title: Reconciling the roles of orbitofrontal cortex in reversal learning and the encoding of outcome expectancies.
abstract: Damage to orbitofrontal cortex (OFC) has long been associated with decision-making deficits. Such deficits are epitomized by impairments in reversal learning. Historically, reversal learning deficits have been linked to a response inhibition function or to the rapid reversal of associative encoding in OFC neurons. However here we will suggest that OFC supports reversal learning not because its encoding is particularly flexible-indeed it actually is not-but rather because output from OFC is critical for flexible associative encoding downstream in basolateral amygdala (ABL). Consistent with this argument, we will show that reversal performance is actually inversely related to the flexibility of associative encoding in OFC (i.e., the better the reversal performance, the less flexible the encoding). Further, we will demonstrate that associative correlates in ABL are more flexible during reversal learning than in OFC, become less flexible after damage to OFC, and are required for the expression of the reversal deficit caused by OFC lesions. We will propose that OFC facilitates associative flexibility in downstream regions, such as ABL, for the same reason that it is critical for outcome-guided behavior in a variety of setting-namely that processing in OFC signals the value of expected outcomes. In addition to their role in guiding behavior, these outcome expectancies permit the rapid recognition of unexpected outcomes, thereby driving new learning.
authors: Department of AAnatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. schoenbg@schoenbaumlab.org
authors: Geoffrey
authors: G
authors: Schoenbaum
authors: Michael P
authors: MP
authors: Saddoris
authors: Thomas A
authors: TA
authors: Stalnaker
mesh_terms: D000818:Animals; D005625:Frontal Lobe / Q000502:physiology*; D006801:Humans; D009488:Neurosciences; D012193:Reversal Learning / Q000502:physiology*
references: J Neurosci. 1999 Aug 1;19(15):6610-4
references: 10414988
references: Eur J Neurosci. 2004 Feb;19(4):1046-54
references: 15009152
references: Exp Neurol. 1964 Jun;9:452-62
references: 14188532
references: Neurobiol Learn Mem. 2005 Mar;83(2):125-33
references: 15721796
references: Neuron. 2005 Apr 21;46(2):321-31
references: 15848809
references: J Neurosci. 2005 May 4;25(18):4626-32
references: 15872110
references: J Neurophysiol. 2005 Oct;94(4):2457-71
references: 15958600
references: J Neurophysiol. 2006 Jan;95(1):301-10
references: 16192329
references: Trends Neurosci. 2006 Feb;29(2):116-24
references: 16406092
references: Nature. 2006 Feb 16;439(7078):865-70
references: 16482160
references: J Neurophysiol. 2006 Mar;95(3):1509-17
references: 16338994
references: Psychol Rev. 2006 Apr;113(2):300-26
references: 16637763
references: Nature. 2006 May 11;441(7090):223-6
references: 16633341
references: Neuron. 2006 Aug 17;51(4):495-507
references: 16908414
references: Neuron. 2006 Aug 17;51(4):509-20
references: 16908415
references: J Neurosci. 2006 Nov 1;26(44):11379-86
references: 17079666
references: Eur J Neurosci. 2006 Nov;24(9):2643-53
references: 17100852
references: Cereb Cortex. 2007 May;17(5):1154-9
references: 16774961
references: Neurobiol Learn Mem. 1999 Nov;72(3):244-51
references: 10536101
references: Nat Neurosci. 2000 Jan;3(1):74-9
references: 10607398
references: Cereb Cortex. 2000 Mar;10(3):263-71
references: 10731221
references: J Neurophysiol. 2000 Apr;83(4):1864-76
references: 10758098
references: Learn Mem. 2001 May-Jun;8(3):148-55
references: 11390634
references: Neuron. 2002 Feb 28;33(5):815-26
references: 11879657
references: Neuroreport. 2002 May 7;13(6):885-90
references: 11997707
references: Nat Rev Neurosci. 2002 Jul;3(7):563-73
references: 12094212
references: J Neurosci. 2002 Oct 1;22(19):8748-53
references: 12351750
references: Science. 2004 Apr 9;304(5668):307-10
references: 15073380
references: J Neurosci. 2004 Aug 25;24(34):7540-8
references: 15329401
references: Exp Neurol. 1972 Aug;36(2):362-77
references: 4626489
references: J Comp Neurol. 1977 Apr 15;172(4):687-722
references: 838895
references: Exp Brain Res. 1983;49(1):93-115
references: 6861938
references: J Neurosci. 1990 Apr;10(4):1062-9
references: 2329367
references: J Comp Neurol. 1990 Aug 1;298(1):40-9
references: 1698828
references: J Neurol Neurosurg Psychiatry. 1994 Dec;57(12):1518-24
references: 7798983
references: Neuron. 1995 Nov;15(5):1029-39
references: 7576647
references: Nature. 1996 Mar 7;380(6569):69-72
references: 8598908
references: Neuron. 2007 Apr 5;54(1):51-8
references: 17408577
references: J Neurosci. 2007 May 2;27(18):4819-25
references: 17475789
references: Nat Neurosci. 2007 Aug;10(8):949-51
references: 17603478
references: J Neurophysiol. 1996 Apr;75(4):1659-72
references: 8727404
references: J Neurophysiol. 1996 May;75(5):1970-81
references: 8734596
references: Neuropsychologia. 1997 Jul;35(7):999-1015
references: 9226661
references: Neuron. 1997 Sep;19(3):613-24
references: 9331352
references: J Comp Neurol. 1998 Oct 5;399(4):440-68
references: 9741477
references: J Neurosci. 1999 Mar 1;19(5):1876-84
references: 10024371
references: Nat Neurosci. 1998 Jun;1(2):155-9
references: 10195132
references: Nat Neurosci. 1999 Jan;2(1):11-2
references: 10195173
references: Nature. 1999 Apr 22;398(6729):704-8
references: 10227292
references: Learn Mem. 2003 Mar-Apr;10(2):129-40
references: 12663751
references: Eur J Neurosci. 2003 Apr;17(8):1680-94
references: 12752386
references: Behav Brain Res. 2003 Jul 14;143(1):49-56
references: 12842295
references: Science. 2003 Aug 22;301(5636):1104-7
references: 12934011
references: Neuron. 2003 Aug 28;39(5):855-67
references: 12948451
references: J Neurosci. 2003 Sep 24;23(25):8771-80
references: 14507977
references: Behav Brain Res. 2003 Nov 30;146(1-2):97-103
references: 14643463
references: J Neurosci. 2003 Dec 3;23(35):11078-84
references: 14657165
references: J Comp Physiol Psychol. 1956 Aug;49(4):381-91
references: 13345917