title: Dynamic coding for cognitive control in prefrontal cortex.
abstract: Cognitive flexibility is fundamental to adaptive intelligent behavior. Prefrontal cortex has long been associated with flexible cognitive function, but the neurophysiological principles that enable prefrontal cells to adapt their response properties according to context-dependent rules remain poorly understood. Here, we use time-resolved population-level neural pattern analyses to explore how context is encoded and maintained in primate prefrontal cortex and used in flexible decision making. We show that an instruction cue triggers a rapid series of state transitions before settling into a stable low-activity state. The postcue state is differentially tuned according to the current task-relevant rule. During decision making, the response to a choice stimulus is characterized by an initial stimulus-specific population response but evolves to different final decision-related states depending on the current rule. These results demonstrate how neural tuning profiles in prefrontal cortex adapt to accommodate changes in behavioral context. Highly flexible tuning could be mediated via short-term synaptic plasticity.
authors.affiliation: Oxford Centre for Human Brain Activity, University of Oxford, Oxford OX3 7JX, UK. mark.stokes@ohba.ox.ac.uk
authors.forename: Mark G
authors.initials: MG
authors.lastname: Stokes
authors.forename: Makoto
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Natasha
authors.initials: N
authors.lastname: Sigala
authors.forename: Hamed
authors.initials: H
authors.lastname: Nili
authors.forename: David
authors.initials: D
authors.lastname: Gaffan
authors.forename: John
authors.initials: J
authors.lastname: Duncan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002755:Choice Behavior / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003463:Cues; D008253:Macaca mulatta; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D017711:Nonlinear Dynamics; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D011930:Reaction Time; D013997:Time Factors
references.citation: J Neurosci. 1999 Jul 1;19(13):5493-505
references.pmid: 10377358
references.citation: Neuron. 2010 Nov 4;68(3):362-85
references.pmid: 21040841
references.citation: Neuroimage. 2004 Aug;22(4):1679-93
references.pmid: 15275924
references.citation: J Neurosci. 2007 Oct 17;27(42):11306-14
references.pmid: 17942725
references.citation: Science. 2008 Mar 14;319(5869):1543-6
references.pmid: 18339943
references.citation: Neuron. 2012 Nov 21;76(4):838-846
references.pmid: 23177967
references.citation: Annu Rev Neurosci. 2009;32:209-24
references.pmid: 19400723
references.citation: Nat Neurosci. 2008 Jul;11(7):823-33
references.pmid: 18516033
references.citation: PLoS Biol. 2009 Dec;7(12):e1000260
references.pmid: 20027205
references.citation: J Cogn Neurosci. 2012 Jan;24(1):61-79
references.pmid: 21955164
references.citation: J Cogn Neurosci. 2011 Nov;23(11):3355-65
references.pmid: 21452948
references.citation: Cereb Cortex. 2009 Nov;19(11):2522-34
references.pmid: 19193714
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11969-74
references.pmid: 18689686
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11252-5
references.pmid: 21690375
references.citation: Nat Rev Neurosci. 2001 Nov;2(11):820-9
references.pmid: 11715058
references.citation: Trends Neurosci. 2001 Aug;24(8):455-63
references.pmid: 11476885
references.citation: J Neurosci. 2011 Oct 12;31(41):14592-9
references.pmid: 21994375
references.citation: Nat Rev Neurosci. 2003 Oct;4(10):829-39
references.pmid: 14523382
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3228-33
references.pmid: 20133762
references.citation: J Neurosci. 1996 Aug 15;16(16):5154-67
references.pmid: 8756444
references.citation: J Neurosci. 2010 Jan 20;30(3):916-29
references.pmid: 20089900
references.citation: Annu Rev Neurosci. 1995;18:193-222
references.pmid: 7605061
references.citation: Bull Math Biol. 1990;52(1-2):99-115; discussion 73-97
references.pmid: 2185863
references.citation: Exp Brain Res. 1999 Jun;126(3):315-35
references.pmid: 10382618
references.citation: Annu Rev Physiol. 2002;64:355-405
references.pmid: 11826273
references.citation: J Neurophysiol. 2008 Sep;100(3):1407-19
references.pmid: 18562555
references.citation: J Neurosci. 2010 Jul 14;30(28):9424-30
references.pmid: 20631171
references.citation: Nature. 2001 Jun 21;411(6840):953-6
references.pmid: 11418860
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4651-6
references.pmid: 22392988
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19569-74
references.pmid: 19887644
references.citation: Science. 2001 Jan 12;291(5502):312-6
references.pmid: 11209083
references.citation: J Neurosci. 2010 Sep 1;30(35):11640-53
references.pmid: 20810885
references.citation: Nat Rev Neurosci. 2009 Feb;10(2):113-25
references.pmid: 19145235
references.citation: J Neurophysiol. 1998 Dec;80(6):2918-40
references.pmid: 9862896
references.citation: Nat Rev Neurosci. 2011 Feb;12(2):105-18
references.pmid: 21248789
references.citation: Annu Rev Neurosci. 2001;24:167-202
references.pmid: 11283309
references.citation: Cereb Cortex. 2004 Dec;14(12):1328-39
references.pmid: 15166104
references.citation: J Cogn Neurosci. 2010 Nov;22(11):2530-40
references.pmid: 19925206
references.citation: PLoS Comput Biol. 2008 May 16;4(5):e1000073
references.pmid: 18464917
references.citation: J Cogn Neurosci. 2010 Apr;22(4):751-60
references.pmid: 19302000
references.citation: Science. 2005 Feb 18;307(5712):1121-4
references.pmid: 15718474
references.citation: J Neurosci. 2010 Jun 23;30(25):8519-28
references.pmid: 20573899
references.citation: Nat Rev Neurosci. 2000 Oct;1(1):59-65
references.pmid: 11252769
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7545-9
references.pmid: 20360555
references.citation: Brain Res. 1986 Sep 10;382(1):1-14
references.pmid: 3768666
references.citation: J Neurosci. 2007 Nov 7;27(45):12321-30
references.pmid: 17989296