Topological reorganization of brain network might contribute to the resilience of cognitive functioning in mildly disabled relapsing remitting multiple sclerosis

TY - JOUR

T1 - Topological reorganization of brain network might contribute to the resilience of cognitive functioning in mildly disabled relapsing remitting multiple sclerosis

AU - Has Silemek, Arzu Ceylan

AU - Nolte, Guido

AU - Pöttgen, Jana

AU - Engel, Andreas K

AU - Heesen, Christoph

AU - Gold, Stefan M

AU - Stellmann, Jan-Patrick

N1 - © 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.

PY - 2023/1

Y1 - 2023/1

N2 - Multiple sclerosis (MS) is an inflammatory and demyelinating disease which leads to impairment in several functional systems including cognition. Alteration of brain networks is linked to disability and its progression. However, results are mostly cross-sectional and yet contradictory as putative adaptive and maladaptive mechanisms were found. Here, we aimed to explore longitudinal reorganization of brain networks over 2-years by combining diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), magnetoencephalography (MEG), and a comprehensive neuropsychological-battery. In 37 relapsing-remitting MS (RRMS) and 39 healthy-controls, cognition remained stable over-time. We reconstructed network models based on the three modalities and analyzed connectivity in relation to the hierarchical topology and functional subnetworks. Network models were compared across modalities and in their association with cognition using linear-mixed-effect-regression models. Loss of hub connectivity and global reduction was observed on a structural level over-years (p < .010), which was similar for functional MEG-networks but not for fMRI-networks. Structural hub connectivity increased in controls (p = .044), suggesting a physiological mechanism of healthy aging. Despite a general loss in structural connectivity in RRMS, hub connectivity was preserved (p = .002) over-time in default-mode-network (DMN). MEG-networks were similar to DTI and weakly correlated with fMRI in MS (p < .050). Lower structural (β between .23-.33) and both lower (β between .40-.59) and higher functional connectivity (β = -.54) in DMN was associated with poorer performance in attention and memory in RRMS (p < .001). MEG-networks involved no association with cognition. Here, cognitive stability despite ongoing neurodegeneration might indicate a resilience mechanism of DMN hubs mimicking a physiological reorganization observed in healthy aging.

AB - Multiple sclerosis (MS) is an inflammatory and demyelinating disease which leads to impairment in several functional systems including cognition. Alteration of brain networks is linked to disability and its progression. However, results are mostly cross-sectional and yet contradictory as putative adaptive and maladaptive mechanisms were found. Here, we aimed to explore longitudinal reorganization of brain networks over 2-years by combining diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), magnetoencephalography (MEG), and a comprehensive neuropsychological-battery. In 37 relapsing-remitting MS (RRMS) and 39 healthy-controls, cognition remained stable over-time. We reconstructed network models based on the three modalities and analyzed connectivity in relation to the hierarchical topology and functional subnetworks. Network models were compared across modalities and in their association with cognition using linear-mixed-effect-regression models. Loss of hub connectivity and global reduction was observed on a structural level over-years (p < .010), which was similar for functional MEG-networks but not for fMRI-networks. Structural hub connectivity increased in controls (p = .044), suggesting a physiological mechanism of healthy aging. Despite a general loss in structural connectivity in RRMS, hub connectivity was preserved (p = .002) over-time in default-mode-network (DMN). MEG-networks were similar to DTI and weakly correlated with fMRI in MS (p < .050). Lower structural (β between .23-.33) and both lower (β between .40-.59) and higher functional connectivity (β = -.54) in DMN was associated with poorer performance in attention and memory in RRMS (p < .001). MEG-networks involved no association with cognition. Here, cognitive stability despite ongoing neurodegeneration might indicate a resilience mechanism of DMN hubs mimicking a physiological reorganization observed in healthy aging.

U2 - 10.1002/jnr.25135

DO - 10.1002/jnr.25135

M3 - SCORING: Journal article

C2 - 36263462

VL - 101

SP - 143

EP - 161

JO - J NEUROSCI RES

JF - J NEUROSCI RES

SN - 0360-4012

IS - 1

ER -