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Cerebellar contribution to behaviour and cognition in children
Abstract
Many studies have confirmed the role of the cerebellum in the organisation of superior brain functions in adults. Congenital cerebellar alterations, particularly global hypoplasia of the vermis or selective hypoplasia of some vermian lobules, are frequently observed in children with neurological diseases. These anatomical alterations are associated with neuropsychological or developmental disorders that often give rise to pictures of various degrees of mental insufficiency of varying severity with behavioural changes that may even lead to autism. Hypoplasia of the VI and VII vermian lobules are accompanied by autistic-like pictures, whereas damage to the VIII, IX and X lobules is associated with attention disturbances. Studies of normally intelligent children with acquired cerebellar lesions (mainly tumours) have made it possible to reveal different neuropsychological profiles depending on the lesioned site: lesions of the vermis are related to behavioural and verbal production disturbances, whereas those affecting the cerebellar hemispheres are associated with patterns of side-specific cognitive dysfunctions.
... The cerebellum accounts for over half the brain's population of neurons and receives inputs from all levels of the CNS, including spinal, vestibular, and cerebral pathways (Schmahmann and Pandya 1997, Dolan 1998). It is well-established that the cerebellum is essential for the coordination of movement and adjustment of posture (Holmes 1930), but recent research has also described various cognitive impairments following damage to the cerebellum (see Schmahmann and Sherman 1998, Lalonde and Botez-Marquard 2000, Levisohn et al. 2000, Riva and Giorgi 2000). In particular, lesions of the hemispheres are associated with intellectual changes (Malm et al. 1998) while damage to the vermis is associated with behavioural changes (Schmahmann and Sherman 1998, Riva 2000). ...
... It is well-established that the cerebellum is essential for the coordination of movement and adjustment of posture (Holmes 1930), but recent research has also described various cognitive impairments following damage to the cerebellum (see Schmahmann and Sherman 1998, Lalonde and Botez-Marquard 2000, Levisohn et al. 2000, Riva and Giorgi 2000). In particular, lesions of the hemispheres are associated with intellectual changes (Malm et al. 1998) while damage to the vermis is associated with behavioural changes (Schmahmann and Sherman 1998, Riva 2000). Reciprocal projections between the cerebellum and the cerebral cortex provide a plausible anatomical basis for a cerebellar role in cognition (Schmahmann and Pandya 1997). ...
... While lesions of either cerebellar hemisphere produce ipsilateral motor deficits, projections from the cerebellum to the cerebral cortex are contralateral. Consistent with this anatomical organization, there is evidence to suggest that lateralized cerebellar lesions produce cognitive deficits similar to those observed following lesions of the contralateral cerebral cortex (Riva and Giorgi 2000), possibly due to the disruption of the metabolic activity in cerebello-cortico pathways (Ackermann 2000, Lalonde and Botez-Marquard 2000). Thus, verbal language and/or literacy deficits (in right-handed individuals) have been associated with right cerebellar lesions (Fiez et al. 1992, Silveri et al. 1994, Gasparini et al. 1999) and visuospatial deficits with left cerebellar lesions (Wallesch and Horn 1990). ...
The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.
... Research among the paediatric population with cerebellum congenital pathologies often shows a severe cognitive incapacity, suggesting that the cerebellum is indispensable in obtaining an appropriate cognitive development [8]. In contrast, lesion studies in children and adolescents with focal cerebellar lesions are insufficient to prove the cerebellar involvement in cognition [9]. ...
Two types of dysgraphia may be distinguished: the core ones, which reflect damage to the linguistic orthographic routes, and the peripheral ones, produced by alterations in the selection or execution of graphic motor patterns. We report the case of an 8-year-old male child, who consulted specialists due to difficulties in writing, with a background of acute cerebellar swelling at the age of 4. The writing pattern he has developed shows characteristic errors of a peripheral dysgraphia. The magnetic resonance imaging taken during the neuropsychological evaluation shows a mild atrophy in the cerebellum cortex. Our case is similar to previous studies of adult patients and equally supports the fact that the functional network responsible for the peripheral control of writing abilities may include the cerebellum, which not only maintains previously learnt writing processes but is also involved in the evolutionary acquisition of this ability.
... (Although emphasis is placed on the basal ganglia and/or cerebellum, these are typically not the only structures implicated in these pathologies by the researchers cited). Commonalities among subsets of this list have been noted (Nicolson & Fawcett, 2007;Riva, 2000;Ring & Serra-Mestres, 2002). It remains a matter for further research as to whether any language or speech disorders evidenced by individuals suffering from these pathologies share similar characteristics. ...
Although it has been shown that some children with Speech Sound Disorders (SSD) have difficulties in the area of productive morphosyntax, there has been little investigation into the possible source of these problems. Such research may nevertheless shed some light on theoretical questions of morphosyntactic abilities in children with atypical speech and/or language development, as well as suggest avenues for remediation of language weaknesses. The current study examined possible effects of speech perception, vocabulary, and articulation skills on concurrent syntax and longitudinal morphology in a group of seventy-nine children with SSD. Structural Equation Modelling techniques were used to model the relationships among the variables. The rationales for the models were drawn from the literature on children with SSD and also from studies of children with Specific Language Impairment (SLI). The latter were paid particular attention, as some children with SSD may also have SLI, and as morphosyntactic skills in individuals with SLI have been rigorously investigated. It was found that, of the three models examined, an articulation model, in which links were posited from articulation to syntax and from articulation to morphology, demonstrated good fit. Although some of the limitations in morphology and syntax seen in these children could be accounted for in terms of frank articulation errors, other explanations for the association between articulation and morphosyntax were also considered. One possibility was that speech motor skills and morphosyntax were dependent on similar neural substrates that may have been impaired in some of the participants investigated. A second possibility was that, given a finite set of resources devoted to language production, laboured articulation in the children with SSD bled resources from other areas of speech/language processing, and from expressive morphosyntax in particular. Further research, especially studies examining possible relationships among articulation and receptive and expressive grammar, is needed. Bien qu'il ait été montré que certains enfants présentant des troubles phonologiques ont aussi des difficultés dans le domaine de la morphosyntaxe productive, peu d'enquêtes ont été faites pour trouver les sources possibles de ces problèmes. Cependant, de telles recherches pourraient éclairer les questions théoriques des habiletés morphosyntaxiques chez les enfants ayant un développement atypique de la parole et/ou du langage, et pourraient aussi suggérer des approches pour remédier aux faiblesses de la langue. La présente étude a examiné les effets possibles des habilités de perception de la parole, du vocabulaire, et de l'articulation sur la syntaxe concurrente et la morphologie longitudinale dans un groupe de soixante-dix-neuf enfants présentant des troubles phonologiques. Les techniques de modèles d'équations structurelles ont été utilisées pour modeler les liens entre les variables. Les exposés raisonnés ont été tirés de la littérature sur les enfants présentant des troubles phonologiques aussi bien que de recherches sur les enfants présentant un trouble primaire (dysphasie) du langage. Une attention toute particulière a été prêtée à ce dernier groupe puisque certains enfants présentant des troubles phonologiques peuvent aussi avoir un trouble primaire du langage et que les habiletés morphosyntaxiques chez les individus présentant un trouble primaire du langage ont été rigoureusement étudiées. On a constaté que, des trois modèles examinés, un modèle d'articulation dans lequel des liens ont été postulés de l'articulation à la syntaxe et de l'articulation à la morphologie se révélait particulièrement approprié. Quoique certaines des limitations en morphologie et syntaxe constatées chez ces enfants puissent provenir de simples erreurs d'articulation, d'autres explications pour le lien entre l'articulation et la morphosyntaxe ont été aussi considérées. Une possibilité serait que les habiletés motrices de la parole et la morphosyntaxe dépendent de substrats neuraux semblables et qui seraient peut-être détériorés chez certains participants à l'étude. Une deuxième possibilité serait que, étant donné qu'il existe un nombre fini de ressources consacrées à la production du langage, l'effort de l'articulation chez les enfants présentant des troubles phonologiques a épuisé les ressources d'autres régions qui s'occupent de la parole/du langage, et en particulier de la morphosyntaxe expressive. D'autres recherches, surtout des études qui examinent les liens qui puissent exister entre l'articulation et la grammaire réceptive et expressive sont nécessaires.
