1994-2001
references.pmid: 11097966
references.citation: Autism Res. 2009 Feb;2(1):2-21
references.pmid: 19358304
references.citation: Neuroimage. 2000 Jun;11(6 Pt 1):735-59
references.pmid: 10860799
references.citation: Neuroreport. 2006 Nov 6;17(16):1687-90
references.pmid: 17047454
references.citation: Neuroimage. 1999 Feb;9(2):195-207
references.pmid: 9931269
references.citation: Brain Cogn. 2008 Dec;68(3):391-414
references.pmid: 18835079
references.citation: Exp Brain Res. 1997 Aug;116(1):50-62
references.pmid: 9305814
references.citation: Neuropsychologia. 1996 Jun;34(6):475-83
references.pmid: 8736560