RESUMEN
The human cerebellum is increasingly recognized to be involved in nonmotor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole brain exploration with a unified analytical framework. Here, we characterized dissociable cortical-cerebellar structural covariation patterns based on regional gray matter volume (GMV) across the brain in n = 38,527 UK Biobank participants. Our results invigorate previous observations in that important shares of cortical-cerebellar structural covariation are described as 1) a dissociation between the higher-level cognitive system and lower-level sensorimotor system and 2) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neuroscience view paves the way for future studies to explore the implications of these structural covariations, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.NEW & NOTEWORTHY Cerebellum's association with the entire cerebral cortex has not been holistically studied in a unified way. Here, we conjointly characterize the population-level cortical-cerebellar structural covariation patterns leveraging â¼40,000 UK Biobank participants whole brain structural scans and â¼1,000 phenotypes. We revitalize the previous hypothesis of an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel ipsilateral cerebral-cerebellar associations. Phenome-wide association (PheWAS) revealed real-world implications of the structural covariation patterns.
Asunto(s)
Cerebelo , Neocórtex , Humanos , Masculino , Femenino , Cerebelo/fisiología , Cerebelo/anatomía & histología , Cerebelo/diagnóstico por imagen , Persona de Mediana Edad , Neocórtex/fisiología , Neocórtex/anatomía & histología , Anciano , Imagen por Resonancia Magnética , Sustancia Gris/anatomía & histología , Sustancia Gris/fisiología , Sustancia Gris/diagnóstico por imagen , Corteza Cerebral/fisiología , Corteza Cerebral/anatomía & histología , Corteza Cerebral/diagnóstico por imagen , Vías Nerviosas/fisiología , Vías Nerviosas/anatomía & histología , AdultoRESUMEN
Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is still being determined. Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum ( h 2 $$ {h}^2 $$ 47%-91%). Additionally, the good to excellent test-retest reliability for a subsample of QTIM participants suggests that non-genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome-wide association studies.
Asunto(s)
Cerebelo , Imagen por Resonancia Magnética , Adolescente , Niño , Humanos , Adulto Joven , Cerebelo/diagnóstico por imagen , Cerebelo/anatomía & histología , Tamaño de los Órganos , Gemelos MonocigóticosRESUMEN
Parcellation of human cerebellar pathways is essential for advancing our understanding of the human brain. Existing diffusion magnetic resonance imaging tractography parcellation methods have been successful in defining major cerebellar fibre tracts, while relying solely on fibre tract structure. However, each fibre tract may relay information related to multiple cognitive and motor functions of the cerebellum. Hence, it may be beneficial for parcellation to consider the potential importance of the fibre tracts for individual motor and cognitive functional performance measures. In this work, we propose a multimodal data-driven method for cerebellar pathway parcellation, which incorporates both measures of microstructure and connectivity, and measures of individual functional performance. Our method involves first training a multitask deep network to predict various cognitive and motor measures from a set of fibre tract structural features. The importance of each structural feature for predicting each functional measure is then computed, resulting in a set of structure-function saliency values that are clustered to parcellate cerebellar pathways. We refer to our method as Deep Multimodal Saliency Parcellation (DeepMSP), as it computes the saliency of structural measures for predicting cognitive and motor functional performance, with these saliencies being applied to the task of parcellation. Applying DeepMSP to a large-scale dataset from the Human Connectome Project Young Adult study (n = 1065), we found that it was feasible to identify multiple cerebellar pathway parcels with unique structure-function saliency patterns that were stable across training folds. We thoroughly experimented with all stages of the DeepMSP pipeline, including network selection, structure-function saliency representation, clustering algorithm, and cluster count. We found that a 1D convolutional neural network architecture and a transformer network architecture both performed comparably for the multitask prediction of endurance, strength, reading decoding, and vocabulary comprehension, with both architectures outperforming a fully connected network architecture. Quantitative experiments demonstrated that a proposed low-dimensional saliency representation with an explicit measure of motor versus cognitive category bias achieved the best parcellation results, while a parcel count of four was most successful according to standard cluster quality metrics. Our results suggested that motor and cognitive saliencies are distributed across the cerebellar white matter pathways. Inspection of the final k = 4 parcellation revealed that the highest-saliency parcel was most salient for the prediction of both motor and cognitive performance scores and included parts of the middle and superior cerebellar peduncles. Our proposed saliency-based parcellation framework, DeepMSP, enables multimodal, data-driven tractography parcellation. Through utilising both structural features and functional performance measures, this parcellation strategy may have the potential to enhance the study of structure-function relationships of the cerebellar pathways.
