Functional correlates of cognitive dysfunction in multiple sclerosis: A multicenter fMRI Study |
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| Authors: | Maria A. Rocca Paola Valsasina Hanneke E. Hulst Khaled Abdel‐Aziz Christian Enzinger Antonio Gallo Debora Pareto Gianna Riccitelli Nils Muhlert Olga Ciccarelli Frederik Barkhof Franz Fazekas Gioacchino Tedeschi Maria J. Arévalo The MAGNIMS fMRI Study Group |
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| Affiliation: | 1. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita‐Salute San Raffaele University, Milan, Italy;2. Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita‐Salute San Raffaele University, Milan, Italy;3. Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands;4. NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom;5. Department of Neurology, Medical University of Graz, Austria;6. MRI Center “SUN‐FISM,” Second University of Naples and Institute of Diagnosis and Care “Hermitage‐Capodimonte,”, Naples, Italy;7. I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy;8. Magnetic Resonance Unit, Department of Radiology, CEM‐Cat, Hospital Universitari Vall d'Hebron, Barcelona, Spain;9. Unitat de Neuroimmunologia Clinica, CEM‐Cat, Hospital Universitari Vall d'Hebron, Barcelona, Spain |
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| Abstract: | In this multicenter study, we applied functional magnetic resonance imaging (fMRI) to define the functional correlates of cognitive dysfunction in patients with multiple sclerosis (MS). fMRI scans during the performance of the N‐back task were acquired from 42 right‐handed relapsing remitting (RR) MS patients and 52 sex‐matched right‐handed healthy controls, studied at six European sites using 3.0 Tesla scanners. Patients with at least two abnormal (<2 standard deviations from the normative values) neuropsychological tests at a standardized evaluation were considered cognitively impaired (CI). FMRI data were analyzed using the SPM8 software, modeling regions showing load‐dependent activations/deactivations with increasing task difficulty. Twenty (47%) MS patients were CI. During the N‐back load condition, compared to controls and CI patients, cognitively preserved (CP) patients had increased recruitment of the right dorsolateral prefrontal cortex. As a function of increasing task difficulty, CI MS patients had reduced activations of several areas located in the fronto‐parieto‐temporal lobes as well as reduced deactivations of regions which are part of the default mode network compared to the other two groups. Significant correlations were found between abnormal fMRI patterns of activations and deactivations and behavioral measures, cognitive performance, and brain T2 and T1 lesion volumes. This multicenter study supports the theory that a preserved fMRI activity of the frontal lobe is associated with a better cognitive profile in MS patients. It also indicates the feasibility of fMRI to monitor disease evolution and treatment effects in future studies. Hum Brain Mapp 35:5799–5814, 2014. © 2014 Wiley Periodicals, Inc. |
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| Keywords: | multiple sclerosis fMRI cognition cognitive impairment prefrontal cortex default mode network functional reserve |
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