Researches On Functional Brain In Amyotrophic Lateral Sclerosis Based On Resting State Functional Magnetic Resonance Imaging

Amyotrophic lateral sclerosis(ALS) is a progressive neurodegenerative disorder involving preliminary upper and lower motor neuron and the trunk, limbs and head and facial muscles it dominate. Sensory dysfunction is the initial symptom in patients with ALS, and it begin to develop into the upper limbs and the trunk. Muscles gradually atrophy, leading to the development of motor dysfunction and the cause of death is respiratory failure, pneumonia, or cardiac arrhythmias. It is widely believed that ALS is a neurodegenerative disease which affects preliminary motor system, however, accumulating studies demonstrate that the degeneration not only affects motor system but also leads to cognitive impairments. The exact pathophysiological mechanism underlying ALS remains unclear until now and ALS currently remains untreatable and entirely fatal.Recent advances in neuroimaging techniques, especially in resting state functional magnetic resonance imaging(fMRI), open the way to provide a deep understanding of the pathophysiology of ALS. Previous resting state fMRI research mainly based on the area or the network of interest, to explore pathophysiological features of ALS, which is dependent strongly on a priori hypothesis rather than investigating resting brain function from a global perspective. Here we applied a voxel-wise method to investigate the changing pattern of fractional amplitude of low-frequency fluctuations and functional network hubs in ALS. We explored the pathophysiology mechanisms underlying ALS from a local energy feature view and a global connectivity feature view. The main contents are:1, Based on resting-state fMRI and voxel-wise fractional amplitude of low-frequency fluctuations(fALFF) method, we investigate low-frequency spontaneous neural activity at the bands of slow-5(0.01–0.027 Hz) and slow-4(0.027–0.073 Hz) in ALS patients and healthy controls. We determined that, at slow-5 band, patients with ALS showed increased fALFF in the right middle frontal gyrus and decreased fALFF in the left middle occipital gyrus. However, compared with healthy controls, patients with ALS exhibited higher fALFF in the right caudate nucleus, left superior frontal gyrus, and right anterior cingulate cortex and lower fALFF in the right inferior occipital gyrus and bilateral middle occipital gyrus at slow-4 band. Furthermore, the f ALFF value in the left superior frontal gyrus at slow-4 band was negatively correlated with functional rating scale-revised score. Our results demonstrated that the fALFF changes in ALS were widespread and frequency dependent.2, With resting-state fMRI, we used whole-brain voxel-wise functional connectivity strength(FCS) to investigate the changing pattern in functional network hubs in ALS. The brain regions with higher FCS value were regarded as functional network hubs. Functional hubs were found mainly in the bilateral precuneus, parietal cortex, medial prefrontal cortex as well as several visual regions and temporal areas in both groups in this study. Within hub regions, ALS patients exhibited higher FCS in the prefrontal cortex as compared with healthy controls. Furthermore, the FCS value in significantly abnormal hub regions was correlated with clinical variables. ALS patients The altered cortical hubs in prefrontal may explain the higher cognitive dysfunction in patients with ALS, providing a novel way to look into the pathophysiology mechanisms underlying ALS.