... Recently, it has been suggested that adult patients with cerebellar damage may suffer from 'Cerebellar Cognitive-Affective Syndrome' (Schmahmann & Sherman, 1998), which is characterized by impairments of executive functions (e.g., planning, verbal fluency and working memory), visuospatial disorganization (including visuospatial memory deficits), language production deficits (agrammatism, mild anomia, dysprosodia) and personality change (disinhibited or inappropriate behavior) (Schmahmann, 1997). Developmental data and studies on cerebellar malformations seem to confirm the fundamental role played by the cerebellum in the development of cognition and affect (Allin et al., 2001;Gardner et al., 2001;Levisohn, Cronin-Golomb, & Schmahmann, 2000;Riva, 2000;Riva & Giorgi, 2000;Scott et al., 2001). ...
Two young adult dizygotic twins with high schooling suffered two strokes at the ages of 26 and 30 years. On the first occasion, Case 2 suffered a stroke only a few months after Case 1; on the second occasion, Case 1 suffered a second stroke a few months after Case 2. In Case 1, lesions were mainly localized to the left cerebellar hemisphere in both stroke episodes. Case 2 suffered lesions localized to the right cerebellar hemisphere in the first stroke episode, and multiple lesions in both cerebellar hemispheres and the vermis, right pons and left thalamus during the second stroke episode. Seven years after the second stroke, despite full recovery of motor functions, the patients still show mild, yet selective, linguistic deficits (syntactic comprehension deficits, mild agrammatism, reading and writing disorders) without speech disturbances. They also present with selective dysfunctions in visuospatial short-term memory. Language disorders are ascribed to a dysfunction of the cerebellum in Case 1, while in Case 2 a dysfunction of the cerebellum and the thalamus is considered as both structures are part of the so-called 'frontal lobe system', which supports language generation. Visuospatial short-term memory disorders are attributed to an impaired ability to appreciate the organizing structure of the visual task and to poor planning strategies, which are in turn ascribed to cerebellar lesions. The role of the cerebellum in cognitive and linguistic functions is discussed.
... 39 Transient disturbances of affect regulation in the period immediately after cerebellar surgery are wellknown. 6,17,25,33,34,40,41 Descriptions of long-term behavioral disturbances 8,13 are rare in childhood and hypospontaneity has previously been described as "a severe lack of spontaneity," whereby the children "tended to speak very little even after being encouraged to do so," 7 and "terse responses, lack of elaboration, reluctance to engage in conversation, long response latencies, and word-finding difficulties" were noted. 8 In contrast, we frequently observed long-term behavioral disturbances with hypospontaneous behavior as a relatively common disorder. ...
To study long-term effects on neurologic, neuropsychological, and behavioral functioning in children treated for cerebellar pilocytic astrocytoma (CPA) without additional radio- and chemotherapy.
The authors assessed speech, language, nonverbal intelligence, attention, memory, executive skills, and visual (-spatial) functions in a consecutive series of 23 children. Neurologic and neuropsychological follow-up ranged from 1 year to 8 years and 10 months after resection.
Long-term sequelae in the investigated domains were found in all children. Apraxia, motor neglect, and dysarthric features, as well as language, sustained attention, visual-spatial, executive, memory, and behavioral problems, were observed in various combinations and to different degrees. No clear pattern of neurocognitive disturbances could be discerned in this group. In addition, significant relationships were revealed between severity of preoperative hydrocephalus and visual-spatial skills. The high percentage of children who needed special education reflects the severity of the impairments.
Despite the current opinion of a good quality of life after CPA treatment, careful long-term neurocognitive follow-up is needed in order to inform parents and teachers about the behavioral and cognitive sequelae and to contribute to timely social and educational intervention.
... 12,13,23,24 The reason for the behavioral hetereogeneity in this sample is unclear, but it is likely determined by multiple factors. For example, the profile of child adaptive and maladaptive behaviors might be related to the degree of cerebellar dysfunction [25][26][27][28][29] and/or cognitive impairment. Variability in the sample might also be due to the difficulty of distinguishing classic Joubert syndrome from other closely related hindbrain malformation syndromes 30 or to concomitant medical or neurologic conditions. ...
This study describes the relationship between parenting stress and behavior in children with Joubert syndrome, a rare genetic neurodevelopmental disorder. Parents (N = 43) reported severely impaired child adaptive behaviors. Most children did not show maladaptive behaviors, but a subset of approximately 20% displayed significant problems in areas such as inattention, overactivity, social withdrawal, and atypical behaviors. Mothers (59%) and fathers (40%) reported elevated levels of parenting stress. A hierarchical regression, including demographics, adaptive behavior, and maladaptive behavior, predicted 67% of the variance in mothers' stress and 40% of the variance in fathers' stress. Maladaptive behaviors uniquely contributed to maternal and paternal stress. The child's adaptive behavior level contributed significantly to parenting stress for mothers but not for fathers. Findings provide a better understanding of the impact of child behavior on parents caring for a child with Joubert syndrome.
Purpose:
Posterior fossa arachnoid cysts (PFAC) are mostly considered as benign lesions of the cerebellum. Although many studies have shown the major role of the cerebellum in modulating movement, language, cognition, and social interaction, there are few studies on the cognitive impact and surgical decompression of PFAC.
Methods:
We present the cases of two brothers successively diagnosed with PFAC and neuropsychological delay. After multidisciplinary discussion with the boys' parents, it was decided to drain these lesions. Clinical signs, cerebral images, and neuropsychological status were assessed on admission and then 1 and 3 years after surgery.
Results:
At presentation, both children had mild cerebellar signs, associated with cognitive and visual-motor impairments and academic regression. CT scans revealed retrovermian cysts, which were shunted. Post-operatively, both brothers demonstrated improved visual-motor skills and behavior. At follow-up, we observed disappearance of dysarthria and academic delay and significant improvement in cognition especially at the intelligence scale and in language. Fine motor skills had improved but remained slower than the average and writing skills appeared limited.
Conclusion:
Except for PFAC which impair cerebrospinal fluid circulation or which are responsible for a significant mass effect, most PFAC are usually considered as "asymptomatic" and do not require surgical treatment. The two cases reported herein suggest that these lesions might be responsible for some associated but potentially reversible neuropsychological impairment. In the future, clinical assessment should include neuropsychological evaluation to help inform decision for surgical decompression in these children with PFAC.
Cerebellum is a Latin word that means “little brain.” While the cerebellum might be little in gross appearance relative to the neocortex, it is certainly not little in terms of its composition and function. The cerebellum actually contains more neurons than the remainder of the human brain, even though it comprises only about ten percent of total brain weight (Houk & Mugnaini, 2003). The cerebellum also lies outside of the cerebral cortex. Perhaps this is one of the reasons why so little attention has historically been paid to understanding its possible contributions to behavior. From the viewpoint of a cortico-centric bias, regions outside the cortex become less important. The cerebellum has traditionally been viewed as a structure coordinating movement, and until recently, this viewpoint has rarely been given a second thought (Bower & Parsons, 2003).
This study describes the relationship between parenting stress and behavior in children with Joubert syndrome, a rare genetic neu-rodevelopmental disorder. Parents (N = 43) reported severely impaired child adaptive behaviors. Most children did not show maladaptive behaviors, but a subset of approximately 20% displayed significant problems in areas such as inattention, overactivity, social withdrawal, and atypical behaviors. Mothers (59%) and fathers (40%) reported elevated levels of parenting stress. A hierarchical regression, including demographics, adaptive behavior, and maladaptive behavior, predicted 67% of the variance in mothers' stress and 40% of the variance in fathers' stress. Maladaptive behaviors uniquely contributed to maternal and paternal stress. The child's adaptive behavior level contributed significantly to parenting stress for mothers but not for fathers. Findings provide a better understanding of the impact of child behavior on parents caring for a child with Joubert syndrome.
