title: Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.
abstract: Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kolbe
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mitchell
authors.forename: Owen
authors.initials: O
authors.lastname: White
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000209:etiology*; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D009483:Neuropsychological Tests; D015835:Ocular Motility Disorders / Q000209:etiology*
keywords: DTI; MRI; antisaccades; cerebellum; cognitive dysfunction; multiple sclerosis
references.citation: J Neurosci. 1996 Nov 15;16(22):7284-96
references.pmid: 8929435
references.citation: Learn Mem. 1997 May-Jun;4(1):1-35
references.pmid: 10456051
references.citation: IEEE Trans Med Imaging. 2001 Jan;20(1):45-57
references.pmid: 11293691
references.citation: Brain. 2006 Feb;129(Pt 2):290-2
references.pmid: 16434422
references.citation: Neuroimage. 2009 May 15;46(1):39-46
references.pmid: 19457380
references.citation: Magn Reson Med. 2003 Nov;50(5):1077-88
references.pmid: 14587019
references.citation: Nat Rev Neurol. 2011 May 10;7(6):332-42
references.pmid: 21556031
references.citation: Cerebellum. 2003;2(3):233-40
references.pmid: 14509573
references.citation: J Neurophysiol. 2009 Feb;101(2):934-47
references.pmid: 19196922
references.citation: Behav Neurol. 2000;12(4):191-200
references.pmid: 11568431
references.citation: Neuroimage. 2009 Feb 15;44(4):1397-403
references.pmid: 19027076
references.citation: J Comp Neurol. 1988 May 22;271(4):473-92
references.pmid: 2454970
references.citation: Cereb Cortex. 2008 May;18(5):1148-59
references.pmid: 17728263
references.citation: Neuroimage. 2009 Jan 1;44(1):83-98
references.pmid: 18501637
references.citation: Neuroimage. 2009 Apr 15;45(3):679-86
references.pmid: 19162205
references.citation: J Neurol Sci. 2006 Jun 15;245(1-2):169-75
references.pmid: 16678209
references.citation: Neural Netw. 1998 Oct;11(7-8):1317-29
references.pmid: 12662752
references.citation: J Neurophysiol. 1998 Oct;80(4):1911-31
references.pmid: 9772249
references.citation: J Comp Neurol. 1988 May 22;271(4):493-506
references.pmid: 2454971
references.citation: Med Image Anal. 2006 Oct;10(5):764-85
references.pmid: 16899392
references.citation: Mult Scler. 2007 Sep;13(8):1004-10
references.pmid: 17623735
references.citation: Med Image Anal. 2001 Jun;5(2):143-56
references.pmid: 11516708
references.citation: Hum Brain Mapp. 2002 Nov;17(3):143-55
references.pmid: 12391568
references.citation: PLoS One. 2012;7(2):e30475
references.pmid: 22319570
references.citation: Brain. 2009 Jan;132(Pt 1):239-49
references.pmid: 18953055
references.citation: Neurology. 2012 Mar 27;78(13):969-75
references.pmid: 22377806
references.citation: Neurosci Lett. 1995 Oct 27;199(3):175-8
references.pmid: 8577391
references.citation: Neuropsychologia. 2009 Jun;47(7):1647-53
references.pmid: 19397859
references.citation: Psychiatry Res. 2004 Jul 30;131(2):147-55
references.pmid: 15313521
references.citation: AJNR Am J Neuroradiol. 2010 Aug;31(7):1240-6
references.pmid: 20299439
references.citation: J Neurol Sci. 2009 Feb 15;277(1-2):32-6
references.pmid: 18977003
references.citation: Hum Brain Mapp. 2002 Jan;15(1):1-25
references.pmid: 11747097
references.citation: Brain Cogn. 2008 Dec;68(3):327-40
references.pmid: 19028265
references.citation: Cortex. 2009 Jul-Aug;45(7):900-3
references.pmid: 19327763
references.citation: Arch Neurol. 2008 Sep;65(9):1223-30
references.pmid: 18779427