In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.
Keywords: connectivity, demyelination, white matter, plasticity, neuroimaging, fMRI
Citation: Helekar SA, Shin JC, Mattson BJ, Bartley K, Stosic M, Saldana-King T, Montague PR and Hutton GJ (2010) Functional brain network changes associated with maintenance of cognitive function in multiple sclerosis. Front. Hum. Neurosci. 4:219. doi: 10.3389/fnhum.2010.00219
Received: 29 July 2010;
Accepted: 30 October 2010;
Published online: 22 November 2010.
Edited by:Hauke R. Heekeren, Max Planck Institute for Human Development, Germany
Reviewed by:Nancy Zucker, Duke University Medical Center, USA
Copyright: © 2010 Helekar, Shin, Mattson, Bartley, Stosic, Saldana-King, Montague and Hutton. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Santosh A. Helekar, Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, BCM 295, Houston, TX 77030, USA.e-mail: firstname.lastname@example.org