Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5.

BACKGROUND AND PURPOSE: White matter (WM) damage is the main target of hereditary spastic paraplegia (HSP), but mounting evidence indicates that genotype-specific grey matter (GM) damage is not uncommon. Our aim was to identify and compare brain GM and WM damage patterns in HSP subtypes and investigate how gene expression contributes to these patterns, and explore the relationship between GM and WM damage. METHODS: In this prospective single-centre cohort study from 2019 to 2022, HSP patients and controls underwent magnetic resonance imaging evaluations. The alterations of GM and WM patterns were compared between groups by applying a source-based morphometry approach. Spearman rank correlation was used to explore the associations between gene expression and GM atrophy patterns in HSP subtypes. Mediation analysis was conducted to investigate the interplay between GM and WM damage. RESULTS: Twenty-one spastic paraplegia type 4 (SPG4) patients (mean age 50.7 years ± 12.0 SD, 15 men), 21 spastic paraplegia type 5 (SPG5) patients (mean age 29.1 years ± 12.8 SD, 14 men) and 42 controls (sex- and age-matched) were evaluated. Compared to controls, SPG4 and SPG5 showed similar WM damage but different GM atrophy patterns. GM atrophy patterns in SPG4 and SPG5 were correlated with corresponding gene expression (ρ = 0.30, p = 0.008, ρ = 0.40, p < 0.001, respectively). Mediation analysis indicated that GM atrophy patterns were mediated by WM damage in HSP. CONCLUSIONS: Grey matter atrophy patterns were distinct between SPG4 and SPG5 and were not only secondary to WM damage but also associated with disease-related gene expression. CLINICAL TRIAL REGISTRATION NO: NCT04006418.

New records of Harpiolaisodon (Chiroptera, Vespertilionidae) from the Chinese mainland.

Background: The new species, Harpiolaisodon Kuo et al., 2006, was described from Taiwan, China. So far, no distribution of this species outside Taiwan has been reported. New information: During two field investigations of small mammals in Guanyin Mountains Provincial Nature Reserve, Yuanyang, Yunnan, China, in April 2022 and May 2023, five individuals of Harpiola were collected in the mid-montane evergreen broad-leaved forest. Our morphological and molecular results reveal that these individuals from the Chinese mainland belong to Harpiolaisodon, extending the occurrence of this species well beyond its known distributions in Taiwan, China and Vietnam.

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Freestanding Crystalline ß-Ga2O3 Flexible Membrane Obtained via Lattice Epitaxy Engineering for High-Performance Optoelectronic Device.

Wearable and flexible ß-Ga2O3-based semiconductor devices have attracted considerable attention, due to their outstanding performance and potential application in real-time optoelectronic monitoring and sensing. However, the unavailability of high-quality crystalline and flexible ß-Ga2O3 membranes limits the fabrication of relevant devices. Here, through lattice epitaxy engineering together with the freestanding method, we demonstrate the preparation of a robust bending-resistant and crystalline ß-Ga2O3 (-201) membrane. Based on this, we fabricate a flexible ß-Ga2O3 photodetector device that shows comparable performance in photocurrent responsivity and spectral selectivity to conventional rigid ß-Ga2O3 film-based devices. Moreover, based on the transferred ß-Ga2O3 membrane on a silicon wafer, the PEDOT:PSS/ß-Ga2O3 p-n heterojunction device with self-powered characteristic was constructed, further demonstrating its superior heterogeneous integration ability with other functional materials. Our results not only demonstrate the feasibility of obtaining a high-quality crystalline and flexible ß-Ga2O3 membrane for an integrated device but also provide a pathway to realize flexible optical and electronic applications for other semiconducting materials.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

Non-destructive monitoring method for leaf area of Brassica napus based on image processing and deep learning.