In the past the cerebellum was assumed to play an almost exclusive role of motor regulator. Recent experimental data obtained also by using the noninvasive imaging methods show that the cerebellum does not only represent a structure involved in motor modulation, but it might participate also in visceral and cognitive processes. The research of non-motor cerebellar functions is therefore in focus. On the basis of published data questions arise as to the possible effect of psychopharmacotherapy on cognitive processes through the modulation of cerebellar functions, as well as to the role of cerebellum in neuroendocrine regulations and the influence of cerebellar lesions on cognitive processes. Since the research of non-motor functions of cerebellum is still only at its beginning it is currently not possible to respond these questions in detail. The aim of this article is therefore to summarize the recent available data about non-motor functions of cerebellum, as well as to attract attention to some questions arising from the latter data and to depict the further possible directions of the research of cerebellar functions.
The aim of the present study was to assess cognitive, affective, and motor long-term sequelae after acquired focal pediatric cerebellar lesions.
Eight patients with a history of isolated acquired hemorrhagic cerebellar lesions before the age of 13 participated in this study. All participants underwent a neurologic examination, including the Zurich Neuromotor Assessment (ZNA) and the International Cooperative Ataxia Rating Scale (ICARS). Cognitive functions have been evaluated with a general cognitive assessment and an extensive neuropsychological battery. Furthermore, patients and parents filled in questionnaires about quality of life and possible behavioral or emotional problems.
The results revealed that all patients exhibited motor problems (ZNA). Most participants had further restricted oculomotor movements (ICARS). Age at injury and the full scale IQ were significantly positively correlated (Pearson correlation 0.779; p = 0.023). Conversely, no overall neuropsychological profile could be identified except for marginally reduced reaction times and susceptibility to interference. In addition, borderline results in semantic and phonemic word fluency tasks were apparent. A dysexecutive syndrome was diagnosed in one patient. However, verbal performance and reading abilities were non-pathologic in all participants. The patients reported having a good quality of life without major physical restrictions.
Emotional disturbances and the presence of a mild cerebellar cognitive affective syndrome (as frequently described in adult patients) could only be confirmed in adolescents with vermis lesions. Nevertheless, in laboratory conditions, neuropsychological impairments were present in all patients. Heterogeneity of age at injury and exact lesion site may have led to interpersonal differences in neuropsychological outcome.
The language skills of 4 children treated for tumors involving the cerebellum and/or fourth ventricle with risk-adapted treatments were compared, as a group, with performance of a group of control children (n = 20). The language skills of the individual cases were also profiled. At the group level, language skill failed to differentiate the 2 groups of children. At an individual level, however, only 1 of the 4 children treated with risk-adapted treatments presented with intact language skills. Variable language profiles were identified in the remaining 3 children. The presence of hydrocephaly was a consistent factor in reduced language outcomes. The findings highlight the importance of prospective language monitoring.
Background: Recent research addressing evidence from functional neuroimaging studies, neurophysiological research, and new advances in neuropsychology together with traditional cerebellar lesion studies have recently implicated the cerebellum in adult language and cognitive functions. However, more limited information is currently available in describing the functional connectivity present in the paediatric population. Aims: It is the purpose of this paper to review recent clinical research pertaining to paediatric populations, outlining the impact of site of lesion and specific associated clinical changes in children with cerebellar disturbances. Main contribution: The specific contribution of the right cerebellar hemisphere to language function is identified to also exist in the paediatric population, highlighting the existence of functional connections between this region of the brain and left frontal cortical areas early in development. Conclusions: Implications for future research in paediatric populations are extensive, as a greater awareness and an understanding of the recently acknowledged involvement of the cerebellum in cognition and nonmotor linguistic function is anticipated to also add new dimension and direction to the analysis of childhood language outcomes associated with the cerebellum.
The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.
Children with a variety of genetic, metabolic, and neurologic disorders can suffer from severe feeding intolerance that is unresponsive to medical, surgical, and nutritional therapy. Developmentally disabled tube-fed children with severe upper gastrointestinal symptoms that persisted after fundoplication who were unresponsive to all medical, surgical, and nutritional interventions underwent a thorough gastrointestinal evaluation, including gastroscopy, pH-metry, upper gastrointestinal barium series, and gastric emptying studies. They were placed on a low-fat diet, and the symptoms before and after the diet were compared. The patients were then rechallenged with incremental increases in fat until the symptoms recurred or the patients reached their former fat concentration. Six children meeting the study criteria were evaluated. Four of these patients had a significant improvement in symptoms, oral intake and feeding tolerance with a decrease in fat intake, and relapse of symptoms when fat calories were increased. Improvement occurred in children who had been intolerant to duodenal feeding. We were subsequently able to wean two children from tube feeding. Dietary fat can provoke upper gastrointestinal symptoms in children with gastric and intestinal dysmotility. Short-term manipulation of dietary fat intake can improve tolerance to feeding.
Childhood-acquired cerebellar studies to date have appeared to present a concordant pattern of specific neuropsychological profiles depending on lesion site. The aim was to determine the impact of a cerebellar tumour specifically on language function in children by reporting both the general and high-level language abilities of 4 cases with differing sites of hemispheric and vermal involvement.
The language abilities of 4 children (aged from 7 years 9 months to 13 years), treated with surgery and/or radiotherapy for cerebellar tumour 6 months to 3 years previously, were examined. A standardized battery of general and high-level language assessments was administered.
Analysis revealed intact abilities across all 4 cases on measures of general language, including receptive language, expressive language, receptive vocabulary and naming. While 2 of the 4 cases also demonstrated intact high-level language skills across all measures, the remaining 2 demonstrated specific deficits in linguistic problem solving at 6 months after treatment. Follow-up assessment of 1 case also demonstrated further decline in this area 12 months later.
Findings of high-level language deficits in problem solving in 2 of the 4 cases examined supported previous reports of specific impairments in high-level language and in thinking flexibility and problem solving following cerebellar hemispheric damage in childhood.
The effect of behavioral activation on cerebral and cerebellar glucose metabolism was studied in normal subjects when performing either a verbal memory task or a tactile somatosensory task. Each subject was also studied in a resting state control condition, either 1 h earlier or later than the activation task. Compared to the resting state, both tasks produced asymmetrical metabolic activation, which was opposite in direction within the cerebral and cerebellar hemispheres. In both tasks, the difference of activation of CMRglc in the right and left hemispheres in the cerebellum was negatively correlated with that in the sensory-motor region. This apparently coupled metabolic activation of one cerebellum and areas within the opposite cerebral hemisphere represents the inverse of the crossed cerebellar diaschisis phenomenon commonly observed when a vascular lesion affects one cerebral hemisphere and hypometabolism occurs in the opposite cerebellum. Because these correlations were selective and concordant with known anatomical connections, and were found in two different tasks, they suggest strong functional connections between these specific brain regions.
A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.
The possibility that neurons in the basal ganglia and cerebellum innervate areas of the cerebral cortex that are involved
in cognitive function has been a controversial subject. Here, retrograde transneuronal transport of herpes simplex virus type
1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex.
This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus
of the cerebellum and in the internal segment of the globus pallidus were labeled by transneuronal transport of virus from
area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral
cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher
cognitive function.
