| Objective: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease affecting one in 3500 males born and is the second most commonly occurring genetically inherited disease in humans. DMD is characterized by the well-known progressive skeletal muscle weakness and different extent of cognitive impairment. DMD is lack of dystrophin protein which is normally localized in brain to cortical pyramidal neurons, hippocampus and cerebellar Pukinje cells, besides to skeletal muscle. Studies on the mdx model (an animal model of Duchenne muscular dystrophy), found the absolute number and the cell packing density of labeled cortico-spinal neurons were lower in mdx than in controls. To date, there have been only a few in vivo brain imaging studies on DMD patients. Previous brain magnetic resonance imaging (MRI) studies on DMD patients and mdx model did not find prominent structural abnormality in DMD subjects. A PET study on ten boys with DMD and 17 normal adults demonstrated decreased glucose metabolism in children with DMD in the right sensorimotor cortex. Abnormal brain activity was also supported by transcranial magnetic stimulation study, in which the DMD patient revealed decreased excitability in the primary motor cortex. Compared to PET, functional MRI (fMRI) has no radioactivity and is therefore more suitable for children studies. However, it has never been used to study the brain function of DMD patients. Low frequency (0.01-0.08 Hz) fluctuation (LFF) of the resting-state functional MRI signal may reflect the spontaneous brain activity. Resting-state fMRI study does not need cognitive tasks and is very easy to be implemented for children study. Many studies have demonstrated that the LFF is highly synchronous between the bilateral sensorimotor cortex, indicating a highly inter-regional functional connectivity. We have proposed a regional homogeneity (ReHo) approach to measure the synchronization of the LFF of resting-state fMRI signal in bilateral sensorimotor cortex in DMD patients.Methods: In this study, 9 boys with DMD (age range, 7.6~14years) and 13 age-matched normal boys (age range, 7.9~13.5 years) were included in this study. The imaging studies were done using a Siemens 1.5-Tesla scanner (Siemens, Germany). The rest-stating fMRI BOLD images were acquired axially using the following parameters: 2000/40 ms (TR/TE), 20 slices, 5.0/1.0 mm (thickness/gap), 220 mm×220 mm (FOV), 64×64 (resolution), 90o (flip angle). The resting-fMRI scanning session lasted for 390 s. MRI image preprocessing was conducted with Statistical Parametric Mapping (SPM2, (http://www.fil.ion.ucl.ac.uk/spm/), including slice-timing, motion correction, spatial normalization and resampling(3×3×3 mm~3). Subjects with head motion larger than 2 mm maximum displacement in x, y, or z and 1oof any angular motion during the fMRI scan were excluded from further analysis. Then, linear trend was removed, and band-pass filter (0.01–0.08Hz) was computed to reduce low-frequency drift and high-frequency noise by using in-house software Resting-State fMRI Data Analysis Toolkit (REST, http://resting-fmri.sourceforge.net). ReHo analysis was performed for each participant and the ReHo of each voxel was divided by the individual global mean of ReHo within a brain-mask. Subsequently, the functional scans were spatially smoothed with a 8mm×8mm×8mm full width at half maximum Gaussian kernel to decrease spatial noise. We defined bilateral primary sensorimotor cortex and supplementary motor area (SMA) from automated anatomical labeling as a mask.Then second-level random-effect two-sample t-tests were performed on the individual ReHo in a voxel-by-voxel manner in the mask.The functional connectivity analysis was computed in the area of the decreased ReHo in DMD patients compared to controls.Result: Compared with normal controls(9.7±1.3 years), boys with DMD(9.4±1.5 years)showed decreased ReHo in the bilateral sensorimotor cortex, indicating decreased intra-regional synchronization of spontaneous activity. Clusters with a threshold at P<0.05, |t|>2.093 and cluster size more than 810 mm~3 were considered as significant difference between the two groups. The functional connectivity analysis showed decreased functional connectivity (P-value=0.035) between the bilateral decreased ReHo of the sensorimotor cortex in the DMD patients compared to controls.Conclusion: This study was the first study to analyze the intra- and inter-regional synchronization of spontaneous activity in DMD patient by using resting state fMRI. In this study, we found decreased intra- and inter-regional synchronization in the bilateral sensorimotor cortex in DMD patients comparing to controls. The results are similar to previous findings of decreased glucose metabolism in right sensorimotor area and decreased excitability in the left motor cortex in DMD patient. The results may be related to the changes of architectural and functional in bilateral sensorimotor cortex in DMD patients. The previous study about mdx showed decreased number and the cell packing density of labeled cortico-spinal neurons. The decreased intra-regional and inter-regional synchronization in bilateral sensorimotor cortex of DMD patients in the current results may be promoted the relationship with the decreased spontaneous activities of the central nervous system and progressive skeletal muscular dystrophy. This is the first fMRI study on DMD patients. We believe that the future fMRI studies could help us to further understand the pathophysiology in the central nervous system of DMD patients. |
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