Introduction: Leaves are important organs for photosynthesis in plants, and the restriction of leaf growth is among the earliest visible effects under abiotic stress such as nutrient deficiency. Rapidly and accurately monitoring plant leaf area is of great importance in understanding plant growth status in modern agricultural production. Method: In this paper, an image processing-based non-destructive monitoring device that includes an image acquisition device and image process deep learning net for acquiring Brassica napus (rapeseed) leaf area is proposed. A total of 1,080 rapeseed leaf image areas from five nutrient amendment treatments were continuously collected using the automatic leaf acquisition device and the commonly used area measurement methods (manual and stretching methods). Results: The average error rate of the manual method is 12.12%, the average error rate of the stretching method is 5.63%, and the average error rate of the splint method is 0.65%. The accuracy of the automatic leaf acquisition device was improved by 11.47% and 4.98% compared with the manual and stretching methods, respectively, and had the advantages of speed and automation. Experiments on the effects of the manual method, stretching method, and splinting method on the growth of rapeseed are conducted, and the growth rate of rapeseed leaves under the stretching method treatment is considerably greater than that of the normal treatment rapeseed. Discussion: The growth rate of leaves under the splinting method treatment was less than that of the normal rapeseed treatment. The mean intersection over union (mIoU) of the UNet-Attention model reached 90%, and the splint method had higher prediction accuracy with little influence on rapeseed.

Protective effect of hot-water and ethanol-aqueous extracts from Anneslea fragrans against acetaminophen-induced acute liver injury in mice.

Anneslea fragrans Wall. (AF) is an important medicinal and edible plant in China. The principal objectives of this study are to explore the hepatoprotective effect of ethanol-aqueous (AFE) and hot-water (AFW) extracts in vitro and in vivo. UPLC-ESI-MS/MS analysis showed that AFW and AFE are rich in dihydrochalcones. Both AFW and AFE significantly up-regulated the expressions of SOD, CAT and GSH, reduced the MDA content in acetaminophen (APAP)-induced HepG2 cells, and suppressed the expressions of NO, TNF-α, IL-1ß, and IL-6 in LPS-induced RAW246.7 cells. In APAP-induced mice, AFW and AFE administration significantly decreased the plasma levels of AST and ALT, and improved liver tissue damage, the collagen deposition and fibrosis formation. Moreover, AFW and AFE decreased the MDA and ROS accumulations via activating Nrf2 pathway to increase the hepatic GSH contents and activities of SOD, CAT, HO-1, and NQO-1, reduced the levels of NO, TNF-α, IL-1ß, and IL-6 by suppressing the JNK/p38/ERK/NF-κB pathways, and alleviated apoptosis via regulating Bcl-2, Bax, caspase-3/9 protein expressions. This study provides a new sight that AFW and AFE may have a potential natural resource for the treatment of liver injury.

PyMAF-X: Towards Well-Aligned Full-Body Model Regression From Monocular Images.

We present PyMAF-X, a regression-based approach to recovering a parametric full-body model from a single image. This task is very challenging since minor parametric deviation may lead to noticeable misalignment between the estimated mesh and the input image. Moreover, when integrating part-specific estimations into the full-body model, existing solutions tend to either degrade the alignment or produce unnatural wrist poses. To address these issues, we propose a Pyramidal Mesh Alignment Feedback (PyMAF) loop in our regression network for well-aligned human mesh recovery and extend it as PyMAF-X for the recovery of expressive full-body models. The core idea of PyMAF is to leverage a feature pyramid and rectify the predicted parameters explicitly based on the mesh-image alignment status. Specifically, given the currently predicted parameters, mesh-aligned evidence will be extracted from finer-resolution features accordingly and fed back for parameter rectification. To enhance the alignment perception, an auxiliary dense supervision is employed to provide mesh-image correspondence guidance while spatial alignment attention is introduced to enable the awareness of the global contexts for our network. When extending PyMAF for full-body mesh recovery, an adaptive integration strategy is proposed in PyMAF-X to produce natural wrist poses while maintaining the well-aligned performance of the part-specific estimations. The efficacy of our approach is validated on several benchmark datasets for body, hand, face, and full-body mesh recovery, where PyMAF and PyMAF-X effectively improve the mesh-image alignment and achieve new The project page with code and video results can be found at https://www.liuyebin.com/pymaf-x.

