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Purkinje's 1838 text and illustration of his description of the monolayer of large corpuscles in the cerebellar cortex.
Source publication
This paper will outline the history of study of the cerebellum from its beginnings to relatively recent times. Although there is no unanimous agreement about what the cerebellum does or how it does it, some principles of its structure and function are well understood. The historical approach can help to identify remaining questions and point the wa...
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Bill Didusch war einer der einflussreichsten Illustratoren der amerikanischen Urologie. Seine Biographie ist neben seinen künstlerischen Leistungen insbesondere wegen seines Engagements in der und für die „American Urological Association“ (AUA) von großer Bedeutung. Er ist der Gründer des historischen Museums der AUA, das heute seinen Namen trägt....
Citations
... He named it the corpus rhomboideum. Later, Félix Vicq d'Ázyr provided a more detailed depiction of the corpus rhomboideum and renamed it corps dentelé [12]. ...
... Vicq d'Ázyr first noticed the distinctness of the indentations on the superior surface of the DN, contrasting with their relative absence on the inferior surface. This difference corresponds to the division of the human DN into two distinct regions: an older dorsal, microgyric, "paleodentatum" and a newer ventral, macrogyric, "neodentatum" [12,47]. ...
Purpose
The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy.
Methods and results
We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity.
Conclusions
Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.
... Cerebellar Ataxia (CA) is the motoric manifestation of cerebellar disease and may be summarized as impaired coordination which effects appendicular, balance and speech function amongst others [10,11]. An important point of clarification is that a broad-based or 'ataxic' gait may broadly have three causes: cerebellar, vestibular and sensory dysfunction. ...
In patients with cerebellar ataxia (CA), symptoms related to oculomotor dysfunction significantly affect quality of life (QoL). This study aimed to analyze the literature on patient-related outcome measures (PROMs) assessing QoL impacts of vestibular and cerebellar oculomotor abnormalities in patients with CA to identify the strengths and limitations of existing scales and highlight any areas of unmet need. A systematic review was conducted (Medline, Embase) of English-language original articles reporting on QoL measures in patients with vertigo, dizziness or CA. Pre-specified parameters were retrieved, including diseases studied, scales applied and conclusions drawn. Our search yielded 3671 articles of which 467 studies (n = 111,606 participants) were deemed relevant. The most frequently studied disease entities were (a) non-specific dizziness/gait imbalance (114 studies; 54,581 participants), (b) vestibular schwannomas (66; 15,360), and (c) vestibular disorders not further specified (66; 10,259). The Dizziness Handicap Inventory (DHI) was the most frequently used PROM to assess QoL (n = 91,851), followed by the Penn Acoustic Neuroma Quality-of-Life Scale (n = 12,027) and the Activities-Specific Balance Confidence Scale (n = 2’471). QoL-scores capturing symptoms related to oculomotor abnormalities in CA were rare, focused on visual impairments (e.g., National-Eye-Institute Visual Function Questionnaire, Oscillopsia Functional Impact, oscillopsia severity score) and were unvalidated. The DHI remains the most widely used and versatile scale for evaluating dizziness. A lack of well-established PROMs for assessing the impact of oculomotor-related symptoms on QoL in CA was noted, emphasizing the need for developing and validating a new QoL-score dedicated to the oculomotor domain for individuals with CA.
... The cerebellum has long been known to play a critical role in controlling movement [1]. A dominant hypothesis is that the cerebellum houses internal models of body and environment dynamics, which it combines with information about motor commands to generate predictions of the sensory consequences of actions (i.e., the forward internal model) [2,3]. ...
Recent work showed that individuals with cerebellar degeneration could leverage intact reinforcement learning (RL) to alter their movement. However, there was marked inter-individual variability in learning, and the factors underlying it were unclear. Cerebellum-dependent sensory prediction may contribute to RL in motor contexts by enhancing body state estimates, which are necessary to solve the credit-assignment problem. The objective of this study was to test the relationship between the predictive component of state estimation and RL in individuals with cerebellar degeneration. Individuals with cerebellar degeneration and neurotypical control participants completed two tasks: an RL task that required them to alter the angle of reaching movements and a state estimation task that tested the somatosensory perception of active and passive movement. The state estimation task permitted the calculation of the active benefit shown by each participant, which is thought to reflect the cerebellum-dependent predictive component of state estimation. We found that the cerebellar and control groups showed similar magnitudes of learning with reinforcement and active benefit on average, but there was substantial variability across individuals. Using multiple regression, we assessed potential predictors of RL. Our analysis included active benefit, somatosensory acuity, clinical ataxia severity, movement variability, movement speed, and age. We found a significant relationship in which greater active benefit predicted better learning with reinforcement in the cerebellar, but not the control group. No other variables showed significant relationships with learning. Overall, our results support the hypothesis that the integrity of sensory prediction is a strong predictor of RL after cerebellar damage.
