+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cognitive and Clinical Dysfunction, Altered MEG Resting-State Networks and Thalamic Atrophy in Multiple Sclerosis

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          The relation between pathological findings and clinical and cognitive decline in Multiple Sclerosis remains unclear. Here, we tested the hypothesis that altered functional connectivity could provide a missing link between structural findings, such as thalamic atrophy and white matter lesion load, and clinical and cognitive dysfunction. Resting-state magnetoencephalography recordings from 21 MS patients and 17 gender- and age matched controls were projected onto atlas-based regions-of–interest using beamforming. Average functional connectivity was computed for each ROI and literature-based resting-state networks using the phase-lag index. Structural measures of whole brain and thalamic atrophy and lesion load were estimated from MRI scans. Global analyses showed lower functional connectivity in the alpha2 band and higher functional connectivity in the beta band in patients with Multiple Sclerosis. Additionally, alpha2 band functional connectivity was lower for the patients in two resting-state networks, namely the default mode network and the visual network. Higher beta band functional connectivity was found in the default mode network and in the temporo-parietal network. Lower alpha2 band functional connectivity in the visual network was related to lower thalamic volumes. Beta band functional connectivity correlated positively with disability scores, most prominently in the default mode network, and correlated negatively with cognitive performance in this network. These findings illustrate the relationship between thalamic atrophy, altered functional connectivity and clinical and cognitive dysfunction in MS, which could serve as a bridge to understand how neurodegeneration is associated with altered functional connectivity and subsequently clinical and cognitive decline.

          Related collections

          Most cited references 75

          • Record: found
          • Abstract: found
          • Article: not found

          Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.

          An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.
            • Record: found
            • Abstract: found
            • Article: not found

            Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).

             J. Kurtzke (1983)
            One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
              • Record: found
              • Abstract: found
              • Article: not found

              Consistent resting-state networks across healthy subjects.

              Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3%. In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.

                Author and article information

                [1 ]Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
                [2 ]Department of Clinical Neurophysiology and Magnetoencephalography Center, VU University Medical Center, Amsterdam, The Netherlands
                [3 ]Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands
                [4 ]Department of Anatomy & Neuroscience, VU University Medical Center, Amsterdam, The Netherlands
                [5 ]Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands
                University College of London - Institute of Neurology, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PT AH FB CJS CHP. Performed the experiments: MMS AH BWD. Analyzed the data: PT AH CJS MMS MLM. Contributed reagents/materials/analysis tools: AH CJS. Wrote the paper: PT MMS FB CJS CHP MLM BWD AH.

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                31 July 2013
                : 8
                : 7

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Pages: 11
                This study was sponsored by the Dutch MS Research Foundation, grant numbers 02-358b, 05-358c, 08-650, 09-358d and 10-718. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Cognitive Neuroscience
                Central Nervous System
                Neural Networks
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Diagnostic Medicine
                Clinical Neurophysiology
                Mental Health
                Cognitive Psychology
                Demyelinating Disorders
                Multiple Sclerosis
                Cognitive Neurology
                Diagnostic Radiology
                Magnetic Resonance Imaging



                Comment on this article