Effects of cerebellar transcranial alternating current stimulation in cerebellar ataxia: study protocol for a randomised controlled trial.

Background: Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. Methods/design: This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. Discussion: The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neuro-rehabilitation setting.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786.

Ultra-High Hydrostatic Pressure Pretreatment on White Que Zui Tea: Chemical Constituents, Antioxidant, Cytoprotective, and Anti-Inflammatory Activities.

Herbal tea has numerous biological activities and exhibits broad benefits for human health. In China, the flower buds of Lyonia ovalifolia are traditionally processed as herbal tea, namely White Que Zui tea (WQT). This study was aimed to evaluate the effect of ultra-high hydrostatic pressure (UHHP) pretreatment on the chemical constituents and biological activities of free, esterified, and insoluble-bound phenolic fractions from WQT. A total of 327 chemical constituents were identified by a quasi-targeted metabolomics analysis. UHHP pretreatment extremely inhibited reactive oxygen species (ROS) production and cell apoptosis in H2O2-induced HepG2 cells, and it increased the activities of intracellular antioxidant enzymes (SOD and CAT) and GSH content in different phenolic fractions from WQT. In addition, after UHHP pretreatment, the anti-inflammatory effects of different phenolic fractions from WQT were improved by inhibiting the production of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-induced RAW264.7 cells. Thus, the UHHP method might be a potential pretreatment strategy for improving the bioavailability of phytochemicals from natural plants.

Fertilization depth effect on mechanized direct-seeded winter rapeseed yield and fertilizer use efficiency.

BACKGROUND: Deep fertilization is effective for improving crop yield and fertilizer use efficiency. However, its impact on mechanized direct-seeded rapeseed and the optimal fertilization depth are poorly understood. A field experiment was conducted to evaluate the fertilization depth effect on mechanized direct-seeded rapeseed growth. Five treatments were designed: surface broadcast fertilizer, no fertilization, and fertilizer banded placement at soil depths of 5 (D5), 10 (D10), and 15 cm (D15). RESULTS: Compared with surface broadcast fertilizer, deep fertilization generally increased seed yield and partial factor productivity by 11.0%, agronomic efficiency (AE) by 22.7%, and recovery efficiency (RE) by 79.2% due to the increase of root mass density (16.8%), plant height (8.6%), height of the first branch (10.6%), stem diameter (22.4%), shoot biomass (16.1%), and shoot nitrogen (35.7%), phosphorus (29.7%), and potassium (26.2%) uptake. D10 had the highest seed yield, oil yield, fertilizer use efficiency, and economic benefits at different fertilization depth treatments. Compared with D5 and D15 respectively, D10 increased seed yield by 5.4% and 46.0%, oil yield by 7.7% and 50.5%, partial factor productivity by 5.4% and 46.0%, AE by 9.0% and 99.5%, RE of nitrogen by 48.9% and 34.9%, RE of phosphorus by 83.1% and 38.0%, and RE of potassium by 57.5% and 32.5%. The economic benefits of D10 were CNY 867.31 ha-1 and CNY 4864.23 ha-1 higher than D5 and D15 respectively. CONCLUSION: Considering rapeseed growth and its economic benefits, this study shows that 10 cm is an appropriate placement depth with regard to mechanized direct-seeded winter rapeseed production. © 2022 Society of Chemical Industry.

Altered brain white matter structural motor network in spinocerebellar ataxia type 3.

OBJECTIVES: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity. METHODS: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed. RESULTS: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients. INTERPRETATION: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD.

Study of the Impact of Industrial Restructuring on the Spatial and Temporal Evolution of Carbon Emission Intensity in Chinese Provinces-Analysis of Mediating Effects Based on Technological Innovation.

