Showing papers in "International Review of Neurobiology in 1997"

The Cerebrocerebellar System

Abstract: The cerebellum has massive reciprocal interconnections with the cerebral cortex and with cerebral subcortical structures that complement its interconnections with the spinal cord and brainstem. The major cerebrocerebellar link is mediated by the feedforward/afferent corticopontine projections and mossy fibers emanating from the pontocerebellar projections, and the feedback/efferent cerebellothalamic and thalamocortical projections. These highly arranged connections link sensorimotor, associative and limbic regions of cerebral cortex with the cerebellum and the intervening pontine nuclei and thalamus in a topographically precise manner. The cerebellum also has reciprocal links with the basal ganglia and hypothalamus, and with structures in the limbic circuit. In addition to these mossy fiber afferents to cerebellum, the inferior olive receives indirect input from motor and associative regions of the cerebral cortex by way of the red nucleus and zona incerta, and it conveys these inputs to cerebellum via climbing fibers. The cerebrocerebellar pathways are organized into segregated loops of information processing and stand in contrast to the cerebellar cortical architecture that is essentially uniform. Knowledge of cerebrocerebellar circuits is critical to understanding theories of the cerebellar contribution to motor and nonmotor function, and to the diagnosis and management of patients with lesions in these pathways.

Cerebellar timing systems.

Abstract: Coordinated movement requires the normal operation of a number of different brain structures. Taking a modular perspective, it is argued that these structures provide unique computations that in concert produce coordinated behavior. The coordination problems of patients with cerebellar lesions can be understood as a problem in controlling and regulating the temporal patterns of movement. The timing capabilities of the cerebellum are not limited to the motor domain, but are utilized in perceptual tasks that require the precise representation of temporal information. Patients with cerebellar lesions are impaired in judging the duration of a short auditory stimulus or the velocity of a moving visual stimulus. The timing hypothesis also provides a computational account of the role of the cerebellum in certain types of learning. In particular, the cerebellum is essential for situations in which the animal must learn the temporal relationship between successive events such as in eyeblink conditioning. Modeling and behavioral studies suggest that the cerebellar timing system is best characterized as providing a near-infinite set of interval type timers rather than as a single clock with pacemaker or oscillatory properties. Thus, the cerebellum will be invoked whenever a task requires its timing function, but the exact neural elements that will be activated vary from task to task. The multiple-timer hypothesis suggests an alternative account of neuroimaging results implicating the cerebellum in higher cognitive processes. The activation may reflect the automatic preparation of multiple responses rather than be associated with processes such as semantic analysis, error detection, attention shifting, or response selection.

Cerebellar output channels.

Abstract: 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.

Cerebellar cognitive affective syndrome.

Abstract: There has been persistent uncertainty as to whether lesions of the cerebellum are associated with clinically significant disturbances of behavior and cognition. To address this question, 20 patients with diseases confined to the cerebellum were studied prospectively over a 7-year period and the nature and severity of the changes in neurological and mental function were evaluated. Neurological examination, bedside mental state testing, neuropsychological studies, and anatomic neuroimaging were administered at the time of presentation and during follow-up assessments. Behavioral changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis and, in some cases, overwhelmed other aspects of the presentation. These changes were characterized by an impairment of working memory, planning, set shifting, verbal fluency, abstract reasoning, and perseveration; visual-spatial disorganization, visual memory deficits, and logical sequencing; and a bland or frankly inappropriate affect. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. This newly defined clinical entity is called the cerebellar cognitive affective syndrome. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits than link frontal, parietal, temporal, and limbic cortices with the cerebellum.

Control of sensory data acquisition

Abstract: This chapter describes a new theory of cerebellar function which posits that the cerebellum is specifically involved in monitoring and adjusting the acquisition of most of the sensory data on which the rest of the nervous system depends. If correct, the cerebellum is not itself responsible for any particular behaviorally related function, whether “motor,” “sensory,” or “cognitive.” Instead the cerebellum facilitates the efficiency with which other brain structures perform their own functions. In this way the cerebellum is seen as being useful but not necessary for many different kinds of brain functions. This chapter describes how this theory of cerebellar function has arisen from detailed study of the pattern of tactile afferent prujections to the rat cerebellum as well as from an analysis of the neural circuitry that processes that information. It is proposed that the breadth of cerebellar involvement is reflected in the growing number of tasks which induce cerebellar activity, including cognitive tasks, even though the cerebellum is not itself directly involved in those tasks.

