title: Dopaminergic modulation of emotional conflict in Parkinson's disease.
abstract: Neuropsychiatric fluctuations in Parkinson's disease (PD) are frequent and disabling. One way to investigate them is to assess the ability to inhibit distractive emotional information by a modified emotional Stroop (ES) task. We compared non-depressed, non-demented PD patients with healthy controls. During an acute levodopa challenge, patients performed a modified ES task during functional MRI and a neuropsychological assessment including Visual Analog Mood (VAMS) and Apathy scales. Ten patients and 12 controls completed the study. The VAMS scores were significantly improved by the acute intake of levodopa (p = 0.02), as was the apathy score (p = 0.03). Negative ES task (i.e. fearful facial expressions with the words "happy" or "fear" written across them), induced a lengthening of the mean reaction time during the incongruent trials compared with the congruent trials in controls (relative difference = 2.7%, p < 0.001) and in ON patients (relative difference = 5.9%, p < 0.001), but not in OFF patients (relative difference = 1.7%, p = 0.28). Controls and ON patients displayed greater activation than OFF patients within the right pregenual anterior cingulate cortex (pACC), an area specifically involved in emotional conflict resolution (p < 0.001 and p < 0.008 respectively, k > 5 uncorrected). No difference in the activation of the pACC was found between controls and ON patients, suggesting a normalization of the activation following levodopa administration. These results suggest that emotional conflict processes could be dopamine-dependent. Pregenual ACC hypoactivation could be directly due to the degeneration of dopaminergic mesocorticolimbic pathway. Our results propose that neuropsychiatric fluctuations in PD patients could be partially explained by pACC hypoactivation and that adjustments of dopaminergic medication might be helpful for their treatment.
authors.affiliation: Department of Neurology, Geneva University Hospital Geneva, Switzerland ; Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fleury
authors.affiliation: Psychology and Neurocognition Laboratory, UMR CNRS 5105, Pierre Mendès-France University Grenoble, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cousin
authors.affiliation: Unit 610, Federation of Nervous System Disease, National Institute of Health and Medical Research (INSERM), Pitié-Salpêtrière Hospital Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Czernecki
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Lhommée
authors.affiliation: Department of Health and Community Medicine, Geneva University Hospital Geneva, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Poncet
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France ; Joseph Fourier University - Grenoble I Grenoble, France ; Grenoble Neuroscience Institute, INSERM-UJF-CEA-CHU U836 Grenoble, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraix
authors.affiliation: IRMaGe, Université Grenoble Alpes Grenoble, France ; US 017, INSERM Grenoble, France ; UMS 3552, CNRS Grenoble, France.
authors.forename: Irène
authors.initials: I
authors.lastname: Troprès
authors.affiliation: Department of Neurology, Geneva University Hospital Geneva, Switzerland ; Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.affiliation: US 017, INSERM Grenoble, France ; UMS 3552, CNRS Grenoble, France ; Neuroradiology and MRI, Grenoble University Hospital Grenoble, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krainik
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital Grenoble, France ; Joseph Fourier University - Grenoble I Grenoble, France ; Grenoble Neuroscience Institute, INSERM-UJF-CEA-CHU U836 Grenoble, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
keywords: Parkinson's disease; cingulate cortex; dopamine; emotional stroop; non-motor fluctuations
references.citation: Nat Rev Neurosci. 2008 Mar;9(3):182-94
references.pmid: 18270514
references.citation: Acta Psychiatr Scand Suppl. 2005;(427):14-21
references.pmid: 15877719
references.citation: Biol Psychiatry. 2001 Dec 15;50(12):932-42
references.pmid: 11750889
references.citation: Brain. 2010 Apr;133(Pt 4):1111-27
references.pmid: 20237128
references.citation: Curr Opin Neurobiol. 2013 Apr;23(2):229-38
references.pmid: 23267662
references.citation: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references.pmid: 1564476
references.citation: Neuropsychiatr Dis Treat. 2005 Sep;1(3):261-8
references.pmid: 18568104
references.citation: Mov Disord. 2012 Feb;27(2):186-99
references.pmid: 22162004
references.citation: Neurology. 2002 Aug 13;59(3):408-13
references.pmid: 12177375
references.citation: Science. 2004 Feb 13;303(5660):1023-6
references.pmid: 14963333
references.citation: Neurology. 1982 May;32(5):514-39
references.pmid: 7200209
references.citation: Soc Neurosci. 2011;6(5-6):653-62
references.pmid: 21400357