In our ongoing attempt to determine the anatomic substrates that could support a cerebellar contribution to cognitive processing, we investigated the prefrontal cortical projections to the basilar pons. A detailed understanding of these pathways is needed, because the prefrontal cortex is critical for a number of complex cognitive operations, and the corticopontine projection is the obligatory first step in the corticopontocerebellar circuit. Prefrontopontine connections were studied using the autoradiographic technique in rhesus monkey. The pontine projections were most prominent and occupied the greatest rostrocaudal extent of the pons when derived from the dorsolateral prefrontal convexity, including areas 8Ad, 9/46d, and 10. Lesser pontine projections were observed from the medial prefrontal convexity and area 45B in the inferior limb of the arcuate sulcus. In contrast, ventral prefrontal and orbitofrontal cortices did not demonstrate pontine projections. The prefrontopontine terminations were located preferentially in the paramedian nucleus and in the medial parts of the peripeduncular nucleus, but each cortical area appeared to have a unique complement of pontine nuclei with which it is connected. The existence of these corticopontine pathways from prefrontal areas concerned with multiple domains of higher-order processing is consistent with the hypothesis that the cerebellum is an essential node in the distributed corticosubcortical neural circuits subserving cognitive operations.
Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.
One of the most fascinating problems in Behavioural Neurology is the question of the cerebral organization for language during childhood. Acquired aphasia in children, albeit rare, is a unique circumstance in which to study the relations between language and the brain during cerebral maturation. Its study further contributes to our understanding of the recovery processes and brain plasticity during childhood. But while there is a great amount of information and experimental work on brain-behaviour relationships in adult subjects, the literature about the effects of focal brain lesions in children is both exiguous and scattered throughout scientific journals and books. We felt it was time to organize a meeting where scientists in this field could compare their experiences and discuss ideas coming from different areas of research. A workshop on Acquired Aphasia in Children was held in Sintra, Portugal, on September 13-15, 1990, and attended by 44 participants from 13 differents countries. The atmosphere was relaxed and informal and the group was kept small to achieve this effect. It was a very lively and pleasant meeting. Some consensus was indeed arrived at concerning methodological problems, definition of terms, and guidelines for future research. The main contributions are collected in this book which, we hope, will serve the scientific community as a reference work on Childhood Aphasia. I,P.M., AC.C.
The problem of language impairment in children with focal brain lesion is complex. It involves many variables such as age and modality of onset, type and size of lesion and finally side and localization. According to this, 2 groups of children, who suffered from vascular accidents were selected. The time of acquisition was classified as “early” (before language acquisition) and “late” (after language acquisition). Results indicate that right as well left lesioned children perform worse than controls in lexical tests, while left lesioned ones perform worse in lexical and syntactic tasks. The influence of age at lesion, lesion size and epilepsy are discussed.
Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD.
We report the case of a 4 years and 2 months old girl, whose development was normal before she suffered from severe viral cerebellitis. When she recovered from the acute phase, a complete loss of speech was evident, although language comprehension was not impaired. Mutism disappeared after about two weeks, giving way to the aphonic utterance of a few words. After three months, her speech was slow and monotonous, without phonetic disturbances. She could only produce very simple and incomplete sentences in both spontaneous and constrained situations and she was able to mantain discourse sequentiality only under continuous guidance. No deficit in single-word recognition or naming was detected. Her sentence reproduction was good, while verbal fluency was very poor when no cue was given, but was normal with category cues.Her intelligence was within the normal range, but activities requiring programming, particularly those involving sequencing, were very defective.The patient's impairment is attributed to the failure of the cerebellar-frontal loops to activate strategies involved in processing and programming verbal and sequential functions.
Observing that the ‘hemispheres’ are essentially a mammalian structure, Edinger (1910) applied the term ‘palaeocerebellum’ to the vermis and flocculus and the term ‘neocerebellum’ to the remainder (Fig. 3). Hausman (1929), elaborating on this concept, stated that a neocerebellar equivalent has been provided for each lobule of the vermis except the lingula. Although useful and expressive, the terms neo- and palaeocerebellum have been used by many different authors to designate somewhat different cerebellar parts, and unless qualified or limited have at present no certain meaning. Further, as Winkler (1923) and others have emphasized repeatedly, new acquisitions to the cerebellum take the form of growth of preexisting parts rather than altogether new structures superimposed on the old. The identification of the vermis, as defined by Edinger, as a morphological entity is misleading and lacks morphological or functional support. Hausman's identification of all lateral cerebellar parts with the neocerebellum seems hardly justified when we realize that both ontogenetically and phylogenetically the cerebellum had a bilateral origin, and that even in man one of the lateral parts, the flocculus, appears very early in the development of the cerebellum. The term neocerebellum has some meaning if reserved for those parts which in the higher mammals have come to be dominated by cortico-pontine connexions; but such a definition allows for no hard and fast delimitation by particular fissures. If the rest of the cerebellum is then designated palaeocerebellum, it must be recognized that it contains subdivisions of varying phylogenetic age.From a functional point of view probably the most important single contribution to cerebellar morphology is that of Sven Ingvar (1918) (Fig. 4). In his earlier monographic work he combines comparative morphological observations, fibre connexion studies, pathological and physiological investigations in an attempt to subdivide correctly the cerebellum. He was impressed with the uniformity of the lobules anterior to the fissura prima and posterior to the fissura prepyramidalis and with the wide variation in the lobules between these two deep and constant fissures in many species of birds and mammals. He noted the presence of two fissures which appeared to correspond to those in the alligator. A case of cerebellar atrophy which was restricted largely to the lobes lying between the primary and prepyramidal fissures was described, and the distribution of the spino-cerebellar fibres rostral and caudal to these fissures was also pointed out. Using all this evidence, Ingvar divided the cerebellum into three lobes, anterior, middle and posterior.This division, however, was less illuminating than a second concept which he emphasized later (Ingvar, 1928). This second classification was based on the distribution of afferent fibre connexions. He presented it in a novel way by comparing the cerebellum to a three-story house. The ‘basement’ consisted of the lobes receiving direct vestibular root fibres, which included the nodulus, uvula, lingula and flocculus. The next story he called the spinal floor. It consists of the lobules anterior to the fissura prima, the pyramis and paraflocculus. The remaining lobes which received predominantly ponto-cerebellar fibres he called the ‘cerebral floor’. This last division has in recent years been frequently identified by the term ‘neocerebellum’.SummaryA review of previous work which has influenced cerebellar terminology is presented. An effort is made to harmonize the various sets of terms applied to lobes and fissures of the mammalian cerebellum with each other and with the terminology of human anatomy. The points in which agreement cannot yet be found and on which homologies with human anatomy are not clear are emphasized.The phylogenetic development of the cerebellum is described with particular attention to the contributions of Larsell in Amphibia, reptiles and primitive mammals. A schema of the folial pattern which seems best suited for the whole vertebrate system is presented, which is designed to show fundamental morphological principles and at the same time to conserve those terms now in most frequent use.The embryological development of the mammalian cerebellum is described in the light of the findings in lower forms. The phylogenetic and ontogenetic importance of the postero-lateral fissure of Larsell and the fundamental difference between the flocculus and paraflocculus of the mammalian cerebellum is stressed.A detailed description of the histology of the cerebellar cortex in mammals is given. Recent advances in the study of the afferent fibre connexions to the cerebellum are brought out and contributions of oscillographic studies emphasized.Each afferent system is analysed in detail both as to origin and termination in the cerebellum. Particular attention is given to the important cortico-ponto-cerebellar system of the higher mammals and the most recent analysis of the olivocerebellar connexion by Brodal. The functional localization in the cerebellum on the basis of the afferent fibre connexions is pointed out. It is emphasized that the termination of the afferent fibres does not favour topographical localization within the respective vestibular, spinal and cortico-pontine parts of the cerebellum.The common features of the vestibulo-cerebellar, spino-cerebellar and pontocerebellar systems are mentioned as well as the fact that the olivo-cerebellar system seems to be distinct from the other afferent systems. A suggestion is made that the mossy fibre endings are from the vestibular, spinal and pontine systems, while the olivo-cerebellar system terminates as climbing fibres. Available evidence, both for and against this conception, is discussed in some detail.Recent findings on the cerebellar cortico-nuclear connexions are presented. The development of the mammalian cerebellar nuclei and their homologies with the nuclei of the human cerebellum are discussed. It is pointed out that until such homologies are better established than at present it is impossible to transfer data from animal experiments to man in so far as the connexions of the globose nucleus is concerned. The efferent connexions of the deep cerebellar nuclei, as determined experimentally, are described in detail. The lack of available anatomical evidence for topographical localization on the basis of efferent cerebellar connexions is pointed out.