Attention Coordination and Anticipatory Control

Abstract: The coordination of the direction of selective attention is an adaptive function that may be one of the many anticipatory tools under cerebellar control. This chapter presents neurobehavioral, neurophysiological, and neuroimaging data to support our hypothesis that the cerebellum plays a role in attentional functions. We discuss the idea that the cerebellum is a master computational system that anticipates and adjusts responsiveness in a variety of brain systems (e.g., sensory, attention, memory, language, affect) to efficiently achieve goals determined by cerebral and other subcortical systems.

The cerebellar-hypothalamic axis: basic circuits and clinical observations.

Abstract: Experimental studies on a variety of mammals, including primates, have revealed direct and reciprocal connections between the hypothalamus and the cerebellum. Although widespread areas of the hypothalamus project to cerebellum, axons arise primarily from cells in the lateral, posterior, and dorsal hypothalamic areas; the supramammillary, tuberomammillary, and lateral mammillary nuclei; the dorsomedial and ventromedial nuclei; and the periventricular zone. Available evidence suggests that hypothalamocerebellar cortical fibers may terminate in relation to neurons in all layers of the cerebellar cortex. Cerebellohypothalamic axons arise from neurons of all four cerebellar nuclei, pass through the superior cerebellar peduncle, cross in its decussation, and enter the hypothalamus. Some axons recross the midline in caudal areas of the hypothalamus. These fibers terminate primarily in lateral, posterior, and dorsal hypothalamic areas and in the dorsomedial and paraventricular nuclei. Evidence of a cerebellar influence on the visceromotor system is presented in two patients with vascular lesions: one with a small defect in the medial cerebellar nucleus and the other with a larger area of damage involving primarily the globose and emboliform nuclei. Both patients exhibited an abnormal visceromotor response. The second, especially, showed abnormal visceromotor activity concurrent with tremor induced by voluntary movement. These experimental and clinical data suggest that the cerebellum is actively involved in the regulation of visceromotor functions.

Posterior fossa syndrome.

Abstract: Transient mutism is a well-recognized sequela of posterior fossa tumor resection in children. A recent review from our institution indicated that 12 of 142 children undergoing such procedures (8.5%) exhibited transient speech impairment, the largest series of such patients reported to date. Each child had a vermian neoplasm that was approached by division of the inferior vermis (n = 10) and/or superior vermis (n = 3). Seven children had medulloblastomas, three had astrocytomas, and two had ependymomas. None of the affected children had cerebellar hemispheric lesions; in contrast, the incidence among children with vermian neoplasms was 13%. In general, mutism developed 1 to 4 days postoperatively and typically was associated with puzzling neurobehavioral abnormalities. All children had bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements; nine exhibited poor oral intake; and five had urinary retention. Detailed neuropsychological testing was performed in seven children and confirmed the presence of widespread impairments not only in speech, but also in initiation of other motor activities. These deficits generally resolved during a period of several weeks to months, although two children had residual impairment. Characteristically, affect and oral intake normalized before the speech began to improve. These deficits were noted to correlate with the presence of edema within the brachium pontis bilaterally, although this association was not absolute. The latter observation suggests that there was not a single locus underlying this disorder, but rather that the involved neural pathways may have been impaired at any one of a number of sites within the posterior fossa. Based on the results in our patients and in others described in the literature, we postulate an important role for the cerebellum and/or its afferent and efferent connections in initiating (rather than merely coordinating) speech and other complex motor activities and a potential role for these structures in influencing overall behavior and affective state.

