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Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

ABSTRACT: Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n?=?12) and non-impaired (MSNI, n?=?9) multiple sclerosis (MS) patients.The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought.A total of 50 patients (EDSS mean ( m)?=?3.2, disease duration (DD) m?=?12?years, and age m?=?40?years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS.A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p?=?0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p?=?0.005, 0.004, respectively).I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.

SUBMITTER: Nelson F

PROVIDER: S-EPMC5344745 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

Nelson Flavia F Akhtar Mohammad A MA Zúñiga Edward E Perez Carlos A CA Hasan Khader M KM Wilken Jeffrey J Wolinsky Jerry S JS Narayana Ponnada A PA Steinberg Joel L JL

Multiple sclerosis (Houndmills, Basingstoke, England) 20160909 6

<h4>Background</h4>Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients.<h4>Objectives</h4>The aim of the study w ...[more]

PMID: 27613119

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Project description:Introduction: Individuals with multiple sclerosis (MS) are vulnerable to deficits in working memory (WM), but the search for neural correlates of WM within circumscribed areas has been inconclusive. Given the widespread neural alterations observed in MS, predictive modeling approaches that capitalize on whole-brain connectivity may better capture individual differences in WM. Materials and Methods: We applied connectome-based predictive modeling to functional magnetic resonance imaging data from WM tasks in two independent samples with relapsing-remitting MS. In the internal sample (ninternal = 36), cross-validation was used to train a model to predict accuracy on the Paced Visual Serial Addition Test from functional connectivity. We hypothesized that this MS-specific model would successfully predict performance on the N-back task in the validation cohort (nvalidation = 36). In addition, we assessed the generalizability of existing WM networks derived in healthy young adults to these samples, and we explored anatomical differences between the healthy and MS networks. Results: We successfully derived an MS-specific predictive model of WM in the internal sample (full: rs = 0.47, permuted p = 0.011), but the predictions were not significant in the validation cohort (rs = -0.047; p = 0.78, mean squared error [MSE] = 0.006, R2 = -2.21%). In contrast, the healthy networks successfully predicted WM in both MS samples (internal: rs = 0.33 p = 0.049, MSE = 0.009, R2 = 13.4%; validation cohort: rs = 0.46, p = 0.005, MSE = 0.005, R2 = 16.9%), demonstrating their translational potential. Discussion: Functional networks identified in a large sample of healthy individuals predicted significant variance in WM in MS. Networks derived in small samples of people with MS may have limited generalizability, potentially due to disease-related heterogeneity. The robustness of models derived in large clinical samples warrants further investigation. ClinicalTrials.gov ID: NCT03244696.

Project description:Purpose: Exercise training reveals high potential to beneficially impact cognitive performance in persons with multiple sclerosis (pwMS). Research indicates that high-intensity interval training (HIIT) has potentially higher effects on physical fitness and cognition compared to moderate continuous exercise. This study (i) compares the effects of a 3-week HIIT and moderate continuous exercise training on cognitive performance and cardiorespiratory fitness of pwMS in an overall analysis and (ii) investigates potential effects based on baseline cognitive status in a subgroup analysis. Methods: Seventy-five pwMS were randomly assigned to an intervention (HIIT: 5 × 1.5-min intervals at 95-100% HRmax, 3 ×/week) or active control group (CG: 24 min continuous exercise at 65% HRmax, 3 ×/week). Cognitive performance was assessed pre- and post-intervention with the Brief International Cognitive Assessment for MS (BICAMS). (I) To examine potential within (time) and interaction (time × group) effects in the overall analysis, separate analyses of covariance (ANCOVA) were conducted. (II) For the subgroup analysis, participants were divided into two groups [intact cognition or impaired cognition (>1.5 standard deviation (SD) compared to healthy, age-matched norm data in at least one of the three tests of the BICAMS]. Potential impacts of cognitive status and intervention were investigated with multivariate analyses of variance (MANOVA). Results: Overall analysis revealed significant time effects for processing speed, verbal learning, rel. VO2peak, and rel. power output. A time*group interaction effect was observed for rel. power output. Subgroup analysis indicated a significant main effect for cognition (impaired cognition vs. intact cognition). Subsequent post-hoc analysis showed significant larger effects on verbal learning in pwMS with impaired cognition. Conclusion: Current results need to be confirmed in a powered randomized controlled trial with cognitive performance as primary endpoint and eligibility based on cognitive performance that is assessed prior to study inclusion.

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Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

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Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

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