The language of the cerebellum

Background: During the past three decades neuroanatomical, neuroimaging, and clinical studies have substantially altered the view on the role of the cerebellum as a sole coordinator of sensorimotor function. Currently, the cerebellum is believed to be also crucially involved in cognitive, affective, and behavioural functioning.

Aims: This paper aims to summarise a number of critical insights from different research areas (anatomy, functional imaging, clinical practice) that provide evidence for a role of the cerebellum in motor speech and nonmotor language processing.

Main contribution: By means of identifying a dense network of crossed reciprocal connections between the cerebellum and the supratentorial association areas, neuroanatomical studies provided a robust basis for the development of new insights in the modulatory role of the cerebellum in neurocognition, including nonmotor language processing. A topological distinction was established between the “motor” cerebellum, projecting to the cortical motor areas, and the “cognitive/affective” cerebellum, connected with the cortical and limbic association areas. Neuroimaging studies demonstrated cerebellar involvement in several different language tasks, even after controlling for motor aspects. In addition, several clinical studies identified a variety of nonmotor linguistic deficits after cerebellar damage, implying a prominent role for the cerebellum in these linguistic processes. Functional neuroimaging confirmed the functional impact of cerebellar lesions on remote, structurally intact cortical regions via crossed cerebello-cerebral diaschisis.

Conclusion: Evidence from neuroanatomical, neuroimaging, and clinical studies suggests a strongly lateralised involvement of the cerebellum in a broad spectrum of nonmotor language functions through crossed cerebello-cerebral connectivity. It is argued that the cerebellum is involved in language in a similar manner as it is involved in motor functions: through monitoring/coordinating cortical functions.     

Age-related changes in the cerebellum: parallel fibers

Between the ages of 3 and 23 months, the cerebella of NIH Fischer 344 rats lose 30% of the thickness of the molecular layer, 60% of the length of parallel fibers, and 80% of the synaptic varicosities along parallel fibers. Nearly 60% of these synaptic varicosities disappear between 3 and 9 months. Thus, the loss of cerebellar synapses is unusual, may have begun early in life, and continue into old age, causing profound synaptic losses in older rats. In addition to serious implications to functional losses, we speculate that these synaptic losses may trigger other age-related cellular losses in the cerebellum.     

Structure of an isolated cerebellum and related nuclei developed within the matrix of a mature ovarian teratoma

The distribution and organization of nerve cells in a microcerebellum and cerebellar stalk, developed within the matrix of a mature ovarian teratoma, were analyzed with respect to recent data on cerebellar histogenesis. It is postulated that a neuroectodermal germinal locus with proliferation capability similar to that found in the alar plates of the normal embryonic rhombencephalon was responsible for the formation of this highly organized neural tissue.     

The contribution of the cerebellum to speech production and speech perception: Clinical and functional imaging data

A classical tenet of clinical neurology proposes that cerebellar disorders may give rise to speech motor disorders (ataxic dysarthria), but spare perceptual and cognitive aspects of verbal communication. During the past two decades, however, a variety of higher-order deficits of speech production, e.g., more or less exclusive agrammatism, amnesic or transcortical motor aphasia, have been noted in patients with vascular cerebellar lesions, and transient mutism following resection of posterior fossa tumors in children may develop into similar constellations. Perfusion studies provided evidence for cerebello-cerebral diaschisis as a possible pathomechanism in these instances. Tight functional connectivity between the language-dominant frontal lobe and the contralateral cerebellar hemisphere represents a prerequisite of such long-distance effects. Recent functional imaging data point at a contribution of the right cerebellar hemisphere, concomitant with language-dominant dorsolateral and medial frontal areas, to the temporal organization of a prearticulatory verbal code ('inner speech'), in terms of the sequencing of syllable strings at a speaker's habitual speech rate. Besides motor control, this network also appears to be engaged in executive functions, e.g., subvocal rehearsal mechanisms of verbal working memory, and seems to be recruited during distinct speech perception tasks. Taken together, thus, a prearticulatory verbal code bound to reciprocal right cerebellar/left frontal interactions might represent a common platform for a variety of cerebellar engagements in cognitive functions. The distinct computational operation provided by cerebellar structures within this framework appears to be the concatenation of syllable strings into coarticulated sequences.     

Dysembryoplastic neuroepithelial tumour of the cerebellum

A case of dysembryoplastic neuroepithelial tumour of the cerebellum occurring in a 28-year-old woman is presented. The lesion extended from the cortex of the inferior vermis upwards into the white matter. Histologically, it exhibited areas of microcystic cerebellar astrocytoma and glial regions with hamartomatous blood vessels as well as areas with oligodendrocyte-like cells (OLC) with a delicate, fibrillary stroma lying in a mucinous, often microcystic matrix. The OLC showed prominent rosette formation and immunohistochemical features suggesting neuronal, i.e. granule cell, differentiation.     

