Abnormal lipid metabolism in skeletal muscle tissue of patients with muscular dystrophy: In vitro,high-resolution NMR spectroscopy based observation in early phase of the disease

PurposeQualitative (assignment of lipid components) and quantitative (quantification of lipid components) analysis of lipid components were performed in skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease as compared to control/normal subjects.MethodsProton nuclear magnetic resonance (NMR) spectroscopy based experiment was performed on the lipid extract of skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease and normal individuals for the analysis of lipid components [triglycerides, phospholipids, total cholesterol and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Specimens of muscle tissue were obtained from patients with Duchenne muscular dystrophy (DMD) [n = 11; Age, Mean ± SD; 9.2 ± 1.4 years; all were males], Becker muscular dystrophy (BMD) [n = 12; Age, Mean ± SD; 21.4 ± 5.0 years; all were males], facioscapulohumeral muscular dystrophy (FSHD) [n = 11; Age, Mean ± SD; 23.7 ± 7.5 years; all were males] and limb girdle muscular dystrophy-2B (LGMD-2B) [n = 18; Age, Mean ± SD; 24.2 ± 4.1 years; all were males]. Muscle specimens were also obtained from [n = 30; Mean age ± SD 23.1 ± 6.0 years; all were males] normal/control subjects.ResultsAssigned lipid components in skeletal muscle tissue were triglycerides (TG), phospholipids (PL), total cholesterol (CHOL) and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Quantity of lipid components was observed in skeletal muscle tissue of DMD, BMD, FSHD and LGMD-2B patients as compared to control/normal subjects. TG was significantly elevated in muscle tissue of DMD, BMD and LGMD-2B patients. Increase level of CHOL was found only in muscle of DMD patients. Level of PL was found insignificant for DMD, BMD and LGMD-2B patients. Quantity of TG, PL and CHOL was unaltered in the muscle of patients with FSHD as compared to control/normal subjects. Linoleic acids were significantly reduced in muscle tissue of DMD, BMD, FSHD and LGMD-2B as compared to normal/control individuals.ConclusionsResults clearly indicate alteration of lipid metabolism in patients with muscular dystrophy in early phase of the disease. Moreover, further evaluation is required to understand whether these changes are primary or secondary to muscular dystrophy. In future, these findings may prove an additional and improved approach for the diagnosis of different forms of muscular dystrophy.     

Our trails and trials in the subsarcolemmal cytoskeleton network and muscular dystrophy researches in the dystrophin era

In 1987, about 150 years after the discovery of Duchenne muscular dystrophy (DMD), its responsible gene, the dystrophin gene, was cloned by Kunkel. This was a new substance. During these 20 odd years after the cloning, our understanding on dystrophin as a component of the subsarcolemmal cytoskeleton networks and on the pathomechanisms of and experimental therapeutics for DMD has been greatly enhanced. During this paradigm change, I was fortunately able to work as an active researcher on its frontiers for 12 years. After we discovered that dystrophin is located on the cell membrane in 1988, we studied the architecture of dystrophin and dystrophin-associated proteins (DAPs) complex in order to investigate the function of dystrophin and pathomechanism of DMD. During the conduct of these studies, we came to consider that the dystrophin-DAP complex serves to transmembranously connect the subsarcolemmal cytoskeleton networks and basal lamina to protect the lipid bilayer. It then became our working hypothesis that injury of the lipid bilayer upon muscle contraction is the cause of DMD. During this process, we predicted that subunits of the sarcoglycan (SG) complex are responsible for respective types of DMD-like muscular dystrophy with autosomal recessive inheritance. Our prediction was confirmed to be true by many researchers including ourselves. In this review, I will try to explain what we observed and how we considered concerning the architecture and function of the dystrophin-DAP complex, and the pathomechanisms of DMD and related muscular dystrophies.     

