TY - JOUR
T1 - Increased flexibility of brain dynamics in patients with multiple sclerosis
AU - von Schwanenflug, Nina
AU - Koch, Stefan P.
AU - Krohn, Stephan
AU - Broeders, Tommy A. A.
AU - Lydon-Staley, David M.
AU - Bassett, Dani S.
AU - Schoonheim, Menno M.
AU - Paul, Friedemann
AU - Finke, Carsten
N1 - Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 327654276 (SFB 1315), FI 2309/1–1, FI 2309/2-1 and PR 1274/6-1 to C.F.); and Deutsches Ministerium für Bildung und Forschung (BMBF, German Ministry of Education and Research, 01GM1908D, CONNECT-GENERATE). D.M.L. acknowledges support from the National Institute on Drug Abuse (K01 DA047417) and the Brain & Behavior Research Foundation. N.S. has been a doctoral scholar at Cusanuswerk—Bischöfliche Studienförderung from 2017 to 2021. F.P. received funding from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Exc 257), Deutsches Ministerium für Bildung und Forschung (BMBF, German Ministry of Education and Research, Competence Network Multiple Sclerosis), Guthy Jackson Charitable Foundation, EU Framework Program 7, National Multiple Sclerosis Society of the USA. The funders had no influence on study design, data collection, data analyses, data interpretation or writing. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 327654276 (SFB 1315), FI 2309/1–1, FI 2309/ 2-1 and PR 1274/6-1 to C.F.); and Deutsches Ministerium für Bildung und Forschung (BMBF, German Ministry of Education and Research, 01GM1908D, CONNECT-GENERATE). D.M.L. acknowledges support from the National Institute on Drug Abuse (K01 DA047417) and the Brain & Behavior Research Foundation. N.S. has been a doctoral scholar at Cusanuswerk—Bischöfliche Studienförderung from 2017 to 2021. F.P. received funding from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Exc 257), Deutsches Ministerium für Bildung und Forschung (BMBF, German Ministry of Education and Research, Competence Network Multiple Sclerosis), Guthy Jackson Charitable Foundation, EU Framework Program 7, National Multiple Sclerosis Society of the USA. The funders had no influence on study design, data collection, data analyses, data interpretation or writing. Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2023
Y1 - 2023
N2 - Patients with multiple sclerosis consistently show widespread changes in functional connectivity. Yet, alterations are heterogeneous across studies, underscoring the complexity of functional reorganization in multiple sclerosis. Here, we aim to provide new insights by applying a time-resolved graph-analytical framework to identify a clinically relevant pattern of dynamic functional connectivity reconfigurations in multiple sclerosis. Resting-state data from 75 patients with multiple sclerosis (N = 75, female:male ratio of 3:2, median age: 42.0 ± 11.0 years, median disease duration: 6 ± 11.4 years) and 75 age- and sex-matched controls (N = 75, female:male ratio of 3:2, median age: 40.2 ± 11.8 years) were analysed using multilayer community detection. Local, resting-state functional system and global levels of dynamic functional connectivity reconfiguration were characterized using graph-theoretical measures including flexibility, promiscuity, cohesion, disjointedness and entropy. Moreover, we quantified hypo- and hyper-flexibility of brain regions and derived the flexibility reorganization index as a summary measure of whole-brain reorganization. Lastly, we explored the relationship between clinical disability and altered functional dynamics. Significant increases in global flexibility (t = 2.38, PFDR = 0.024), promiscuity (t = 1.94, PFDR = 0.038), entropy (t = 2.17, PFDR = 0.027) and cohesion (t = 2.45, PFDR = 0.024) were observed in patients and were driven by pericentral, limbic and subcortical regions. Importantly, these graph metrics were correlated with clinical disability such that greater reconfiguration dynamics tracked greater disability. Moreover, patients demonstrate a systematic shift in flexibility from sensorimotor areas to transmodal areas, with the most pronounced increases located in regions with generally low dynamics in controls. Together, these findings reveal a hyperflexible reorganization of brain activity in multiple sclerosis that clusters in pericentral, subcortical and limbic areas. This functional reorganization was linked to clinical disability, providing new evidence that alterations of multilayer temporal dynamics play a role in the manifestation of multiple sclerosis.
AB - Patients with multiple sclerosis consistently show widespread changes in functional connectivity. Yet, alterations are heterogeneous across studies, underscoring the complexity of functional reorganization in multiple sclerosis. Here, we aim to provide new insights by applying a time-resolved graph-analytical framework to identify a clinically relevant pattern of dynamic functional connectivity reconfigurations in multiple sclerosis. Resting-state data from 75 patients with multiple sclerosis (N = 75, female:male ratio of 3:2, median age: 42.0 ± 11.0 years, median disease duration: 6 ± 11.4 years) and 75 age- and sex-matched controls (N = 75, female:male ratio of 3:2, median age: 40.2 ± 11.8 years) were analysed using multilayer community detection. Local, resting-state functional system and global levels of dynamic functional connectivity reconfiguration were characterized using graph-theoretical measures including flexibility, promiscuity, cohesion, disjointedness and entropy. Moreover, we quantified hypo- and hyper-flexibility of brain regions and derived the flexibility reorganization index as a summary measure of whole-brain reorganization. Lastly, we explored the relationship between clinical disability and altered functional dynamics. Significant increases in global flexibility (t = 2.38, PFDR = 0.024), promiscuity (t = 1.94, PFDR = 0.038), entropy (t = 2.17, PFDR = 0.027) and cohesion (t = 2.45, PFDR = 0.024) were observed in patients and were driven by pericentral, limbic and subcortical regions. Importantly, these graph metrics were correlated with clinical disability such that greater reconfiguration dynamics tracked greater disability. Moreover, patients demonstrate a systematic shift in flexibility from sensorimotor areas to transmodal areas, with the most pronounced increases located in regions with generally low dynamics in controls. Together, these findings reveal a hyperflexible reorganization of brain activity in multiple sclerosis that clusters in pericentral, subcortical and limbic areas. This functional reorganization was linked to clinical disability, providing new evidence that alterations of multilayer temporal dynamics play a role in the manifestation of multiple sclerosis.
KW - EDSS
KW - functional reorganization
KW - temporal core–periphery
KW - time-varying functional connectivity
UR - http://www.scopus.com/inward/record.url?scp=85161082930&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/braincomms/fcad143
DO - https://doi.org/10.1093/braincomms/fcad143
M3 - Article
C2 - 37188221
SN - 2632-1297
VL - 5
JO - Brain Communications
JF - Brain Communications
IS - 3
M1 - fcad143
ER -