references.citation: J Neuropsychiatry Clin Neurosci. 1992 Spring;4(2):134-9
references.pmid: 1627973
references.citation: Mov Disord. 2010 Nov 15;25(15):2649-53
references.pmid: 21069833
references.citation: Ann Neurol. 1997 Sep;42(3):283-91
references.pmid: 9307248
references.citation: Brain. 2013 May;136(Pt 5):1568-77
references.pmid: 23543483
references.citation: Neuron. 2006 Sep 21;51(6):871-82
references.pmid: 16982430
references.citation: Ann Neurol. 1992 Dec;32(6):749-57
references.pmid: 1471865
references.citation: Mov Disord. 2008 Jan 30;23(2):183-9; quiz 313
references.pmid: 17987654
references.citation: J Comp Neurol. 1989 Jan 8;279(2):249-71
references.pmid: 2563268
references.citation: Science. 1997 Nov 28;278(5343):1548-9
references.pmid: 9411769
references.citation: Annu Rev Psychol. 2010;61:27-48, C1-8
references.pmid: 19958178
references.citation: Cereb Cortex. 2008 Jun;18(6):1374-83
references.pmid: 17928332
references.citation: Brain. 2010 Jan;133(Pt 1):225-33
references.pmid: 19995871
references.citation: Brain Res Bull. 2005 Nov 15;67(5):403-12
references.pmid: 16216687
references.citation: J Anxiety Disord. 2001 May-Jun;15(3):147-59
references.pmid: 11442135
references.citation: Neurology. 1995 Sep;45(9):1757-60
references.pmid: 7675241
references.citation: Nat Rev Neurosci. 2008 Feb;9(2):148-58
references.pmid: 18209732
references.citation: Neuropsychologia. 2002;40(13):2257-67
references.pmid: 12417456
references.citation: Trends Cogn Sci. 2004 Apr;8(4):170-7
references.pmid: 15050513
references.citation: J Neurol Neurosurg Psychiatry. 2014 Oct;85(10):1153-8
references.pmid: 24403280
references.citation: Lancet Neurol. 2014 Mar;13(3):287-305
references.pmid: 24556007
references.citation: J Nerv Ment Dis. 2002 Jun;190(6):407-10
references.pmid: 12080213
references.citation: Cereb Cortex. 2008 Jun;18(6):1475-84
references.pmid: 17940084
references.citation: Neurology. 2000 Dec 12;55(11):1621-6
references.pmid: 11113214
references.citation: Parkinsonism Relat Disord. 2012 Jun;18(5):553-6
references.pmid: 22405839
references.citation: Curr Opin Neurol. 2011 Aug;24(4):324-30
references.pmid: 21725242
references.citation: J Neuropsychiatry Clin Neurosci. 1991 Summer;3(3):243-54
references.pmid: 1821241
references.citation: Brain. 2004 Jan;127(Pt 1):4-20
references.pmid: 14607789
references.citation: Neuroscience. 2008 Jul 31;155(1):203-20
references.pmid: 18562124
references.citation: Mov Disord. 2008;23 Suppl 3:S509-14
references.pmid: 18781677
references.citation: Psychol Bull. 1996 Jul;120(1):3-24
references.pmid: 8711015
references.citation: Lancet Neurol. 2009 May;8(5):464-74
references.pmid: 19375664
references.citation: Neuroimage. 2001 May;13(5):903-19
references.pmid: 11304086
references.citation: J Neurol Sci. 2006 Oct 25;248(1-2):151-7
references.pmid: 16797028
references.citation: Addiction. 2006 Sep;101(9):1306-12
references.pmid: 16911730
references.citation: Neurology. 1993 Aug;43(8):1459-64
references.pmid: 8350996
references.citation: Neuropharmacology. 1971 Mar;10(21):181-91
references.pmid: 5093959
references.citation: Brain Res. 1987 May;434(2):117-65
references.pmid: 3107759
references.citation: Mov Disord. 2010 May 15;25(7):838-45
references.pmid: 20461800
references.citation: Nat Neurosci. 2004 Feb;7(2):184-8
references.pmid: 14703573
references.citation: Science. 2002 May 31;296(5573):1610-1 author reply 1610-1
references.pmid: 12041532
references.citation: Neurology. 1994 May;44(5):964-6
references.pmid: 8190307
references.citation: Biol Psychiatry. 1998 Dec 15;44(12):1219-28
references.pmid: 9861465
references.citation: Rev Neurol (Paris). 2009 Nov;165(11):845-56
references.pmid: 19683776
references.citation: Nature. 1999 Nov 11;402(6758):179-81
references.pmid: 10647008
references.citation: Brain. 1995 Feb;118 ( Pt 1):279-306
references.pmid: 7895011
references.citation: Psychosomatics. 1989 Winter;30(1):94-9
references.pmid: 2913602
references.citation: Brain. 2012 May;135(Pt 5):1463-77
references.pmid: 22508959
references.citation: Mov Disord. 1995 May;10(3):329-32
references.pmid: 7651451
references.citation: Neurology. 2013 Feb 26;80(9):800-9
references.pmid: 23365054
references.citation: J Psychiatr Res. 2008 Mar;42(4):268-77
references.pmid: 17400251
references.citation: J Neurosci. 2007 Jan 10;27(2):371-8
references.pmid: 17215398
references.citation: Neuroimage. 1998 Jan;7(1):30-40
references.pmid: 9500830
references.citation: Annu Rev Neurosci. 1986;9:357-81
references.pmid: 3085570
references.citation: Neuropsychiatry Neuropsychol Behav Neurol. 1999 Jan;12(1):52-7
references.pmid: 10082333
references.citation: J Neurosci. 2014 Apr 23;34(17):5918-26
references.pmid: 24760851
references.citation: Annu Rev Psychol. 1994;45:1-23
references.pmid: 8135502
references.citation: J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):18-22
references.pmid: 22991345
references.citation: Parkinsons Dis. 2010 Jul 28;2010:930627
references.pmid: 20976097