In vitro mouse model in Duchenne muscular dystrophy diagnosis using 50-MHz ultrasound waves

Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, the protein that plays a key mechanical role in maintaining muscle membrane integrity. One of the major consequences of dystrophin deficiency is the degeneration of muscle fibres, with a progressive loss in muscle strength. The objective of this research was to find an ultrasonic parameter sensitive to DMD, which could give relevant information related to microstructure if compared to traditional investigations such as morphometrical analysis. This “in vitro” study focused on the Mdx mouse model and investigated the potential differences between wild-type and dystrophin-deficient mice diaphragms. Using a 50 MHz ultrasonic sensor built in our group, we recorded an increase in ultrasonic wave attenuation in the dystrophin-deficient samples in comparison with normal muscles. A correlation between attenuation, mouse age and the percentage of non-muscular proportion in muscle was observed. As Mdx mouse is the best animal model for DMD and reproduces the degenerative pattern observed in human DMD muscles, this approach could be a powerful tool for in vitro DMD investigation and, more generally, for the characterisation of muscle properties.     

Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport

Background

Duchenne musclar dystrophy (DMD) is an X-linked recessive disease caused by mutations of dystrophin gene, there is no effective treatment for this disorder at present. Plasmid-mediated gene therapy is a promising therapeutical approach for the treatment of DMD. One of the major issues with plasmid-mediated gene therapy for DMD is poor transfection efficiency and distribution. The herpes simplex virus protein VP22 has the capacity to spread from a primary transduced cell to surrounding cells and improve the outcome of gene transfer. To improve the efficiency of plasmid-mediated gene therapy and investigate the utility of the intercellular trafficking properties of VP22-linked protein for the treatment for DMD, expression vectors for C-terminal versions of VP22-microdystrophin fusion protein was constructed and the VP22-mediated shuttle effect was evaluated both in vitro and in vivo.

Results

Our results clearly demonstrate that the VP22-microdystrophin fusion protein could transport into C2C12 cells from 3T3 cells, moreover, the VP22-microdystrophin fusion protein enhanced greatly the amount of microdystrophin that accumulated following microdystrophin gene transfer in both transfected 3T3 cells and in the muscles of dystrophin-deficient (mdx) mice.

Conclusion

These results highlight the efficiency of the VP22-mediated intercellular protein delivery for potential therapy of DMD and suggested that protein transduction may be a potential and versatile tool to enhance the effects of gene delivery for somatic gene therapy of DMD.     

Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS)

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies.     

Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study

The metabolic differences in the skeletal muscle of patients with Duchenne muscular dystrophy (DMD) and normal subjects (controls) were investigated using in-vitro high-resolution proton NMR spectroscopy. In all, 56 metabolites were unambiguously identified in the perchloric acid extract of muscle tissue using one- and two-dimensional NMR. The concentrations of glycolytic substrate glucose (Glc; p < 0.05), gluconeogenic amino acids such as glutamine (Gln; p < 0.05) and alanine (Ala; p < 0.05) and the glycolytic product lactate (Lac; p < 0.05) were statistically significantly lower in DMD patients as compared to controls. A significant reduction in the concentrations of total creatine (TCr; p < 0.05), glycerophosphoryl choline + phosphoryl choline + carnitine (GPC/PC/Car; p < 0.05), choline (Cho; p < 0.05) and acetate (Ace; p < 0.05) was also observed in these patients. Decrease in the level of glucose may be attributed to the reduction in the concentrations of gluconeogenic substrates or membrane abnormalities in degenerated muscle of DMD patients. Lower levels of choline containing compounds indicate membrane abnormalities. Decrease in the concentration of lactate in the muscle of DMD patients may be due to the reduction in anaerobic glycolytic activity or lower substrate concentration. The decrease in the concentration of acetate may reflect reduced transport of fatty acids into mitochondria due to decreased concentration of carnitine in DMD patients. Kreb's cycle intermediate alpha-ketoglutarate was observed only in the diseased muscle, which is suggestive of predominant oxidative metabolism for energy generation.     

利用小波变换和神经网络对罕见病DMD的MRI进行分类识别

杜兴氏肌营养不良(DMD)是一种严重的儿童腿部神经肌肉罕见病。传统的诊断和检测方案一般为有创手段,会带给患儿极大的痛苦。基于受试者的磁共振图像(MRI),采用计算机辅助检测手段探索了有效的无创检测方法。实验分别选用sym4和db4两种小波基函数,对患儿组和健康对照组的MRI进行三种尺度的小波分解,从所得的分解图像中提取12个纹理特征参数,并利用人工神经网络(ANN)算法对图像参数进行分类识别。结果显示:在受试者的两类MRI加权图像(T1和T2)中,T1图像能更好地区分患儿与健康儿童;利用db4函数对图像进行小波分解,其效果略优于sym4函数,且在三种小波分解尺度中,以二层分解最优;利用ANN算法对图像进行分类识别,其灵敏度、特异度和准确率分别高达98.5%、97.3%和97.9%。该处理方法有望为临床提供客观有效的辅助诊断手段,可作为DMD疾病无创检测的尝试探索。     

