Abstract
Objective: To identify the abnormal regional spontaneous brain activity associated with relapsing-remitting multiple sclerosis (RRMS) using fractional amplitude of low-frequency fluctuation (fALFF) analysis and their relationships with clinical features.Methods: A total of 26 RRMS (11 males, 15 females; age, 36.58 ± 10.82 years) and 27 status-matched healthy group (HGs; 12 males, 15 females; age, 35.85 ± 12.05 years) underwent an Expanded Disability Status Scale (EDSS) examination. fALFF was applied to evaluate the abnormal regional brain activity associated with RRMS. Pearson's correlation analysis was applied to calculate the correlations between the signal values of brain areas that exhibited abnormal fALFF values and clinical features. Receiver operating characteristic (ROC) curve was performed to evaluate the sensitivity and specificity of those altered brain areas to distinguish between RRMS and HGs.Results: Compared with HGs, RRMS exhibited higher fALFF in the right cerebellum posterior lobe, left orbitofrontal cortex, left dorsolateral prefrontal cortex, bilateral supplementary motor area, and right fusiform gyrus and lower fALFF values in the left hippocampus and right precuneus. ROC revealed that these areas showed two good and five fair AUC values (0.77 ± 0.03, 0.729~0.822). However, four combinations with more than five brain regions received the same best discriminatory power with a sensitivity of 96.3% and a specificity of 88.5%. EDSS revealed a negative correlation with supplementary motor area (r = −0.395, p = 0.046).Conclusions: RRMS is associated with abnormal regional brain activity deficits of motor- and cognitive-related areas. The fALFF parameter may serve as a potential biological marker to discriminate between the two groups.
Highlights
Multiple sclerosis (MS) is a demyelinating disease in axonal degeneration with commonly diagnosed in the prime of life
Plata-Bello et al found a decrease of amplitude of low-frequency fluctuations (ALFF) in the left inferior frontal gyrus in MS patients, and this area correlated with the gray matter volume of the left inferior parietal lobule [11]. van Geest et al found that compared to non-depressed MS patients, depressed MS patients had lower white matter volume (p < 0.01), decreased fractional anisotropy of the uncinate fasciculus (p < 0.05), and lower resting-state functional connectivity between the amygdala and the frontal regions (p < 0.05) [12]
Since the different fALFF areas might be utilized as markers to separate the relapsing-remitting MS (RRMS) from the healthy groups (HGs), the mean fALFF values of these different areas were extracted and used for ROC curve to explore whether the fALFF have the potential ability to distinguish the RRMS from the HGs
Summary
Multiple sclerosis (MS) is a demyelinating disease in axonal degeneration with commonly diagnosed in the prime of life. In addition to classic inflammatory white matter lesions, extensive gray matter demyelination have been gradually known [1, 2]. Cordani et al found widespread gray matter atrophy, microstructural white matter abnormalities, and decreased resting state functional connectivity in motor and cognitive networks in patients with MS, which contribute to explain motor disability in MS patients [10]. The disease duration, fractional anisotropy of the uncinate fasciculus, and the functional connectivity pair could explain 48% of variance in the severity of depression. These findings help us understand the pathophysiology of the MS
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