title: Improving prefrontal cortex function in schizophrenia through focused training of cognitive control.
abstract: Previous research has shown that individuals with schizophrenia show deficits in cognitive control functions thought to depend on the lateral prefrontal cortex (PFC), and its interactions with related regions. The current study explored the effects of instructed strategy training on improving cognitive control functioning in patients with schizophrenia. Event-related fMRI was used to test whether effects of such training were associated with changes in brain activity dynamics during task performance. Patients with schizophrenia (N = 22) performed the AX-CPT cognitive control task in two-sessions, with the first occurring pre-training and second following strategy training. The training protocol emphasized direct encoding of contextual cues and updating response selection goals in accordance with cue information. A matched group of healthy controls (N = 14) underwent the same protocol but were only scanned in the pre-training session. In the pre-training session, patients exhibited behavioral evidence of impaired utilization of contextual cue information, along with reduced cue-related activity - but increased activation during probe and response periods - in a network of regions associated with cognitive control, centered on the lateral PFC. Following training, this pattern of activation dynamics significantly shifted, normalizing towards the pattern observed in controls. These activation effects were associated with both clinical symptoms and behavioral performance improvements. The results suggest that focused strategy training may facilitate cognitive task performance in patients with schizophrenia by changing the dynamics of activity within critical control-related brain regions.
authors.affiliation: Departments of Psychology, Washington University St. Louis, MO, USA.
authors.forename: Bethany G
authors.initials: BG
authors.lastname: Edwards
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Barch
authors.forename: Todd S
authors.initials: TS
authors.lastname: Braver
references.citation: Am J Psychiatry. 2009 Sep;166(9):1055-62
references.pmid: 19570929
references.citation: Biol Psychiatry. 2004 Dec 15;56(12):951-6
references.pmid: 15601605
references.citation: Br J Psychiatry. 1987 Aug;151:145-51
references.pmid: 3690102
references.citation: Br J Psychiatry. 2007 May;190:421-7
references.pmid: 17470957
references.citation: Br J Psychiatry. 2002 Aug;181:144-52
references.pmid: 12151286
references.citation: Neuropsychologia. 1971 Mar;9(1):97-113
references.pmid: 5146491
references.citation: Neuropsychology. 2006 Sep;20(5):497-510
references.pmid: 16938013
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7351-6
references.pmid: 19380750
references.citation: J Abnorm Psychol. 2003 Feb;112(1):132-43
references.pmid: 12653421
references.citation: Trends Cogn Sci. 2005 Jul;9(7):314-6
references.pmid: 15927520
references.citation: Am J Psychiatry. 2009 Jul;166(7):805-11
references.pmid: 19448187
references.citation: J Comput Assist Tomogr. 1992 Jul-Aug;16(4):620-33
references.pmid: 1629424
references.citation: Am J Psychiatry. 2005 Mar;162(3):475-84
references.pmid: 15741464
references.citation: Curr Opin Psychiatry. 2009 Mar;22(2):161-7
references.pmid: 19553870
references.citation: Cereb Cortex. 2008 May;18(5):1010-28
references.pmid: 17804479
references.citation: Am J Psychiatr Rehabil. 2008 Apr;11(2):144-163
references.pmid: 19198664
references.citation: Arch Gen Psychiatry. 1996 Dec;53(12):1105-12
references.pmid: 8956676
references.citation: Psychol Aging. 2006 Sep;21(3):499-509
references.pmid: 16953712
references.citation: Schizophr Bull. 1985;11(3):380-9
references.pmid: 2863870
references.citation: Cereb Cortex. 2000 Nov;10(11):1078-92
references.pmid: 11053229
references.citation: Neuropsychopharmacology. 2010 Aug;35(9):1850-9
references.pmid: 20428109
references.citation: Am J Psychiatry. 1997 Mar;154(3):371-7
references.pmid: 9054785
references.citation: Science. 2000 Jun 9;288(5472):1835-8
references.pmid: 10846167
references.citation: J Comput Assist Tomogr. 1998 Jan-Feb;22(1):139-52
references.pmid: 9448779
references.citation: Schizophr Bull. 1997;23(3):437-58
references.pmid: 9327508
references.citation: Schizophr Bull. 1983;9(3):368-76
references.pmid: 6622994
references.citation: Neuropsychologia. 1997 Oct;35(10):1373-80
references.pmid: 9347483
references.citation: Cogn Affect Behav Neurosci. 2003 Dec;3(4):255-74
references.pmid: 15040547
references.citation: Philos Trans R Soc Lond B Biol Sci. 1996 Oct 29;351(1346):1515-27
references.pmid: 8941963
references.citation: Psychiatry Res. 2003 Feb 15;122(2):69-87
references.pmid: 12714172
references.citation: Schizophr Bull. 2010 Jul;36(4):869-79
references.pmid: 19269924
references.citation: Biol Psychiatry. 1999 Aug 1;46(3):312-28
references.pmid: 10435197
references.citation: Schizophr Res. 2003 Apr 1;60(2-3):285-98
references.pmid: 12591590
references.citation: Neuroimage. 2008 Oct 1;42(4):1577-86
references.pmid: 18634891
references.citation: Schizophr Res. 2005 Jun 15;75(2-3):183-92
references.pmid: 15885509
references.citation: Compr Psychiatry. 1993 Jul-Aug;34(4):221-6
references.pmid: 8348799
references.citation: Schizophr Res. 1995 Nov;17(3):257-65
references.pmid: 8664205
references.citation: Cogn Affect Behav Neurosci. 2008 Sep;8(3):239-53
references.pmid: 18814461
references.citation: J Abnorm Psychol. 1999 Feb;108(1):120-33
references.pmid: 10066998
references.citation: J Abnorm Psychol. 2003 Nov;112(4):689-97
references.pmid: 14674880
references.citation: Psychol Rev. 1992 Jan;99(1):45-77
references.pmid: 1546118
references.citation: Schizophr Bull. 2003;29(2):359-82
references.pmid: 14552510
references.citation: Schizophr Bull. 1999;25(4):749-62
references.pmid: 10667745
references.citation: Psychol Bull. 2007 Sep;133(5):833-58
references.pmid: 17723032
references.citation: Arch Gen Psychiatry. 1982 Jul;39(7):789-94
references.pmid: 7165478
references.citation: Am J Psychiatry. 2008 Aug;165(8):1006-14
references.pmid: 18519527
references.citation: Hum Brain Mapp. 2005 May;25(1):46-59
references.pmid: 15846822
references.citation: Hum Brain Mapp. 2005 May;25(1):60-9
references.pmid: 15846819
references.citation: Schizophr Res. 2005 Jul 15;76(2-3):199-206
references.pmid: 15949653
references.citation: Arch Gen Psychiatry. 2000 Dec;57(12):1131-7
references.pmid: 11115326
references.citation: Arch Gen Psychiatry. 2009 Aug;66(8):811-22
references.pmid: 19652121
references.citation: Biol Psychiatry. 2003 Jan 1;53(1):25-38
references.pmid: 12513942
references.citation: Arch Gen Psychiatry. 2001 Mar;58(3):280-8
references.pmid: 11231835
references.citation: Schizophr Res. 2009 Mar;108(1-3):143-50
references.pmid: 19196494
references.citation: Arch Gen Psychiatry. 2003 Jan;60(1):57-65
references.pmid: 12511173
references.citation: Magn Reson Med. 1996 Mar;35(3):346-55
references.pmid: 8699946