Sirio Cocozza1,2, Giuseppe Pontillo2, Camilla Russo2, Cinzia Valeria Russo3, Teresa Costabile3, Alessio Pepe1, Enrico Tedeschi2, Roberta Lanzillo3, Vincenzo Brescia Morra3, Arturo Brunetti2, Matilde Inglese4,5,6, Maria Petracca1,3. 1. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. 3. Department of Neurosciences, Reproductive and Odonto-stomatological Sciences, University of Naples Federico II, Naples, Italy. 4. Departments of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1137, New York, NY, 10029-6579, USA. matilde.inglese@mssm.edu. 5. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Perinatal Sciences, University of Genoa, Genoa, Italy. matilde.inglese@mssm.edu. 6. IRCCS Azienda Ospedale Università San Martino-IST, Genoa, Italy. matilde.inglese@mssm.edu.
Abstract
BACKGROUND: The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMS patients in relation to cognition. METHODS: In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMS patients (11 males, mean age 51.2 ± 11.9 years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8 years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient. RESULTS: When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMS patients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMS patients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = - 0.393; p = 0.03). CONCLUSION: PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.
BACKGROUND: The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMSpatients in relation to cognition. METHODS: In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMSpatients (11 males, mean age 51.2 ± 11.9 years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8 years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient. RESULTS: When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMSpatients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMSpatients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = - 0.393; p = 0.03). CONCLUSION:PMSpatients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.
Entities:
Keywords:
Cerebellum; Functional connectivity; Progressive multiple sclerosis; Resting state fMRI
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