... Traditionally, the cerebellum has been viewed as a brain structure that plays a critical role in the coordination and timing of movements, as well as motor learning [1,2]. However, converging evidence from neuropsychology, functional brain imaging and studies in non-human primates over the past twenty-five years suggests that the cerebellum also plays a role in a variety of different cognitive and affective functions ranging from working memory, sensory processing, and language, to emotion, executive functions, and attention [e.g., [1][2][3][4][5][6][7][8][9]. ...
... Traditionally, the cerebellum has been viewed as a brain structure that plays a critical role in the coordination and timing of movements, as well as motor learning [1,2]. However, converging evidence from neuropsychology, functional brain imaging and studies in non-human primates over the past twenty-five years suggests that the cerebellum also plays a role in a variety of different cognitive and affective functions ranging from working memory, sensory processing, and language, to emotion, executive functions, and attention [e.g., [1][2][3][4][5][6][7][8][9]. The cerebellum's role in an array of different cognitive functions is supported through its rich structural and functional connectivity with the cerebral cortex [7,[10][11][12][13][14]. ...
Each cerebellar hemisphere projects to the contralateral cerebral hemisphere. Previous research suggests a lateralization of cognitive functions in the cerebellum that mirrors the cerebral cortex, with attention/visuospatial functions represented in the left cerebellar hemisphere, and language functions in the right cerebellar hemisphere. Although there is good evidence supporting the role of the right cerebellum with language functions, the evidence supporting the notion that attention and visuospatial functions are left lateralized is less clear. Given that spatial neglect is one of the most common disorders arising from right cortical damage, we reasoned that damage to the left cerebellum would result in increased spatial neglect-like symptoms, without necessarily leading to an official diagnosis of spatial neglect. To examine this disconnection hypothesis, we analyzed neglect screening data (line bisection, cancellation, figure copying) from 20 patients with isolated unilateral cerebellar stroke. Results indicated that left cerebellar patients (n = 9) missed significantly more targets on the left side of cancellation tasks compared to a normative sample. No significant effects were observed for right cerebellar patients (n = 11). A lesion overlap analysis indicated that Crus II (78% overlap), and lobules VII and IX (66% overlap) were the regions most commonly damaged in left cerebellar patients. Our results are consistent with the notion that the left cerebellum may be important for attention and visuospatial functions. Given the poor prognosis typically associated with neglect, we suggest that screening for neglect symptoms, and visuospatial deficits more generally, may be important for tailoring rehabilitative efforts to help maximize recovery in cerebellar patients.
... A strength of his approach was that his methods for data acquisition were consistent across a wide range of species, thus facilitating the ability to compare cerebellar structures between species in his sample. With the advent of modern methods of neuroanatomical inquiry-including imaging, molecular, and histological techniques-there are ample opportunities to create high-resolution, multimodal neuroanatomical atlases across species that build upon the foundation of comparative cerebellar anatomy set by Larsell and others, such as Bolk (Glickstein and Voogd 1995;Glickstein et al. 2009). ...
Increased appreciation of the functional heterogeneity of the cerebellum and its contribution to various neuropsychiatric impairments has sparked a resurgence of interest in its comparative anatomy and evolution. Recent evidence suggests that (1) the cerebellar lobules play a prominent role in cognitive, social, and behavioral computations (Desmond et al. 1997; Schmahmann and Sherman 1998; Stoodley and Schmahmann 2009a), and that (2) select portions of the cerebellum may have undergone evolutionary expansion in some lineages of mammals, including humans (Balsters et al. 2010; Smaers et al. 2018), thus creating a need for a higher neuroanatomical resolution of the cerebellum across a broad comparative sample. Here, we provide a detailed magnetic resonance imaging (MRI) atlas of the chimpanzee cerebellum as well as a methodology for the systematic delineation of the vermal and hemispheric lobules. Group averaging across 67 individuals facilitated the characterization of 32 cerebellar masks across the anterior, posterior, and flocculonodular lobes of the cerebellum. A segmentation protocol, including detailed anatomical definitions of each structure, provides the foundation for the construction of future multimodal cerebellar atlases that can deliver insight into cerebellar evolution and pathology.
... The cerebellum is a highly conserved structure among vertebrates and is well known for its important role in motor coordination [37]. GH is involved in the growth of the cerebellum since GH-deficient mice presented a 20% reduction in the size of this organ in comparison with normal mice [38]. ...