Rediscovery of an Early Concept

Abstract: The study of the cerebellum has been dominated by interest in its role in movement and motor control. From the earliest days of the neuroscientific era, however, clinical reports and physiological and behavioral investigations have suggested that overt motor dysfunction is but one manifestation of cerebellar disease. The nature of cerebellar involvement in autonomic, sensory, and cognitive functions has been investigated for many years, and possible mechanisms that could subserve this relationship have been specifically addressed. This work has not been incorporated into the mainstream of neuroscience or clinical neurological thinking. This chapter traces the history of these early investigations that demonstrated the need to revise the notion that cerebellar function is confined to the motor realm. The collaboration across disciplines and the advances in the methods and concepts of contemporary neuroscience have facilitated the maturation of this field of inquiry. The "new" story of the cerebellum and cognition, in fact, represents the evolution of a century-old revolutionary concept.

Executive Function and Motor Skill Learning

Abstract: Publisher Summary Evidence from behavioral studies of patients with cerebellar atrophy implies that the cerebellum plays a role in visuomotor learning and adaptation, planning, strategic thinking, time processing, and associative learning. Evidence from studies using functional neuroimaging supports this implication and substantiates the hypothesis that the cerebellum acts in concert with other structures as part of a frontal subcortical system devoted to the storage and organization of timed sequential behaviors. The role of the cerebellum in timed sequential cognitive processing may be analogous to its role in motor processing and suggests a mechanism by which cognitive events become sequenced and temporally labeled. Motor learning is a complex phenomenon with many components. Depending on the particular task, different anatomical structures are involved. The cerebellum takes the principal part in adaptation learning. The role of the cerebellum in timed sequential cognitive processing is analogous to its role in motor processing and suggests a mechanism by which cognitive events become sequenced and temporally labeled.

Context-response linkage.

Abstract: Brindley (1969) proposed that we initially generate movements “consciously,” under higher cerebral control. As the movement is practiced, the cerebellum learns to link within itself the context in which the movement is made to the lower level movement generators. Marr, (1969) Albus (1971), and Ito (1972) proposed that the linkage is established by a special input from the inferior olive, which plays upon an input-output element within the cerebellum during the period of the learning. When the linkage is complete, the occurrence of the context (represented by a certain input to the cerebellum) will trigger (through the cerebellum) the appropriate motor response. The “learned” movement is distinguished from the “unlearned” conscious movement by being automatic, rapid, and stereotyped. Another important variable can be added to the idea of the context-response linkage: novel combinations of downstream elements. With regard to the motor system, this could explain how varied combinations of muscles may become active in precise time-amplitude specifications so as to produce coordinated movements appropriate to specific contexts. This chapter further extends this idea to the prernotor parts of the brain and their role in cognition. These areas receive influences from the cerebellum and are active both in planning movements that are to be executed and in thinking about movements that are not to be executed. Evidence shows that the cerebellar output extends even to what has been characterized as the ultimate frontal planning area, the “prefrontal” cortex, area 46. The cerebellum thus may be involved in context-response linkage and in response combination even at these higher levels. The implication would be that, through practice, an experiential context would automatically evoke a certain mental action plan. The plan would be in the realm of thought and could-but need not-lead to execution. The specific cerebellar contribution would be one of the context linkage and the shaping of the response through trial and error learning. The prefrontal and premotor areas could still plan without the help of the cerebellum, but not so automatically, rapidly, stereotypically, so precisely linked to context, or so free of error. Nor would their activities improve optimally with mental practice.