Global warming caused by greenhouse gas emissions seriously threatens a region's sustainable environmental and socioeconomic development. Promoting industrial restructuring and strengthening technological innovation have become an important path to achieving pollution and carbon reduction as well as the green transformation of economic structure. This paper explored the mechanism of the mediating effect of technological innovation on industrial restructuring and carbon reduction while accounting for the direct effect of industrial restructuring on carbon emissions. Then, based on China's provincial panel data from 2001 to 2019, we estimated the carbon emission intensity using the Intergovernmental Panel on Climate Change (IPCC)'s methods and analyzed its spatiotemporal evolution characteristics. Finally, we constructed a fixed-effect model and a mediating effect model to empirically analyze how industrial restructuring and technological innovation affect carbon emission intensity. The results are as follows: (1) From 2001 to 2019, China's carbon emission intensity showed a continuous downward trend, with a pronounced convergence trend; there were obvious differences in carbon emission intensity between eastern, central, and western regions (western region > central region > eastern region) due to the unbalanced industrial structure. (2) In terms of direct effects, industrial restructuring can significantly reduce carbon emission intensity. The intensity of the effect is inversely proportional to the level of industrial restructuring, and the results of sub-regional tests are similar. Nevertheless, there is an obvious regional difference in the size of the carbon emission reduction effect of industrial restructuring in the east, central, and western regions. (3) In terms of indirect effects, industrial restructuring can reduce carbon emission intensity by enhancing technological innovation, and it acts as a mediating variable in the process of industrial restructuring to reduce carbon emission. Finally, we put forward recommendations for promoting industrial restructuring, strengthening green technological innovation, and properly formulating carbon reduction measures to provide a reference for countries and regions to achieve the goals of carbon neutrality, carbon peaking, and high-quality economic development.

Estimating the Decoupling between Net Carbon Emissions and Construction Land and Its Driving Factors: Evidence from Shandong Province, China.

Human activities and land transformation are important factors in the growth of carbon emissions. In recent years, construction land for urban use in China has expanded rapidly. At the same time, carbon emissions in China are among the highest in the world. However, little is known about the relationship between the two factors. This study seeks to estimate the carbon emissions and carbon sequestrations of various types of land based on the land cover data of 137 county-level administrative regions in Shandong Province, China, from 2000 to 2020.The study estimated the carbon emissions for energy consumption using energy consumption data and night-time light images, hence, net carbon emissions. The Tapio decoupling coefficient was used to analyze the decoupling between the net carbon emissions and construction land, and where the model for the decoupling effort was constructed to explore the driving factors of decoupling. The results showed that net carbon emissions in Shandong Province continued to increase, and the areas with high carbon emissions were concentrated primarily in specific districts of the province. The relationship between net carbon emissions and construction land evolved from an expansive negative decoupling type to a strong negative decoupling type. Spatially, most areas in the province featured an expansive negative decoupling, but the areas with a strong negative decoupling have gradually increased. The intensive rate of land use and efficiencies in technological innovation have restrained carbon emissions, and they have contributed to an ideal decoupling situation. Although the intensity of carbon emission and the size of the population have restrained carbon emissions, efforts towards decoupling have faded. The degree of land use has facilitated carbon emissions, and in recent years, efforts have been made to achieve an ideal decoupling. The method of estimation of net carbon emissions devised in this research can lend itself to studies on other regions, and the conclusions provide a reference for China, going forward, to balance urbanization and carbon emissions.

E Se tea alleviates acetaminophen-induced liver injury by activating the Nrf2 signaling pathway.

E Se tea is a traditional herbal tea used in the prevention of liver diseases. However, the hepatoprotective effect of E Se tea has not been investigated. This study aimed to determine the protective effect of E Se tea on acetaminophen (APAP)-induced acute liver injury and its potential mechanism. Hot water extracts and aqueous-ethanol extracts of E Se tea were obtained, which were analyzed to determine the chemical constituents of the tea. Phlorizin and phloretin were found to be the dominant chemical compounds. Histopathological analysis showed that E Se tea extract inhibited APAP-induced inflammatory infiltration, necrosis, and cellular vacuolization of hepatocytes in the liver tissue. The E Se tea extract could significantly ameliorate liver injury, inhibit an inflammatory response, and reduce oxidative stress. Western blot analysis revealed that E Se tea extract upregulated the expressions of nuclear Nrf2, HO-1 and NQO1 proteins and downregulated the expressions of cytoplasmic Nrf2 and Keap1 proteins in the hepatocyte. qPCR results showed that E Se tea extract also increased the expression of antioxidant genes (SOD2, Gpx1, GCLC and GCLM). These findings exhibited that E Se tea, enriched in dihydrochalcones, can be used to effectively prevent and manage liver dysfunction.

Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3.

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism. Methods: A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon's signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson's correlation analysis. Results: After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = - 0.831, p = 0.02). Conclusion: The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

Structural Covariance of the Ipsilesional Primary Motor Cortex in Subcortical Stroke Patients with Motor Deficits.

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.

Brain structural abnormalities in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3): evaluation by MRI morphometry, diffusion tensor imaging and neurite orientation dispersion and density imaging.

OBJECTIVE: To investigate whether neurite orientation dispersion and density imaging (NODDI) could provide the added value for detecting brain microstructural alterations in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) compared with MRI morphometry and diffusion tensor imaging (DTI). METHODS: Twenty preclinical MJD/SCA3 patients and 21 healthy controls were enrolled. Three b values DWI and 3D T1-weighted images were acquired at 3.0 T. Tract-based spatial statistics (TBSS) approach was used to investigate the white matter (WM) alterations in the DTI metrics and NODDI metrics. Gray matter-based spatial statistics (GBSS) approach was used to investigate the grey matter (GM) alterations in the NODDI metrics. Voxel-based morphometry (VBM) approach was performed on the 3D T1-weighted images. The relationship between the cytosine-adenine-guanine (CAG) repeat length and brain microstructural alterations of preclinical MJD/SCA3 was identified. RESULTS: Compared with healthy controls, the preclinical MJD/SCA3 patients showed decreased FA and NDI as well as increased MD, AD, and RD in the WM of cerebellum and brainstem (corrected P < 0.05), and decreased NDI in the GM of cerebellar vermis (corrected P < 0.05). The CAG repeat length in preclinical MJD/SCA3 patients was negatively correlated with the reduced FA and NDI of the infratentorial WM and the reduced NDI of the cerebellum, and positively with the increased MD and RD of the infratentorial WM. CONCLUSIONS: NOODI can provide novel quantitative microstructural changes in MJD/SCA3 carriers, expanding our understanding of the gray and white matter (axons and dendrites) degeneration in this frequent ataxia syndrome.

Pattern of cerebellar grey matter loss associated with ataxia severity in spinocerebellar ataxias type 3: a multi-voxel pattern analysis.

Spinocerebellar ataxias type 3 (SCA3) patients are clinically characterized by progressive cerebellar ataxia combined with degeneration of the cerebellum. Previous neuroimaging studies have indicated ataxia severity associated with cerebellar atrophy using univariate methods. However, whether cerebellar atrophy patterns can be used to quantitatively predict ataxia severity in SCA3 patients at the individual level remains largely unexplored. In this study, a group of 66 SCA3 patients and 58 healthy controls were included. Disease duration and ataxia assessment, including the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), were collected for SCA3 patients. The high-resolution T1-weighted MRI was obtained, and cerebellar grey matter (GM) was extracted using a spatially unbiased infratentorial template toolbox for all participants. We investigated the association between the pattern of cerebellar grey matter (GM) loss and ataxia assessment in SCA3 by using a multivariate machine learning technique. We found that the application of RVR allowed quantitative prediction of both SARA scores (leave-one-subject-out cross-validation: correlation = 0.56, p-value = 0.001; mean squared error (MSE) = 20.51, p-value = 0.001; ten-fold cross-validation: correlation = 0.52, p-value = 0.001; MSE = 21.00, p-value = 0.001) and ICARS score (leave-one-subject-out cross-validation: correlation = 0.59, p-value = 0.001; MSE = 139.69, p-value = 0.001; ten-fold cross-validation: correlation = 0.57, p-value = 0.001; MSE = 145.371, p-value = 0.001) with statistically significant accuracy. These results provide proof-of-concept that ataxia severity in SCA3 patients can be predicted by the alteration pattern of cerebellar GM using multi-voxel pattern analysis.