Search

Background: Eyeblink conditioning is used in many different species to study motor learning and make inferences about cerebellar function. However, considerable discrepancies in performance between different species combined with evidence that awareness of stimulus contingencies affects performance indicates that eyeblink conditioning in part reflects activity in non-cerebellar regions. This questions whether eyeblink conditioning can be used as a pure measure of cerebellar function in humans. Methods: Here we explored two ways to reduce non-cerebellar influences on performance in eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Data were analyzed, and the influence of the interstimulus interval and working memory tasks was assessed using a linear mixed effects model. Results: Our results show that subjects trained with a short interstimulus interval (150ms and 250ms) produce few conditioned responses after 100 trials. For subjects trained with a longer interstimulus interval (500ms), those who did working memory tasks produced fewer conditioned responses and had a more gradual learning curve, more akin to those reported in the animal literature. Conclusions: Our results suggest that having subjects perform working memory tasks during eyeblink conditioning can be a viable strategy to reduce non-cerebellar interference in the learning.

Axonal plasticity allows neurons to control their output, which critically determines the flow of information in the brain. Axon diameter can be regulated by activity, yet how morphological changes in an axon impact its function remains poorly understood. Axonal swellings have been found on Purkinje cell axons in the cerebellum both in healthy development and in neurodegenerative diseases, and computational models predicts that axonal swellings impair axonal function. Here we report that in young Purkinje cells, axons with swellings propagated action potentials with higher fidelity than those without, and that axonal swellings form when axonal failures are high. Furthermore, we observed that healthy young adult mice with more axonal swellings learn better on cerebellar-related tasks than mice with fewer swellings. Our findings suggest that axonal swellings underlie a form of axonal plasticity that optimizes the fidelity of action potential propagation in axons, resulting in enhanced learning., Axonal swellings have been found on Purkinje cell axons in the cerebellum both during development and disease. The authors show that axons with swellings propagate action potentials with higher fidelity than those without and that mice with more axonal swellings learn cerebellar-related tasks better.

Background Climbing fibers (CFs) innervate Purkinje cells (PCs) with 1:1 relationship to ensure proper cerebellar function. Although CFs abnormally extend into the parallel fiber domain of PC dendrites in essential tremor (ET), the architecture of CFs in relation to PCs has yet to be investigated in detail. Objective The aim of this work was to study the architecture of CFs in relation to PCs in ET. Methods The number of PC somas and PC dendrites that a single CF crossed was quantified in the postmortem cerebellum of 15 ET cases and 15 control cases. Results In ET, CFs crossed a greater number of PC somas and PC dendrites than in control cases, raising the possibility that there is abnormal CF wiring onto the PCs. Interestingly, the increase in CF-PC crossings positively correlated with tremor severity. Conclusions Patients with ET have increased CF crossings on PC dendrites. This abnormal architectural arrangement may contribute to synchronous brain activity and tremor. © 2021 International Parkinson and Movement Disorder Society.

Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance of ASD diagnosis may be as high as 90% for monozygotic twins and 30% for dizygotic twins, and hundreds of mutations in single genes have been associated with ASD. Nevertheless, only 5–30% of ASD cases can be explained by a known genetic cause, suggesting that genetics is not the only factor at play. More recently, several studies reported that up to 40% of infants with cerebellar hemorrhages and lesions are diagnosed with ASD. These hemorrhages are overrepresented in severely premature infants, who are born during a period of highly dynamic cerebellar development that encompasses an approximately 5-fold size expansion, an increase in structural complexity, and remarkable rearrangements of local neural circuits. The incidence of ASD-causing cerebellar hemorrhages during this window supports the hypothesis that abnormal cerebellar development may be a primary risk factor for ASD. However, the links between developmental deficits in the cerebellum and the neurological dysfunctions underlying ASD are not completely understood. Here, we discuss key processes in cerebellar development, what happens to the cerebellar circuit when development is interrupted, and how impaired cerebellar function leads to social and cognitive impairments. We explore a central question: Is cerebellar development important for the generation of the social and cognitive brain or is the cerebellum part of the social and cognitive brain itself?