Autonomic and vasomotor regulation

Abstract: The cerebellum not only modulates the systemic circulation, but also profoundly influences cerebral blood flow (rCBF) and metabolism (rCGU), and initiates long-term protection of the brain from ischemia. Electrical stimulation of the rostral ventral pole of the fastigial nucleus (FN), elevates arterial pressure (AP), releases vasoactive hormones, elicits consummatory behavioral and other autonomic events and site specifically elevates rCBF independently of changes in rCGU. Cerebral vasodilation results from the antidromic excitation of axons of brain stem neurons which innervate cerebellum and, through their collaterals, neurons in the rostral ventrolateral reticular nucleus (RVL). RVL neurons initiate cerebral vasodilation over polysynaptic vasodilator pathways which engage a population of vasodilator neurons in the cerebral cortex. In contrast, intrinsic neurons of FN, when excited, elicit widespread reductions in rCGU and, secondarily, rCBF, along with sympathetic inhibition. Electrical stimulation of FN can reduce the volume of a focal cerebral infarction produced by occlusion of the middle cerebral artery by 50%. This central neurogenic neuroprotection is long lasting (weeks) and is not due to changes in rCBF or rCGU. Rather, it appears to reflect alterations in neuronal excitability and/or downregulation of inflammatory responses in cerebral vessels. The FN, therefore, appears to be involved in widespread autonomic, metabolic, and behavioral control, independent of motor control. The findings imply that the FN receives inputs from neurons, probably widely represented in the central autonomic core, which may provide continuing information processing of autonomic and behavioral states. The cerebellum may also widely modulate the state of cortical reactivity to ischemia, hypoxia, and possibly other neurodegenerative events.

Verbal fluency and agrammatism.

Abstract: Since the beginning of this century it has been documented that cerebellar lesions induce speech deficits but these were thought to result from lack of motor coordination in the muscular activity needed for phonation. The pure motor nature of the cerebellum has been challenged on different grounds, and cerebellar activation has been documented in language-related tasks independently from motor activity. This chapter reviews the available evidence in favor of a cerebellar contribution to linguistic processing, focusing mainly on clinical observations in patients. The clinical findings are discussed in the light of recent theories on cerebellar functions.

Duality of cerebellar motor and cognitive functions.

Abstract: This chapter develops a specific perspective regarding the interrelation- ship of the cerebellum, motor behaviors, and cognitive processes. The advent of the proposals regarding the cerebellum and cognition has challenged many investigators to examine this issue aggressively and to address the extent to which current concepts, definitions, and experimental approaches are adequate for deriving new insights into the interfaces between the domains of motor execution and adaptive modifications in behavior. This chapter contends that the dichotomy often made between motor processes and cognitive processes is inconsistent with the organization of behaviors in general and that, when a broader, more integrative view is adopted, a role of the cerebellum in “cognitive” processes is not only expected but also necessary given this structure's contribution to motor coordination and behavioral adaptations.

Sensory and cognitive functions

Abstract: New neuroimaging studies provide striking evidence that the cerebellum is intensely and selectively active during sensory and cognitive tasks, even in the absence of explicit or implicit motor behavior. Focal activity is observed in the lateral cerebellar hemispheres during the processing of auditory, visual, cutaneous, spatial, and tactile information, and in anterior medial cerebellar regions during somatomotor behavior. Moreover, a double dissociation exists between (a) cerebellar activity and sensory processing and (b) motor behavior and activity in known motor areas in the cerebral cortex. These findings contradict the classical motor coordination theory of cerebellar function but are predicted by, or are at least consistent with, new alternative theories.

Neural Representations of Moving Systems

Abstract: The cerebellum is necessary for moving smoothly and accurately, but this does not imply that the cerebellum generates or modifies movement control signals. Cerebellar function can be explained by assuming that it is involved in constructing neural representations of moving systems, including the body, its parts, and objects in the environment. To draw a technological analogy, the cerebellum could be a neural analogue of a dynamical state estimator, or a part of one. This explanation is able to account not only for cerebellar involvement in motor control, motor learning, and certain kinds of reflex conditioning, but also cerebellar involvement in certain kinds of perceptual and cognitive tasks unrelated to the production of movements. Evidence for the hypothesis that the cerebellum is involved in a neural analogue of state estimation is (1) across phylogeny, cerebellar morphology reflects animals' use of particular sensory systems for analyzing their own movements and the movements of objects in the environment; (2) cerebellar "oculomotor" neurons are active in relation to movements of salient objects in the environment, regardless of whether the animal moves its eyes to look at them; (3) compensatory eye movements have dynamic characteristics indicating that the control signals are constructed from an underlying optimal head state representation; and (4) the motor symptoms of cerebellar dysfunction resemble the effects of faulty state estimation in artificial control systems. The state estimator hypothesis explains the participation of the cerebellum in controlling, perceiving, and imagining systems that move.