The parietothalamic projections have been shown to be heterogeneous and appear to be a reflection of the detailed architectonic parcellation of the parietal lobe. In the present study WGA-HRP injections were placed in the different subdivisions of the posterior parietal cortex of the rhesus monkey to determine whether a similarly complex pattern also exists in the thalamocortical pathway. Additionally, in an attempt to determine whether there is an intranuclear specificity of projections from individual thalamic nuclei to different subdivisions of the parietal lobe, multiple retrograde fluorescent tracers were injected into the rostral to caudal sectors of the parietal lobe of the same animal. Different subdivisions of the parietal lobe appear to receive different sets of thalamic input. Thus the superior parietal lobule (SPL) projections are derived from more lateral regions in the thalamus, arising predominantly from the lateral posterior (LP) and pulvinar oralis (PO) nuclei, with additional contributions from the pulvinar lateralis (PL) and pulvinar medialis (PM) nuclei. The inferior parietal lobule (IPL), by contrast, receives its projections from more medial thalamic regions, its main thalamic input originating from PM, and aided by LP, PL, and PO. Both the SPL and IPL also receive projections from the mediodorsal (MD), ventroposterior, ventrolateral, intralaminar, and limbic nuclei, albeit from different components within these nuclei.
The projections to the basis pontis from cytoarchitectonically defined subregions of the superior (SPL) and inferior (IPL) parietal lobules were investigated in 14 rhesus monkeys by using the anterograde tracing techniques of autoradiography and horseradish peroxidase histochemistry. The results of our study confirm and complement available information regarding the parietopontine projections. The projections are found in clusters distributed in lamellae approximately concentric to the peduncle. They are directed most heavily towards the peripeduncular and lateral nuclei of the pons. There are also lesser, but nevertheless substantial projections to other nuclei including the intrapeduncular, ventral, dorsolateral, extreme dorsolateral, and dorsal nuclei. The dorsomedial, paramedian, and NRTP nuclei receive only minor projections. The SPL projections are relatively widespread with respect to the more focussed IPL projections. The IPL projections are, in general, situated more laterally and at more rostral levels of the pontine nuclei than are those of the SPL.
Two sisters with autosomal recessive cerebellar hypoplasia and severe nonprogressive retinal pigmentary disease are presented. This syndrome has been previously described in only 1 patient. The retinal changes may be difficult to discern and we suggest that all patients with congenital ataxia have a detailed ophthalmologic assessment, including electroretinography.
Recent clinical and research reports suggest that the cerebellum may contribute to the modulation of higher order behavior. This article presents a critical review of both earlier and more current clinical observations that raise this possibility, as well as a review of the salient laboratory data that appear to support this contention. It also summarizes the relevant anatomic work concerning the contributions to the corticopontocerebellar pathways from the higher order cerebral association areas, which have been implicated as partial anatomic substrates for this putative cerebellar role in higher function. Finally, it provides a framework for the understanding of this correlation, concludes with suggestions for future areas of investigation, and recommends that patients with cerebellar lesions be studied from a neurobehavioral point of view.
In the last decade, neuroimaging research has established that neuroanatomical abnormalities often occur in autistic individuals, but no single type of reported abnormality is ubiquitous in autism. Abnormalities in cerebral cortex, thalamus, basal ganglia, and brainstem have been inconsistently found or infrequently reported, but definitive studies remain to be done. Enlargement of cerebrospinal fluid spaces is present in some autistic people.1-10 One of the most frequently found abnormalities in autism with and without mental retardation is a reduction of cerebellar tissue.1,2,4,5,11-22 The reduction in cerebellar tissue appears to be greatest in neocerebellar regions within the vermis and hemispheres.4,11,12,15,16,18-22 The reduction appears to be the result of developmental hypoplasia rather than damage following full development, and so it may serve as a temporal marker to identify the events that damage the developing brain in autism, including other neural structures that may be concomitantly damaged.11
CEREBRAL HEMISPHERES, THALMUS, BASAL GANGLIA, AND LATERAL AND THIRD VENTRICLES
Quantitative Imaging Studies
Early quantitative computed tomography (CT) studies reported unusual parietooccipital and frontal asymmetries in autistic patients.23 Fourteen recent CT and magnetic resonance (MR) studies involving 283 autistic subjects have quantitated the size, volume, night-left asymmetry, and radio density on signal intensity of either the cerebral hemispheres, thalamus, basal ganglia, limbic structures, lateral ventricles, or third ventricle (Tables 1 and 2). In addition, these structures have been microscopically examined at autopsy in several cases of autism (Table 1).
As seen in Tables 1 and 2, in quantitative neuroimaging studies there is no substantial evidence of abnormality in the cerebral hemispheres, corpus callosum, thalamus, basal ganglia, brain volume, lateral ventricles, and third ventricles.
Three patients aged 5 1/2 to 9 years old with mutism after posterior fossa surgery are presented. The entity is discussed with a review of 15 additional previously reported cases in children aged 2 to 11 years. In all 18 patients, a large midline tumor of the posterior fossa (medulloblastoma in nine cases, astrocytoma in five, and ependymoma in four), often attached to one or both lateral recesses of the fourth ventricle, was removed. Mutism developed 18 to 72 hours after the operation (mean 41.5 hours) in patients with no disturbance of consciousness and no deficits of the lower cranial nerves or of the organs of phonation. All of these children had spoken in the first hours after surgery. The disorder lasted from 3 to 16 weeks (mean 7.9 weeks). Speech was regained after a period of dysarthria in six of the 10 cases for whom this information was available. The various hypotheses advanced to explain the pathogenesis of this speech disorder are analyzed.
A characteristic malformation of the cerebellum, including dysgenesis of the vermis and enlargement of the fourth ventricle was observed on computed tomography (CT) in 16 children on review of our consecutive material. Seven of these children underwent magnetic resonance imaging (MRI) which showed hypoplasia of the brainstem in addition to cerebellar vermian dysgenesis. One child had, in addition, dysgenesis of the corpus callosum. All these children were developmentally delayed, and many had neonatal breathing abnormalities, congenital retinal dystrophy and supranuclear ocular motor abnormalities. Joubert's syndrome should be suspected in children in whom dysgenesis of the cerebellar vermis and hypoplasia of the brainstem is shown on CT or MRI.
Neuropsychological impairment after removal of posterior fossa tumors is a recurrent issue in child neuropsychology and neurosurgery. The aim of this study was to assess verbal and performance intelligence, as well as immediate and sustained attention, in children with medulloblastoma or astrocytoma operated on for total removal of the lesion. Surgical treatment of medulloblastoma was always followed by chemoradiotherapy. Siblings of both tumor groups (without a history of neurological disease, even suspected) were examined as controls. The results were as follows: the cognitive performances were significantly poorer than the controls in both groups; the children with medulloblastoma scored below normal. Attention deficits were present in both groups as well when the usual clinical tests were used. When assessed by means of computerized methodology, the same function was normal. Considering that both groups of children underwent the same surgical treatment and all had hydrocephalus, the severe intellectual impairment reported only in patients with medulloblastoma can be ascribed to chemoradiotherapy. In contrast, the attention deficits present in both groups could be ascribed to the proximity of lesions to the ascending activating system. Malfunctioning of the activating system seems to be bypassed by the computerized administration of stimuli, which supplies motivation and kindles attention.