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that is used for treating various neurological disorders such as major depressive disorder. TMS has been gaining popularity in the field of neurostimulation of the cerebellum, since the cerebellum is a complex structure connected with almost the entire central nervous system and TMS has promise for non-invasively probing cerebellar function. Recent studies have discovered that the cerebellum plays an important role not only in motor planning and behavior but also in the cognitive domain. However, few studies have explored how different coil designs and anatomical variations affect the effectiveness of cerebellar TMS. Therefore, in this paper, we investigated the effects of cerebellar TMS with different coil designs positioning on several locations. Finite-element modeling was conducted with Figure-8 coil and D-B80 coil. Each coil was positioned in the center, 1 and 3 cm to the left of center of the cerebellum, and all the locations were tangential to the scalp at a distance of 5 mm. Furthermore, 50 MRI derived head models were used in the computer modeling to examine how anatomical variations affect the distribution and intensity of electric field in cerebellar TMS.

Cerebellar malfunctions significantly impact the regulation of the sleep–wakefulness transition. The possible mechanism for this effect is still unknown. Evidence on the role of cerebellar processing in the sleep–wake cycle is derived mainly from animal studies, and clinical management of the sleep–wake cycle is also challenging. The purpose of this review is to investigate the role of cerebellar activity during normal sleep and the association between cerebellar dysfunction and sleep disorders. Large-scale, multicenter trials are still needed to confirm these findings and provide early identification and intervention strategies to improve cerebellar function and the sleep quality of patients.

Cerebellar granule neurons (CGNs) undergo programmed cell death during the first postnatal week of mouse development, coincident with sustained expression of the death receptor p75NTR. Although ablation of p75NTR does not affect CGN cell death, deletion of the downstream effector RIP2 significantly increases CGN apoptosis, resulting in reduced adult CGN number and impaired behaviors associated with cerebellar function. Remarkably, CGN death is restored to basal levels when p75NTR is deleted in RIP2-deficient mice. We find that RIP2 gates the signaling output of p75NTR by competing with TRAF6 for binding to the receptor intracellular domain. In CGNs lacking RIP2, more TRAF6 is associated with p75NTR, leading to increased JNK-dependent apoptosis. In agreement with this, pharmacological inhibition or genetic ablation of TRAF6 restores cell death levels in CGNs lacking RIP2. These results reveal an unexpected mechanism controlling CGN number and highlight how competitive interactions govern the logic of death receptor function.

The view of cerebellar functions has been extended from controlling sensorimotor processes to processing “contextual” information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors: The role for cerebellar granule cells in multimodal integration in the cerebellar cortex and the long-range connectivity between the deep cerebellar nuclei and the basal ganglia. Lastly, we discuss how studies on synapses and circuits of the cerebellum in rodent models of autism-spectrum disorders might contribute to our understanding of the pathophysiology of this class of neurodevelopmental disorders.

