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Abstract

Objectives:

To map the regional patterns of white matter (WM) microstructural abnormalities and gray matter (GM) atrophy exclusively associated with reduced performance in the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting (RR) multiple sclerosis (MS) patients.

Methods:

In all, 177 RRMS patients and 80 healthy controls (HC) were studied. WM microstructural abnormalities were investigated on diffusion tensor images using tract-based spatial statistics analysis, and regional GM atrophy was estimated on three-dimensional (3D) T1-weighted images using voxel-based morphometry.

Results:

Compared to HC, RRMS patients showed the expected pattern of cortical–subcortical GM atrophy and WM microstructural abnormalities. In patients, diffusivity abnormalities of supratentorial WM tracts correlated with both SDMT and PASAT scores. Lower SDMT performance was also associated with WM damage in several infratentorial WM tracts. Lower SDMT scores correlated with atrophy of the right anterior cingulate cortex, left postcentral gyrus, and right middle temporal gyrus, whereas lower PASAT scores correlated with atrophy of the deep GM nuclei, bilaterally, and several fronto-temporo-occipital regions.

Conclusion:

In RRMS patients, regional damage of different neural systems helps explaining reduced performance in SDMT and PASAT. WM microstructural damage typified reduced SDMT performance, whereas atrophy of several GM regions distinguished reduced PASAT performance.

Keywords

White matter gray matter regional damage cognition multiple sclerosis

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References

DeLuca

Chelune

Tulsky

et al . Is speed of processing or working memory the primary information processing deficit in multiple sclerosis? J Clin Exp Neuropsychol 2004; 26: 550–562.

Gronwall

DM.

Paced auditory serial-addition task: A measure of recovery from concussion. Percept Mot Skills 1977; 44: 367–373.

Smith

Symbol digits modalities test: Manual, 1982. Los Angeles: Western Psychological Services.

Benedict

DeLuca

Phillips

et al . Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler 2017; 23: 721–733.

Rao

Leo

Bernardin

et al . Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41: 685–691.

Hiscock

Caroselli

Kimball

LE.

Paced serial addition: Modality-specific and arithmetic-specific factors. J Clin Exp Neuropsychol 1998; 20: 463–472.

Costa

Genova

DeLuca

et al . Information processing speed in multiple sclerosis: Past, present, and future. Mult Scler 2017; 23: 772–789.

Forn

Belenguer

Belloch

et al . Anatomical and functional differences between the Paced Auditory Serial Addition Test and the Symbol Digit Modalities Test. J Clin Exp Neuropsychol 2011; 33: 42–50.

Ashburner

Hutton

Frackowiak

et al . Identifying global anatomical differences: Deformation-based morphometry. Hum Brain Mapp 1998; 6: 348–357.

10.

Amato

Portaccio

Goretti

et al . The Rao’s Brief Repeatable Battery and Stroop Test: Normative values with age, education and gender corrections in an Italian population. Mult Scler 2006; 12: 787–793.

11.

Portaccio

Goretti

Zipoli

et al . A short version of Rao’s Brief Repeatable Battery as a screening tool for cognitive impairment in multiple sclerosis. Clin Neuropsychol 2009; 23: 268–275.

12.

Basser

Mattiello

LeBihan

Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 1994; 103: 247–254.

13.

Nichols

Holmes

AP.

Nonparametric permutation tests for functional neuroimaging: A primer with examples. Hum Brain Mapp 2002; 15: 1–25.

14.

Strober

Rao

Lee

et al . Cognitive impairment in multiple sclerosis: An 18 year follow-up study. Mult Scler Relat Disord 2014; 3: 473–481.

15.

Dineen

Vilisaar

Hlinka

et al . Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. Brain 2009; 132: 239–249.

16.

Sbardella

Petsas

Tona

et al . Assessing the correlation between grey and white matter damage with motor and cognitive impairment in multiple sclerosis patients. PLoS ONE 2013; 8: e63250.

17.

Christodoulou

Bhise

et al . Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. Neuroimage 2012; 59: 3713–3722.

18.

Giorgio

Palace

Johansen-Berg

et al . Relationships of brain white matter microstructure with clinical and MR measures in relapsing-remitting multiple sclerosis. J Magn Reson Imaging 2010; 31: 309–316.

19.

Roosendaal

Geurts

Vrenken

et al . Regional DTI differences in multiple sclerosis patients. Neuroimage 2009; 44: 1397–1403.

20.

Schmahmann

JD.

From movement to thought: Anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp 1996; 4: 174–198.

21.

Allen

Buxton

Wong

et al . Attentional activation of the cerebellum independent of motor involvement. Science 1997; 275: 1940–1943.

22.

Stoodley

Valera

Schmahmann

JD.

An fMRI study of intra-individual functional topography in the human cerebellum. Behav Neurol 2010; 23: 65–79.

23.

Peterburs

Desmond

JE.

The role of the human cerebellum in performance monitoring. Curr Opin Neurobiol 2016; 40: 38–44.

24.

Valentino

Cerasa

Chiriaco

et al . Cognitive deficits in multiple sclerosis patients with cerebellar symptoms. Mult Scler 2009; 15: 854–859.

25.

Moroso

Ruet

Lamargue-Hamel

et al . Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis. J Neurol Neurosurg Psychiatry 2017; 88: 146–151.

26.

Cerasa

Passamonti

Valentino

et al . Cerebellar-parietal dysfunctions in multiple sclerosis patients with cerebellar signs. Exp Neurol 2012; 237: 418–426.

27.

Minagar

Barnett

Benedict

et al . The thalamus and multiple sclerosis: Modern views on pathologic, imaging, and clinical aspects. Neurology 2013; 80: 210–219.

28.

Rocca

Amato

De Stefano

et al . Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol 2015; 14: 302–317.

29.

Bush

Luu

Posner

MI.

Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 4: 215–222.

30.

Collette

Van der Linden

Brain imaging of the central executive component of working memory. Neurosci Biobehav Rev 2002; 26: 105–125.

31.

Bush

Whalen

Rosen

et al . The counting Stroop: An interference task specialized for functional neuroimaging–validation study with functional MRI. Hum Brain Mapp 1998; 6: 270–282.

32.

Vogt

Finch

Olson

CR.

Functional heterogeneity in cingulate cortex: The anterior executive and posterior evaluative regions. Cereb Cortex 1992; 2: 435–443.

33.

Devinsky

Morrell

Vogt

BA.

Contributions of anterior cingulate cortex to behaviour. Brain 1995; 118(Pt 1): 279–306.

34.

Drevets

Raichle

ME.

Suppression of regional cerebral blood during emotional versus higher cognitive implications for interactions between emotion and cognition. Cognition Emotion 1998; 12: 353–385.

35.

Morgen

Sammer

Courtney

et al . Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS. Neuroimage 2006; 30: 891–898.

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Imaging patterns of gray and white matter abnormalities associated with PASAT and SDMT performance in relapsing-remitting multiple sclerosis

Abstract

Objectives:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material