Functional and molecular alterations in the cerebellum are among the most widely recognised associates of autism spectrum disorders (ASD). As a critical computational hub of the brain, the cerebellum controls and coordinates a range of motor, affective and cognitive processes. Despite well-described circuits and integrative mechanisms, specific changes that underlie cerebellar impairments in ASD remain elusive. Studies in experimental animals have been critical in uncovering molecular pathology and neuro-behavioural correlates, providing a model for investigating complex disease conditions. Herein, we review commonalities and differences of the most extensively characterised genetic lines of ASD with reference to the cerebellum. We revisit structural, functional, and molecular alterations which may contribute to neurobehavioral phenotypes. The cross-model analysis of this study provides an integrated outlook on the role of cerebellar alterations in pathobiology of ASD that may benefit future translational research and development of therapies.
OBJECTIVE: To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. METHODS: Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3 T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. RESULTS: VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. CONCLUSIONS: iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.
Recent fMRI resting-state findings show aberrant functional connectivity within somatomotor network (SMN) in schizophrenia. Moreover, functional connectivity aberrations of the motor system are often reported to be related to the severity of psychotic symptoms. Thus, it is important to validate those findings and confirm their relationship with psychopathology. Therefore, we decided to take an entirely data-driven approach in our fMRI resting-state study of 30 chronic schizophrenia outpatients and 30 matched control subjects. We used independent component analysis (ICA), dual regression, and seed-based connectivity analysis. We found reduced functional connectivity within SMN in schizophrenia patients compared to controls and SMN hypoconnectivity with the cerebellum in schizophrenia patients. The latter was strongly correlated with the severity of alogia, one of the main psychotic symptoms, i.e. poverty of speech and reduction in spontaneous speech,. Our results are consistent with the recent knowledge about the role of the cerebellum in cognitive functioning and its abnormalities in psychiatric disorders, e.g. schizophrenia. In conclusion, the presented results, for the first time clearly showed the involvement of the cerebellum hypoconnectivity with SMN in the persistence and severity of alogia symptoms in schizophrenia.
- MeSH
- afázie patofyziologie diagnostické zobrazování etiologie patologie MeSH
- chronická nemoc MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozeček * diagnostické zobrazování patofyziologie MeSH
- nervová síť diagnostické zobrazování patofyziologie MeSH
- nervové dráhy patofyziologie diagnostické zobrazování MeSH
- schizofrenie * diagnostické zobrazování patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).
- MeSH
- elektrický šok MeSH
- kůra mozečku fyziologie MeSH
- mozeček fyziologie MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- strach * fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.
- MeSH
- depresivní porucha unipolární * MeSH
- dospělí MeSH
- konsensus MeSH
- kvalita života MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mozeček patologie MeSH
- průřezové studie MeSH
- senioři MeSH
- stárnutí MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Degenerative effects of nerve tissues are often accompanied by changes in vascularization. In this regard, knowledge about hereditary cerebellar degeneration is limited. In this study, we compared the vascularity of the individual cerebellar components of 3-month-old wild-type mice (n = 8) and Purkinje cell degeneration (pcd) mutant mice, which represent a model of hereditary cerebellar degeneration (n = 8). Systematic random samples of tissue sections were processed, and laminin was immunostained to visualize microvessels. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in cerebellar layers. Our results in pcd mice revealed a 45% (p < 0.01) reduction in the total volume of the cerebellum, a 28% (p < 0.05) reduction in the total number of vessels and a lower total length, approaching 50% (p < 0.001), compared to the control mice. In pcd mutants, cerebellar degeneration is accompanied by significant reduction in the microvascular network that is proportional to the cerebellar volume reduction therefore does not change density of in the cerebellar gray matter of pcd mice.
- MeSH
- mikrocévy MeSH
- mozeček * MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Purkyňovy buňky * fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Recently, transcranial electrical stimulation (tES) has gained increasing popularity among researchers, especially for recovery and improvement, but interpretation of these results is difficult due to variations in study methods and outcome measurements. The main goal of this study was to better understand the postural and balance indicators affected by cerebellar tES, as the cerebellum is the main brain region responsible for controlling balance. For this systematic literature review, three databases were searched for articles where the cerebellum was stimulated by any type of tES in either healthy participants or those with neurologic disorders. Postural, dynamic, and/or static stability measurements were recorded, and risk of bias was assessed on the PEDro scale. A total of 21 studies were included in the analysis. 17 studies reported improvements after application of tES. 14 studies stimulated the cerebellum unilaterally and 15 used this modality for 20 min. Moreover, all studies exclusively used transcranial direct current as the type of stimulation. Evaluation of PEDro results showed that studies included in the analysis utilized good methodology. Although there were some inconsistencies in study results, overall, it was demonstrated that tES can improve balance and postural index under both healthy and neurological conditions. Further research of bilateral cerebellar stimulation or the use of transcranial alternating current stimulation, transcranial random noise stimulation, and transcranial pulsed current stimulation is needed for a more comprehensive assessment of the potential positive effects of cerebellar tES on the balance system.
