Exploring functional and structural connectivity disruptions in spinocerebellar ataxia type 3: Insights from gradient analysis.

AIMS: Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3. METHODS: We prospectively recruited 51 patients with SCA3 and 59 age-and sex-matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting-state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored. RESULTS: Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor-to-supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables. CONCLUSION: Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor-to-supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy.

Imbalanced optimal feedback motor control system in spinocerebellar ataxia type 3.

BACKGROUND AND PURPOSE: Human motor planning and control depend highly on optimal feedback control systems, such as the neocortex-cerebellum circuit. Here, diffusion tensor imaging was used to verify the disruption of the neocortex-cerebellum circuit in spinocerebellar ataxia type 3 (SCA3), and the circuit's disruption correlation with SCA3 motor dysfunction was investigated. METHODS: This study included 45 patients with familial SCA3, aged 17-67 years, and 49 age- and sex-matched healthy controls, aged 21-64 years. Tract-based spatial statistics and probabilistic tractography was conducted using magnetic resonance images of the patients and controls. The correlation between the local probability of probabilistic tractography traced from the cerebellum and clinical symptoms measured using specified symptom scales was also calculated. RESULTS: The cerebellum-originated probabilistic tractography analysis showed that structural connectivity, mainly in the subcortical cerebellar-thalamo-cortical tract, was significantly reduced and the cortico-ponto-cerebellar tract was significantly stronger in the SCA3 group than in the control group. The enhanced tract was extended to the right lateral parietal region and the right primary motor cortex. The enhanced neocortex-cerebellum connections were highly associated with disease progression, including duration and symptomatic deterioration. Tractography probabilities from the cerebellar to parietal and sensorimotor areas were significantly negatively correlated with motor abilities in patients with SCA3. CONCLUSION: To our knowledge, this study is the first to reveal that disrupting the neocortex-cerebellum loop can cause SCA3-induced motor dysfunctions. The specific interaction between the cerebellar-thalamo-cortical and cortico-ponto-cerebellar pathways in patients with SCA3 and its relationship with ataxia symptoms provides a new direction for future research.

Walkability assessment of metro catchment area: A machine learning method based on the fusion of subject-objective perspectives.

China's metro system is developing rapidly. Walking is the most frequently adopted mode to connect to the metro, the attributes of the pedestrian-built environment around the stations directly influence people's willingness to use the metro. However, few studies have paid attention to the comprehensive assessments of the built environment in the metro catchment area. Thus, this paper attempts to construct a walkability evaluation model that combines subjective and objective perspectives. We collected field data of the built environment factors affecting on walkability in the 800 m buffer zone of eight case metro stations in Dalian city, China. We also collected on-site interviews from 867 passengers to evaluate the walkability. A machine learning-based approach was developed to calculate the weights of walkability variables, followed by constructing a Score-Effectiveness framework to identify the built environment factors in the metro catchment area that need to be improved. The study found that the shading facilities, obstacle barriers, and resting seats around pedestrian walkways are the most efficient and imbalanced variables recognized by the crowd. The convenience of overpasses and underpasses are additional efficient imbalance-type variables for leisure and commuting populations, respectively. This indicates that the current level of construction of the above five built environment factors is relatively low, but the construction has a significant impact on the degree of friendliness in supporting pedestrian walkability. In this paper, improvement measures are proposed in a targeted manner in order to achieve the effect of effectively improving the current level of metro catchment area's walkability. The results of the study can provide references to provide strategies for precise pedestrian planning in the metro catchment area, leading to a pedestrian environment with high walking quality.

Pd-Catalyzed C(sp2)-H aminocarbonylation using the Langlois reagent as a carbonyl source.

A Pd-catalyzed C(sp2)-H aminocarbonylation of aryl carboxamides assisted by an N,S-bidentate directing group was developed, in which cheap and stable sodium trifluoromethanesulfinate was first utilized as a carbonyl source. The reaction can be applicable to a wide range of carboxamides with good functional group tolerance and afford isoindole-1,3-diones in moderate to good yields.