ALFF Value in Right Parahippocampal Gyrus Acts as a Potential Marker Monitoring Amyotrophic Lateral Sclerosis Progression: a Neuropsychological, Voxel-Based Morphometry, and Resting-State Functional MRI Study

The aim of this study is to analyze cognitive impairment in amyotrophic lateral sclerosis (ALS). Forty-four participants matched for age, sex, and educational background were enrolled as the sporadic ALS group (n = 22) and the control group (n = 22). All participants completed comprehensive neuropsychological tests, including the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Stroop Color-Word Interference Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery. The participants underwent a series of 3.0 Tesla magnetic resonance imaging (MRI) scans. Resting-state functional MRI (Rs-fMRI) using the amplitude of low-frequency fluctuation (ALFF) was performed. Three-dimensional T1-weighted anatomical images obtained by voxel-based morphometry (VBM) were used to conduct correlation analyses and group comparisons with the demographic and neuropsychological characteristics. The results indicated that the decreased gray matter (GM) volume in the bilateral precentral gyri and increased ALFF values in the right parahippocampal gyrus, left inferior temporal gyrus, left anterior cingulate gyrus, right superior frontal gyrus, and left middle occipital gyrus were identified in the sporadic ALS group. The increased ALFF value in the right parahippocampal gyrus was positively correlated with ALS progression rate. The ALS patients exhibited poor performances on cognitive and executive tests, which were significantly or marginally significantly correlated with the ALFF values in the anterior cingulate gyrus and the frontal, temporal, and parahippocampal cortices. In conclusion, these findings provide evidence of an extramotor involvement and suggest that the ALFF value in the right parahippocampal gyrus could represent a potential marker to monitor disease progression.