Cerebellar hypoplasia is found in association with a variety of neurologic and systemic disorders. It is the primary finding in the uncommonly reported condition of autosomal recessive cerebellar hypoplasia. We describe two siblings with cerebellar hypoplasia documented in both by magnetic resonance imaging (MRI) and review the clinical features of previously reported cases of autosomal recessive cerebellar hypoplasia. The most common findings in this disorder are nonprogressive ataxia, strabismus, mental retardation, and speech delay with dysarthria. Previously reported cases have been confirmed by autopsy, pneumoencephalography, or computed tomographic (CT) scans. MRI clearly documents diffuse cerebellar hypoplasia and aids in distinguishing autosomal recessive cerebellar hypoplasia from other disorders. The pathophysiology of this disorder is uncertain, however, studies of the weaver mutant mouse (an animal model of autosomal recessive cerebellar hypoplasia) suggest that an abnormality of the Bergmann glia may lead to the observed granule cell layer deficiency in these patients. This diagnosis should be considered for children with nonprogressive ataxia and families should be made aware of the 25% recurrence risk.
The time of origin, site of origin, migratory path and settling pattern of the Purkinje cells of the cerebellar hemispheres, anterior vermis, and posterior vermis were investigated in thymidine radiograms and plastic-embedded materials from rat embryos ranging in age from 15 to 22 days. In the hemispheres there is a rostral-to-caudal cytogenetic gradient: the Purkinje cells of lobulus simplex, crus I, and crus II are produced earlier than the Purkinje cells of the paramedian lobule and paraflocculus, followed by the Purkinje cells of the flocculus. The Purkinje cells of the vermis, in general, are generated later than those of the hemispheres, and with a reverse gradient from caudal to rostral: the Purkinje cells of the posterior vermis (lobules X–VI) being produced ahead of the Purkinje cells of the anterior posteriorly directed wedge of early-produced Purkinje cells through the vermis.
Eight left-hemisphere lesioned children and eight right-hemisphere lesioned children between 18 months and 8 years of age were compared to control subjects on a battery of intelligence and language measures. Both left- and right-lesioned subjects had lower IQ scores than their controls, yet most functioned within the normal range or higher. Lexical comprehension and production were depressed in both subject groups and appeared to be depressed to a greater degree in right-lesioned subjects than in those with left lesions. In contrast, syntactic production in left-lesioned subjects was markedly deficient in comparison to controls as well as right-lesioned subjects. Although both subjects and controls included children with articulation errors, the number of misarticulating children and misarticulated sounds was greatest in the left-lesioned group. Finally, fluency disorders were observed in both right- and left-lesioned subjects but were not observed in controls. The study provides further evidence that the right and left hemispheres are not equipotential for language and that left-hemisphere lesions acquired early in childhood impair syntactic development to a greater degree than do right-hemisphere lesions.
Early infantile autism is a behaviorally defined syndrome that is often associated with abnormalities on neurologic examination and seizures. We report on the brain of a 29-year-old autistic man as compared with that of an age- and sex-matched normal control, using gapless sections of whole brain. Abnormalities were found in the hippocampus, subiculum, entorhinal cortex, septal nuclei, mamillary body, selected nuclei of the amygdala, neocerebellar cortex, roof nuclei of the cerebellum, and inferior olivary nucleus.
Acute bilateral damage to large areas of both cerebellar hemispheres including the dentate nuclei led to temporary loss of speech in six children. In each case muteness was unassociated with motor paralysis, loss of higher cognitive functions, or cranial nerve dysfunction. Muteness lasted one to three months. All patients were severely dysarthric during recovery. We conclude that transient muteness may result from acute bilateral cerebellar injury.
This study describes the distribution of labeled hypothalamic neurons in squirrel monkey following pressure injections of horseradish peroxidase (HRP) into cerebellar cortex and the pattern of labeling in the cerebellar nuclei subsequent to iontophoretic injections localized in the hypothalamus. Two types of HRP (HRP and a wheat germ agglutinin conjugate, HRP-WGA) were used as tracers; tetramethylbenzidine was the chromogen.
Retrogradely filled neurons were found in lateral (LHAr) and posterior (PHAr) hypothalamic areas, and in the lateral mammillary (LMNu) and supramammillary (SMNu) nuclei following injections into ansiform and paramedian lobules and into the paraflocculus. Labeled cells were occasionally seen in the medial mammillary nucleus (parafloccular cases) and among fascicles of the mammillothalamic tract (all posterior lobe cases) immediately above the medial nucleus. After injections into the anterior lobe, labelling was again found in the LHAr, PHAr, LMNu, and SMNu. In addition, retrogradely filled cells were present in ventromedial, dorsomedial, and dorsal hypothalamic nuclei and in the dorsal hypothalamic area. Labeled cells were occasionally found among fascicles of the fornix along its intrahypothalamic course. In general, labeling extends into slightly more rostral hypothalamic levels in anterior lobe cases when compared to posterior lobe experiments. We interpret these data as indicating that some hypothalamic neurons project directly to the cerebellar cortex (i.e., hypo-thalamo-cerebellar fibers); this projection is bilateral with an ipsilateral preponderance.
In experiments with injections of HRP-WGA into the cerebellar nuclei, anterogradely filled axons were traced into the contralateral PHAr and LHAr; this was suggestive of a direct cerebello-hypothalamic projection. Following iontophoretic injections localized in the LHAr and the medial mammillary nucleus, labeling was seen in the medial (NM), posterior interposed (NIP), and lateral (NL) cerebellar nuclei; this is essentially a contralateral projection. Retrogradely labeled cells were found in the rostral and ventral NM, the ventral and dorsocaudal NL, and diffusely throughout the NIP. On the basis of the known distribution of cerebello-thalamic fibers and other criteria, these labeled cells are representative of a true cerebello-hypothalamic projection. It is suggested that the cerebellum, through these pathways, may have a relatively direct influence on visceral centers in the brainstem and spinal cord.
Fifteen patients with Friedreich's ataxia underwent a battery of neuropsychologic tests. All subjects had normal visual acuity. There was no indication that Friedreich's ataxia is a dementing disease. The patients showed an impairment in tests of spatial construction and in one test of conceptual perception. Cerebellar structures may be involved in certain spatial tasks, and a lack of training of action in space, as a result of the disease, may also account for the deficits. The motor and somatosensory impairment could be ruled out as a major cause.
Age-related changes in synaptic density in human visual cortical area 17 (striate cortex) were determined, based on counts in material prepared for electron microscopy with the phosphotungstic acid method. The results were correlated with measurements of the volume of striate cortex from celloidin sections. Two periods were defined, one of rapid synapse production which ends at about postnatal age 8 months, and a subsequent longer period of synapse elimination which extends past age 3 years. Exuberant synaptic connections during early childhood may impart to the immature cerebral cortex plasticity which is lost in the adult.
The corticopontine projections of the cingulate cortices were investigated in the rhesus monkey with the use of autoradiography. A well-organized topography of projections was observed with anterior cingulate cortex projecting to the medial part of the pontine gray matter and posterior cingulate cortex projecting to the lateral part. Together these projections form a circle of termination around the periphery of the pontine gray matter.
We describe seven children with the carbohydrate-deficient glycoprotein syndrome, an autosomal recessive inborn error of protein glycosylation characterised by failure to thrive, neurological dysfunction and a unique pattern of physical abnormalities. Neuro-radiological investigations revealed cerebellar hypoplasia in all seven children. Two children also developed supratentorial atrophy following episodes of neurological deterioration.
A child with hypoplasia of the cerebellum and brainstem in association with an unbalanced translocation, resulting in a partial deletion of the short arm of chromosome 5 and a partial trisomy of the short arm of chromosome 10, is described.
A balanced translocation was present in his mother and maternal grandmother. A maternal uncle had died at the age of 4 years with the same clinical picture. After reviewing the literature, we conclude that the monosomy 5p is the most likely cause for this malformation. We suggest that the possible existence of chromosomal anomalies should always be considered in the differential diagnosis of hypoplasia of the cerebellum and/or brainstem.