Several motor, sensory, cognitive, and behavioral dysfunctions are associated with neural lesions occurring after a hypoxic injury (HI) in preterm infants. Growth hormone (GH) expression is upregulated in several brain areas when exposed to HI conditions, suggesting actions as a local neurotrophic factor. It is known that GH, either exogenous and/or locally expressed, exerts neuroprotective and regenerative actions in cerebellar neurons in response to HI. However, it is still controversial whether GH can cross the blood–brain barrier (BBB), and if its effects are exerted directly or if they are mediated by other neurotrophic factors. Here, we found that in ovo microinjection of Cy3-labeled chicken GH resulted in a wide distribution of fluorescence within several brain areas in the chicken embryo (choroid plexus, cortex, hypothalamus, periventricular areas, hippocampus, and cerebellum) in both normoxic and hypoxic conditions. In the cerebellum, Cy3-GH and GH receptor (GHR) co-localized in the granular and Purkinje layers and in deep cerebellar nuclei under hypoxic conditions, suggesting direct actions. Histological analysis showed that hypoxia provoked a significant modification in the size and organization of cerebellar layers; however, GH administration restored the width of external granular layer (EGL) and molecular layer (ML) and improved the Purkinje and granular neurons survival. Additionally, GH treatment provoked a significant reduction in apoptosis and lipoperoxidation; decreased the mRNA expression of the inflammatory mediators (TNFα, IL-6, IL-1β, and iNOS); and upregulated the expression of several neurotrophic factors (IGF-1, VEGF, and BDNF). Interestingly, we also found an upregulation of cerebellar GH and GHR mRNA expression, which suggests the existence of an endogenous protective mechanism in response to hypoxia. Overall, the results demonstrate that, in the chicken embryo exposed to hypoxia, GH crosses the BBB and reaches the cerebellum, where it exerts antiapoptotic, antioxidative, anti-inflammatory, neuroprotective, and neuroregenerative actions.
... Both Eling [4], in his short biography of Jelgersma and I in several historical reviews of cerebellar research [47],Voogd and Koehler [48], emphasized Jelgersma's theory of amoeboid mobility of nerve cells, a theory leading to a self-generating neural network that subserves neuronal plasticity. However, reading more about the history of neuronal spines [49], I found that Jelgersma never mentioned that this theory was initiated by a group of Belgian and French histologists in the late nineteenth century. ...
Gerbrandus Jelgersma published extensively on the (pathological) anatomy of the cerebellum between 1886 and 1934. Based on his observations on the double innervation of the Purkinje cells, he formulated a hypothesis on the function of the cerebellum. Both afferent systems of the cerebellum, the mossy fiber-parallel fiber system and the climbing fibers terminate on the Purkinje cell dendrites. According to Jelgersma, the mossy fiber-parallel fiber system is derived from the pontine nuclei and the inferior olive, and would transmit the movement images derived from the cerebral cortex. Spinocerebellar climbing fibers would transmit information about the execution of the movement. When the Purkinje cell compares these inputs and notices a difference between instruction and execution, it sends a correction through the descending limb of the superior cerebellar peduncle to the anterior horn cells. Jelgersma postulates that this cerebro-cerebellar coordination system shares plasticity with other nervous connections because nerve cell dendritic protrusions possess what he called amoeboid mobility: dendritic protrusions can be extended or retracted and are so able to create new connections or to abolish them. Jelgersma’s theories are discussed against the background of more recent theories of cerebellar function that, similarly, are based on the double innervation of the Purkinje cells. The amoeboid hypothesis is traced to its roots in the late nineteenth century.
... From the very beginning of history, the anatomical complexity of the cerebellum was obvious and its complex structure, including hemispheres, sulci and gyri were well described by morphologists [21]. Erasistratus is considered the first author to distinguish the cerebellum from other brain regions in the 4 th century BC, followed by Galen, who proposed the idea of the cerebellum being a source of motor nerves with cerebellar vermis being a valve for body spirits [22]. Later, various functions of the cerebellum were discovered and suggested, such as memory, involuntary movement control, sensory integration, and even sexual function [23]. ...
The cerebellum is a well-established primary brain center in charge of controlling sensorimotor functions and non-motor functions. Recent reports depicted the significance of cerebellum in higher-order cognitive functions including emotion-processing, language, reward-related behavior, working memory, and social behavior. As it can influence diverse behavioral patterns, any defects in cerebellar functions could invoke neuropsychiatric diseases as indicated by the incidence of alexithymia and induce alterations in emotional and behavioral patterns. Furthermore, its defects can trigger motor diseases, such as ataxia and Parkinson’s disease (PD). In this review, we have extensively discussed the role of cerebellum in motor and non-motor functions and how the cerebellum malfunctions in relation to the neural circuit wiring as it could impact brain function and behavioral outcomes in the patients with neuropsychiatric diseases. Relevant data regarding cerebellar non-motor functions have been vividly described along with anatomy and physiology of these functions. In addition to the defects in basal ganglia, the lack of activity in motor related regions of the cerebellum could be associated with the severity of motor symptoms. All together, this review delineates the importance of cerebellar involvement in patients with PD and unravels a crucial link for various clinical aspects of PD with specific cerebellar sub-regions.