Asunto(s)
Cerebelo , Aprendizaje Profundo , Imagen de Difusión Tensora , Humanos , Cerebelo/fisiología , Cerebelo/diagnóstico por imagen , Cerebelo/anatomía & histología , Imagen de Difusión Tensora/métodos , Adulto , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/anatomía & histología , Conectoma/métodos , Masculino , Femenino , Adulto Joven , Procesamiento de Imagen Asistido por Computador/métodos , Actividad Motora/fisiologíaRESUMEN
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.
Asunto(s)
Cerebelo , Recien Nacido Prematuro , Imagen por Resonancia Magnética , Nacimiento Prematuro , Humanos , Cerebelo/crecimiento & desarrollo , Cerebelo/diagnóstico por imagen , Cerebelo/anatomía & histología , Femenino , Masculino , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido , Nacimiento Prematuro/patología , Conectoma , Edad GestacionalRESUMEN
Multiple lines of evidence across human functional, lesion, and animal data point to a cerebellar role, in particular of crus I, crus II, and lobule VIIB, in cognitive function. However, a mapping of distinct facets of cognitive function to cerebellar structure is missing. We analyzed structural neuroimaging data from the Healthy Brain Network (HBN). Cerebellar parcellation was performed with a validated automated segmentation pipeline (CERES) and stringent visual quality check (n = 662 subjects retained from initial n = 1452). Canonical correlation analyses (CCA) examined regional gray matter volumetric (GMV) differences in association to cognitive function (quantified with NIH Toolbox Cognition domain, NIH-TB), accounting for psychopathology severity, age, sex, scan location, and intracranial volume. Multivariate CCA uncovered a significant correlation between two components entailing a latent cognitive canonical (NIH-TB subscales) and a brain canonical variate (cerebellar GMV and intracranial volume, ICV), surviving bootstrapping and permutation procedures. The components correspond to partly shared cerebellar-cognitive function relationship with a first map encompassing cognitive flexibility (r = 0.89), speed of processing (r = 0.65), and working memory (r = 0.52) associated with regional GMV in crus II (r = 0.57) and lobule X (r = 0.59) and a second map including the crus I (r = 0.49) and lobule VI (r = 0.49) associated with working memory (r = 0.51). We show evidence for a structural subspecialization of the cerebellum topography for cognitive function in a transdiagnostic sample.
Asunto(s)
Cerebelo , Cognición , Imagen por Resonancia Magnética , Humanos , Femenino , Cerebelo/diagnóstico por imagen , Cerebelo/anatomía & histología , Masculino , Cognición/fisiología , Adulto , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto Joven , Sustancia Gris/diagnóstico por imagen , Pruebas Neuropsicológicas , AncianoRESUMEN
The fourth ventricle is a small, fluid-filled cavity located within the brain that plays a vital role in the body's physiological functions. Therefore, the anatomical elements forming it bear significant clinical relevance. However, the exact relations between the elements that form its roof are still debated in the neuroanatomical literature; the inferior medullary velum, and the ventricle's median aperture in particular. In some atlases, the inferior medullary velum is placed in the midline, while in others, it is placed in the transverse plane. The median aperture is also displayed in different ways in midsagittal drawings: as a round perforation of a midline velum, as a foramen in an uncharacterized part of the ventricle, and as a gap between the nodule and the brainstem. This work aims to provide a comprehensive review of the different descriptions of the fourth ventricle, in order to gain a clearer understanding of the ventricular system's structure.
