ECTRIMS eLearning

Functional connectome analysis reveals different alterations between relapsing remitting multiple sclerosis with short and longer disease duration
Author(s): ,
G. Castellazzi
Affiliations:
NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom; Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
,
L. Debernard
Affiliations:
New Zealand Brain Research Institute; University of Otago
,
T.R. Melzer
Affiliations:
New Zealand Brain Research Institute; University of Otago; Brain Research New Zealand
,
J.C. Dalrymple-Alford
Affiliations:
New Zealand Brain Research Institute; Brain Research New Zealand; University of Canterbury, Christchurch, New Zealand
,
E. D’Angelo
Affiliations:
Department of Brain and Behavioral Sciences, University of Pavia; Brain Connectivity Center, IRCCS Mondino Foundation, Pavia, Italy
,
D.H. Miller
Affiliations:
NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom; New Zealand Brain Research Institute; University of Otago
,
D.F. Mason
Affiliations:
New Zealand Brain Research Institute; University of Otago; Department of Neurology, Christchurch Hospital, Christchurch, New Zealand
C.A. Gandini Wheeler-Kingshott
Affiliations:
NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom; Department of Brain and Behavioral Sciences, University of Pavia; Brain MRI 3T Center, IRCCS Mondino Foundation, Pavia, Italy
ECTRIMS Learn. Castellazzi G. 10/12/18; 228959; P1119
Gloria Castellazzi
Gloria Castellazzi
Contributions
Abstract

Abstract: P1119

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: In a previous study, we demonstrated that functional connectivity (FC) alterations in relapsing remitting MS (RRMS) extend over several resting state networks (RSNs) and that this functional dysfunction is influenced by disease duration. We used these findings as a starting point to further explore whether and how functional interactions among brain areas differ, causing a reorganization of the brain functional connectome (f-connectome), in two groups of RRMS subjects with mild disability but different disease duration.
Methods: 35 RRMS patients with recent disease onset (≤5yrs, mean EDSS=1.4±0.9; MSshort) and 26 RRMS patients with later disease (>5yrs duration; mean EDSS=2.2±1.4; MSlong) underwent 3T MRI examination including resting state functional MRI (rs-fMRI) and 3D T1-weighted imaging. For each subject, rs-fMRI images were preprocessed and then parcellated into 108 distinct regions derived by combining the automatic anatomical labelling (AAL) atlas with the maps of 18 RSNs previously identified. For each region, the mean rs-fMRI signal was extracted and used to calculate the graph edges defined as the Pearson's correlations between all pairs of regions (graph nodes). The resulting cross-correlation matrices were thresholded (p=12%) and then processed with the Network Based Statistics (NBS) toolbox to identify the connections that were significantly different between the groups.
Results: Compared to MSlong, the MSshort group showed significant (p≤0.05, FDR-corr.) weaker connections between inferior frontal gyrus (IFR) and precuneus, IFR and vermis-6 in the anterior cerebellum, insula and superior temporal gyrus, thalamus and paracentral lobule as well as between cerebellar vermis 4-5 and vermis-6. At the network level, these weaker connections mainly involved Salience Network (SN), Frontal Cortex Network (FCN), Sensory Motor Network (SMN) and Cerebellar Network (CBLN). No significant results were obtained when looking for weaker connections in MSlong (compared to MSshort).
Conclusions: Our analysis revealed that early and later RRMS (MSshort and MSlong) are characterised by different f-connectome profiles. Indeed, MSshort subjects presented a f-connectome with multiple weaker connections than MSlong, which might be indicative of potential differences in the pathophysiology of the two MS groups. Further longitudinal studies are needed to assess whether these changes may predict the future course of the disease.
Disclosure: Gloria Castellazzi: is supported by ECTRIMS (ECTRIMS postdoctoral research fellowship exchange programme). Laëtitia Debernard: nothing to disclose. Tracy R. Melzer: nothing to disclose. John C. Dalrymple-Alford: nothing to disclose. David H. Miller: has received honoraria through payments to UCL Institute of Neurology, for Advisory Committee and/or Consultancy advice in multiple sclerosis studies from Novartis and Mitsubishi Pharma Europe and compensation through payments to UCL Institute of Neurology for performing central MRI analysis of a multiple sclerosis trial from Novartis. Egidio D´Angelo: nothing to disclose. Deborah F. Mason: has received honoraria and travel grants from Biogen Idec, Novartis and TEVA. Claudia A.M. Gandini Wheeler-Kingshott: has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.

Abstract: P1119

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: In a previous study, we demonstrated that functional connectivity (FC) alterations in relapsing remitting MS (RRMS) extend over several resting state networks (RSNs) and that this functional dysfunction is influenced by disease duration. We used these findings as a starting point to further explore whether and how functional interactions among brain areas differ, causing a reorganization of the brain functional connectome (f-connectome), in two groups of RRMS subjects with mild disability but different disease duration.
Methods: 35 RRMS patients with recent disease onset (≤5yrs, mean EDSS=1.4±0.9; MSshort) and 26 RRMS patients with later disease (>5yrs duration; mean EDSS=2.2±1.4; MSlong) underwent 3T MRI examination including resting state functional MRI (rs-fMRI) and 3D T1-weighted imaging. For each subject, rs-fMRI images were preprocessed and then parcellated into 108 distinct regions derived by combining the automatic anatomical labelling (AAL) atlas with the maps of 18 RSNs previously identified. For each region, the mean rs-fMRI signal was extracted and used to calculate the graph edges defined as the Pearson's correlations between all pairs of regions (graph nodes). The resulting cross-correlation matrices were thresholded (p=12%) and then processed with the Network Based Statistics (NBS) toolbox to identify the connections that were significantly different between the groups.
Results: Compared to MSlong, the MSshort group showed significant (p≤0.05, FDR-corr.) weaker connections between inferior frontal gyrus (IFR) and precuneus, IFR and vermis-6 in the anterior cerebellum, insula and superior temporal gyrus, thalamus and paracentral lobule as well as between cerebellar vermis 4-5 and vermis-6. At the network level, these weaker connections mainly involved Salience Network (SN), Frontal Cortex Network (FCN), Sensory Motor Network (SMN) and Cerebellar Network (CBLN). No significant results were obtained when looking for weaker connections in MSlong (compared to MSshort).
Conclusions: Our analysis revealed that early and later RRMS (MSshort and MSlong) are characterised by different f-connectome profiles. Indeed, MSshort subjects presented a f-connectome with multiple weaker connections than MSlong, which might be indicative of potential differences in the pathophysiology of the two MS groups. Further longitudinal studies are needed to assess whether these changes may predict the future course of the disease.
Disclosure: Gloria Castellazzi: is supported by ECTRIMS (ECTRIMS postdoctoral research fellowship exchange programme). Laëtitia Debernard: nothing to disclose. Tracy R. Melzer: nothing to disclose. John C. Dalrymple-Alford: nothing to disclose. David H. Miller: has received honoraria through payments to UCL Institute of Neurology, for Advisory Committee and/or Consultancy advice in multiple sclerosis studies from Novartis and Mitsubishi Pharma Europe and compensation through payments to UCL Institute of Neurology for performing central MRI analysis of a multiple sclerosis trial from Novartis. Egidio D´Angelo: nothing to disclose. Deborah F. Mason: has received honoraria and travel grants from Biogen Idec, Novartis and TEVA. Claudia A.M. Gandini Wheeler-Kingshott: has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.

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