... It is indicated that the primary sensorimotor cortex may be involved in and play an important role in the impairment of swallowing function of ATM patients. The cerebellum has long been considered critical for the control of motor (21,22) and is a major target for thyroid hormone. The cerebellum integrates the received sensorimotor information and is involved in regulating the precision and coordination of swallowing-related muscle groups. ...
Objective
The independent component analysis (ICA) was applied to explore the correlation between clinical manifestation and the functional connectivity changes of the sensorimotor network (SMN) and left frontoparietal network (LFPN) in patients with acute thyrotoxic myopathy (ATM), which was expected to provide a functional imaging basis for the exploration of the pathophysiological mechanism of ATM.
Methods
13 ATM patients (ATM) and 12 non-ATM patients (nATM) who met the diagnostic and inclusion criteria were enrolled. Their resting-state brain function images were obtained with resting-state functional magnetic resonance imaging (rs-fMRI). GIFT software was used for independent component analysis to obtain the brain regions with SMN and LFPN changes. The correlation between the functional connectivity of these brain regions and clinical indicators was calculated.
Results
The SMN functional connectivity of ATM patients was increased at the posterior lobe of cerebellum, anterior lobe of cerebellum, right superior temporal gyrus, left cingulate gyrus, left precuneus, and left postcentral gyrus compared with that of nATM patients. However, it was decreased at the occipital lobe, right dorsolateral superior frontal gyrus, paracentral lobule, angular gyrus, and superior parietal gyrus (FDR correction, P<0.05). The LFPN functional connectivity of ATM patients was increased at the posterior lobe of cerebellum, middle temporal gyrus, inferior temporal gyrus, and right cingulate gyrus compared with that of nATM patients; but was decreased at frontal lobe, parahippocampal gyrus, precentral gyrus and postcentral gyrus (FDR correction, P<0.05) Correlation analysis results showed that the enhancement of SMN functional connection at right superior temporal gyrus was significantly negatively correlated with the free thyroxine level, and the decrease of SMN functional connectivity at occipital lobe was significantly positively correlated to the thyroid stimulating hormone level. The SMN and LFPN functional connectivity changes in other brain regions were not found to be significantly correlated with thyroid function parameters.
Conclusion
The bulbar paralysis (such as dysphagia, dysarthria) in ATM patients may be related to the functional connectivity changes of resting-state SMN and LFPN. The fMRI is expected to be one of the objective imaging indicators for the early clinical intervention of ATM patients.
... Félix Vicq dÁzyr (1746-1794), two French physicians, then described the cerebellar nuclei (Glickstein et al., 2009). ...
... He notices that the number of folia is variable between individual and that it seems to be lower in mentally impaired people. Thus, he advances the idea that the cerebellum could be involved in learning (Glickstein et al., 2009). ...
... In 1964 Masao Ito and coworkers would finally describe the inhibitory nature of Purkinje Cells (PC) projecting on the cerebellar nuclei (Ito et al., 1964). A discovery that challenged the popular belief that principal cells were exclusively excitatory (Glickstein et al., 2009). In the same years, the Inferior Olive (IO) is described to be a major input to contralateral cerebellar cortex (Szentágothai & Rajkovits, 1959) and that climbing fibers (CF) elicit strong excitatory inputs in PCs (Eccles et al., 1966), called "complex spikes" in contrast with the "simple spikes" ...
A growing body of literature is showing an involvement of the cerebellum in managing time predictions and expectations of motor and cognitive events. On the other hand the medial prefrontal cortex (mPFC) is widely considered the area where there is the integration between internal models and cognition. Moreover, mPFC is involved in most of the models for time perception, making it an ideal candidate for handling predictive behaviors. Both tracing experiments and interval timing task highlighted a connection between these two areas. We thus developed a model to investigate the role of the cerebellum in the creation and update of implicit temporal predictions in mPFC of mice. We recorded the extracellular activity in the mPFC (specifically left prelimbic area, PrL) while the head-restrained mice perform the following variable foreperiod task : two cues are presented in a sequence followed by a reward delivered at either a fixed or a variable time point (randomly chosen between two possible delays). At the same time, we photoactivate cerebellar Purkinje cells of L7-Channelrhdopsin2 mice at specific frequencies, above contralateral Crus I. The aim of the optogenetic stimulation is to interfere with neuronal discharge in the mPFC. We confirm the foreperiod effect, already described in the literature, for which responses are faster and more accurate when an interval between a cue and a go signal/reward (foreperiod) is constant. Interestingly we report different behavior of two important prefrontal oscillations: delta (1.5-4Hz) and theta (4-10Hz). They show ramping behavior only when the foreperiod is variable and fixed, respectively. Moreover, cerebellar photostimulation affects these oscillations only if they are ramping. This is probably representative of different neural substrates recruited by the two foreperiod conditions.
