Cerebellum最新文献

Motor performance declines with age, particularly affecting reaction time and proactive response inhibition. While cortical influences on age-related motor decline are well-documented, the cerebellum's role remains unclear. Cerebellar Brain Inhibition (CBI), which can be measured through dual-site transcranial magnetic stimulation (TMS), may provide insights into age-related changes in motor control. We aimed to (1) compare resting-state CBI between young and older adults, (2) investigate the relationship between CBI and upper limb motor performance, and (3) examine whether this relationship differs between age groups. Using dual-site TMS, resting-state CBI was assessed in young and older adults. Motor performance was evaluated using a task battery measuring simple and choice reaction times, and response inhibition. As expected, older adults exhibited significantly longer reaction times and reduced reactive inhibition with lower accuracy compared to younger adults. No significant differences in resting CBI were observed between age groups, and no association was found between CBI and motor performance outcomes. Despite clear age-related differences in motor performance, resting CBI revealed no difference between age groups and showed no association with motor control measures. These findings suggest that the effect of aging on dual-site TMS-derived cerebellar inhibition at rest and its association with motor performance might be limited. However, age-related cerebellar effects on motor control might manifest during task execution rather than at rest, highlighting the potential importance of investigating CBI modulation during motor performance in the context of aging.

The current study presents a novel method for imaging the cerebellar dentate nucleus, combining ultra-high field (7T) and quantitative susceptibility mapping (QSM) to enhance tissue boundary identification and segmentation. After assessing segmentation reliability, we assessed validity by evaluating volume and resting state functional connectivity (FC) of the dorsal vs. ventral dentate subregions. Neurotypical adults (n = 30, 15 females) completed 7T susceptibility-weighted imaging (SWI) and resting state fMRI. QSM maps were used to segment the dentate (whole, dorsal, ventral subregions). Reliability of the segmentation protocol was established across three raters (inter-rater) and one rater who performed the segmentations twice (intra-rater) using the Dice coefficient (d). Dorsal and ventral dentate volumes were calculated, and whole-brain seed-to-voxel FC patterns were assessed from the whole dentate, dorsal, and ventral subregions. Group-level contrasts for each subregion and between subregions were thresholded at voxel-level p <.005, with a cluster-level FDR-correction of p <.05. Segmentation reliability was high (inter-rater d = 0.89, intra-rater d = 0.93), and the dorsal subregion was significantly smaller than the ventral (p <.001). The dorsal dentate showed greater FC with regions involved in sensorimotor processing (cerebellar vermis I-V, IX-X, lobules VIII-IX, fusiform, cuneus), and the ventral dentate showed greater FC with regions involved in cognitive processing (cerebellar lobule VII, angular gyrus, middle and superior frontal gyri, middle and superior temporal gyri, temporal pole). We present an innovative, reliable, and valid method for imaging the dentate. Dentate volumes and FC were consistent with anatomical mapping from animal and human studies. Future directions include application to clinical populations with anomalous cerebellar development and injury.

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare condition caused by mutations in ABHD12. We present the first documented case of PHARC in a Brazilian patient. Describe the clinical and genetic aspects of patients diagnosed with PHARC through a literature review. A literature review was conducted in February 2024 using Pubmed/Medline database. We also report a 37-year-old Brazilian woman diagnosed with PHARC. Between 38 patients diagnosed with this condition, the majority were male (74.35%) and the median age was 35.7 years. The most common symptom reported was ataxia (79.4%). The main finding of Brain MRI was cerebellar atrophy, and demyelinating polyneuropathy was the commonest finding in electroneuromyography, both were found in 28.2% of patients. PHARC syndrome is a rare autosomal recessive condition that is increasingly reported in the literature. Refsum disease and Usher syndrome are the main differential diagnosis. A multidisciplinary approach and follow-up are crucial for accurate diagnosis and treatment.

Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available. This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 9,326,057 AE reports were collected, among which 820 reports were associated with omaveloxolone. All AEs were categorized into 25 System Organ Classes (SOCs) and 67 positive Preferred Terms (PTs). Investigations represented the most frequently reported SOC, followed by gastrointestinal disorders and general disorders and administration site conditions. Hepatic enzyme increased emerged as the most prominent adverse event, demonstrating both high reporting frequency and strong signal intensity, primarily manifesting as elevated ALT and AST levels. Other commonly reported AEs included fatigue, nausea, headache, and blood cholesterol increased. The study also identified several novel potential AEs, such as urinary tract infection, diabetes mellitus, urine odour abnormal, atrial flutter, and urosepsis. Although some of these AEs were reported in relatively low frequencies, their clinical severity and elevated signal strengths suggest that omaveloxolone may potentially affect patients' urinary and endocrine systems, warranting particular attention during clinical administration. In conclusion, while omaveloxolone demonstrates multifaceted benefits in improving neurological function in patients with FRDA, its clinical application necessitates comprehensive evaluation of potential risks, and the development of safe and rational therapeutic strategies is crucial for optimizing treatment outcomes.

Antibodies directed against the enzyme diacylglycerol lipase alpha (DAGLA) have been recently discovered to cause a severe autoimmune cerebellar syndrome. We report a patient with DAGLA antibodies with prominent tremor and ataxia occurring in the context of a malignant melanoma, indicating that these antibodies may also occur in paraneoplastic cerebellar degeneration.

