Abstract
By detecting spontaneous low-frequency fluctuations (LFF) of blood oxygen level–dependent (BOLD) signals, resting-state functional magnetic resonance imaging (rfMRI) measurements are believed to reflect spontaneous cerebral neural activity. Previous fMRI studies were focused on the examination of motor-related areas and little is known about the functional changes in the extra-motor areas in amyotrophic lateral sclerosis (ALS) patients. The aim of this study is to investigate functional cerebral abnormalities in ALS patients on a whole brain scale. Twenty ALS patients and twenty age- and sex-matched healthy volunteers were enrolled. Voxel-based analysis was used to characterize the alteration of amplitude of low frequency fluctuation (ALFF). Compared with the controls, the ALS patients showed significantly decreased ALFF in the visual cortex, fusiform gyri and right postcentral gyrus; and significantly increased ALFF in the left medial frontal gyrus, and in right inferior frontal areas after grey matter (GM) correction. Taking GM volume as covariates, the ALFF results were approximately consistent with those without GM correction. In addition, ALFF value in left medial frontal gyrus was negatively correlated with the rate of disease progression and duration. Decreased functional activity observed in the present study indicates the underlying deficits of the sensory processing system in ALS. Increased functional activity points to a compensatory mechanism. Our findings suggest that ALS is a multisystem disease other than merely motor dysfunction and provide evidence that alterations of ALFF in the frontal areas may be a special marker of ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive atrophy and weakness of the bulbar, limb, and respiratory muscles, with a median survival of 3–5 years from symptom onset. [1] ALS is predominantly a motor-system-degeneration disease, cognitive and behavioral symptoms have been observed in ALS patients [2]
We applied amplitude of low frequency fluctuation (ALFF) measurement to conduct a whole brain voxel-based analysis of cerebral function during the resting state, and our results revealed the abnormal neural activity outside the motor cortex in ALS patients which remained approximately consistent after controlling for the structural difference
We found reduced ALFF in the inferior occipital lobe, bilateral fusiform gyri, and postcentral gyrus, while increased ALFF was found in left middle frontal gyrus, and in right inferior frontal gyrus after grey matter (GM) correction
Summary
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive atrophy and weakness of the bulbar, limb, and respiratory muscles, with a median survival of 3–5 years from symptom onset. [1] ALS is predominantly a motor-system-degeneration disease, cognitive and behavioral symptoms have been observed in ALS patients [2]. [1] ALS is predominantly a motor-system-degeneration disease, cognitive and behavioral symptoms have been observed in ALS patients [2]. Almost half of ALS patients may have variable degrees of cognitive impairment with typical frontal executive deficits. Fourteen percent of ALS patients may have a clinical subtype of frontotemporal lobar degeneration called frontotemporal dementia [3]. Widespread cerebral degeneration of neurons in typical ALS cases [6,7,8] have been observed in post-mortem studies. Previous studies have suggested that dysfunction of extra-motor systems occurred in ALS patients, such as neurobehavioral dysfunction or frontotemporal dementia, might have negative effects on outcomes of patients [2,9,10]. It is of utmost importance to elucidate functional changes in both motor and extra-motor systems of the brain of ALS patients
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