Abstract Details

Title Characterizing Dynamic Functional Connectivity in the Main Clinical Phenotypes of Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-005

Objective To investigate resting state (RS) dynamic functional connectivity (dFC) abnormalities in the main clinical phenotypes of multiple sclerosis (MS).

Background

dFC is a novel analysis technique that measures temporal RS FC fluctuations occurring during the course of fMRI acquisition.

Design/Methods RS fMRI data were acquired from 128 MS patients (53 relapsing remitting [RR] MS, 16 benign [B] MS, 34 secondary progressive [SP] MS, 25 primary progressive [PP] MS), and 40 healthy controls (HC). Forty-two relevant independent components were identified and assigned to sensorimotor, default-mode, frontal/attention, salience, executive, visual, temporal/auditory, and cerebellar networks. dFC properties were assessed using sliding windows correlations and grouping FC matrices into recurrent states (hard-clustering analysis). Between-group dFC differences and correlations between dFC abnormalities and motor and cognitive performances were assessed.

Results Hard-clustering analysis revealed 3 dFC states in HC and MS patients: State 1 (frequency=57%, low dFC strength), State 2 (frequency=19%, middle-high dFC strength), and State 3 (frequency=24%, high dFC strength within sensorimotor and visual networks). MS patients showed overall dFC reduction in all States vs HC, along with increased dFC in sensorimotor and default-mode networks in State 2, and increased dFC in the frontal/attention network in State 3. Similar findings were detected when comparing PPMS and RRMS patients vs HC, and SPMS vs RRMS patients. In BMS vs RRMS patients, the overall reduction of dFC was accompanied by significantly increased dFC in the sensorimotor, default-mode and frontal/attention networks in State 1. In MS patients, reduced dFC in State 1 and increased dFC in States 2 and 3 of sensorimotor, default-mode and frontal/attention networks correlated with more severe motor disability and worse cognitive impairment.

Conclusions Significant dFC abnormalities, mainly in sensorimotor and cognitive networks, contributed to explain MS phenotypic heterogeneity, clinical disability and cognitive impairment, suggesting the presence of maladaptive responses in progressive MS patients and compensatory mechanisms in BMS.

Authors/Disclosures
Milagros Hidalgo de la Cruz PRESENTER	Milagros Hidalgo de la Cruz has nothing to disclose.
Paola Valsasina	Paola Valsasina has nothing to disclose.
Francesca Sangalli	No disclosure on file
Federica Esposito	Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Federica Esposito has received research support from Italian MS Society. The institution of Federica Esposito has received research support from Italian Ministry of Health. The institution of Federica Esposito has received research support from ERA Net. The institution of Federica Esposito has received research support from European Commission. Federica Esposito has received intellectual property interests from a discovery or technology relating to health care.
Massimo Filippi, MD, F�鶹��ýӳ�� (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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