Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study

Background: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. Objective: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. Methods: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. Results: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. Conclusion: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.

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Five years functional connectivity reorganization without clinical or cognitive decline in MS

10.1101/2020.06.19.20135558 ◽

2020 ◽

Author(s):

Einar August Høgestøl ◽

Samuele Ghezzo ◽

Gro Owren Nygaard ◽

Thomas Espeseth ◽

Piotr Sowa ◽

...

Keyword(s):

Functional Connectivity ◽

Brain Atrophy ◽

Structural Mri ◽

Resting State Fmri ◽

Network Modelling ◽

Brain Connectome ◽

Relapsing Remitting ◽

Structural Brain Damage ◽

Time Changes ◽

Over Time

ABSTRACTObjective1) To assess fMRI-based functional connectivity (FC) anomalies in early multiple sclerosis (MS), 2) To determine the relation between FC changes and structural brain damage due to disease progression 3) To study the association between FC changes and cognitive and physical disability.MethodsStructural MRI and resting-state fMRI were acquired from 76 early relapsing-remitting MS patients at baseline (average disease duration 71.7 months ± 63) and after five years. Ninety-four healthy controls (HCs) matched for age and sex were included at baseline. Independent component analysis (ICA) and network modelling were used to measure FC. FC variation was related to expanded disability status scale and neuropsychological outcomes. Brain and lesion volumes were quantified using standard methods. We used the 25 independent components obtained from ICA to estimate the longitudinal stability of the brain connectome as a proxy for functional reorganization over time.ResultsThe MS subjects were clinically and cognitively stable. Compared to HCs, FC abnormalities were detected within networks and in single connections in patients with early MS at baseline. Over time, FC was relatively invariable, but changes in FC were associated with progression of brain atrophy (ρ = 0.39, p = .06). No significant relationship with clinical and cognitive measures or lesion load was detected.ConclusionPatients with MS showed evidence of altered FC in the early stages of the disease. Over time, changes in FC seem to be related to a progression of brain atrophy, which are known to precede changes in clinical and cognitive functioning.

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Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study

Journal of Neurology ◽

10.1007/s00415-014-7528-z ◽

2014 ◽

Vol 262 (1) ◽

pp. 91-100 ◽

Cited By ~ 59

Author(s):

S. Bonavita ◽

R. Sacco ◽

M. Della Corte ◽

S. Esposito ◽

M. Sparaco ◽

...

Keyword(s):

Multiple Sclerosis ◽

Functional Connectivity ◽

Exploratory Study ◽

Cognitive Rehabilitation ◽

Relapsing Remitting ◽

Computer Aided ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Brain Functional Connectivity ◽

Relapsing Remitting Multiple Sclerosis

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Brain Functional Connectivity in OCD

10.1093/med/9780190228163.003.0024 ◽

2017 ◽

Cited By ~ 1

Author(s):

Carles Soriano-Mas ◽

Ben J. Harrison

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Large Scale ◽

Resting State Fmri ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Regulatory Systems ◽

Variable Nature ◽

Brain Functional Connectivity ◽

Or Task

This chapter provides an overview of studies assessing alterations in brain functional connectivity in obsessive-compulsive disorder (OCD) as assessed by functional magnetic resonance imaging (fMRI). Although most of the reviewed studies relate to the analysis of resting-state fMRI data, the chapter also reviews studies that have combined resting-state with structural or task-based approaches, as well as task-based studies in which the analysis of functional connectivity was reported. The main conclusions to be drawn from this review are that patients with OCD consistently demonstrate altered patterns of brain functional connectivity in large-scale “frontostriatal” and “default mode” networks, and that the heterogeneity of OCD symptoms is likely to partly arise via distinct modulatory influences on these networks by broader disturbances of affective, motivational, and regulatory systems. The variable nature of some findings across studies as well as the influence of medications on functional connectivity measures is also discussed.

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Functional connectivity changes within specific networks parallel the clinical evolution of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513515082 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1050-1057 ◽

Cited By ~ 21

Author(s):

B Basile ◽

M Castelli ◽

F Monteleone ◽

U Nocentini ◽

C Caltagirone ◽

...

Keyword(s):

Multiple Sclerosis ◽

Functional Connectivity ◽

Clinical Symptoms ◽

Clinical State ◽

Pathophysiological Mechanism ◽

Focal Lesions ◽

Motor Network ◽

Relapsing Remitting ◽

Sensory Motor ◽

Brain Functional Connectivity

Background: In multiple sclerosis (MS), the location of focal lesions does not always correlate with clinical symptoms, suggesting disconnection as a major pathophysiological mechanism. Resting-state (RS) functional magnetic resonance imaging (fMRI) is believed to reflect brain functional connectivity (FC) within specific neuronal networks. Objective: RS-fMRI was used to investigate changes in FC within two critical networks for the understanding of MS disabilities, namely, the sensory-motor network (SMN) and the default-mode network (DMN), respectively, implicated in sensory-motor and cognitive functions. Methods: Thirty-four relapsing–remitting (RR), 14 secondary progressive (SP) MS patients and 25 healthy controls underwent MRI at 3T, including conventional images, T1-weighted volumes, and RS-fMRI sequences. Independent component analysis (ICA) was employed to extract maps of the relevant RS networks for every participant. Group analyses were performed to assess changes in FC within the SMN and DMN in the two MS phenotypes. Results: Increased FC was found in both networks of MS patients. Interestingly, specific changes in either direction were observed also between RR and SP MS groups. Conclusions: FC changes seem to parallel patients’ clinical state and capability of compensating for the severity of clinical/cognitive disabilities.