Early Infantile Autism

Abstract: Publisher Summary Autism is a behaviorally defined syndrome. Symptoms become evident by three years of age and include atypical social interaction, disordered language and cognitive skills, impaired imaginary play, poor eye contact, and an obsessive insistence on sameness. Perseveration, repetitive, and stereoptypic behavior and a restricted range of interests may be present in some cases. In physical appearance, a significant number of autistic individuals exhibit hypotonia, dyspraxia, and a disordered modulation of sensory input. Some clinical features of autism have been reported in conditions such as tuberous sclerosis, phenylketonuria, and fragile X syndrome; however in most cases, a specific etiology cannot be identified. With the introduction of magnetic resonance imaging (MRI), morphometric analysis of specific brain structures became the focus of neuroimaging research in autism. These studies have largely concentrated on the cerebellum. Consistent microscopic abnormalities were observed in the brains of nine autistic individuals that were confined to the limbic system and cerebellar circuits. The findings in the cerebellum and related inferior olive suggested that the process, which resulted in these morphologic changes, occurred or had its onset before birth.

How Fibers Subserve Computing Capabilities: Similarities Between Brains and Machines

Abstract: Can the principles underlying the design of computers help to explain the cognitive capabilities of the human brain? This chapter shows that these principles can provide insight into the capabilities of the human cerebellum, the internal structure of which bears a remarkable resemblance to the design of a versatile computer. In computers, information processing is accomplished both by the hardware in the system (its circuitry) and by the software (the communication capabilities inherent in its circuitry), which in combination can produce a versatile information-processing system, capable of performing a wide variety of functions, including motor, sensory, cognitive, and linguistic ones. Such versatility of function is achieved by computer hardware in which many modules of similar circuits are organized into parallel processing networks; this struc- tural organization is exemplified in the cerebellum by its longitudinal modules of similar circuits, which are arrayed in parallel zones throughout the structure. On the basis of this known cerebellar “hardware,” it is possible to investigate the “software” capabilities inherent in the circuitry of the modules. Each module in the lateral cerebellum seems able to communicate with the cerebral cortex by sending out signals over a segregated bundle of nerve fibers, which is a powerful way of communicating information. We show why this bundling of fibers can enable the cerebellum to communicate with the cerebral cortex (including the prefrontal cortex) at a high level of discourse by using internal languages that are capable of conveying complex information about what to do and when to do it. We propose that such communication activity is reflected in the activation obtained on functional imaging of the cerebro-cerebellar system during the performance by humans of complex motor, sensory, cognitive, linguistic, and affective tasks. Further, we propose a new way of analyzing such cerebrocerebellar activation, in order to ascertain whether the cere- bellar circuitry can (like the circuitry in a versatile computer) perform a wide repertoire of computations on this wide range of information. It seems important to ascertain whether cerebellar circuitry is versatile in its computing capabilities because the demonstration of such versatile capabilities would enable theorist? to resolve many of the current contro- versies about cognitive processing in the mammalian brain.

Neuropsychological abnormalities in cerebellar syndromes--fact or fiction?

Abstract: In recent years, theoretical considerations and a large number of empirical investigations have been published in support of a cerebellar involvement in cognitive processing. This chapter aims at a critical evaluation of the neuropsychological findings from clinical studies of patients with cerebellar syndromes. The discussion will mainly consider data from patients with selective cerebellar dysfunction, as data from patients with combined cerebellar and extracerebellar damage are of limited value for the issue of a cerebellar involvement in cognition. Early clinical observations indicated that degenerative diseases or selective cerebellar lesions did not necessarily give rise to general intellectual impairment such as dementia. Recent neuropsychological evidence based on standardized testing does not yet provide a clear picture. Deficits in motor learning or temporal processing are consistently observed in patients with cerebellar syndromes, while the cerebellum does not appear to be critically involved in general intellectual capacities or memory. Deficits in frontal lobe function, visuospatial processing or nonmotor skill learning have been reported in several studies, but have not been replicated in others. Such discrepancies may relate to a number of methodological problems. Future neuropsychological studies should take such methodological issues into account by using patients with selective cerebellar dysfunction, adequately matched clinical and non-clinical comparison groups, and theory-driven iesl batteries comprising a wide range of tests.

