TY - JOUR
T1 - Dynamic modular-level alterations of structural-functional coupling in clinically isolated syndrome
AU - Koubiyr, Ismail
AU - Besson, Pierre
AU - Deloire, Mathilde
AU - Charre-Morin, Julie
AU - Saubusse, Aurore
AU - Tourdias, Thomas
AU - Brochet, Bruno
AU - Ruet, Aurélie
N1 - Funding Information:
The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Translational Research and Advanced Imaging Laboratory (TRAIL), laboratory of excellence (ANR-10-LABX-57). The SCI-COG study was also supported by a grant from TEVA and ARSEP (Fondation ARSEP pour la recherche sur la sclérose en plaques). This work has been performed with the help of the French Observatoire of Multiple Sclerosis (OFSEP), which is supported by a grant provided by the French State and handled by the “Agence Nationale de la Recherche”, within the framework of the “Investments for the Future” program, under the reference no. ANR-10-COHO-002.
Funding Information:
B.B. reports grants from the French Ministry of Health during the conduct of the study; personal fees and nonfinancial support from Biogen-idec, grants from Merck-serono, personal fees and non-financial support from Novartis, personal fees and non-financial support from Genzyme, grants, personal fees and non-financial support from TEVA, grants and non-financial support from Bayer, outside the submitted work. A.R. reports grants from TEVA, during the conduct of the study; personal fees and non-financial support from Novartis, personal fees and non-financial support from Biogen, grants, personal fees and non-financial support from TEVA, grants and non-financial support from Roche, grants and non-financial support from Merck, grants and non-financial support from Genzyme, non-financial support from Medday, grants from Bayer, outside the submitted work.
Publisher Copyright:
© The Author(s) (2019).
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Structural and functional connectivity abnormalities have been reported previously in multiple sclerosis. However, little is known about how each modality evolution relates to the other. Recent studies in other neurological disorders have suggested that structural- functional coupling may be more sensitive in detecting brain alterations than any single modality. Accordingly, this study aimed to investigate the longitudinal evolution of structural-functional coupling, both at the global and modular levels, in the first year following clinically isolated syndrome. We hypothesized that during the course of multiple sclerosis, patients exhibit a decoupling between functional and structural connectivity due to the disruptive nature of the disease. Forty-one consecutive patients with clinically isolated syndrome were prospectively enrolled in this study, along with 19 age-, sex- and educational level-matched healthy control subjects. These participants were followed for 1 year and underwent resting-state functional MRI and diffusion tensor imaging at each time point, along with an extensive neuropsychological assessment. Graph theory analysis revealed structural reorganization at baseline that appeared as an increase in the clustering coefficient in patients compared to controls (P<0.05), as well as modular-specific alterations. After 1 year of follow-up, both structural and functional reorganization was depicted with abnormal modular-specific connectivity and an increase of the functional betweenness centrality in patients compared to controls (P<0.01). More importantly, structural-functional decoupling was observed in the salience, visual and somatomotor networks. These alterations were present along with preserved cognitive performance at this stage. These results depict structural damage preceding functional reorganization at a global and modular level during the first year following clinically isolated syndrome along with normal cognitive performance, suggesting a compensation mechanism at this stage of the disease. Principally, structural-functional decoupling observed for the first time in multiple sclerosis suggests that functional reorganization occurs along indirect anatomical pathways.
AB - Structural and functional connectivity abnormalities have been reported previously in multiple sclerosis. However, little is known about how each modality evolution relates to the other. Recent studies in other neurological disorders have suggested that structural- functional coupling may be more sensitive in detecting brain alterations than any single modality. Accordingly, this study aimed to investigate the longitudinal evolution of structural-functional coupling, both at the global and modular levels, in the first year following clinically isolated syndrome. We hypothesized that during the course of multiple sclerosis, patients exhibit a decoupling between functional and structural connectivity due to the disruptive nature of the disease. Forty-one consecutive patients with clinically isolated syndrome were prospectively enrolled in this study, along with 19 age-, sex- and educational level-matched healthy control subjects. These participants were followed for 1 year and underwent resting-state functional MRI and diffusion tensor imaging at each time point, along with an extensive neuropsychological assessment. Graph theory analysis revealed structural reorganization at baseline that appeared as an increase in the clustering coefficient in patients compared to controls (P<0.05), as well as modular-specific alterations. After 1 year of follow-up, both structural and functional reorganization was depicted with abnormal modular-specific connectivity and an increase of the functional betweenness centrality in patients compared to controls (P<0.01). More importantly, structural-functional decoupling was observed in the salience, visual and somatomotor networks. These alterations were present along with preserved cognitive performance at this stage. These results depict structural damage preceding functional reorganization at a global and modular level during the first year following clinically isolated syndrome along with normal cognitive performance, suggesting a compensation mechanism at this stage of the disease. Principally, structural-functional decoupling observed for the first time in multiple sclerosis suggests that functional reorganization occurs along indirect anatomical pathways.
KW - Clinically isolated syndrome
KW - Diffusion tensor imaging
KW - Functional MRI
KW - Graph theory
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85074307080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074307080&partnerID=8YFLogxK
U2 - 10.1093/brain/awz270
DO - 10.1093/brain/awz270
M3 - Article
C2 - 31504228
AN - SCOPUS:85074307080
VL - 142
SP - 3428
EP - 3439
JO - Brain
JF - Brain
SN - 0006-8950
IS - 11
ER -