Asunto(s)
Cerebelo , Cuarto Ventrículo , Cuarto Ventrículo/anatomía & histología , Cerebelo/anatomía & histología , Neuroanatomía , Tronco Encefálico , CabezaRESUMEN
The basal ganglia and the cerebellum are considered to be distinct subcortical systems that perform unique functional operations. The outputs of the basal ganglia and the cerebellum influence many of the same cortical areas but do so by projecting to distinct thalamic nuclei. As a consequence, the two subcortical systems were thought to be independent and to communicate only at the level of the cerebral cortex. Here, we review recent data showing that the basal ganglia and the cerebellum are interconnected at the subcortical level. The subthalamic nucleus in the basal ganglia is the source of a dense disynaptic projection to the cerebellar cortex. Similarly, the dentate nucleus in the cerebellum is the source of a dense disynaptic projection to the striatum. These observations lead to a new functional perspective that the basal ganglia, the cerebellum and the cerebral cortex form an integrated network. This network is topographically organized so that the motor, cognitive and affective territories of each node in the network are interconnected. This perspective explains how synaptic modifications or abnormal activity at one node can have network-wide effects. A future challenge is to define how the unique learning mechanisms at each network node interact to improve performance.
Asunto(s)
Ganglios Basales/fisiología , Cerebelo/fisiología , Animales , Ganglios Basales/anatomía & histología , Cerebelo/anatomía & histología , Humanos , Modelos Neurológicos , Motivación , Enfermedades del Sistema Nervioso/fisiopatología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Recompensa , Núcleo Subtalámico/anatomía & histología , Núcleo Subtalámico/fisiología , Tálamo/anatomía & histología , Tálamo/fisiologíaRESUMEN
The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. It was computationally reconstructed for the first time to the level of all individual folia from multicontrast high-resolution postmortem MRI scans. Its total shrinkage-corrected surface area (1,590 cm2) was larger than expected or previously reported, equal to 78% of the total surface area of the human neocortex. The unfolded and flattened surface comprised a narrow strip 10 cm wide but almost 1 m long. By applying the same methods to the neocortex and cerebellum of the macaque monkey, we found that its cerebellum was relatively much smaller, approximately 33% of the total surface area of its neocortex. This suggests a prominent role for the cerebellum in the evolution of distinctively human behaviors and cognition.
Asunto(s)
Cerebelo/anatomía & histología , Neocórtex/anatomía & histología , Animales , Corteza Cerebelosa/anatomía & histología , Corteza Cerebelosa/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Macaca , Imagen por Resonancia Magnética , Neocórtex/diagnóstico por imagenRESUMEN
BACKGROUND: In this morphometric study, we describe the anatomy of the TIGR triangle, which is bordered by the tentorial surface of the cerebellum, the internal cerebral vein and vein of Galen complex, and the vein of Rosenthal. These structures define the window, or deep keyhole, to access the pineal region in non-midline supracerebellar infratentorial approaches. METHODS: The posterior fossa anatomy of 16 patients was studied in virtual reality (VR), and the TIGR triangles were defined and measured with special attention on its angular orientation in the posterior fossa. The angular expanse of the posterior fossa was measured and recorded as the transverse-sigmoid junction (TSJ) angle. Because a perpendicular corridor through an anatomic aperture provides the best exposure, we studied the starting point along the TSJ angle that offers the best exposure of TIGR. RESULTS: In the 31 posterior fossa sides included in the study, the perpendicular trajectory through the TIGR triangle was on average 27.13° CI 95% (range: 5.97°-48.53°) from the midline. When comparing the SCIT variants, both the paramedian and lateral approaches provided near-perpendicular trajectory through the TIGR triangle in a majority of specimens. However, the modified paramedian approach, with starting point defined as TSJ angle/3, provided the most perpendicular path through the TIGR triangle. CONCLUSION: We studied the size, spatial orientation, and morphology of the TIGR triangle. Our data indicated that the best exposure of TIGR is through a modified paramedian SCIT approach, in which the starting point one third of the way from midline to the TSJ.
