title: Dissociable roles of medial orbitofrontal cortex in human operant extinction learning.
abstract: Operant extinction, which features modification of instrumental responses to stimuli following a change in associated reinforcement, is an important form of learning for organisms in dynamic environments. Animal studies have highlighted orbital and medial prefrontal cortex and amygdala as mediators of operant extinction. Yet little is known about the neural mediators of operant extinction learning in humans. Using a novel fMRI paradigm, we report dissociable functional responses in distinct regions of medial orbitofrontal cortex (mOFC) during successful appetitive and aversive based operant extinction. During successful operant extinction, increased activity was observed in frontopolar OFC, while decreased activity was observed in caudal mOFC and rostral anterior cingulate cortex (rACC) relative to both (i) successful control trials where the reinforcement associated with the stimulus does not change; and (ii) successful acquisition trials during initial learning of the stimulus-reinforcement associations. Functional connectivity analysis demonstrated inverse connectivity between frontopolar OFC and both rACC and the amygdala. These data support animal models suggesting the importance of mOFC-amygdala interaction during operant extinction and expand our knowledge of the neural systems in humans. These findings suggest that in humans, frontopolar OFC modulates activity in caudal mOFC, rACC and amygdala during successful operant extinction learning.
authors.affiliation: Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Elizabeth.Finger@lhsc.on.ca
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Finger
authors.forename: Derek G V
authors.initials: DG
authors.lastname: Mitchell
authors.forename: Matthew
authors.initials: M
authors.lastname: Jones
authors.forename: R J R
authors.initials: RJ
authors.lastname: Blair
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D003216:Conditioning, Operant / Q000502:physiology*; D004193:Discrimination Learning / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male
references.citation: Neuroimage. 2006 Feb 1;29(3):721-33
references.pmid: 16249100
references.citation: J Neurophysiol. 2000 Apr;83(4):1864-76
references.pmid: 10758098
references.citation: J Neurosci. 2002 Jun 1;22(11):4563-7
references.pmid: 12040063
references.citation: Nat Neurosci. 2004 Oct;7(10):1144-52
references.pmid: 15361879
references.citation: J Neurosci. 2000 Aug 15;20(16):6225-31
references.pmid: 10934272
references.citation: J Comp Neurol. 1989 Aug 15;286(3):353-75
references.pmid: 2768563
references.citation: J Neurosci. 2004 Aug 25;24(34):7540-8
references.pmid: 15329401
references.citation: J Comp Neurol. 1984 Dec 20;230(4):465-96
references.pmid: 6520247
references.citation: J Neurosci. 2007 Apr 11;27(15):4019-26
references.pmid: 17428979
references.citation: Neuroimage. 2007 Mar;35(1):430-40
references.pmid: 17239620
references.citation: J Neurosci. 1999 Aug 1;19(15):6610-4
references.pmid: 10414988
references.citation: Neuron. 2003 May 22;38(4):625-36
references.pmid: 12765613
references.citation: Neuroimage. 2007 Feb 15;34(4):1754-65
references.pmid: 17188518
references.citation: Neuron. 1998 May;20(5):937-45
references.pmid: 9620698
references.citation: Neuron. 2005 Sep 1;47(5):633-6
references.pmid: 16129393
references.citation: Neuroreport. 2002 May 7;13(6):885-90
references.pmid: 11997707
references.citation: J Neurophysiol. 1995 Aug;74(2):751-62
references.pmid: 7472379
references.citation: J Neurosci. 2003 Sep 24;23(25):8771-80
references.pmid: 14507977
references.citation: Neuron. 2005 Apr 21;46(2):321-31
references.pmid: 15848809
references.citation: Ann N Y Acad Sci. 2007 Dec;1121:355-75
references.pmid: 17698989
references.citation: Neuroimage. 2006 Feb 15;29(4):1161-72
references.pmid: 16387514
references.citation: Ann N Y Acad Sci. 2007 Dec;1121:320-35
references.pmid: 17698988
references.citation: Neuroreport. 2005 Nov 28;16(17):1909-12
references.pmid: 16272877
references.citation: Cereb Cortex. 2007 Mar;17(3):643-52
references.pmid: 16699083
references.citation: J Neurosci. 2005 May 4;25(18):4626-32
references.pmid: 15872110
references.citation: Neuroimage. 2008 Apr 1;40(2):859-868
references.pmid: 18234519
references.citation: Learn Mem. 2003 Mar-Apr;10(2):129-40
references.pmid: 12663751
references.citation: Neuron. 2004 Sep 16;43(6):897-905
references.pmid: 15363399
references.citation: Biol Psychiatry. 2003 Mar 15;53(6):502-10
references.pmid: 12644355
references.citation: Neuron. 2003 Aug 28;39(5):855-67
references.pmid: 12948451
references.citation: J Neurosci. 2006 Nov 1;26(44):11379-86
references.pmid: 17079666
references.citation: J Comp Neurol. 1987 Feb 1;256(1):88-103
references.pmid: 3819040
references.citation: J Neurosci. 1999 Mar 1;19(5):1876-84
references.pmid: 10024371
references.citation: J Neurosci. 2003 Aug 27;23(21):7931-9
references.pmid: 12944524
references.citation: Behav Neurosci. 2005 Feb;119(1):317-22
references.pmid: 15727536
references.citation: Brain. 2004 May;127(Pt 5):1108-26
references.pmid: 14985269
references.citation: NMR Biomed. 1997 Jun-Aug;10(4-5):171-8
references.pmid: 9430344
references.citation: Biol Psychiatry. 2007 Sep 1;62(5):446-54
references.pmid: 17217927
references.citation: Nature. 2002 Nov 7;420(6911):70-4
references.pmid: 12422216
references.citation: Eur J Neurosci. 2005 Nov;22(9):2341-6
references.pmid: 16262672
references.citation: Ann N Y Acad Sci. 2007 Dec;1121:254-72
references.pmid: 17872386
references.citation: Nat Neurosci. 1998 Jun;1(2):155-9
references.pmid: 10195132
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10706-11
references.pmid: 16024728
references.citation: Nat Rev Neurosci. 2002 Jul;3(7):563-73
references.pmid: 12094212
references.citation: J Abnorm Psychol. 1986 Aug;95(3):252-6
references.pmid: 3745647
references.citation: J Neurosci. 2000 Jul 1;20(13):5179-89
references.pmid: 10864975
references.citation: J Abnorm Psychol. 1957 Jul;55(1):6-10
references.pmid: 13462652
references.citation: J Neurosci. 2005 Aug 24;25(34):7763-70
references.pmid: 16120777
references.citation: J Neurosci. 2007 Jan 31;27(5):1054-62
references.pmid: 17267559