Brain activity changes in cognitive networks in relapsing-remitting multiple sclerosis - insights from a longitudinal FMRI study.
BACKGROUND
Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology.


METHODS
13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability.


RESULTS
Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance.


CONCLUSIONS
Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.
Department of Neurology, Medical University of Graz, Graz, Austria.
Marisa
M
Loitfelder
Department of Neurology, Medical University of Graz, Graz, Austria.
Franz
F
Fazekas
Institute of Psychology, Karl-Franzens-University Graz, Graz, Austria, on behalf of the Bio TechMed Initiative.
Karl
K
Koschutnig
Department of Neurology, Medical University of Graz, Graz, Austria.
Siegrid
S
Fuchs
Department of Neurology, Medical University of Graz, Graz, Austria.
Katja
K
Petrovic
Department of Neurology, Medical University of Graz, Graz, Austria.
Stefan
S
Ropele
Department of Neurology, Medical University of Graz, Graz, Austria.
Alexander
A
Pichler
Division of Neuroradiology, Department of Radiology, Medical University of Graz, Graz, Austria.
Margit
M
Jehna
Department of Neurology, Medical University of Graz, Graz, Austria.
Christian
C
Langkammer
Department of Neurology, Medical University of Graz, Graz, Austria.
Reinhold
R
Schmidt
Institute of Psychology, Karl-Franzens-University Graz, Graz, Austria, on behalf of the Bio TechMed Initiative.
Christa
C
Neuper
Department of Neurology, Medical University of Graz, Graz, Austria; Division of Neuroradiology, Department of Radiology, Medical University of Graz, Graz, Austria.
Christian
C
Enzinger
D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D016000:Cluster Analysis; D003071:Cognition / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D013647:Task Performance and Analysis; D013997:Time Factors