To investigate the effects of cortical thickness on the identification accuracy of fractional amplitude of low-frequency fluctuation (fALFF) in patients with multiple sclerosis (MS). Resting-state functional magnetic resonance imaging data were collected from 31 remitting MS, 20 acute MS, and 42 healthy controls (HCs). After preprocessing, we first calculated two-dimensional fALFF (2d-fALFF) maps using the DPABISurf toolkit, and 2d-fALFF per unit thickness was obtained by dividing 2d-fALFF by cortical thickness. Then, between-group comparison, clinical correlation, and classification analyses were performed in 2d-fALFF and 2d-fALFF per unit thickness maps. Finally, we also examined whether the effect of cortical thickness on 2d-fALFF maps was affected by the subfrequency band. In contrast with 2d-fALFF, more changed regions in 2d-fALFF per unit thickness maps were detected in MS patients, such as increased region of the right inferior frontal cortex and faded regions of the right paracentral lobule, middle cingulate cortex, and right medial temporal cortex. There was a significant positive correlation between the disease duration and the 2d-fALFF values in the left early visual cortex in remitting MS patients (r = 0.517, Bonferroni-corrected, p = 0.008 × 4 < 0.05). In contrast with 2d-fALFF, we detected a positive correlation between the 2d-fALFF per unit thickness of the right ventral stream visual cortex and the modified Fatigue Impact Scale (MFIS) scores (r = 0.555, Bonferroni-corrected, p = 0.017 × 4 > 0.05). For detecting MS patients, 2d-fALFF and 2d- fALFF per unit thickness both performed remarkably well in support vector machine (SVM) analysis, especially in the remitting phase (AUC = 86, 83%). Compared with 2d-fALFF, the SVM model of 2d-fALFF per unit thickness had significantly higher classification performance in distinguishing between remitting and acute MS. More changed regions and more clinically relevant 2d-fALFF per unit thickness maps in the subfrequency band were also detected in MS patients. By dividing the functional value by the cortical thickness, the identification accuracy of fALFF in MS patients was detected to be potentially influenced by cortical thickness. Additionally, 2d-fALFF per unit thickness is a potential diagnostic marker that can be utilized to distinguish between acute and remitting MS patients. Notably, we observed similar variations in the subfrequency band.
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