Asunto(s)
Craneotomía , Glándula Pineal , Humanos , Glándula Pineal/cirugía , Cerebelo/cirugía , Cerebelo/anatomía & histología , DuramadreRESUMEN
The cerebellum is a conserved structure of vertebrate brains that develops at the most anterior region of the alar rhombencephalon. All vertebrates display a cerebellum, making it one of the most highly conserved structures of the brain. Although it greatly varies at the morphological level, several lines of research point to strong conservation of its internal neural circuitry. To test the conservation of the cerebellar circuit, we compared the developmental history of the neurons comprising this circuit in three amniote species: mouse, chick, and gecko. We specifically researched the developmental time of generation of the main neuronal types of the cerebellar cortex. This developmental trajectory is known for the mammalian cell types but barely understood for sauropsid species. We show that the neurogenesis of the GABAergic lineage proceeds following the same chronological sequence in the three species compared: Purkinje cells are the first ones generated in the cerebellar cortex, followed by Golgi interneurons of the granule cell layer, and lately by the interneurons of the molecular layer. In the cerebellar glutamatergic lineage, we observed the same conservation of neurogenesis throughout amniotes, and the same vastly prolonged neurogenesis of granule cells, extending much further than for any other brain region. Together these data show that the cerebellar circuitry develops following a tightly conserved chronological sequence of neurogenesis, which is responsible for the preservation of the cerebellum and its function. Our data reinforce the developmental perspective of homology, whereby similarities in neurons and circuits are likely due to similarities in developmental sequence.
Asunto(s)
Cerebelo , Neurogénesis , Animales , Cerebelo/anatomía & histología , Mamíferos , Ratones , Neurogénesis/fisiología , Neuronas/metabolismo , Células de PurkinjeRESUMEN
A better understanding of the surgical anatomy of the cerebellar peduncles in different surgical approaches and their relationship with other neural structures are delineated through cadaveric dissections. We aimed to revisit the surgical anatomy of the cerebellar peduncles to describe their courses along the brain stem and the cerebellum and revise their segmental classification in surgical areas exposed through different approaches. Stepwise fiber microdissection was performed along the cerebellar tentorial and suboccipital surfaces. Multiple surgical approaches in each of the cerebellar peduncles were compared in eight silicone-injected cadaveric whole heads to evaluate the peduncular exposure areas. From a neurosurgical point of view, the middle cerebellar peduncle (MCP) was divided into a proximal cisternal and a distal intracerebellar segments; the inferior cerebellar peduncle (ICP) into a ventricular segment followed by a posterior curve and a subsequent intracerebellar segment; the superior cerebellar peduncle (SCP) into an initial congregated, an intermediate intraventricular, and a distal intramesencephalic segment. Retrosigmoid and anterior petrosectomy approaches exposed the junction of the MCP segments; telovelar, supratonsillar, and lateral ICP approaches each reached different segments of ICP; paramedian supracerebellar infratentorial, suboccipital transtentorial, and combined posterior transpetrosal approaches displayed the predecussation SCP within the cerbellomesencephalic fissure, whereas the telovelar approach revealed the intraventricular SCP within the superolateral recess of the fourth ventricle. Better understanding of the microsurgical anatomy of the cerebellar peduncles in various surgical approaches and their exposure limits constitute the most critical aspect for the prevention of surgical morbidity during surgery in and around the pons and the upper medulla. Our findings help in evaluating radiological data and planning an operative procedure for cerebellar peduncles.
Asunto(s)
Cerebelo , Puente , Tronco Encefálico/cirugía , Cadáver , Cerebelo/anatomía & histología , Cerebelo/cirugía , Cuarto Ventrículo/cirugía , Humanos , Puente/cirugíaRESUMEN
Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state-of-the-art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I-II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.
