Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

Meijer, Kim; Eijlers, A. J. C.; Geurts, Jeroen J. G.; Schoonheim, Menno M.

doi:10.1136/jnnp-2017-316329

Cited by 29 publications

(19 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…also incorporate tau aggregation, hypoactivity is also predominant (Marinkovic et al, 2019;Menkes-Caspi et al, 2015). In any case, prevailing evidence of functional imaging in human MS points to altered activity and 10 circuit disconnection (Meijer et al, 2018;Rocca et al, 2010), relating to the findings at the cellular level in our model. Given the profound structural and functional pathology that emerges from a single bout of cortical neuroinflammation, a remarkable observation of our study is the fact that such deficits can be entirely reversible once inflammation subsides.…”

supporting

confidence: 53%

Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation

Jafari

Schumacher

Snaidero

et al. 2019

Preprint

View full text Add to dashboard Cite

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical 5 inflammation disrupt cortical circuit activity coincident with a widespread but transient loss of dendritic spines. Spines destined for removal show a local calcium accumulation and are subsequently removed by invading macrophages and activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of 10 inflammatory gray matter lesions that is amenable to immunomodulatory therapy. HIGHLIGHTS:• Widespread, but transient loss of synapses in inflammatory lesions and beyond • Reversible impairment of neuronal firing and circuit function in the inflamed cortex • Calcium dyshomeostasis of single spines precedes swift synapse loss 20• Phagocyte-mediated spine pruning as targetable mechanism of synapse loss Jafari, Schumacher, Snaidero et al.2

show abstract

supporting

confidence: 53%

Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation

Jafari

Schumacher

Snaidero

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Strictly speaking, an FC change is simply a change in the level of coherence of the affected voxels with the rest of the voxels in the network (Tahedl et al ., 2018). Recent studies have been combining rs-fMRI with other MR modalities to understand FC changes better, and emerging evidence suggests that the direction of FC changes reflects structural damage (Meijer et al ., 2018; Patel et al ., 2018; Tewarie et al ., 2018). Both Patel et al 2018 and Tewarie et al 2018 showed, in their computational modelling studies, that early disconnection mechanisms in the white matter induce increases in functional network connectivity, followed by decreases as structural damage accumulates.…”

Section: Discussionmentioning

confidence: 99%

Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients

Jandric

Lipp

Paling

et al. 2020

Preprint

View full text Add to dashboard Cite

Cognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities.Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics.We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow.Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.

show abstract

“…[7][8][9] Resting-state functional imaging studies in MS have shown the potential to non-invasively map the intrinsic functional brain networks and to detect early functional brain changes. 6,[10][11][12] Furthermore, graph theory has proved to depict the topological organization of the brain by visualizing the overall connectivity patterns and by characterizing the brain's global organization. 13 Recent studies investigated brain network topology at the CIS stage.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of functional brain network reorganization in clinically isolated syndrome

et al. 2018

View full text Add to dashboard Cite

Background: There is a lack of longitudinal studies exploring the topological organization of functional brain networks at the early stages of multiple sclerosis (MS). Objective: This study aims to assess potential brain functional reorganization at rest in patients with CIS (PwCIS) after 1 year of evolution and to characterize the dynamics of functional brain networks at the early stage of the disease. Methods: We prospectively included 41 PwCIS and 19 matched healthy controls (HCs). They were scanned at baseline and after 1 year. Using graph theory, topological metrics were calculated for each region. Hub disruption index was computed for each metric. Results: Hub disruption indexes of degree and betweenness centrality were negative at baseline in patients ( p < 0.05), suggesting brain reorganization. After 1 year, hub disruption indexes for degree and betweenness centrality were still negative ( p < 0.00001), but such reorganization appeared more pronounced than at baseline. Different brain regions were driving these alterations. No global efficiency differences were observed between PwCIS and HCs either at baseline or at 1 year. Conclusion: Dynamic changes in functional brain networks appear at the early stages of MS and are associated with the maintenance of normal global efficiency in the brain, suggesting a compensatory effect.

show abstract

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

Abstract: Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.

Cited by 29 publications

References 38 publications

Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation

Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation

Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients

Longitudinal study of functional brain network reorganization in clinically isolated syndrome

Contact Info

Product

Resources

About