Patterns of spontaneous brain activity in amyotrophic lateral sclerosis: a resting-state FMRI study

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.

Figure 1. Differences in the spatial patterns of ALFF.

(A) ALFF differences between ALS and control groups without GM correction. There were significant decreased ALFF in visual cortex, fusiform gyrus and right postcentral gyrus, as well as increased ALFF in left middle frontal lobe. (B) ALFF differences between ALS and control groups with GM correction. There were significant decreased ALFF in visual cortex, fusiform gyrus and right postcentral gyrus, as well as increased ALFF in left middle frontal lobe and right inferior frontal gyrus. There were some slight changes after GM correction. For instance, after GM correction, the increased intrinsic brain activities in right inferior frontal gyrus reached significant level (marked by red arrow). Green indicates that ALS patients had decreased ALFF compared with the controls and the red indicates the opposite. The statistical threshold was set at voxel-wise t>3.32 (P<0.001) and cluster level of p<0.05 corrected by FWE.

Figure 2. Correlations between ALFF value in left middle frontal gyrus and clinical measurements.

Left middle frontal gyrus shows increased ALFF and scatter plots show correlations between ALFF of this area and disease progression rate and disease duration in the ALS group.