Interleukins and cerebral ischaemia.

Abstract: Publisher Summary Interleukins (ILs) are cytokines, best known for their actions on immune cells and as mediators of systemic inflammation and responses to systemic tissue damage. The IL family includes peptides of molecular size 8–25 kDa but with diverse actions. Interleukin 1 (IL-1) was first proposed as a modulator of neuronal damage several years ago, but early studies implied that it might promote repair and regeneration. IL-1 exerts a number of potentially beneficial actions, including synthesis of nerve growth factor (NGF), which is neuroprotective, and neurovascularization. In pure neuronal cultures, IL-1 and interleukin 6 (IL-6) inhibit excitotoxic damage. Studies relating to the role of other cytokines in cerebral ischemia are largely circumstantial as few studies have investigated the effects of blocking endogenous brain cytokines. Preliminary data indicate that the central administration of physiological relevant doses of recombinant IL-6 inhibit ischemic brain damage.

NMDA antagonists: their role in neuroprotection.

Abstract: Publisher Summary A wave of clinical trials testing the efficacy of N -methyl-D-aspartate (NMDA) antagonists in the treatment of cerebral ischemia was launched in the 1990s. Cis -4-(phosphonomethyl)-2-piperidine carboxylic acid (CGS 19755) had impressive preclinical data demonstrating dramatic cytoprotection in gerbil models of severe transient forebrain ischemia. It was efficacious when administered post-ischemically, and it did not produce psychotomimetic effects in monkeys at doses that were neuroprotective. The failure of CGS 19755 in clinical trials might have been predicted had more careful attention been paid to monitoring and maintaining control over physiological variables, such as temperature in the preclinical animal studies. This chapter critically assesses the utility of NMDA antagonists in the treatment of cerebral ischemia. The chapter presents concepts of a modified excitotoxicity with a description of the NMDA receptor physiology and pharmacology as it pertains to excitotoxicity. The chapter reviews published data for in vitro and in vivo models of ischemia using NMDA antagonists.

Olivopontocerebellar Atrophy and Friedreich's Ataxia: Neuropsychological Consequences of Bilateral Versus Unilateral Cerebellar Lesions

Abstract: This chapter deals with neuropsychological disturbances in patients with bilateral cerebellar damage (BCD), i.e., epileptic patients chronically receiving phenytoin, patients with olivopontocerebellar atrophy (OPCA), and Friedreich's ataxia (FA) versus those with unilateral cerebellar damage (UCD), i.e., patients with cerebellar strokes. BCD patients showed: (i) impaired executive functions in planning and programming of daily activities, elaborating and using structures, and difficulty in abstract thinking, functions that are related to cerebello-frontal loops; (ii) deficits in visuospatial organization for a concrete task and deficient visual-spatial working memory, functions related to cerebello-parietal loops; (iii) lower general intellectual abilities than controls (especially those with OPCA); (iv) difficulties with memory retrieval, diminished global memory quotient, and reduced spatial working memory ability; and (v) slower speed of information processing, as measured by simple and multiple choice reaction time (RT). In UCD patients, neuropsychological and neurobehavioral abilities were deficient for 2-5 months; after this time period, their performances returned to normal. In both BCD and UCD patients, single photon emission computed tomography (SPECT) studies showed different degrees of "reverse" cerebellar-->basal ganglia-->frontoparietal diaschisis which may underlie permanent or transitory neuropsychological deficits. The relationships among neuropsychological findings, SPECT studies, and chemical neuroanatomy are discussed.