Asunto(s)
Cerebelo , Sustancia Gris , Desarrollo Humano/fisiología , Imagen por Resonancia Magnética/métodos , Sustancia Blanca , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cerebelo/anatomía & histología , Cerebelo/diagnóstico por imagen , Cerebelo/crecimiento & desarrollo , Niño , Preescolar , Femenino , Sustancia Gris/anatomía & histología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Masculino , Persona de Mediana Edad , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Adulto JovenRESUMEN
Guinea pigs have proved useful as experimental animal models in studying cerebellar anatomical and structural alterations in human neurological disease; however, they are also currently acquiring increasing veterinary interest as companion animals. The morphometric features of the normal cerebellum in guinea pigs have not been previously investigated using stereology. The objective of the present work was to establish normal volumetric and quantitative stereological parameters for cerebellar tissues in guinea pigs, by means of unbiased design-based stereology. Cerebellar total volume, gray and white matter volume fractions, molecular and granular layers volume fractions, cerebellar surface area, Purkinje cellular and nuclear volumes, and the Purkinje cell total count were stereologically estimated. For this purpose, cerebellar hemispheres from six adult male guinea pigs were employed. Isotropic, uniform random sections were obtained by applying the orientator method, and subsequently processed for light microscopy. The cerebellar total volume, the white and grey matter volume fractions, and the molecular and granular layer volumes were estimated using the Cavalieri's principle and the point counting system. The cerebellar surface area was estimated through the use of test lines; Purkinje cellular and nuclear volumes were analysed using the nucleator technique, whereas the Purkinje cell total count was obtained by means of the optical disector technique. The mean ± standard deviation total volume of a guinea-pig cerebellar hemisphere was 0.11 ± 0.01 cm3 . The mean volumetric proportions occupied by the gray and white matters were, respectively, 78.0 ± 2.6% and 22.0 ± 2.6%, whereas their mean absolute volumes were found to be 0.21 ± 0.02 cm3 and 0.059 ± 0.006 cm3 . The volumes of the molecular and granular layers were estimated at 112.4 ± 20.6 mm3 and 104.4 ± 7.3 mm3 , whereas their mean thicknesses were calculated to be 0.184 ± 0.020 mm and 0.17 ± 0.02 mm. The molecular and granular layers accounted for 40.7 ± 3.9% and 37.4 ± 1.8% of total cerebellar volume respectively. The surface area of the cerebellum measured 611.4 ± 96.8 mm2 . Purkinje cells with a cellular volume of 3210.1 µm3 and with a nuclear volume of 470.9 µm3 had a higher incidence of occurrence. The mean total number of Purkinje cells for a cerebellar hemisphere was calculated to be 253,090 ± 34,754. The morphometric data emerging from the present study provide a set of reference data which might prove valuable as basic anatomical contribution for practical applications in veterinary neurology.
Asunto(s)
Cerebelo/anatomía & histología , Cobayas/anatomía & histología , Animales , Masculino , Microscopía/métodos , Células de PurkinjeRESUMEN
Motor-skill learning is associated with cerebellar synaptogenesis and astrocytic hypertrophy, but most of these assessments of cerebellar ultrastructure have been completed after one month of training. After one month of training, the motor-skills necessary to complete these tasks have been acquired for weeks. This experiment aimed to characterize cerebellar ultrastructure during the acquisition phase of motor-skill learning, at a point when performance is still improving. Male and female rats trained for four days on the acrobatic motor learning task, which involved traversing challenging obstacles such as narrow beams and ladders. Concurrently, rats in the motor control condition walked a flat alleyway requiring no skilled movements. After training was complete, all rats were euthanized, and tissue was prepared for electron microscopy. Unbiased stereology techniques were used to assess synaptic and astrocytic plasticity. Results indicated that during the initial days of training, female rats made fewer errors and had shorter latencies on the acrobatic course compared to male rats. However, there were no sex differences in cerebellar ultrastructure. Male and female rats that completed four days of acrobatic training displayed an increase in the density of parallel fiber-Purkinje cell synapses per Purkinje cell and an increase in astrocytic volume, relative to rats in the motor control group.
