Cerebellum最新文献

The search for digital biomarkers of gait ataxia is a key research priority in spinocerebellar ataxias (SCAs), especially in the early stages when traditional clinical scales are less effective. Despite existing evidence supporting the effectiveness of suitable digital biomarkers, their use in assessing early disease progression remains limited. This study was aimed to evaluate the progression of digitally measured gait ataxia features in preclinical SCA2. Twenty-seven preclinical carriers of the SCA2 mutation were monitored four times over four years. Participants completed a 10-meter walking test (back and forth) using six body-worn inertial measurement units. We assessed stride-to-stride means and variability of eight gait features indicative of subtle abnormalities in SCA2 carriers, alongside the Scale for the Assessment and Rating of Ataxia (SARA). Mean stride-to-stride variables demonstrated significant progression more frequently than variability measures, with means primarily exhibiting non-linear patterns and variability metrics showing mainly linear trajectories. Significant progression of mean stride-to-stride variables was also observed in unconverted carriers. CAG repeat length significantly influences progression of some gait kinematics in preclinical SCA2 carriers. Notably, several digitally measured gait parameters required smaller sample sizes to detect progression in hypothetical clinical trials than the SARA clinical scale. This study confirmed the progressive deterioration of subtle gait function in preclinical SCA2 and highlighted the clinical utility of digitally derived metrics for tracking longitudinal changes at early disease stages. These digital measures may provide more sensitive and reliable biomarkers of disease progression than conventional clinical rating scales, supporting their potential use in future clinical trials.

Introduction functional impairments in schizophrenia may arise from disruptions in large-scale brain networks. Emerging evidence highlights the cerebellum's role in cognitive and affective regulations, yet its directional influence remains poorly understood. This study examines effective connectivity (EC) within cortico-striato-cerebellar networks in schizophrenia and healthy adults. Methods resting-state functional magnetic resonance imaging data from the Centers of Biomedical Research Excellence (COBRE), including people with schizophrenia and healthy controls (n = 134), were used to analyze intrinsic activity and effective connectivity. Cerebellar clusters showing reduced amplitude of low frequency fluctuations (ALFF) and fractional ALFF in schizophrenia were mapped to the Buckner 17-network atlas to define regions of interest (ROIs). Along with prefrontal and striatal ROIs defined a priori, these served as nodes in Group Iterative Multiple Model Estimation (GIMME). In addition to the best-fitting model of the full sample, schizophrenia participants were stratified by symptomology according to the positive and negative syndrome scale. Results four cerebellar voxel clusters in the posterolateral and anteromedial regions showed lower ALFF/fALFF in schizophrenia compared to controls. GIMME revealed distinct intra-cerebellar and cerebello-prefrontal EC patterns in schizophrenia that were absent in controls, including novel directed paths involving the cerebellar control network representation, consistent with its emergence as a central hub. These patterns persisted across symptom-defined subgroups, suggesting core network reorganization. Conclusions findings support the cerebellum's involvement in disrupted network dynamics in schizophrenia, particularly its directional influence over prefrontal targets. EC analyses uncovered cerebellar reorganization that may underlie affective deficits in schizophrenia, offering novel targets for circuit-level interventions.

Parkinsonian symptoms such as tremors, rigidity, bradykinesia, and postural instability typically arise from basal ganglia dysfunction, but growing evidence suggests cerebellar circuits also play a key role. Here, we investigated multiunit activity (MUA) in the inferior olive (IO), dentate nucleus (DN), and Crus II of the cerebellum in a rat model of tract lesion-induced parkinsonism triggered by ventrolateral striatum (VLS) injury. Thirty-six male Wistar rats were divided into a Lesion group and an Intact group. Monopolar electrodes were implanted to record MUA in IO, DN, or Crus II for four consecutive weeks. Basal and tremor-associated signals were analyzed using generalized linear models and post hoc comparisons. In rats with VLS lesions, IO activity initially increased and then declined over time, whereas DN activity remained consistently elevated, suggesting compensatory upregulation. Crus II showed no significant shifts in baseline activity. During tremor episodes, all three structures exhibited distinct temporal fluctuations in MUA. These findings reveal cerebellar structure-specific responses to striatal injury and highlight the cerebellum's role in both the acute and chronic phases of Parkinsonian motor dysfunction. Careful consideration of possible inflammatory responses to electrode implantation remains essential for future studies.