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Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study

Multiple Sclerosis Journal ◽

10.1177/1352458516628657 ◽

2016 ◽

Vol 22 (13) ◽

pp. 1695-1708 ◽

Cited By ~ 22

Author(s):

Anthony Faivre ◽

Emmanuelle Robinet ◽

Maxime Guye ◽

Celia Rousseau ◽

Adil Maarouf ◽

...

Keyword(s):

Multiple Sclerosis ◽

Functional Connectivity ◽

Long Range ◽

Resting State ◽

Short Range ◽

Resting State Fmri ◽

Disability Progression ◽

Fmri Study ◽

Brain Functional Connectivity

Background: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial. Objective: To characterize the relationships between brain functional connectivity changes and disability progression in RRMS. Methods: Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 ± 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later. Results: At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections’ density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow-up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression. Conclusion: The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression.

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Faculty Opinions recommendation of Cognitive performance in relapsing remitting multiple sclerosis: a longitudinal study in daily practice using a brief computerized cognitive battery.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13357101.14726411 ◽

2011 ◽

Author(s):

Nancy Richert ◽

Francesca Bagnato

Keyword(s):

Multiple Sclerosis ◽

Longitudinal Study ◽

Cognitive Performance ◽

Daily Practice ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis

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Spatiotemporal distribution of white matter lesions in relapsing–remitting and secondary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512442756 ◽

2012 ◽

Vol 18 (11) ◽

pp. 1577-1584 ◽

Cited By ~ 14

Author(s):

Lukas Filli ◽

Louis Hofstetter ◽

Pascal Kuster ◽

Stefan Traud ◽

Nicole Mueller-Lenke ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Disease Progression ◽

Spatiotemporal Distribution ◽

Centrum Semiovale ◽

Cross Sectional ◽

Secondary Progressive ◽

Lateral Ventricles ◽

Relapsing Remitting ◽

T1 And T2

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. MS lesions show a typical distribution pattern and primarily affect the white matter (WM) in the periventricular zone and in the centrum semiovale. Objective: To track lesion development during disease progression, we compared the spatiotemporal distribution patterns of lesions in relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). Methods: We used T1 and T2 weighted MR images of 209 RRMS and 62 SPMS patients acquired on two different 1.5 Tesla MR scanners in two clinical centers followed up for 25 (± 1.7) months. Both cross-sectional and longitudinal differences in lesion distribution between RRMS and SPMS patients were analyzed with lesion probability maps (LPMs) and permutation-based inference. Results: MS lesions clustered around the lateral ventricles and in the centrum semiovale. Cross-sectionally, compared to RRMS patients, the SPMS patients showed a significantly higher regional probability of T1 hypointense lesions ( p≤0.03) in the callosal body, the corticospinal tract, and other tracts adjacent to the lateral ventricles, but not of T2 lesions (peak probabilities were RRMS: T1 9%, T2 18%; SPMS: T1 21%, T2 27%). No longitudinal changes of regional T1 and T2 lesion volumes between baseline and follow-up scan were found. Conclusion: The results suggest a particular vulnerability to neurodegeneration during disease progression in a number of WM tracts.

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FP14-TU-03 The effect of disease duration on grey matter volume and cognitive performance in relapsing-remitting multiple sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(09)70337-5 ◽

2009 ◽

Vol 285 ◽

pp. S79 ◽

Cited By ~ 1

Author(s):

A.A. Achiron ◽

S. Tal ◽

D. Magalashvili ◽

A. Achiron

Keyword(s):

Multiple Sclerosis ◽

Cognitive Performance ◽

Grey Matter ◽

Disease Duration ◽

Grey Matter Volume ◽

Matter Volume ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

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Disease phenotype analyses of relapsing-remitting multiple sclerosis in Canada and Saudi Arabia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.151 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S32-S32

Author(s):

M Alluqmani ◽

M Alqermli ◽

G Blevins ◽

B Alotibi ◽

F Giuliani ◽

...

Keyword(s):

Multiple Sclerosis ◽

Saudi Arabia ◽

Geographic Location ◽

Clinical Findings ◽

Cross Sectional ◽

Relapsing Remitting ◽

Similar Disease ◽

The Mean ◽

Sectional Analysis ◽

Relapsing Remitting Multiple Sclerosis

Background: Multiple sclerosis (MS) exhibits a spectrum of clinical findings, especially in relapsing-remitting MS (RR-MS). To assess the effects of geographic location and ethnicity on RR-MS phenotype, we investigated RR-MS patients in Canada and Saudi Arabia. Methods: A retrospective cross-sectional analysis of patients receiving active care in MS Clinics was performed in Medina, Saudi Arabia and Edmonton, Alberta. Demographic and clinical data was collected for each patient. Results: 98 patients with treated RR-MS were recruited (n=51, Medina; n=47, Edmonton); 40 patients were Caucasian (Edmonton) while 46 patients were Bedouin (Medina). Although the disease duration was longer in the Edmonton (5.7+2.3 yr) compared to the Medina group (4.4+1.4 yr) (p<0.05), the mean age of RR-MS onset, relapse rate and EDSS change were similar. The female:male ratio was comparable in Edmonton (35:12) and Medina (32:19), as was the risk of optic neuritis. The likelihood of an infratentorial lesion-associated presentation differed (Edmonton, n=23; Medina; n=13) among groups (p<0.05). Spinal cord lesions on MRI were more frequent in Edmonton (n=18) compared to Medina (n=1) patients (p<0.05). Conclusions: Despite differences in location, ethnicity, and a predominance of infratentorial lesion burden the Edmonton group, the RR-MS phenotype displayed similar disease severity and trajectory in these cohorts.

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