title: Neural circuitry underlying the regulation of conditioned fear and its relation to extinction.
abstract: Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction.
authors.affiliation: Department of Psychology, Rutgers University, Newark, NJ 07102, USA.
authors.forename: Mauricio R
authors.initials: MR
authors.lastname: Delgado
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Nearing
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Ledoux
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Phelps
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000098:blood supply; D010100:Oxygen / Q000097:blood
chemical_list: D010100:Oxygen
references.citation: J Cogn Neurosci. 2002 Nov 15;14(8):1215-29
references.pmid: 12495527
references.citation: J Cogn Neurosci. 2007 May;19(5):776-98
references.pmid: 17488204
references.citation: Biol Psychiatry. 2005 Feb 1;57(3):210-9
references.pmid: 15691521
references.citation: Neuron. 2005 Oct 20;48(2):175-87
references.pmid: 16242399
references.citation: Trends Cogn Sci. 2005 May;9(5):242-9
references.pmid: 15866151
references.citation: Hum Brain Mapp. 2007 May;28(5):409-23
references.pmid: 17133391
references.citation: Learn Mem. 2002 Nov-Dec;9(6):402-7
references.pmid: 12464700
references.citation: J Psychopharmacol. 1997;11(2):99-106
references.pmid: 9208373
references.citation: J Neurosci. 2006 Apr 19;26(16):4415-25
references.pmid: 16624961
references.citation: Neuroscience. 1996 Mar;71(1):55-75
references.pmid: 8834392
references.citation: J Cogn Neurosci. 2002 Aug 15;14(6):913-21
references.pmid: 12191458
references.citation: Am J Psychiatry. 2001 Dec;158(12):1953-5
references.pmid: 11729007
references.citation: Biol Psychiatry. 2007 Sep 1;62(5):446-54
references.pmid: 17217927
references.citation: Neuroimage. 2006 Mar;30(1):313-24
references.pmid: 16249098
references.citation: Nature. 1999 Nov 18;402(6759):294-6
references.pmid: 10580500
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10706-11
references.pmid: 16024728
references.citation: Psychopharmacology (Berl). 2005 Aug;180(4):774-80
references.pmid: 15864557
references.citation: Neuron. 2003 Dec 18;40(6):1251-7
references.pmid: 14687557
references.citation: Cogn Affect Behav Neurosci. 2004 Sep;4(3):317-25
references.pmid: 15535167
references.citation: Nat Neurosci. 2007 Sep;10(9):1095-102
references.pmid: 17726475
references.citation: J Cogn Neurosci. 2004 Dec;16(10):1746-72
references.pmid: 15701226
references.citation: Neuron. 1998 May;20(5):937-45
references.pmid: 9620698
references.citation: Biol Psychiatry. 2006 Aug 15;60(4):369-75
references.pmid: 16919524
references.citation: Biol Psychiatry. 2006 Aug 15;60(4):376-82
references.pmid: 16919525
references.citation: J Neurosci. 1995 Oct;15(10):6846-55
references.pmid: 7472442
references.citation: Brain. 2000 Jul;123 ( Pt 7):1293-326
references.pmid: 10869045
references.citation: J Comp Neurol. 2002 Sep 30;451(4):301-23
references.pmid: 12210126
references.citation: Biol Psychol. 2006 Jul;73(1):39-48
references.pmid: 16472906
references.citation: Behav Neurosci. 1995 Aug;109(4):681-8
references.pmid: 7576212
references.citation: J Cogn Neurosci. 2005 Jun;17(6):874-83
references.pmid: 15969906
references.citation: Curr Opin Neurobiol. 2000 Apr;10(2):219-23
references.pmid: 10753800
references.citation: Neuron. 1998 May;20(5):947-57
references.pmid: 9620699
references.citation: Neuroimage. 2004 Oct;23(2):483-99
references.pmid: 15488398
references.citation: Biol Psychiatry. 2002 Jan 1;51(1):11-7
references.pmid: 11801227
references.citation: J Cogn Neurosci. 2001 Aug 15;13(6):721-9
references.pmid: 11564317
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: Pain. 2005 Apr;114(3):347-357
references.pmid: 15777860
references.citation: Science. 1999 Mar 12;283(5408):1657-61
references.pmid: 10073923
references.citation: J Neurosci. 2001 Sep 15;21(18):RC165
references.pmid: 11549754
references.citation: Nature. 2002 Nov 7;420(6911):70-4
references.pmid: 12422216
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1680-5
references.pmid: 9990084
references.citation: Nat Neurosci. 2001 Apr;4(4):437-41
references.pmid: 11276236
references.citation: Neuroreport. 2003 Dec 19;14(18):2317-22
references.pmid: 14663183
references.citation: J Cogn Neurosci. 2007 Jun;19(6):993-1003
references.pmid: 17536969
references.citation: Brain Res Bull. 2000 Jul 15;52(5):319-30
references.pmid: 10922509