Measuring parallel fiber length in the rat cerebellum

A new approach was devised to obtain the mean length of parallel fibers in Golgi sections of the rat cerebellum. This method was based on the principle that within a given region of the cerebellum the mean length of parallel fibers should be inversely proportional to the likelihood of spotting the ends of parallel fibers. An experimental protocol was designed based on the statistical relationship between the mean fiber length and the number of the ends of parallel fibers for a given total length of parallel fibers examined. Our methodology was simple and could have advantages over other existing methods.     

The cerebellum and its contribution to complex tasks in higher primates: A comparative perspective

Many aspects of the involvement of the cerebellum in motor control and cognition are still quite unclear or relatively unexplored. In particular, very little is known about the evolution of cerebellar contribution to complex behavior in higher primate species. In this paper, we provide an overview of existing and ongoing comparative studies of the role of the cerebellum in primate behavior. In particular, we discuss evidence that great apes show greater cerebellar relative size than monkeys and that such interspecific difference is mainly explained by growth of the lateral neocerebellum in evolution with converse changes in the vermis. Furthermore, we present evidence that volumetric differences as well as lateral asymmetry of the cerebellum are related to both performance and hand preference for skilled tasks like tool use and aimed throwing. Finally we suggest future directions for this comparative research area that may offer further valuable clues into the involvement of the cerebellum in complex behavior and its evolutionary origin in primate species.     

Functional asymmetry in the cerebellum: A brief review

Recent discoveries on the way in which the cerebellum carries out higher non-motor functions, have stimulated a proliferation of researches into functional integration and neural mechanisms in the cerebellum. Cerebellar functional asymmetry is a special characteristic of cerebellar functional organization and the cerebro-cerebellar circuitry that underlies task performance. Multi-level neuroimaging studies demonstrate that cerebellar functional asymmetry has a rather complex pattern, and may be correlated with practice or certain disorders. In this review, we summarize some new and important advances in the understanding of functional laterality of the cerebellum in primary motor and higher cognitive functions, and highlight the differences in the patterns of cerebellar functional asymmetry in the various functional domains. We propose that cerebellar functional asymmetry may be associated with the pattern of connectivity between a large number of widely distributed brain areas and between special cerebellar functional regions. It is suggested that cerebro-cerebellar circuits in particular play an important role in cerebellar functional asymmetry. Finally, we propose that multi-scale connectivity analyses and careful studies of high-level cerebellar functional asymmetry would make an important contribution to the understanding of the human cerebellum and cerebral neural networks.     

The cerebellum and sensorimotor coupling: Looking at the problem from the perspective of vestibular reflexes

Cerebellar modules process afferent information and deliver outputs relevant for both reflex and voluntary movements. The response of cerebellar modules to a given input depends on the whole array of signals impinging on them. Studies on vestibular reflexes indicate that the response of the cerebellar circuits to the vestibular input is modified by the integration of multiple visual, vestibular and somatosensory afferent signals. In this way the cerebellum slowly adapts these reflexes when they are not adequate to the behavioural condition and allows their fast modifications when the relative position of the body segments and that of the body in space are changed. Studies on voluntary movements indicate that the cerebellum is responsible for motor learning that consists of the development of new input-output associations. Several theoretical, anatomical and clinical studies are consistent with the hypothesis that the cerebellum allows the delivery of motor commands which vary according to the condition of the motor apparatus. Finally, the cerebellum could change the relation between visual information and aimed reaching movements according to the position of the eyes in the orbit and of the neck over the body. We propose that, due to the large expansion of its cortex, an important function of the cerebellum could be that of expanding the range of sensorimotor associations according to all the factors characterizing the behavioural condition. Indeed, following cerebellar lesion, learning is often lost, the movement results impaired and requires an increased attention. In the light of the recently discovered connections of the cerebellum with the rostral regions of the frontal lobe, it can be suggested that the ability of cerebellar circuits to modify the rules of input-output coupling according to a general context is a fundamental property allowing the cerebellum to control not only motor but also cognitive functions.     

The cerebellum: organization, functions and its role in nociception

Our vision of the cerebellum has been gradually transformed throughout the last century from a ‘little brain’ to a ‘neuronal machine’ capable of multitasks, all arguably based on a principle computational model. We review here the main functions of the cerebellum in light of its organization and connectivity. In addition to providing a clear and extensive review of the cerebellar literature, we emphasize the role of the cerebellum in nociception, which is novel to the neurophysiology of pain. However, it is premature to conclude that the cerebellum influences sensory experience in the absence of clinical data.     