Background: Oculomotor apraxia (OMA), the clinical manifestation of impaired voluntary initiation of saccadic eye movements, has long been associated with several disorders and genetic mutations in the literature.

Objectives: The present study aims to review all the disorders and genetic mutations associated with OMA reported in the literature.

Methods: PubMed, MEDLINE, Scopus, EMBASE, and Web of Science databases were systematically searched for related keywords, and related publications from January 2000 to January 2024 were reviewed.

Results: All the disorders and genetic mutations presented with OMA in the literature were reported. Clinical manifestations of the congenital disorders- particularly members of autosomal recessive cerebellar ataxias- including Joubert syndrome, ataxia with oculomotor apraxia, ataxia-telangiectasia, and other disorders were discussed, Additionally, the pathophysiology of the genetic mutations in the anatomical pathway of OMA is discussed in this paper.

Conclusions: Most of the cases with OMA present this sign early in their disease course; thus, evaluating the possible differential diagnoses can guide clinicians to a more accurate diagnosis. Understanding the spectrum of disorders and clinical manifestations with OMA also provides valuable insights into further clinic-pathological and genetic evaluations of this clinical manifestation.

The motor learning theory anticipates that cerebro-cerebellar loops perform sensorimotor prediction, thereby regulating motor control during action execution (AE) and observation (AO), but the causal interaction between the cerebellum and cerebral cortex remains unclear. Therefore, our aim was to understand what triggers neuronal activity between brain areas engaged in a visuo-motor task that involves cortico-cerebellar interactions, organised in loops. We used Dynamic Causal Modelling (DCM) to study functional MRI (fMRI) data obtained in healthy participants during a squeeze-ball task in either execution or observation conditions. In both cases, active regions included bilateral primary visual cortex (V1), left primary motor cortex (M1), supplementary motor and premotor cortex (SMAPMC), cingulate cortex (CC), superior parietal lobule (SPL), and right cerebellum (CRBL). Networks supporting executing or observing an action showed the same effective connectivity, with pathways between regions wired in closed loops. However, the cerebellar communication towards the cerebral cortex switched from excitatory in execution to inhibitory in observation. Moreover, when executing the action signal modulation was non-linear from SMAPMC to CRBL and within the CRBL self-connection, supporting that the CRBL elaborates motor plans received from SMAPMC. Thus, the need for motor planning and the presence of a sensorimotor feedback in action execution discriminate the modality of forward control operated by the CRBL. Interestingly, this study also showed that the CRBL differentially controls the excitatory/inhibitory dynamics of inter-regional effective connectivity, depending on its functional engagement. These findings are fundamental for understanding brain dynamics in health and disease and for designing artificial sensorimotor controllers.

Individuals affected by spinocerebellar ataxia 38 (SCA 38) progressively lose the ability to efficiently perform important activities of daily living involving the use of upper limbs, like personal care and feeding. However, it is important to note that data on the extent of upper limb motor dysfunction in SCAs are generally limited, and specifically, no information is currently available for SCA38-particularly in the context of performing functional tasks. To partly fill this gap, in this study we analyze the kinematic features of the Hand-to-Mouth task in 7 individuals with SCA 38 and an equally sized group matched for age and sex using an optical motion capture system, by analyzing performance, stability and smoothness parameters based on the 3D hand trajectory. The results show that, in comparison with unaffected individuals, those with SCA 38 required longer time to complete the task, especially during the going phase towards the mouth, perform more adjustment in proximity of the target and their movement results more fragmented and less smooth. Such findings provide new and relevant insights regarding the upper limb residual functions under 'real-life' conditions in SCA 38, and represent a complementary tool to the usual clinical assessment to support better monitoring the disease progression as well as the design of specific tailored therapeutic interventions.

The cerebellum plays a crucial role in sensorimotor control through cerebellofugal projections from the cerebellar nuclei. However, little is known about the cerebellofugal projection features involved in jaw sensorimotor control, although the dorsolateral parts of the interposed cerebellar nucleus (IntDL) and medial cerebellar nucleus (MedDL) do receive proprioceptive signals bilaterally from rat jaw-closing muscle spindles (JCMSs). This study aimed to detail the cerebellofugal projection features involved in jaw sensorimotor control. Anterograde tracer was injected into regions of the rat IntDL and MedDL receiving JCMS proprioceptive inputs (i.e., jcms-IntDL and jcms-MedDL). Axon terminals arising from the jcms-IntDL were labeled bilaterally with an ipsilateral predominance in several pontomedullary regions, although very few terminals were labeled in the dorsolateral and ventromedial divisions (5dl and 5vm) of the trigeminal motor nucleus. In contrast, terminals from the jcms-MedDL were labeled bilaterally with a contralateral predominance in several pontomedullary regions and a few terminals were labeled in the contralateral 5dl and 5vm. Thus, the projections from the jcms-IntDL and jcms-MedDL were well segregated. Subsequent retrograde tracer injections into the pontomedullary regions demonstrated that amongst the entire cerebellar nuclei the nucleofugal projections principally arose from the IntDL and MedDL. Additionally, many premotoneurons for the 5dl or 5vm were widely labeled in the pontomedullary regions where many axons from the jcms-IntDL or jcms-MedDL terminated. The various connections involving the jcms-IntDL and jcms-MedDL may play a crucial role in jaw sensorimotor control, mainly through indirect cerebellofugal pathways to the 5dl and 5vm via their premotoneurons.