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Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, and -degenerative disease that affects the brain's neurophysiological functioning through brain atrophy, a reduced conduction velocity and decreased connectivity. Currently, little is known on how MS affects the fast temporal dynamics of activation and deactivation of the different large-scale, ongoing brain networks. In this study, we investigated whether these temporal dynamics are affected in MS patients and whether these changes are induced by the pathology or by the use of benzodiazepines (BZDs), an important symptomatic treatment that aims at reducing insomnia, spasticity and anxiety and reinforces the inhibitory effect of GABA. To this aim, we employed a novel method capable of detecting these fast dynamics in 90 MS patients and 46 healthy controls. We demonstrated a less dynamic frontal default mode network in male MS patients and a reduced activation of the same network in female MS patients, regardless of BZD usage. Additionally, BZDs strongly altered the brain's dynamics by increasing the time spent in the deactivating sensorimotor network and the activating occipital network. Furthermore, BZDs induced a decreased power in the theta band and an increased power in the beta band. The latter was strongly expressed in those states without activation of the sensorimotor network. In summary, we demonstrate gender-dependent changes to the brain dynamics in the frontal DMN and strong effects from BZDs. This study is the first to characterise the effect of multiple sclerosis and BZDs in vivo in a spatially, temporally and spectrally defined way.

Original publication

DOI

10.1002/hbm.24737

Type

Journal article

Journal

Hum Brain Mapp

Publication Date

01/11/2019

Volume

40

Pages

4789 - 4800

Keywords

benzodiazepines, hidden Markov model, multiple sclerosis, transient brain dynamics, Adult, Benzodiazepines, Beta Rhythm, Brain, Brain Mapping, Cohort Studies, Female, Humans, Hypnotics and Sedatives, Magnetic Resonance Imaging, Magnetoencephalography, Male, Markov Chains, Middle Aged, Multiple Sclerosis, Nerve Net, Sex Characteristics, Theta Rhythm