The Cerebellum最新文献

Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses plays an important role in cerebellum-related motor coordination and learning. LTD is induced by the conjunction of PF stimulation and climbing fiber (CF) stimulation or somatic PC depolarization, while long-term potentiation (LTP) is induced by PF stimulation alone. Therefore, it is considered that different types of stimulation induce different types of synaptic plasticity. However, we found that a small number of conjunctive stimulations (PF + somatic depolarization of PC) induced LTP, but did not induce LTD of a small size. This LTP was not associated with changes in paired-pulse ratio, suggesting postsynaptic origin. Additionally this LTP was dependent on nitric oxide. This LTP was also induced by a smaller number of physiological conjunctive PF and CF stimuli. These results suggested that a larger number or longer period of conjunctive stimulation is required to induce LTD by overcoming LTP. Ca²⁺ transients at the PC dendritic region was measured by calcium imaging during LTD-inducing conjunctive stimulation. Peak amplitude of Ca²⁺ transients increased gradually during repetitive conjunctive stimulation. Instantaneous peak amplitude was not different between the early phase and late phase, but the average amplitude was larger in the later phase than in the early phase. These results show that LTD overcomes LTP, and increased Ca²⁺ integration or a number of stimulations is required for LTD induction.

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn’s disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn’s Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study’s findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum’s potential role in modulating gut-brain interactions.

Disease-specific oculomotor assessments play a crucial role in the early diagnosis of hereditary cerebellar ataxias. Whereas several studies have reported on quantitative oculomotor and vestibular measurements in Friedreich’s Ataxia (FRDA), the value of specific oculomotor paradigms remains unclear. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in FRDA. MEDLINE and Embase were searched for studies reporting on quantitative oculomotor and/or vestibular measurements in FRDA-patients. Data on oculomotor and vestibular parameters were extracted and correlations with a range of clinical parameters were sought. Included studies (n = 17) reported on 185 patients. Abnormalities observed included the presence of saccadic intrusions (143/161) such as square-wave jerks (SWJ, 90/109) and ocular flutter (21/43), impaired eccentric gaze-holding (40/104), abnormal pursuit (81/93) and angular vestibulo-ocular reflex (aVOR) deficits (39/48). For visually-guided saccades (VGS), we frequently observed increases in saccade latency (27/38) and dysmetric saccades (71/93), whereas saccade velocity was more often preserved (37/43). Augmented anti-saccade (AS) latency, downbeat nystagmus and frequent macro-SWJ correlated with disease duration. Increased AS-latency and VGS-latency, frequent macro-SWJ, reduced aVOR-gain and augmented aVOR peak-latency correlated with disease severity. A broad range of oculomotor and vestibular deficits are documented in the literature. Impairments in pursuit, saccades and aVOR-responses are most commonly reported, and as such, should be prioritized as disease markers. Quantitative oculomotor testing in FRDA may facilitate early diagnosis and prove valuable in monitoring disease progression and treatment response.

The evolution of the prominent role of the cerebellum in the development of composite tools, and cumulative culture, leading to the rise of Homo sapiens is examined. Following Stout and Hecht's (2017) detailed description of stone-tool making, eight key repetitive involvements of the cerebellum are highlighted. These key cerebellar learning involvements include the following: (1) optimization of cognitive-social control, (2) prediction (3) focus of attention, (4) automaticity of smoothness, appropriateness, and speed of movement and cognition, (5) refined movement and social cognition, (6) learns models of extended practice, (7) learns models of Theory of Mind (ToM) of teachers, (8) is predominant in acquisition of novel behavior and cognition that accrues from the blending of cerebellar models sent to conscious working memory in the cerebral cortex. Within this context, the evolution of generalization and blending of cerebellar internal models toward optimization of social-cognitive learning is described. It is concluded that (1) repetition of movement and social cognition involving the optimization of internal models in the cerebellum during stone-tool making was the key selection factor toward social-cognitive and technological advancement, (2) observational learning during stone-tool making was the basis for both technological and social-cognitive evolution and, through an optimizing positive feedback loop between the cerebellum and cerebral cortex, the development of cumulative culture occurred, and (3) the generalization and blending of cerebellar internal models related to the unconscious forward control of the optimization of imagined future states in working memory was the most important brain adaptation leading to intertwined advances in stone-tool technology, cognitive-social processes behind cumulative culture (including the emergence of language and art) and, thereby, with the rise of Homo sapiens.

Cerebellar pathology engenders the disturbance of movement that characterizes Friedreich ataxia (FRDA), yet the impact of cerebellar pathology on cognition in FRDA remains unclear. Numerous studies have unequivocally demonstrated the role of the cerebellar pathology in disturbed cognitive, language and affective regulation, referred to as Cerebellar Cognitive Affective Syndrome (CCAS), and quantified by the CCAS-Scale (CCAS-S). The presence of dysarthria in many individuals with ataxia, particularly FRDA, may confound results on some items of the CCAS-S resulting in false-positive scores. This study explored the relationship between performance on the CCAS-S and clinical metrics of disease severity in 57 adults with FRDA. In addition, this study explored the relationship between measures of intelligibility and naturalness of speech and scores on the CCAS-S in a subgroup of 39 individuals with FRDA. We demonstrated a significant relationship between clinical metrics and performance on the CCAS-S. In addition, we confirmed the items that returned the greatest rate of failure were based on Verbal Fluency Tasks, revealing a significant relationship between these items and measures of speech. Measures of speech explained over half of the variance in the CCAS-S score suggesting the role of dysarthria in the performance on the CCAS-S is not clear. Further work is required prior to adopting the CCAS-S as a cognitive screening tool for individuals with FRDA.

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.

Graphical Abstract

The perceptual and motor systems appear to have a set of movement primitives that exhibit certain geometric and kinematic invariances. Complex patterns and mental representations can be produced by (re)combining some simple motor elements in various ways using basic operations, transformations, and respecting a set of laws referred to as kinematic laws of motion. For example, point-to-point hand movements are characterized by straight hand paths with single-peaked-bell-shaped velocity profiles, whereas hand speed profiles for curved trajectories are often irregular and more variable, with speed valleys and inflections extrema occurring at the peak curvature. Curvature and speed are generically related by the 2/3 power law. Mathematically, such laws can be deduced from a combination of Euclidean, affine, and equi-affine geometries, whose neural correlates have been partially detected in various brain areas including the cerebellum and the basal ganglia. The cerebellum has been found to play an important role in the control of coordination, balance, posture, and timing over the past years. It is also assumed that the cerebellum computes forward internal models in relationship with specific cortical and subcortical brain regions but its motor relationship with the perceptual space is unclear. A renewed interest in the geometrical and spatial role of the cerebellum may enable a better understanding of its specific contribution to the action-perception loop and behavior’s adaptation. In this sense, we complete this overview with an innovative theoretical framework that describes a possible implementation and selection by the cerebellum of geometries adhering to different mathematical laws.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.

This was a study of 12 cerebellar cortical dysplasias (CCDs) fetuses, these cases were characterized by a disorder of cerebellar fissures. Historically, CCD diagnosis was primarily performed using postnatal imaging. Unique to this study was the case series of CCD for prenatal diagnosis using prenatal ultrasound, as well as we found that AXIN1 and FOXC1 mutations may be related to CCD.

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.