Assessment of second language proficiency in bilingual children with specific language impairment: a clinical perspective

The goal of this study was to examine to what extent the conditions of restricted input of L2 and SLI have an additive impact on language acquisition. Therefore, the Dutch language achievement of 6-, 7-, and 8-year-old bilingual children with SLI was compared with that of typically developing monolingual Dutch children, typically developing bilingual children, and monolingual Dutch children with SLI. Assuming that speaking a language in varying environments involves distinct subskills that can be acquired in differential patterns, the achievement of phonological, lexical, morphosyntactic and textual abilities were assessed separately. For each of these abilities, it was determined to what extent the conditions of restricted input (first vs. second language) and language deficit (typically developing vs. SLI) cause stagnation or a delay in language acquisition. Bilingual children with SLI perform at a lower level than the other groups in almost all aspects of achievement in Dutch. For language tasks related to the mental lexicon and grammar, an additional disadvantage was evidenced as a result of the combination of learning Dutch as second language and having SLI.     

Grammatical analysis of developmental language disorders: A study of the morphosyntax of children with specific language disorders,with hearing impairment and with Down's syndrome

Using a Dutch adaptation of the LARSP procedure by Crystal, Fletcher and Garman (1976) this investigation aimed at two questions: (1) is it possible to discern patterns in the morphosyntax of three groups of language-disordered children: children with specific language disorders, children with hearing impairment and children with Down's syndrome? and (2) can these patterns be related to the clinical characteristics of the children? Analysis of samples of spontaneous speech produced an affirmative answer to the first question. The answer to the second question is that the different clinical characteristics of the children did not so much lead to different kinds of language disorders as to differences in the degree of being language-disordered. The three groups of children showed more commonalities than differences in producing morphosyntax.     

Speech and song: The role of the cerebellum

An exploration into cerebellar activity during the perception and production of speech and song may elucidate general underlying cerebellar functions. Recently, the cerebellum has been hypothesized to be involved with sharpening sensory input, temporal coordination and processing of motor articulation and perception, as well as instantiation of internal models that simulate the input-output characteristics of a specific system. Sung language and spoken language share many common features (physiology for articulation and perception as well as phonology, phonotactics, syntax, and semantics of the underlying language), although they differ in certain vocal and prosodic aspects. A review of the literature on perception and production of singing and speech reveals considerable overlap in the lateral aspect of the VI lobule of the posterior cerebellum, a region known to somatotopically represent the lips and tongue. This region may instantiate internal models of vocal tract articulation that simulate well learned phonological and/or segmental articulatory—auditory/orosensory mappings utilized for both speech and singing. Recent results show tendencies for left cerebellar hemispheric specialization for processing of singing and right specialization for processing of speech, both in the VI lobule of the cerebellum, inferior to that found for representing both speech and singing. Given the crossed pattern of cerebellar-cortical anatomical connectivity the findings are consistent with the hypothesis that the right cerebellum differentially processes high pass filtered information (segmental properties) and the left cerebellum differentially processes low pass filtered information (prosodic, melodic properties). Further research is necessary to examine these hypotheses and their alternatives directly.     

The nature and extent of cerebellar atrophy in chronic temporal lobe epilepsy

Purpose: Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. Methods: Study participants were 46 persons with TLE and 31 age‐ and gender‐ matched healthy controls. All participants underwent high‐resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). Key Findings: There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p’s > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. Significance: Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross‐sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity‐related (superior posterior lobe) features of the disorder.     

Evidence for a link among cognition, language and emotion in cerebellar malformations

We compared the neurobehavioral profiles of children with Joubert syndrome (JS participants), a rare autosomal recessive condition characterized on magnetic resonance imaging (MRI) by hypoplasia of the cerebellar vermis and midbrain-hindbrain malformations, and children with malformations confined to the cerebellar vermis and one or both hemispheres (Cerebellar malformations - CM participants). We aimed at investigating the influence of anatomo-clinical similarities (vermian malformation) and differences (intact cerebellar hemispheres vs sparing of the pons, respectively) with respect to cognitive, linguistic and emotional development, assuming as a reference framework the Cerebellar Cognitive Affective Syndrome (CCAS). Results show that severe to moderate mental retardation is infrequent in JS children, while it is present in more than half the sample of CM children. Affect development was generally preserved in JS, in high-functioning CM individuals and also in some of the CM children with moderate mental retardation, which raised questions as to the role of a cerebellar vermis lesion in determining affect disorders. Further, cognitive and linguistic profiles on both intellectual and neuropsychological evaluations provided evidence for distinct patterns of peaks and valleys in the two groups, with JS children being significantly more impaired in language and verbal working memory and CM individuals showing a significant impairment of executive functions and emotional development. The overall evidence provides support for an important role of cerebellar structures per se in shaping emotional, cognitive and linguistic development, when vermian lesions are associated to cerebellar hemispheric lesions. Cerebellar vermis and brainstem lesions instead appear to have a major impact on motor-related skills, including oro-motor abilities and verbal working memory.     

