Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis.
Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark of the resting brain. In relapsing-remitting multiple sclerosis (RRMS) several fMRI studies have suggested altered resting-state connectivity patterns. Topographical EEG analysis reveals much faster temporal fluctuations in the tens of milliseconds time range (termed "microstates"), which showed altered properties in a number of neuropsychiatric conditions. We investigated whether these microstates were altered in patients with RRMS, and if the microstates' temporal properties reflected a link to the patients' clinical features. We acquired 256-channel EEG in 53 patients (mean age 37.6 years, 45 females, mean disease duration 9.99 years, Expanded Disability Status Scale ≤ 4, mean 2.2) and 49 healthy controls (mean age 36.4 years, 33 females). We analyzed segments of a total of 5 min of EEG during resting wakefulness and determined for both groups the four predominant microstates using established clustering methods. We found significant differences in the temporal dynamics of two of the four microstates between healthy controls and patients with RRMS in terms of increased appearance and prolonged duration. Using stepwise multiple linear regression models with 8-fold cross-validation, we found evidence that these electrophysiological measures predicted a patient's total disease duration, annual relapse rate, disability score, as well as depression score, and cognitive fatigue measure. In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.
Department of Neurology, University Hospital Geneva, Geneva, Switzerland; Functional Brain Mapping Laboratory, Department of Neuroscience, Biotech Campus, University of Geneva, Geneva, Switzerland.
Markus
M
Gschwind
Neurologic Clinic and Policlinic and Clinical Neurophysiology, Departments of Medicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Martin
M
Hardmeier
Department of Radiology, Center for Biomedical Imaging, University Hospital Geneva, Geneva, Switzerland; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Center for Biomedical Imaging, Lausanne and Geneva, Switzerland.
Dimitri
D
Van De Ville
Functional Brain Mapping Laboratory, Department of Neuroscience, Biotech Campus, University of Geneva, Geneva, Switzerland.
Miralena I
MI
Tomescu
Department of Cognitive Psychology and Methodology, University of Basel, Basel, Switzerland.
Iris-Katharina
IK
Penner
Neurologic Clinic and Policlinic and Clinical Neurophysiology, Departments of Medicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Yvonne
Y
Naegelin
Neurologic Clinic and Policlinic and Clinical Neurophysiology, Departments of Medicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Peter
P
Fuhr
Functional Brain Mapping Laboratory, Department of Neuroscience, Biotech Campus, University of Geneva, Geneva, Switzerland; Center for Biomedical Imaging, Lausanne and Geneva, Switzerland.
Christoph M
CM
Michel
Department of Neurology, University Hospital Geneva, Geneva, Switzerland; Functional Brain Mapping Laboratory, Department of Neuroscience, Biotech Campus, University of Geneva, Geneva, Switzerland.
Margitta
M
Seeck
D000328:Adult; D001931:Brain Mapping; D058256:Brain Waves / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales
D010100:Oxygen
Annual relapse rate; Center for Epidemiologic Studies Depression Scale; Disease duration; Expanded Disability Status Scale; Fatigue Scale for Motor and Cognitive Functions; High-density EEG; Microstates; Topographical EEG analysis