Asunto(s)
Astrocitos/fisiología , Cerebelo/fisiología , Aprendizaje/fisiología , Destreza Motora/fisiología , Plasticidad Neuronal/fisiología , Animales , Recuento de Células , Cerebelo/anatomía & histología , Femenino , Masculino , Microscopía Electrónica de Rastreo , Neurogénesis/fisiología , Células de Purkinje , Ratas , Ratas Long-Evans , Sinapsis/ultraestructuraRESUMEN
The perineuronal net (PNN) is a specialized type of extracellular matrix found in the central nervous system. The PNN forms on fast spiking neurons during postnatal development but the ontogeny of PNN development has yet to be elucidated. By studying the development and prevalence of the PNN in the juvenile and adult rat brain, we may be able to understand the PNN's role in development and learning and memory. We show that the PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by P18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we are able to study how digestion of the PNN affects cerebellar-dependent eyeblink conditioning in vivo and perform electrophysiological recordings from DCN neurons in vitro. In vivo degradation of the PNN resulted in significant differences in eyeblink conditioning amplitude and area. Female animals in the vehicle group demonstrated higher levels of conditioning as well as significantly higher post-probe conditioned responses compared to males in that group, differences not present in the ChABC group. In vitro, we found that DCN neurons with a disrupted PNN following exposure to ChABC had altered membrane properties, fewer rebound spikes, and decreased intrinsic excitability. Together, this study further elucidates the role of the PNN in cerebellar learning in the DCN and is the first to demonstrate PNN degradation may erase sex differences in delay conditioning.
Asunto(s)
Cerebelo/fisiología , Condicionamiento Clásico/fisiología , Neuronas/fisiología , Animales , Parpadeo/fisiología , Núcleos Cerebelosos/efectos de los fármacos , Núcleos Cerebelosos/fisiología , Cerebelo/anatomía & histología , Cerebelo/efectos de los fármacos , Condroitina ABC Liasa/farmacología , Condicionamiento Clásico/efectos de los fármacos , Electrofisiología , Femenino , Masculino , Neuronas/efectos de los fármacos , Técnicas de Placa-Clamp , Ratas , Ratas Long-Evans , Factores SexualesRESUMEN
The paper is an English translation of Heinrich Obersteiner's lecture on the significance of the granular layer of the cerebellum, rendered from the original German text that was published under the title Über die Bedeutung der Körnerschichte des Kleinhirns in the Jahrbücher für Psychiatrie und Neurologie (the official organ of the Society for Psychiatry and Neurology in Vienna), volume 30, pages 192-200, 1909, communicated on 21 September 1909 before the Session on Neurology and Psychiatry at the 81st meeting of the Society of German Natural Scientists and Physicians held in Salzburg, Austria.
Asunto(s)
Cerebelo/fisiología , Neurociencias/historia , Austria , Berlin , Cerebelo/anatomía & histología , Historia del Siglo XX , Humanos , Células de Purkinje/fisiología , TraduccionesRESUMEN
This commentary highlights a "cerebellar classic" by Heinrich Obersteiner (1847-1922), the founder of Vienna's Neurological Institute. Obersteiner had a long-standing interest in the cerebellar cortex, its development, and pathology, having provided one of the early accurate descriptions of the external germinal layer (sometimes called the "marginal zone of Obersteiner" or "Obersteiner layer"). In his communication before the 81st meeting of the Society of German Natural Scientists and Physicians in Salzburg in September 1909, Obersteiner placed special emphasis on the histophysiology of the granule cell layer of the cerebellum and covered most of the fundamental elements of the cerebellar circuitry, on the basis of Ramón y Cajal's neuronism. Those elements are discussed in a historic and a modern perspective, including some recent ideas about the role of granule cells, beyond the mere relay of sensorimotor information from mossy fibers to the Purkinje cells, in learning and cognition.