The Change of Grip Strength in a Patient with Congenital Myotonic Dystrophy Over a 4-year Period

Myotonic dystrophy (MyD) is a neuromuscular disease that is autosomal dominant and the most common form of muscular dystrophy affecting adults. The clinical features of MyD include a multisystemic disorder characterized by myotonia, progressive muscle weakness and wasting, cataracts, premature balding and mental retardation. The most severe type of MyD is classified as congenital MyD (CMyD). The muscle weakness in CMyD is very severe, but muscle development can be observed in the period of growth. However, no clinical case of this type has been reported yet. Therefore, we report on a girl with CMyD who had an increase in muscle strength over a four-year period. The girl with CMyD participated in this study from the age of 9 to the age of 12. The measurement of muscle strength was recorded as the maximum score of grip strength with the use of dynamometers. Grip strength was assessed once a year by the same two physical therapists. Grip strength of CMyD for each year was markedly weak when compared with the normal controls, but muscle strength changed within some specific growth areas. The muscle weakness in CMyD was remarkable, but the result showed that specific muscle strength of CMyD in childhood was actually increased.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

Evaluation of muscle degeneration in inherited muscular dystrophy by nuclear magnetic resonance techniques

Nuclear magnetic resonance (NMR) techniques were applied to study the muscular dystrophy in chicks. The water proton spin-lattice relaxation times (T₁) of fast, slow, and mixed muscles and plasma were measured. The T₁ values of dystrophic pectoralis major and posterior latissimus dorsi (PLD) were significantly higher than those of the normal pectoralis and PLD muscles. The present results establish a direct relationship between the differences in T₁ values and the severity of muscle degeneration. Consistent with this conclusion, it was also found that the T₁ values of muscles unaffected in muscular dystrophy, namely, the gastrocnemius, and anterior latissimus dorsi (ALD), were not different between the normal and dystrophic chicks. Although the affected muscles of dystrophic chicks contained higher percent water and fat than those of normal chicks, the results show that the higher T₁ values is dystrophic muscles were not solely due to variations in their water content. The increase in the T₁ values is principally a result of altered interaction between cellular water and macromolecules in the diseased muscles. These data also point out the potential use of NMR imaging in evaluating muscle degeneration.     

Pixel-based partially coherent image method for maskless lithography system

Maskless lithography (ML) provides a fast and low-cost method for projecting the images of IC or micro features onto photoresist. However, it needs an efficient simulation method to evaluate the performance of lithography process. In this paper, a pixel-based partially coherent image method for digital micro-mirror device (DMD) based ML is proposed based on the linear invariant theory. In our method, the mask is sampled by DMD pixel (each pixel corresponding to each micro-mirror) and expressed by rect function. Using the shift theory of Fourier transform and the stacked pupil operator approach, we build a matrix Φ for system response function of rect function. If the DMD pixel state matrix is S, then the aerial image can be calculated with two matrix multiplication I(x,y) = SΦ.     

Diffusion tensor imaging in horizontal gaze palsywith progressive scoliosis

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare disorder characterized by absence of conjugate horizontal eye movements, preservation of vertical gaze and convergence, progressive scoliosis developing in childhood and adolescence. It is caused by mutations in the ROBO3 gene which are critical for the crossing of long ascending medial lemniscal and descending corticospinal tracts in the medulla. Diffusion tensor imaging on a 14-year-old boy with HGPPS revealed ipsilateral ascending and descending connectivity in the brainstem without any crossing over of the major tracts although normal interhemispheric connections in the corpus callosum was demonstrable. Absent decussation of smaller sized superior cerebellar peduncles but with normal crossing over of the middle cerebellar peduncle was also observed. Tractography is a valuable investigative modality to assess neuronal connections in the brain and is a useful adjunct to the structural magnetic resonance imaging in confirming the diagnosis of HGPPS.     

