Frequency-dependent changes in the amplitude of low-frequency fluctuations in patients with Wilson’s disease: a resting-state fMRI study

To investigate the frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) in patients with Wilson’s disease (WD). Resting-state function magnetic resonance imaging (R-fMRI) were employed to measure the amplitude of ALFF in 28 patients with WD and 27 matched normal controls. Slow-5 (0.01–0.027 Hz) and slow-4 (0.027–0.073 Hz) frequency bands were analyzed. Apart from the observation of atrophy in the cerebellum, basal ganglia, occipital gyrus, frontal gyrus, precentral gyrus, and paracentral lobule, we also found widespread differences in ALFF of the two bands in the medial frontal gyrus, inferior temporal gyrus, insula, basal ganglia, hippocampus/parahippocampal gyrus, and thalamus bilaterally. Compared to normal controls, WD patients had increased ALFF in the posterior lobe of the cerebellum, inferior temporal gyrus, brain stem, basal ganglia, and decreased ALFF in the anterior lobe of the cerebellum and medial frontal gyrus. Specifically, we observed that the ALFF abnormalities in the cerebellum and middle frontal gyrus were greater in the slow-5 than in the slow-4 band. Correlation analysis showed consistently positive correlations between urinary copper excretion (Cu), serum ceruloplasmin (CP) and ALFFs in the cerebellum. Our study suggests the accumulation of copper profoundly impaired intrinsic brain activity and the impairments seem to be frequency-dependent. These results provide further insights into the understanding of the pathophysiology of WD.