Asunto(s)
Cerebelo/fisiología , Neurociencias/historia , Animales , Berlin , Cerebelo/anatomía & histología , Cognición/fisiología , Gránulos Citoplasmáticos/fisiología , Historia del Siglo XX , Humanos , Aprendizaje/fisiología , Fibras Nerviosas , Células de Purkinje/fisiologíaRESUMEN
To identify robust and reproducible methods of cerebellar morphometry that can be used in future large-scale structural MRI studies, we investigated the replicability, repeatability, and long-term reproducibility of three fully automated software tools: FreeSurfer, CEREbellum Segmentation (CERES), and automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization (ACAPULCO). Replicability was defined as computational replicability, determined by comparing two analyses of the same high-resolution MRI data set performed with identical analysis software and computer hardware. Repeatability was determined by comparing the analyses of two MRI scans of the same participant taken during two independent MRI sessions on the same day for the Kirby-21 study. Long-term reproducibility was assessed by analyzing two MRI scans of the same participant in the longitudinal OASIS-2 study. We determined percent difference, the image intraclass correlation coefficient, the coefficient of variation, and the intraclass correlation coefficient between two analyses. Our results show that CERES and ACAPULCO use stochastic algorithms that result in surprisingly high differences between identical analyses for ACAPULCO and small differences for CERES. Changes between two consecutive scans from the Kirby-21 study were less than ± 5% in most cases for FreeSurfer and CERES (i.e., demonstrating high repeatability). As expected, long-term reproducibility was lower than repeatability for all software tools. In summary, CERES is an accurate, as demonstrated before, and reproducible tool for fully automated segmentation and parcellation of the cerebellum. We conclude with recommendations for the assessment of replicability, repeatability, and long-term reproducibility in future studies on cerebellar structure.
Asunto(s)
Cerebelo/anatomía & histología , Cerebelo/diagnóstico por imagen , Adulto , Anciano , Algoritmos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Programas Informáticos , Procesos EstocásticosRESUMEN
The cerebellum allows us to rapidly adjust motor behavior to the needs of the situation. It is commonly assumed that cerebellum-based motor learning is guided by the difference between the desired and the actual behavior, i.e., by error information. Not only immediate but also future behavior will benefit from an error because it induces lasting changes of parallel fiber synapses on Purkinje cells (PCs), whose output mediates the behavioral adjustments. Olivary climbing fibers, likewise connecting with PCs, are thought to transport information on instant errors needed for the synaptic modification yet not to contribute to error memory. Here, we report work on monkeys tested in a saccadic learning paradigm that challenges this concept. We demonstrate not only a clear complex spikes (CS) signature of the error at the time of its occurrence but also a reverberation of this signature much later, before a new manifestation of the behavior, suitable to improve it.
Asunto(s)
Potenciales de Acción/fisiología , Cerebelo/fisiología , Aprendizaje/fisiología , Reconocimiento Visual de Modelos/fisiología , Células de Purkinje/fisiología , Movimientos Sacádicos/fisiología , Animales , Axones/fisiología , Cerebelo/anatomía & histología , Cerebelo/citología , Electrodos Implantados , Macaca mulatta , Masculino , Modelos Neurológicos , Desempeño Psicomotor/fisiología , Células de Purkinje/citología , Técnicas Estereotáxicas , Sinapsis/fisiologíaRESUMEN
BACKGROUND: Volumes of cerebellar posterior lobes have been associated with cognitive skills, such as language functioning. Children born very preterm (VPT) often have language problems. However, only total cerebellar volume has been associated with language functioning, with contradicting results. The objective of this study was to ascertain whether total cerebellar structures or specific posterior lobular structures are associated with language ability of school-aged VPT children. METHODS: This is a prospective cohort study of 42 school-aged VPT children without major handicaps. Structural MRI was performed and the cerebellum segmentation pipeline was used for segmentation of separate lobules. Narrative retelling assessment was performed and language content and language structure scores were extracted. Linear regression analyses were used to associate language scores with whole gray matter (GM) cerebellar volume and right Crus I+II GM volume. RESULTS: Whole cerebellar GM volume was not significantly associated with language content nor with language structure; however, right Crus I+II GM volume was significantly associated with language content (ß = 0.192 (CI = 0.033, 0.351), p = 0.020). CONCLUSIONS: GM volume of Crus I+II appears to be associated with language functions in school-aged VPT children without major handicaps, while whole cerebellar volume is not. This study showed the importance of studying cerebellar lobules separately, rather than whole cerebellar volume only, in relation to VPT children's language functions. IMPACT: GM volume of Crus I+II is associated with semantic language functions in school-aged very preterm children without overt brain injury, whereas whole cerebellar volume is not. This study showed the importance of studying cerebellar lobules separately, rather than whole cerebellar volume only, in relation to very preterm children's language functions. This study might impact future research in very preterm children. Lobular structures rather than whole cerebellar structures should be the region of interest in relation to language functions.