We describe a patient who, after a right cerebellar infarction, developed a right hemicerebellar syndrome and agrammatic speech without other cognitive impairments. We hypothesize that the cerebellum provides the temporal interplay among the neural structures underlying the processes responsible for production of sentences.
"Cerebellar" mutism refers to a specific childhood disorder in which a complete but transient loss of speech, followed by dysarthria, occurs after removal of a cerebellar tumor. We present a consecutive series of 15 children with this disorder, which we prefer to designate "mutism and subsequent dysarthria." The conditions in which it develops suggest also an extracerebellar component of cerebellar mutism. Hydrocephalus at presentation, localization of tumor adjacent to the fourth ventricle, and postsurgical edema of the pontine tegmentum are involved in its development.
Congenital cerebellar atrophy associated with a non-progressive cerebellar syndrome and mild cognitive retardation is described in seven cases, four of them familial. Their occurrence is consistent with an autosomal recessive inheritance. Clinical and neuroimaging data seem to exclude supratentorial changes. Even though it is not possible to definitely rule out a possible role of the forebrain in determining the mental defect, the neuropsychological study supplies arguments stressing the relationship between cerebellar defect and cognitive development.
We used tritiated amino acids to study projections to the basilar pons from prestriate cortices in 18 rhesus monkeys to determine how connectional and functional heterogeneity of these regions are reflected in corticopontine circuitry. Fibers travelled with those from other parasensory associative cortices before terminating in the pontine nuclei. Prelunate projections were derived from area 19 (OA) at the medial convexity (including areas V3 and PO) and from the lateral convexity dorsal to the caudal tip of the Sylvian fissure (including areas DP and the dorsal part of area V4d). Pontine projections also arose from area 19 (OA), and areas TF, TL, and TH in the posterior aspect of the parahippocampal gyrus. No pontine projections arose from the prelunate convexity ventral to the caudal tip of the Sylvian fissure (ventral part of area V4d and area V4v), area TEO, the inferior temporal gyrus, or the lateral ventral temporal region. Terminations in the pons were distributed in the dorsolateral and lateral nuclei, and the lateral part of the peripeduncular nucleus. Medial convexity injections produced more extensive rostrocaudal pontine labeling, as well as terminations in the extreme dorsolateral nucleus and the nucleus reticularis tegmenti pontis. Dorsal prelunate injections had additional terminations in the ventral pontine nucleus. Posterior parahippocampal gyrus injections resulted in discrete label in the lateral and dorsolateral nuclei.
Corticopontine projections destined for the cerebellum appear to be derived from extrastriate areas concerned mainly with visual spatial parameters, visual motion, and the peripheral field of vision, but not from areas subserving visual object identification and the central field of vision. Pontine afferents from the posterior parahippocampal gyrus may facilitate a cerebellar contribution to visual spatial memory, particularly when invested with motivational valence.
Infantile autism is a neurologic disorder of social, cognitive, and language development. Earlier MRI studies found hypoplasia of posterior vermal lobules VI and VII and cerebellar hemispheres in the majority of autistic patients, and recent autopsy analyses find severe Purkinje neuron loss in the posterior vermis (lobules VI and VII and VIII to X) and hemispheres. A second type of cerebellar pathology in infantile autism was recently found: hyperplasia (excessive enlargement) of posterior vermal lobules VI and VII. If the autistic samples in some MRI studies that did not detect cerebellar hypoplasia were actually composed of both the hypoplasia and hyperplasia subtypes, then the autistic mean size reported in such studies would have appeared to be near the normal mean size only because it would be the sum of the two opposite subtypes. To test this possibility, we statistically reanalyzed previously published vermal area measures of 78 autistic patients from four separate studies. The results revealed that the autistic patient samples from these four studies were indeed composed of both the hypoplasia subtype (87%, 92%, 89%, and 84% of patients) and the hyperplasia subtype (13%, 8%, 11%, and 16% of patients). Cerebellar abnormalities have been found in 15 autopsy and quantitative MRI reports from nine laboratories involving a total of 226 autistic cases. Autism may be one of the first developmental neuropsychiatric disorders for which substantial concordance exists among several independent microscopic and macroscopic studies as to the location and type of neuroanatomic maldevelopment. Onset might be as early as the second trimester. Discovery of the etiologies underlying cerebellar maldevelopment may be the key to uncovering some of the causes of infantile autism.
Cerebellar mutism has been reported after surgery for posterior fossa tumors in children and, rarely, in adults. The pathogenesis of this syndrome remains unclear, and controversy exists regarding whether it is a purely psychogenic disorder or an organic syndrome. The anatomical substrate for the mutism also remains unknown. We encountered five cases of postoperative transient cerebellar mutism in a consecutive series of 63 children with posterior fossa tumors. These cases were analyzed and compared with the patients without mutism to find predictive factors for the occurrence of mutism, with the hope of elucidating further the pathophysiological mechanism. The most significant finding was the presence in all cases of a period of cerebellar dysarthria after resolution of the muteness. We, therefore, believe that cerebellar mutism is an extreme form of dysarthria, rather than a real cognitive deficit or a psychological disturbance.
MUTISM AND A variety of other neurobehavioral symptoms have been reported anecdotally after the removal of posterior fossa mass lesions. To determine the incidence and clinical spectrum of this syndrome, a detailed review was performed of patients undergoing resection of infratentorial tumors at our institution during the last 9 years; 12 of 142 patients (8.5%) manifested this syndrome, the largest series of such patients reported to date. Each child had a lesion that involved the vermis; seven had medulloblastomas, three had astrocytomas, and two had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten children underwent division of the inferior vermis during tumor resection, and three had a superior vermian incision; one child underwent both superior and inferior vermian incisions. In 10 children, mutism developed in a delayed fashion postoperatively. The speech disturbance was associated with poor oral intake in 9 children, urinary retention in 5, long-tract signs in 6, and bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements in all 12. Neuropsychiatric testing, performed in seven children, confirmed impairments not only in speech but also in initiation of other motor activities. Ten children regained normal speech, bladder control, and neurological functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks; two children had significant residual deficits. Characteristically, affect and oral intake returned to their preoperative baseline before the speech difficulties began to resolve. A detailed radiological review of these cases in parallel with 24 cases of vermian tumors without mutism identified only one factor that was significantly associated with the mutism syndrome, bilateral edema within the brachium pontis (P < 0.01). Neither the size of the tumor nor the length of vermian incision was associated with the development of mutism. The clinical features of this syndrome in the context of these imaging findings suggest that the mutism syndrome results from transient impairment of the afferent and/or efferent pathways of the dendate nuclei that are involved in initiating complex volitional movements. The clinical courses of our patients are presented and compared with those of similar cases in the literature in an attempt to evaluate the validity of this hypothesis.
The feedforward limb of the cerebrocerebellar system is directed largely through the corticopontine pathway. We determined the extent to which higher order corticopontine projections are derived from prefrontal associative cortices by injecting anterograde tracers into multiple prefrontal regions in rhesus monkeys. Most prefrontopontine projections were derived from the dorsolateral and dorsomedial convexities, including areas 8A, 46 dorsal, 9, and 10; and lighter projections arose from medial and ventrolateral cortices. These findings strengthen the observation that the cerebrocerebellar system incorporates associative cerebral regions, and they enhance the notion that the cerebellum participates in the organization of cognitive function.
