Abstract
The correlation between fatigue and cognitive performance in multiple sclerosis (MS) is well reported, but the intimate mechanisms of the fatigue impact on cognition are not fully defined yet. The aim of this study is to investigate blood oxygen level–dependent (BOLD) activations in relapsing remitting MS (RRMS) patients with and without cognitive dysfunction and the impact of fatigue on cortical activations. Forty-two patients with RRMS were enrolled in the study. Cognitive functioning was assessed by the Symbol Digit Modalities Test (SDMT) and Paced Serial Addition Test (PASAT). A cutoff point of a total score of 55 on the SDMT was used to divide the patients into two groups: cognitively impaired (CI), SDMT score equal to or below 55 points, and cognitively preserved (CP), SMDT score above 55 points. Fatigue was assessed by the Modified Fatigue Impact Scale (MFIS). Participants were assessed with the Beck Depression Inventory (BDI) prior to inclusion in order to exclude major depressive episode. Functional Magnetic Resonance Imaging (fMRI) scanning was performed on a 3T MRI. The PVSAT (Paced Visual Serial Addition Test) paradigm was applied as a cognitive task. All functional data were analyzed with SPM12 and statistical analysis with SPSS 19.0. No statistically significant differences between CI and CP patients were found (p=0.953, p=0.322) in the MFIS and BDI score. Performance on the PASAT in CI patients was 34.07±13.721, for CP patients 46.42±11.453, and the SDMT performance in the CI patient group was 42.40±9.179, in the CP group 57.83±2.552. Between-group analysis revealed increased activations in left Brodmann area (BA) 40 in CP patients with several clusters located in the left supramarginal gyrus. Regression analysis showed increased BOLD signal in left BA 40, right BA 40, and left BA 6, associated with a higher score on MFIS. Stronger BOLD signal in left BA 31 was associated with a lower score on MFIS. Significance level was set to p<0.05, FWE (family-wise error) corrected. The differences in BOLD activations suggest the presence of cortical reorganization in our CP patients. The impact of fatigue on cortical activation during a cognitive task is demonstrated by inconformity of activated areas depending on the MFIS score. Our results suggest that activation in BA 40 may represent a mechanism for diminishing fatigue impact on cognitive functioning in CP patients.
Highlights
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) characterized with widespread lesions in brain and spinal cord
A cutoff point of a total score of 55 on the Symbol Digit Modalities Test (SDMT) was used to divide the patients into two groups: cognitively impaired (CI), SDMT score equal to or below 55 points, and cognitively preserved (CP), SMDT score above 55 points, based on the predictive value of the SDMT score proven by Parmenter et al [10]
The neuropsychological assessment of our subjects confirmed the predictive value of SDMT for cognitive dysfunction as established by Parmenter et al This is evidenced by the significant difference in performance on the Paced Serial Addition Test (PASAT) in both groups [10]
Summary
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) characterized with widespread lesions in brain and spinal cord. The MS-related cognitive dysfunction appears in various domains such as attention, information processing speed, processing efficiency, executive functioning, and working memory. These deficits affect many aspects of daily life, resulting in decreased quality of life [2]. The assessment of fatigue is most often conducted with selfreport questionnaires They range from single-item scales such as a visual analogue scale (VAS) to multidimensional scales incorporating several dimensions of fatigue such as physical and mental. The aim of this study is to investigate blood oxygen level–dependent (BOLD) activations in RRMS patients with and without cognitive dysfunction and the impact of fatigue on cortical activations
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