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      Case-Based fMRI Analysis after Cognitive Rehabilitation in MS: A Novel Approach

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          Abstract

          Background

          Cognitive decline in multiple sclerosis (MS) negatively impacts patients’ everyday functioning and quality of life. Since symptomatic pharmacological treatment is not yet available alternative treatment strategies such as cognitive rehabilitation are of particular interest.

          Objectives

          To analyse the ways in which MS patients respond to cognitive training, by combining behavioral and fMRI data in a case-based triangulation approach.

          Methods

          Ten relapsing-remitting (RR) MS patients aged between 39 and 58 years and between 1 and 8 years post MS diagnosis were included. EDSS ranged from 1 to 3.5. Participants had normal to high intelligence levels. Six patients were assigned to the training group (TG) and four to the control group (CG) without intervention. The TG received a 4-week computerized working memory (WM) training, consisting of 16 training sessions of 45 min duration each. Before and after the training a neuropsychological examination and fMRI investigation by using an N-back task of different complexity was applied.

          Results

          Patients in the TG responded differently to cognitive training. Four participants did not meet the triangulation criteria for being treatment responders. The two responders showed two distinct changes regarding activation patterns after training: (I) decreased brain activation associated with increased processing speed and (II) increased brain activation associated with higher processing speed and WM performance.

          Conclusion

          The occurrence of different and opposed response patterns after the same training indicates a risk in applying classical group statistics. Different and especially opposed patterns within the same sample may distort results of classical statistical comparisons. Thus, underlying processes may not be discovered and lead to misinterpretation of results.

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          Most cited references26

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          The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue.

          Fatigue symptoms are reported by a majority of patients with multiple sclerosis (MS). Reliable assessment, however, is a demanding issue as the symptoms are experienced subjectively and as objective assessment strategies are missing. The objective of this study was to develop and validate a new tool, the Fatigue Scale for Motor and Cognitive Functions (FSMC), for the assessment of MS-related cognitive and motor fatigue. A total of 309 MS patients and 147 healthy controls were included into the validation study. The FSMC was tested against several external criteria (e.g. cognition, motivation, personality and other fatigue scales). The item-analysis and validation procedure showed that the FSMC is highly sensitive and specific in detecting fatigued MS patients, that both subscales significantly differentiated between patients and controls (p 0.91) as well as test-retest reliability (r > 0.80) were high. Cut-off values were determined to classify patients as mildly, moderately or severely fatigued. In conclusion, the FSMC is a new scale that has undergone validation based on a large sample of patients and that provides differential quantification and graduation of cognitive and motor fatigue.
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            Plasticity of executive functioning in young and older adults: immediate training gains, transfer, and long-term maintenance.

            The authors investigated immediate training gains, transfer effects, and 18-month maintenance after 5 weeks of computer-based training in updating of information in working memory in young and older subjects. Trained young and older adults improved significantly more than controls on the criterion task (letter memory), and these gains were maintained 18 months later. Transfer effects were in general limited and restricted to the young participants, who showed transfer to an untrained task that required updating (3-back). The findings demonstrate substantial and durable plasticity of executive functioning across adulthood and old age, although there appear to be age-related constraints in the ability to generalize the acquired updating skill. Copyright (c) 2009 APA, all rights reserved.
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              Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures--an explorative study.

              To evaluate brain changes after cognitive rehabilitation in patients with clinically stable relapsing-remitting (RR) multiple sclerosis (MS) by using neuropsychologic assessment and structural and functional magnetic resonance (MR) imaging techniques. The study was conducted with approval of the involved institutional review boards. Written informed consent was obtained from each participant. Twenty patients with RR MS and cognitive deficits at baseline were randomly assigned to undergo treatment (n = 10), which entailed computer-assisted cognitive rehabilitation of attention and information processing and executive functions, or to serve as a control subjects (n = 10) without cognitive rehabilitation. All patients underwent a standardized neuropsychologic assessment and MR imaging at baseline and after 12 weeks. Changes in gray matter (GM) volumes on three-dimensional T1-weighted images and changes in normal-appearing white matter (NAWM) architecture on diffusion-weighted images were assessed. Changes in functional activity at functional MR imaging during the Stroop task and at rest were also investigated by using linear models. As compared with their performance at baseline, the patients in the treatment group improved at tests of attention and information processing and executive functions. Neither structural modifications to GM volume nor modifications to NAWM architecture were detected at follow-up in both groups. Functional MR imaging demonstrated modifications of the activity of the posterior cingulate cortex (PCC)/precuneus and dorsolateral prefrontal cortex (PFC) during the Stroop task, as well as modifications of the activity of the anterior cingulum, PCC and/or precuneus, left dorsolateral PFC, and right inferior parietal lobule at rest in the treatment group compared with the control group. In the treatment group, functional MR imaging changes were correlated with cognitive improvement (P < .0001 to .01). Rehabilitation of attention and information processing and executive functions in RR MS may be effected through enhanced recruitment of brain networks subserving the trained functions. © RSNA, 2012.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/211627
                URI : http://frontiersin.org/people/u/22050
                URI : http://frontiersin.org/people/u/92671
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                08 April 2015
                2015
                : 6
                : 78
                Affiliations
                [1] 1Department of Cognitive Psychology and Methodology, University of Basel , Basel, Switzerland
                [2] 2Department of Neurology, University Hospital Basel , Basel, Switzerland
                Author notes

                Edited by: Maria Assunta Rocca, Vita-Salute San Raffaele University, Italy

                Reviewed by: Victoria M. Leavitt, Manhattan Memory Center, USA; Ekaterina Dobryakova, Kessler Foundation, USA

                *Correspondence: Iris-Katharina Penner, Department of Cognitive Psychology and Methodology, University of Basel, Missionsstrasse 60/62, Basel CH 4055, Switzerland e-mail: ik.penner@ 123456unibas.ch

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology.

                Article
                10.3389/fneur.2015.00078
                4389546
                25904893
                204d0011-b171-434f-8fb0-49bdad602a89
                Copyright © 2015 Hubacher, Kappos, Weier, Stöcklin, Opwis and Penner.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 January 2015
                : 23 March 2015
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 42, Pages: 8, Words: 5968
                Categories
                Neuroscience
                Original Research

                Neurology
                working memory,cognitive training,rehabilitation,plasticity,multiple sclerosis,fmri
                Neurology
                working memory, cognitive training, rehabilitation, plasticity, multiple sclerosis, fmri

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