利用DMD获取高动态范围图像技术

高动态范围的图像可用于同时探测具有较大对比度的亮暗目标,利用数字微镜(DMD)获取高动态范围图像是目前最为先进的一种技术。本文在分析DMD工作原理的基础上,设计了一种像素级的高动态范围图像获取系统,该系统由光学系统、机械系统、DMD像素级调光算法及成像单元组成。光学系统采用二次成像光路,其中第一次成像物镜采用像方远心光路,第二次成像的转置镜头采用放大倍率近似1: 1的准对称结构,机械系统采用光学元件的包边设计和定心车工艺,达到秒级的光学装配精度;DMD像素级调光算法采用搜索单个微镜像素在图像帧周期间的控制权值实现,成像单元可同时兼顾科学级12 bit sCMOS和8 bit CCD,设计完成的原理样机验证了系统设计的正确性,其获取的图像动态范围可达140 dB以上,远高于传统摄像机78 dB的动态范围。     

DMD和POD对超燃冲压发动机凹腔流动的稳定性分析

开式凹腔作为超燃冲压发动机中增加掺混和稳焰的装置, 其流动稳定性的研究对深入理解凹腔增加掺混和稳焰机理以及凹腔的设计有着重要的学术意义和工程应用价值.基于大涡模拟方法对超燃冲压发动机开式凹腔流动进行数值模拟, 分别采用动力学模态分解(dynamic mode decomposition, DMD)和本征正交分解方法(proper orthogonal decomposition, POD)对自激振荡流动进行稳定性分析. DMD方法可准确提取凹腔的振荡频率, 与Rossiter模型以及压力脉动FFT分析得到的频率吻合较好, 且DMD中对应Rossiter前3阶频率的模态在流动中的主导作用顺序也与FFT分析结果一致, 自激振荡中RossiterⅢ模态占据主导作用, 同时DMD方法对Rossiter 3阶以上模态频率的预测能力明显强于FFT分析方法.在对低频的提取方面, DMD方法比Rossiter模型更具有优势.与前6阶Rossiter模态对应DMD模态均缓慢收敛, 主要表现为剪切层中的分离涡结构和中部及下游区域中的涡结构.前3阶不稳定模态中的分离涡结构主要集中在中部剪切层以及后缘附近区域. POD方法中较少的模态包含流场绝大部分的能量.但是, 通过POD方法提取的模态频率在分辨率上效果不佳, 提取到最低频率为Rossiter 3阶模态对应的频率, 且模态中均存在次频, 次频与主频之间的耦合导致模态的形态相差较大.另外, 与DMD方法相比POD方法无法判断所提取的模态的稳定性.      

Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control (p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group (p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group (p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.     

Digital Micro-mirror Device-based broadband optical image sensor for robust imaging applications

To the best of the authors' knowledge, presented for the first time is the design of a robust broadband optical image sensor using a Digital Micro-mirror Device (DMD). Electronic focus control of the imaging lens and full programmability of the spatial sampling aperture shape, size, and location on the DMD plane that mechanically scans the incident incoherent optical irradiance distribution lead to imaging smartness. Dual port single-point photo-detection design provides imaging operation robustness to the global light irradiance variations such as via environmental effects, e.g., moving clouds. As the Texas Instruments (TI) DMD can provide light modulation over 400 nm to 2500 nm wavelengths, visible, Near Infrared (NIR), and Short-Wave Infrared (SWIR) bands can be simultaneously processed to generate three independent band images via three point photo-detectors. A proof-of-concept experiment in the SWIR band at 1580 nm is conducted using an incoherent heart-shaped target that is sampled using the DMD imager set for a 68.4 μm side square moving pinhole. A 60 × 60 pixel image from the proposed imager produces a 0.94 cross-correlation peak when compared to an optically attenuated heart shape image produced by a near 9 μm pixel size phosphor coated Charge Coupled Device (CCD) imager. Using the dual-detection method, robust 633 nm visible light imaging of an Air Force (AF) Chart figure is successfully demonstrated for 3 Hz global light fluctuation. Applications for the proposed imager include optical sensing in the fields of astronomy, defense, medicine, and security.     

