Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis

Objectives: We investigated clinical, behavioural and functional magnetic resonance imaging (fMRI) correlates of working memory load in relapse-onset multiple sclerosis (MS) patients. Methods: In total, 12 clinically isolated syndromes (CIS) patients at risk of MS, 38 relapsing-remitting multiple sclerosis (RRMS), 22 secondary progressive multiple sclerosis (SPMS) and 24 healthy controls (HC) performed an N-back fMRI task. Correlations between fMRI abnormalities and clinico-behavioural and structural magnetic resonance imaging (MRI) measures were assessed. Results: Participants activated brain regions of the working memory network, especially in fronto-parietal lobes and cerebellum, and deactivated areas of the default mode network (DMN). During the N-back load contrast, compared to HC, the three groups of MS patients had a common pattern of decreased activation of the right superior parietal lobule, left inferior parietal lobule and left middle frontal gyrus. Areas specifically more active in CIS patients compared to the other study groups were found in the left medial superior frontal gyrus and right anterior cingulate cortex, whereas SPMS patients selectively activated the left parahippocampal gyrus and left superior temporal pole (STP). Worse accuracy and global cognitive scores correlated with increased STP activation. Conclusion: Load-dependent alterations of working memory network recruitment occur in MS. Frontal hyperactivation is maintained in CIS and lost in SPMS. Abnormal recruitment of DMN areas is related to worse cognitive and behavioural outcomes.

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Cognition in Early Relapsing-Remitting Multiple Sclerosis: Consequences May Be Relative to Working Memory

Journal of the International Neuropsychological Society ◽

10.1017/s1355617713000696 ◽

2013 ◽

Vol 19 (8) ◽

pp. 938-949 ◽

Cited By ~ 12

Author(s):

Lindsay I. Berrigan ◽

Jo-Anne LeFevre ◽

Laura M. Rees ◽

Jason Berard ◽

Mark S. Freedman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Working Memory ◽

Processing Speed ◽

Cognitive Functions ◽

Group Membership ◽

Equation Modeling ◽

Mediating Role ◽

Relapsing Remitting ◽

Disease Stages

AbstractThe Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed, as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages. (JINS, 2013, 19, 1–12)

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Functional and structural MRI correlates of executive functions in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/13524585211033184 ◽

2021 ◽

pp. 135245852110331

Author(s):

Olga Marchesi ◽

Raffaello Bonacchi ◽

Paola Valsasina ◽

Paolo Preziosa ◽

Elisabetta Pagani ◽

...

Keyword(s):

Multiple Sclerosis ◽

Working Memory ◽

A Priori ◽

Structural Mri ◽

Wisconsin Card Sorting Test ◽

Cognitive Networks ◽

Superior Cerebellar Peduncle ◽

Card Sorting ◽

Cerebellar Peduncle ◽

Magnetic Resonance Imaging Mri

Background: Executive dysfunctions, including difficulties in attention, working memory, planning, and inhibition affect 15%–28% of multiple sclerosis (MS) patients. Objectives: To investigate structural and functional magnetic resonance imaging (MRI) abnormalities underlying executive function (EF) in MS patients. Methods: A total 116 MS patients and 65 controls underwent resting-state (RS) and diffusion-weighted sequences and neuropsychological examination, including Wisconsin Card Sorting Test (WCST) to test EF. Brain RS cognitive networks and fractional anisotropy (FA) from a priori selected white matter tracts were derived. Associations of WCST scores with RS functional connectivity (FC) and FA abnormalities were investigated. Results: In MS patients, predictors of working memory/updating were: lower corpus callosum (CC) FA, lower left working-memory network (WMN), right WMN RS FC for worse performance; lower executive control network (ECN), higher default-mode network (DMN), and salience network (SN) RS FC for better performance ( R2 = 0.35). Predictors of attention were lower CC genu FA, lower left WMN, and DMN RS FC for worse performance; higher left WMN and ECN RS FC for better performance ( R2 = 0.24). Predictors of worse shifting/inhibition were lower CC genu and superior cerebellar peduncle (SCP) FA, lower left WMN RS FC for worse performance; and higher ECN RS FC for better performance ( R2 = 0.24). Conclusions: CC and SCP microstructural damage and RS FC abnormalities in cognitive networks underlie EF frailty in MS.

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