Cílem naší práce bylo čtenáři neurochirurgovi přiblížit detailní anatomii mozečkové tonzily se zaměřením i na její jednotlivé povrchy, jelikož ve většině publikací je tato prezentována pouze v rámci anatomie celé mozečkové hemisféry, případně anatomie cerebelomedulární fissury nebo průběhu arteria cerebelli posterior inferior. Laboratorní kadaverózní disekce tonzily jsme prováděli na čtyřech (v rovině vermis sagitálně rozdělených) mozečkových hemisférách a jednom kompletním mozečku i s jeho pedunkly a spodinou fossa rhomboidea. Tu jsme využili k demonstraci telovelárního přístupu. Domníváme se, že pro bezpečné zvládnutí telovelárního přístupu na operačním sále je laboratorní disekce velice vhodná a umožní neurochirurgovi poznat i méně známé struktury laterálního recessu, cerebelomedulární fissury i pochopit telovelární junkci. V přehledném referátu dokumentujeme také jednotlivé operace vztahující se k tonzile i telovelárnímu přístupu: operaci Chiariho malformace se syringomyelií, plexus papilomu IV. komory či kavernomu jejího laterálního recessu a cystického hemangioblastomu medulla oblongata. Na základě literárních údajů dokumentujeme historii vzniku operačního přístupu, který je příkladnou ukázkou spolupráce dvou světových neurochirurgů (Rhoton a Matsushima) a byla podložena dlouhodobou laboratorní prací. V referátu se věnujeme vrozeným variantám herniace tonzil mozečku (Chiariho malformace), ale i příčinám sekundárním a možnostem jejich zobrazení. Zmiňujeme klinický význam patologického sestupu tonzil a souvislost se syringomyelií.
The goal of our work was to acquaint the reader-neurosurgeon with the detailed anatomy of the cerebellar tonsil, focusing on its individual surfaces. This is because, in most publications, the tonsil is presented only within the context of the anatomy of the entire cerebellar hemisphere, or possibly the anatomy of the cerebellomedullary fissure or the course of the arteria cerebelli posterior inferior. We conducted cadaveric dissections of the tonsil on 4 cerebellar hemispheres (divided sagittally in the plane of the vermis) and on one complete cerebellum with its peduncles and the floor of the fossa rhomboidea. We used this for demonstrating the telovelar approach. We believe that for the safe mastering of the telovelar approach in the operating room, laboratory dissection is mandatory. It allows the neurosurgeon to recognize even less known structures of the lateral recess, cerebellomedullary fissure, and understand the telovelar junction. In a comprehensive review, we also document individual surgeries related to the tonsil and telovelar approach: the surgery for Chiari malformation with syringomyelia, tumor of the IVth ventricle, cavernoma of its lateral recess, and cystic hemangioblastoma of the medulla oblongata. Based on literary data, we document the history of the surgical approach, which is an exemplary demonstration of the collaboration between two world-renowned neurosurgeons (Rhoton and Matsushima), and was underpinned by extensive laboratory work. In the review, we address congenital variants of cerebellar tonsil herniation (Chiari malformation) as well as secondary causes and their imaging possibilities. We mention the clinical significance of the pathological descent of tonsils and their association with syringomyelia.
- Klíčová slova
- tonsilla cerebelli, telovelární přístup, Chiariho malformace,
- MeSH
- foramen magnum anatomie a histologie chirurgie MeSH
- lidé MeSH
- mozeček * anatomie a histologie chirurgie MeSH
- mozkový kmen anatomie a histologie chirurgie MeSH
- neurochirurgické výkony MeSH
- syringomyelie chirurgie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.
- MeSH
- bílá hmota patologie diagnostické zobrazování MeSH
- deep learning MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mozeček * patologie diagnostické zobrazování MeSH
- posttraumatická stresová porucha * patologie patofyziologie diagnostické zobrazování MeSH
- šedá hmota patologie MeSH
- velikost orgánu MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