Comments on the electric modulus formalism model and superior alternatives to it for the analysis of the frequency response of ionic conductors

Because of the past and continuing wide usage of the 1973 original modulus formalism (OMF) model for analyzing dispersive frequency-response data of ion-conducting materials, it is important to discuss and demonstrate its theoretical and experimental inadequacies to help avoid its future use and to describe and illustrate important alternatives to it. The OMF fits data with a K1 response model alone, one indirectly derived from stretched-exponential temporal behavior, while the corrected modulus formalism (CMF) involves the composite CK1 model, one that includes in addition a separate free, parallel bulk dielectric parameter, ε_D∞. The crucial error of the OMF approach is its identification of a high-frequency-limiting dielectric constant intrinsic to K1 response and associated entirely with conductive effects, with the full high-frequency-limiting dielectric constant of the material, ε_∞, one that must include the non-ionic, primarily dipolar quantity ε_D∞. Comparison here of OMF fitting results with those of the CMF CK1 model for both an experimental data set and an exact one derived from it demonstrate the incorrectness of the OMF and the virtues of the CK1 alternative. The OMF fitting approach, but not the CMF one, leads to crucial inconsistency between the estimates of its β shape parameter for fits of the data expressed at all immittance levels except those of σ′ and ε″, where it yields the same results as the CK1. Its incorrect β estimates, extensively used in the Ngai coupling model and interpreted as being associated with ion–ion correlations, also lead to erroneous “excess wing” effects in plots of the imaginary part of the data and fit at the modulus level. Further, OMF modulus-level fits yield non-physical estimated values of the characteristic relaxation time of the K1 model. Finally, some possible alternatives to the CK1 model are discussed for situations involving dielectric-system dispersion.     

投影系统中DMD衍射效率的研究北大核心CSCD

数字微镜阵列(DMD)作为空间调制元件常用于投影光学系统,入射光为长波红外时产生的衍射效应会影响进入系统的能量分布,该文主要讨论光源入射角度对衍射效应的影响,将DMD作为闪耀光栅模型,研究其在长波红外波段产生的衍射效应。从光程差的角度分析在主、副对角线分别处于“开态”情况下的衍射效应,发现衍射效应与入射角度有关;将DMD作为闪耀光栅模型,采用矢量衍射理论计算7.7μm~9.5μm波段下DMD处于“开态”下的衍射效率。计算结果表明:当TM偏振光以44°角照射时,1级衍射达到闪耀状态,衍射效率可达到70%。     

Functional MRI changes in the central motor system in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disease involving multiple organ systems including central nervous system (CNS) and muscles. Few studies have focused on the central motor system in DM1, pointing to a subclinical abnormality in the CNS. The aim of our study was to investigate patterns of cerebral activation in DM1 during a motor task using functional MRI (fMRI). Fifteen DM1 patients, aged 20 to 59 years, and 15 controls of comparable age were scanned during a self-paced sequential finger-to-thumb opposition task of their dominant right hand. Functional MRI images were analyzed using SPM99. Patients underwent clinical and genetic assessment; all subjects underwent a conventional MR study. Myotonic dystrophy type 1 patients showed greater activation than controls in bilateral sensorimotor areas and inferior parietal lobules, basal ganglia and thalami, in the ipsilateral premotor area, insula and supplementary motor area (corrected P<.05). Analysis of the interaction between disease and age showed that correlation with age was significantly greater in patients than in controls in bilateral sensorimotor areas and in contralateral parietal areas. Other clinical and MR characteristics did not correlate with fMRI. Functional changes in DM1 may represent compensatory mechanisms such as reorganization and redistribution of functional networks to compensate for ultrastructural and neurochemical changes occurring as part of the accelerated aging process.     

Change in brain activity through virtual reality-based brain-machine communication in a chronic tetraplegic subject with muscular dystrophy

Background  

For severely paralyzed people, a brain-computer interface (BCI) provides a way of re-establishing communication. Although subjects with muscular dystrophy (MD) appear to be potential BCI users, the actual long-term effects of BCI use on brain activities in MD subjects have yet to be clarified. To investigate these effects, we followed BCI use by a chronic tetraplegic subject with MD over 5 months. The topographic changes in an electroencephalogram (EEG) after long-term use of the virtual reality (VR)-based BCI were also assessed. Our originally developed BCI system was used to classify an EEG recorded over the sensorimotor cortex in real time and estimate the user's motor intention (MI) in 3 different limb movements: feet, left hand, and right hand. An avatar in the internet-based VR was controlled in accordance with the results of the EEG classification by the BCI. The subject was trained to control his avatar via the BCI by strolling in the VR for 1 hour a day and then continued the same training twice a month at his home.