Amelioration of Aggression: Response to Selective Cerebellar Lesions in the Rhesus Monkey

Abstract: Publisher Summary One of the best-established etiologies of aggression in the monkey is a lack of social interaction during development. Monkeys that are raised in individual cages, with visual and auditory contact but no bodily contact with each other, develop a number of bizarre behaviors. They indulge in a great deal of head or body rocking, sucking of body parts, and self-clutching. They are timorous of human approaches and, when placed with their peers, do not indulge in the usual social interactions of young primates. If such infants are maintained in partial isolation, then as adults they manifest violent aggressive behaviors directed at themselves and others. It was demonstrated that much of the abnormal behavior of partially isolated infant monkeys could be prevented by providing them with mobile rather than stationary surrogate mothers. A reduction of aggression was observed, only in those animals with lesions that included the vermis. Isolation-reared animals were probably more vicious and aggressive. There is now an increasing understanding that the cerebellum, in addition to its role in motor control, is implicated in higher brain functions and affective behavior.

Techniques for assessing neuroprotective drugs in vitro

Abstract: Publisher Summary In vitro models of cerebral ischemia may yield information about the pharmacological properties of new drugs at a resolution not possible in vivo . In vitro models allow determination of drug actions on neuronal biochemistry, physiology, or gene expression. While each of these parameters provides vital information about cellular mechanisms of injury, systems intended to assess potential neuroprotective agents require a different experimental endpoint: the survival or demise of the neuron. Culture systems are especially useful for assessing neuroprotection because they allow a sufficient period of observation to distinguish among cells destined to survive or die. This chapter describes two culture models of ischemic neuronal injury: dissociated cortical neuronal cultures and organotypic hippocampal slice cultures. Both models make use of an anaerobic chamber to deprive cells of oxygen and glucose under defined conditions. Cells are maintained in culture before and after neuronal injury. Both models assess potential protective drugs using the specific endpoint of neuronal death or survival. The chapter describes the application of these models and discusses the advantages and disadvantages of in vitro models.

Spatial event processing.

Abstract: The present review advances experimental evidence on the cerebellar involvement in spatial data processing. In particular, data on Morris water maze (MWM) performances of hemicerebellectomized (HCbed) rats indicate a specific cerebellar role within the procedural aspects of spatial functions. In MWM testing, HCbed animals are impaired in developing efficient exploration strategies and display only old and rather ineffective ways for acquiring spatial information, such as peripheral circling around the pool. This behavior is not exhibited if spatial mapping abilities are preoperatively acquired. Thus, MWM experimental data point toward a procedural deficit that specifically impairs the acquisition phase. The characteristics of the cerebellar involvement in affecting the procedures needed for spatial data management are discussed in the light of recent theories on spatial data processing and on cerebellar timing and ordering functions.

Therapeutic and research implications.

Abstract: Investigations into the relationship between the cerebellum and nonmotor processing have produced a substantial body of evidence which seems to require a revision of accepted notions about the functional role of the cerebellum. This chapter presents a perspective on the contemporary and possible future therapeutic and research implications of these findings. These include the need for patients and their families to know of the behavioral consequences of cerebellar disease processes; potential a p proaches for improvement through rehabilitation therapies; and future treatment strategies, such as electrical stimulation of the cerebellum and psychosurgical approaches applied to the cerebellum. In addition, some areas of basic science investigation that could prove informative in understanding this relationship are addressed. It will be important to obtain a more complete characterization of the anatomy, physiology, and functional topography of the cerebellum in humans and in animal models, and a greater understanding of the clinical consequences of cerebellar lesions.

Inherited cerebellar diseases.

Abstract: Publisher Summary This chapter analyzes the neuropsychological deficits in inherited cerebellar diseases and compares their symptomatology with animal models in which the exact anatomical localization of degeneration is known and limited to the cerebellum. Both animal and human data suggest that cerebellar cortical atrophy affects functions of the frontal lobe system. Olivopontocerebellar atrophy is genetically and clinically inhomogeneous. The dementia syndrome that occurs in a proportion of patients does not seem to be linked with cerebellar dysfunction. Patients suffering from Friedreich's disease are described as exhibiting cognitive slowing and deficits in spatial tasks. Because other structures are more prominently involved than the cerebellum in this disease, other pathoanatomical correlates explain the symptomatology. This chapter considers the following pathologies: animal models, cerebellar cortical atrophy, olivopontocerebellar atrophy, and Friedreich's disease. The outlined anatomical connections support the hypothesis that cerebellar disease may affect forebrain cortical, and especially frontal and parietal cognitive functions.