The cerebellum in cognitive processes: Supporting studies in children

Over the last decade, increasing evidence of cognitive functions of the cerebellum during development and learning processes could be ascertained. Posterior fossa malformations such as cerebellar hypoplasia or Joubert syndrome are known to be related to developmental problems in a marked to moderate extent. More detailed analyses reveal special deficits in attention, processing speed, visuospatial functions and language. A study about Dandy Walker syndrome states a relationship of abnormalities in vermis lobulation with developmental problems. Further lobulation or volume abnormalities of the cerebellum and/or vermis can be detected in disorders as fragile X syndrome, Downs’s syndrome or William’s syndrome. Neuropsychological studies reveal a relation of dyslexia and attention deficit disorder with cerebellar functions. These functional studies are supported by structural abnormalities in neuroimaging in these disorders. Acquired cerebellar or vermis atrophy was found in groups of children with developmental problems such as prenatal alcohol exposure or extreme prematurity. Also focal lesions during childhood or adolescence such as cerebellar tumour or stroke are related with neuropsychological abnormalities, which are most pronounced in visuo-spatial, language and memory functions. In addition, cerebellar atrophy was shown to be a bad prognostic factor considering cognitive outcome in children after brain trauma and leukaemia. In ataxia teleangiectasia, a neurodegenerative disorder affecting primarily the cerebellar cortex, a reduced verbal IQ and problems of judgment of duration are a hint of the importance of the cerebellum in cognition. In conclusion, the cerebellum seems to play an important role in many higher cognitive functions especially in learning. There is a suggestion that the earlier the incorrect influence the more pronounced the problems.     

Immunofluorescent labeling of nonhuman cerebellar tissue with sera from patients with systemic cancer and paraneoplastic cerebellar degeneration

Summary Sera from patients with paraneoplastic cerebellar degeneration have been shown to contain high titers of antibody to human Purkinje cells. It is not known, however, whether these sera react with cerebellar material from species other than man. The present study was conducted to determine whether cerebellar tissue of nonhuman species could be used to screen human sera for anticerebellar antibodies and whether similarities in cerebellar antigens between nonhuman and human material might permit attempts to transmit cerebellar degeneration to experimental animals by passive transfer of patient sera. Sections of human, monkey, pig, sheep, cat, rabbit, and rat cerebellar tissue were overlaid with serial dilutions of positive sera from patients with cancer and with paraneoplastic cerebellar degeneration and were stained using indirect immunofluorescence methods. All sera stained specific Purkinje cells when reacted with monkey, pig, and rabbit cerebellar sections, but not all sera stained sheep, cat, or rat tissue. Immunofluorescent labeling of animal cerebellar tissue was less bright than that obtained with human cerebellar sections, and anticerebellar antibody titers were invariably lower when assayed with nonhuman than with human material. Although human anticerebellar antibodies react with cerebellar tissue from other animal species, patient-to-patient variation in staining is sufficiently great that not all patient sera might be suitable for passive transfer experiments, and that attempts to identify anticerebellar antibodies by reacting patient sera with nonhuman cerebellar tissue could be negative where these antibodies are in fact present and could be demonstrated using human material.     

小脑出血83例临床分析

目的探讨小脑出血的病因、临床表现及治疗方法。方法对1997-2002年我院收治的83例小脑出血患者的临床资料进行回顾性分析。结果该病50-79岁为高发年龄段,占76．9％。小脑半球的出血69例,占83．1％,蚓部出血14例,占16．9％。Ⅰ组为出血未破入脑室型共30例,Ⅱ组为小脑出血仅破入第四脑室,且其他脑室不大共31例,Ⅲ组为并发幕上脑室系统(三脑室、侧脑室等)出现积血或扩张共22例。52例保守治疗,有效率为84％,死亡率为16％。33例外科手术治疗,有效率为75．8％,死亡率为15．2％。脑疝为主要死亡原因。结论根据小脑出血的出血量及脑室系统改变进行分组有利于临床表现及病情变化的评价,及时正确的采取不同的治疗方案,降低死亡率。