Sporadic nonsyndromic cerebellar hypoplasia is a radiological diagnosis with clinical features and a relation with developmental disability that are presently not known. Through a retrospective review of a comprehensive standardized computerized database containing more than 2,500 patients examined consecutively by a pediatric neurologist, 11 with nonfamilial, nonsyndromic cerebellar hypoplasia on neuroimaging (CT and/or MRI) were identified. With the exception of two patients, all had been originally referred during infancy or the preschool years for assessment of a developmental disability. All 11 had "cerebellar" findings on initial examination and five were microcephalic; three others were below the 10th percentile. All exhibited developmental disability, commonly of mild to moderate degree. Motor involvement predominated, often involving fine motor skills more than gross motor functions. Imaging consistently disclosed vermis hypoplasia with additional supratentorial cerebral dysgenesis in one child and cerebellar hemispheric hypoplasia in another. Cerebellar hypoplasia is a developmental anomaly that appears to be either etiologically related to, or a marker for, developmental disability, thus confirming the intact cerebellum's integral role in normal psychomotor development. This series suggests that cerebellar hypoplasia should be considered in the young child presenting with developmental delay with prominent motor involvement, together with cerebellar signs and/or microcephaly.
A developmental chronometry hypothesis of early brain damage is suggested in which regions of the brain with a protracted course of postnatal development will be more vulnerable than earlier maturing areas to deleterious effects of early insult and, therefore, may become common sites of abnormality across many disorders originating in early childhood. Initial investigations of the cerebellum and frontal lobes are presented using MRI and neuropsychological measures. Planimetric measures of the cerebellar vermis (lobuli I-V and VI-VII) and pons, and neuropsychological frontal lobe measures were obtained from high functioning individuals with autism (A), survivors of acute lymphoblastic leukemia (ALL) with brain sequelae following radiation and chemotherapy, and from rigorously selected healthy controls (C). The neuropsychological results were clustered according to functions commonly related to frontal brain, posterior brain, and left and right hemispheres. The A and ALL groups, as compared to C, yielded modest but consistently reduced MRI measures for vermal lobuli I-V and VI-VII. Hypoplasia of lobuli VI-VII was more marked than I-V. Performance on neuropsychological tests for frontal lobe functions was generally depressed in both groups, with more severe deficits in A. Between-group differences in verbal, visual-spatial, and emotional-social skills are discussed. The cerebellar and frontal brain deficits that are present in both clinical groups (A and ALL) may be common to other developmental and acquired disorders of early childhood. Such joint manifestation of cerebellar and frontal lobe abnormalities is in agreement with the concept of cerebellar significance for the development of higher cognitive functions.
We addressed the controversies surrounding the size of the neocerebellar vermis in autism and examined cerebellar size in light of recent reports of enlarged brain size in this disorder. In this study we use detailed MRI (1.5 mm) to examine the area of cerebellar lobules I through V and VI and VII and the volume of the total cerebellum in 35 autistic subjects and 36 controls. No abnormalities in the size of cerebellar lobules VI and VII in autistic individuals were detected, but the volume of the total cerebellum was significantly increased. We conclude that selective neocerebellar size abnormalities are not present in autistic individuals. Enlarged total cerebellar volume detected in this study is consistent with previous reports of regional brain enlargement in autism and also consistent with theories hypothesizing that the primary defect in autism is the result of abnormal development of a distributed neural network involving a number of regions of the brain.
The cerebellum has long been regarded as involved in the control of movement, in part through its connections with the cerebral cortex. These connections were thought to combine inputs from widespread regions of the cerebral cortex and "funnel" them into the motor system at the level of the primary motor cortex. Retrograde transneuronal transport of herpes simplex virus type I has recently been used to identify areas of the cerebral cortex that are "directly" influenced by the output of the cerebellum. Results suggest that cerebellar output projects via the thalamus to multiple cortical areas, including premotor and prefrontal cortex, as well as the primary motor cortex. In addition, the projections to different cortical areas appear to originate from distinct regions of the deep cerebellar nuclei. These observations have led to the proposal that cerebellar output is composed of a number of separate "output channels." Evidence from functional imaging studies in humans and single neuron recording studies in monkeys suggests that individual output channels are concerned with different aspects of motor or cognitive behavior.
If there is a cerebellar contribution to nonmotor function, particularly to cognitive abilities and affective states, then there must be corresponding anatomic substrates that support this. The cerebellum is strongly interconnected with the cerebral hemispheres in both feedforward (cerebral hemispheres to cerebellum) and feedback directions. This relationship has long been recognized, particularly with respect to the motor and sensory cortices. Investigations performed over the last decade however, have demonstrated for the first time the organization and strength of the connections that link the cerebellum with areas of the cerebral cortex known to be concerned with higher order behavior rather than with motor control. The feedforward projections from these higher order areas, namely the associative and paralimbic cortices, seem to be matched, at least in the limited but definite demonstrations to date, by cerebellar projections back to these same areas. These observations are important because they are congruent with the notion that cognitive functions are distributed among multiple cortical and subcortical nodes, each of which functions in concert but in a unique manner to produce an ultimate behavior pattern. This chapter describes the neural circuitry postulated to subserve the cerebellar contribution to nonmotor processing, particularly cognitive and affective modulation, and discusses the theoretical implications of these anatomic findings.
We examined whether posterior vermis size is smaller in individuals with fragile X syndrome (fra X) than in control subjects and whether this decreased size is associated with cognitive performance. Cognitive and behavioral dysfunctions have been identified in fra X; however, underlying neuropathogenic mechanisms remain unclear. MRI was used to investigate the posterior fossa in 32 males with fra X, 28 males with other causes of cognitive disability (CD), and 38 males with normal development (ND) as well as and in 37 females with fra X and 53 female control subjects. Among females with fra X, neurocognitive correlates of posterior vermis size were examined. Posterior vermis size (cross-sectional area) in males with fra X was significantly smaller compared with CD and ND groups, particularly when corrected for intracranial area. Posterior vermis size corrected for intracranial area was significantly smaller in females with fra X compared with control subjects. Compared with males with fra X and non-fra X control subjects, posterior vermis size in females with fra X was intermediate. After statistically removing the effect of mean parental IQ, posterior vermis size predicted a significant proportion of the variance (10 to 23%) of performance on full-scale, verbal, and performance IQ; block design; categories achieved on the Wisconsin Card Sorting Test; and the Rey inventory score. The size of the posterior vermis is significantly decreased in fra X, more so in males than in females. In females with fra X, posterior vermis size predicts performance on selected cognitive measures.
Autism is a behaviorally defined, life-long static developmental disorder of the brain that is poised for neurobiological investigation. It affects at least 1 or 2 in 1000 persons and has a broad range of severity. It has multiple causes, with genetics playing a major role. According to the DSM-IV, defining features are impaired sociability, language and communication, and range of interests and activities. Mental deficiency is frequent but by no means universal. The cognitive profile is characteristic, occasionally with a superior but narrow talent. Perseveration, concreteness, affective blunting, and lack of insight into other persons' thinking may be conspicuous. The neurological basis of autism's many sensorimotor features, including stereotypies, is unknown. Attention and sleep are affected, and one third of individuals experience epilepsy by adulthood. Whether subclinical epilepsy plays a role in the developmental regression of the one third of the toddlers who lose their language skills and become autistic remains to be determined. Clinical neuroimaging and biochemical investigations are generally unremarkable. Fewer than 35 brains have been examined pathologically, none with modern techniques. The findings thus far suggest subtle prenatal neuronal maldevelopment in the cerebellum and certain limbic structures. Abnormalities in distributed networks involving serotonin and perhaps other neurotransmitters require further documentation.
We report the case of a 4 years and 2 months old girl, whose development was normal before she suffered from severe viral cerebellitis. When she recovered from the acute phase, a complete loss of speech was evident, although language comprehension was not impaired. Mutism disappeared after about two weeks, giving way to the aphonic utterance of a few words. After three months, her speech was slow and monotonous, without phonetic disturbances. She could only produce very simple and incomplete sentences in both spontaneous and constrained situations and she was able to maintain discourse sequentiality only under continuous guidance. No deficit in single-word recognition or naming was detected. Her sentence reproduction was good, while verbal fluency was very poor when no cue was given, but was normal with category cues. Her intelligence was within the normal range, but activities requiring programming, particularly those involving sequencing, were very defective. The patient's impairment is attributed to the failure of the cerebellar-frontal loops to activate strategies involved in processing and programming verbal and sequential functions.