Contributions
Abstract: 54
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Functional network disturbances are common in cognitively impaired (CI) multiple sclerosis (MS) patients, often involving regions forming the default-mode network. Up to now, these studies examining brain functioning have focused on static network changes across the entire resting-state time series, while recent studies on dynamic connectivity show that this communication varies considerably over time. The clinical significance of this variation is unclear. In this study, we specifically investigate the dynamics of brain functioning, to study whether brain regions are abnormally flexible or rigid in CI-MS patients.
Methods: A total of 332 MS patients, divided into cognitively impaired (CI, N=87); mildly cognitively impaired (MCI, N=65) and cognitively preserved (CP, N=180) groups based on extensive neuropsychological testing, and 96 healthy controls (HCs) were included. Resting-state fMRI scans were analysed using partially overlapping 44-second windows for which voxel-wise eigenvector centrality was computed separately, and the variability across windows was assessed. Eigenvector centrality determines the hierarchical position or importance of a brain region within the functional network based on both the number and centrality of its neighbours, favouring both strong connections and central neighbours. Group differences in variability were assessed using a cluster-wise permutation-based method.
Results: Network centrality dynamics were only decreased in CI patients in the posterior cingulate gyrus (compared to CP), as well as the left angular gyrus and the medial prefrontal cortex (compared to CP and HC). Static eigenvector centrality was increased in the default-mode network only, as previously reported.
Conclusion: CI patients demonstrated decreased dynamics, but increased static centrality, in several core regions of the default-mode network. These changes indicate that this pivotal network is stuck in a highly central and more rigid state in cognitively impaired MS patients, which may prohibit its normally highly flexible functioning in cognitive processing. Future studies are required to elucidate which factors lead to this disturbed default-mode network functioning as well as their prognostic power on the severity of cognitive impairment in MS.
Disclosure: Mr. Eijlers receives research support from the Dutch MS Research Foundation, grant number 14-358e.
Mr. Wink: nothing to disclose.
Ms. Meijer receives a research grant from Biogen.
Ms. Douw: nothing to disclose.
Dr. Schoonheim receives research support from the Dutch MS Research Foundation, grant number 13-820, has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen and serves on the editorial board of Frontiers in Neurology.
Prof. Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Genzyme.
Abstract: 54
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Functional network disturbances are common in cognitively impaired (CI) multiple sclerosis (MS) patients, often involving regions forming the default-mode network. Up to now, these studies examining brain functioning have focused on static network changes across the entire resting-state time series, while recent studies on dynamic connectivity show that this communication varies considerably over time. The clinical significance of this variation is unclear. In this study, we specifically investigate the dynamics of brain functioning, to study whether brain regions are abnormally flexible or rigid in CI-MS patients.
Methods: A total of 332 MS patients, divided into cognitively impaired (CI, N=87); mildly cognitively impaired (MCI, N=65) and cognitively preserved (CP, N=180) groups based on extensive neuropsychological testing, and 96 healthy controls (HCs) were included. Resting-state fMRI scans were analysed using partially overlapping 44-second windows for which voxel-wise eigenvector centrality was computed separately, and the variability across windows was assessed. Eigenvector centrality determines the hierarchical position or importance of a brain region within the functional network based on both the number and centrality of its neighbours, favouring both strong connections and central neighbours. Group differences in variability were assessed using a cluster-wise permutation-based method.
Results: Network centrality dynamics were only decreased in CI patients in the posterior cingulate gyrus (compared to CP), as well as the left angular gyrus and the medial prefrontal cortex (compared to CP and HC). Static eigenvector centrality was increased in the default-mode network only, as previously reported.
Conclusion: CI patients demonstrated decreased dynamics, but increased static centrality, in several core regions of the default-mode network. These changes indicate that this pivotal network is stuck in a highly central and more rigid state in cognitively impaired MS patients, which may prohibit its normally highly flexible functioning in cognitive processing. Future studies are required to elucidate which factors lead to this disturbed default-mode network functioning as well as their prognostic power on the severity of cognitive impairment in MS.
Disclosure: Mr. Eijlers receives research support from the Dutch MS Research Foundation, grant number 14-358e.
Mr. Wink: nothing to disclose.
Ms. Meijer receives a research grant from Biogen.
Ms. Douw: nothing to disclose.
Dr. Schoonheim receives research support from the Dutch MS Research Foundation, grant number 13-820, has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen and serves on the editorial board of Frontiers in Neurology.
Prof. Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Genzyme.