Reorganization in cognitive networks with progression of multiple sclerosis

Loitfelder, Marisa; Fazekas, Franz; Petrovic, Katja; Fuchs, Siegrid; Ropele, Stefan; Wallner-Blazek, M; Jehna, Margit; Aspeck, E; Khalil, Michael; Schmidt, Reinhold; Neuper, Christa; Enzinger, Christian

doi:10.1212/wnl.0b013e31820b75cf

Cited by 73 publications

(68 citation statements)

References 31 publications

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“…Although the sample size examined might be considered as comparatively small, the network activated by the go/no-go task in this group of patients with MS and healthy control subjects acquired across multiple centers is consistent with the activations defined in a previous single-center study (29). The results of the current study therefore can be considered as robust.…”

Section: Neuroradiology: Use Of Structural and Functional Mr Imaging supporting

confidence: 85%

Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study

Koini¹,

Filippi²,

Rocca³

et al. 2016

Radiology

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q RSNA, 2016 Purpose:To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods:Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results:Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P , .001). Among tested variables, thalamic volume (b = 0.606, P = .001), together with thalamic activation (b = 20.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion:This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning.q RSNA, 2016

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Section: Neuroradiology: Use Of Structural and Functional Mr Imaging supporting

confidence: 85%

Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study

Koini¹,

Filippi²,

Rocca³

et al. 2016

Radiology

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“…First, cortical plasticity processes may be central to our results. A well-replicated finding in task activation studies is that patients in various stages of the disease will show an enhanced recruitment of task-relevant areas (46)(47)(48)(49). These effects specifically involve an extension of the activation patterns to additional and functionally related brain areas.…”

Section: Discussionmentioning

confidence: 83%

Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis

Hawellek

Hipp

Lewis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

247

233

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Correlations in spontaneous brain activity provide powerful access to large-scale organizational principles of the CNS. However, making inferences about cognitive processes requires a detailed understanding of the link between these couplings and the structural integrity of the CNS. We studied the impact of multiple sclerosis, which leads to the severe disintegration of the central white matter, on functional connectivity patterns in spontaneous cortical activity. Using a data driven approach based on the strength of a salient pattern of cognitive pathology, we identified distinct networks that exhibit increases in functional connectivity despite the presence of strong and diffuse reductions of the central white-matter integrity. The default mode network emerged as a core target of these connectivity modulations, showing enhanced functional coupling in bilateral inferior parietal cortex, posterior cingulate, and medial prefrontal cortex. These findings imply a complex and diverging relation of anatomical and functional connectivity in early multiple sclerosis and, thus, add an important observation for understanding how cognitive abilities and CNS integrity may be reflected in the intrinsic covariance of functional signals.resting state | BOLD fMRI | diffusion tensor imaging | fractional anisotropy | neurological U nderstanding how disease processes affect functional interactions in the CNS is a core challenge of neuroscience research. fMRI connectivity has become an important tool for revealing large-scale network interactions by analyzing correlations in intrinsic fluctuations of the BOLD signal (1). This method is sensitive to plastic as well as developmental changes of the functional architecture (2-5), and has successfully linked specific cognitive syndromes to the pathology of distinct functional systems (e.g., spatial neglect after stroke, different forms of dementias, and healthy aging) (6-8). The structural wiring of the brain plays an essential role in shaping the spatial patterns of functional interactions (9, 10). However, the activity correlations are not fully determined by the anatomical connections and, thus, provide complementary information about network organization (11). Especially in the context of neurological damage, the functional covariance structure may document pathological effects well beyond focal damage, indicating the complex changes of interactions that occur in distributed networks (12)(13)(14). Commonly, the coupling strength of spontaneous brain activity is thought to be a direct proxy for the functioning of brain networks, with stronger interactions also reflecting a stronger computational capacity (15,16).In this study we have investigated how cognitive pathology due to neurological damage in multiple sclerosis (MS) is reflected in changes of structural and functional connectivity. Compared with other CNS pathologies, MS stands out due to the prominent involvement of the central white matter. During the disease process, the immune system exerts inflammatory insults to neurona...

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“…Given the correlation between functional and structural abnormalities (30), the former appear to partly limit the functional consequences of structural damage in MS. fMRI abnormalities already occur in CIS, but differences in activation patterns between phenotypes are striking (32, 33), suggesting profound changes in the functional organization of the MS brain with disease progression. Final exhaustion of adaptive capacity may constitute one key factor for unfavorable clinical evolution or cognitive decline, although the decisive factors driving transition from adaption to maladaptation are unknown.…”

Section: Functional Mri As One Approach To Gain Functional Informationmentioning

confidence: 99%

Measuring Gray Matter and White Matter Damage in MS: Why This is Not Enough

Enzinger

Fazekas

2015

Front. Neurol.

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Reorganization in cognitive networks with progression of multiple sclerosis

Abstract: Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.

Cited by 73 publications

References 31 publications

Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study

Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study

Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis

Measuring Gray Matter and White Matter Damage in MS: Why This is Not Enough

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