Objective Arachnoid cysts are often congenital and asymptomatic, however, they may contribute to neurocognitive symptoms when there is a mass effect on the brain. This case study describes how a 17-year-old with cerebellar arachnoid cyst, and minimal mass effect exhibited symptoms of cerebellar cognitive affective syndrome (CCAS), which has been mostly associated with brain tumor or injury in prior research. Method In this case study, a posterior cerebellar arachnoid cyst (midline) was identified incidentally (via CT scan and later MRI) following a panic attack associated with face twitching, motor tremors, and clumsiness. Background history was collected via medical records, neurologist consultation, and parent and patient interview. Patient history was significant for speech, language, motor, and academic delays. Results Results of a comprehensive evaluation revealed deficits in perceptual reasoning, visual memory, fine motor functioning, attention, processing speed, executive functioning, social cognition and receptive/expressive language. Multi-informant ratings indicated anxiety. Reading, writing, and mathematics fell several years below grade- level in the context of low average intellectual ability (WAIS-IV: GAI = 88). Conclusions Many deficits in this neuropsychological profile are typically subsumed by the cerebellum or its associated networks, and overlap with CCAS. The findings of this case study warrant consideration by clinicians of functional impairment related to cerebellar cysts and expansion of our knowledge-base of cerebellar function.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field. The present research was supported by the European Commission 7th Framework Programme (FP7/2007-2013), “Challenge 2—Cognitive Systems, Interaction, Robotics,” grant agreement No. ICT IP-231722, project “IM-CLeVeR—Intrinsically Motivated Cumulative Learning Versatile Robots” to D. Caligiore; by the Human Frontier Science Program (HFSP), award number RGY0088/2014 to G. Pezzulo; in parts by funds from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs and National Institutes of Health Grants R01 NS24328, R01 MH56661, P40 OD010996, and P30 NS076405 to P. L. Strick; by the European Research Council project MotMotLearn (637488) to J. Galea; by the MRC (grant R/J012610/1) to R.C. Miall and Wellcome Trust, grant WT087554 to R.C. Miall and A. Lago-Rodriguez; by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 341196 to P. F. M. J. Verschure; and by the European Commission’s Horizon 2020 socSMC (under agreement number socSMC-641321H2020-FETPROACT-2014) to I. Herreros. We thank the two anonymous reviewers and Professor Michael A. Arbib who have contributed to enhance the quality of this consensus paper with precious comments.

This review aims to highlight the important contribution of the cerebellum in the Anticipatory Postural Adjustments (APAs). These are unconscious muscular activities, accompanying every voluntary movement, which are crucial for optimizing motor performance by contrasting any destabilization of the whole body and of each single segment. Moreover, APAs are deeply involved in initiating the displacement of the center of mass in whole-body reaching movements or when starting gait. Here we present literature that illustrates how the peculiar abilities of the cerebellum i) to predict, and contrast in advance, the upcoming mechanical events; ii) to adapt motor outputs to the mechanical context, and iii) to control the temporal relationship between task-relevant events, are all exploited in the APA control. Moreover, recent papers are discussed which underline the key role of cerebellum ontogenesis in the correct maturation of APAs. Finally, on the basis of a survey of animal and human studies about cortical and subcortical compensatory processes that follow brain lesions, we propose a candidate neural network that could compensate for cerebellar deficits and suggest how to verify such a hypothesis.

Contains fulltext : 155885.pdf (Publisher’s version ) (Closed access) Depressive disorder is associated with abnormalities in the processing of reward and punishment signals and disturbances in homeostatic regulation. These abnormalities are proposed to impair error minimization routines for reducing uncertainty. Several lines of research point towards a role of the cerebellum in reward- and punishment-related predictive coding and homeostatic regulatory function in depressive disorder. Available functional and anatomical evidence suggests that in addition to the cortico-limbic networks, the cerebellum is part of the dysfunctional brain circuit in depressive disorder as well. It is proposed that impaired cerebellar function contributes to abnormalities in predictive coding and homeostatic dysregulation in depressive disorder. Further research on the role of the cerebellum in depressive disorder may further extend our knowledge on the functional and neural mechanisms of depressive disorder and development of novel antidepressant treatments strategies targeting the cerebellum. 4 p.

Objectives Functional neuroimaging and voxel-based morphometry studies have confirmed the important role of the cerebellum in motor behavior. However, little is known about the relationship between cerebellar gray (GMv) and white matter (WMv) volume and manual motor performance in aging individuals. This study aims to quantify the relationship between cerebellar tissue volume and manual motor performance. Experimental design To gain more insight into cerebellar function and how it relates to the role of the primary motor cortex (M1), we related cerebellar GMv, WMv, and M1v to manual motor performance in 217 healthy older individuals. Left and right cerebellar GMv and WMv, and M1v were obtained using FreeSurfer. The following motor measures were obtained: grip force, tapping speed, bimanual visuomotor coordination, and manual dexterity. Principal observations Significant positive relationships were observed between cerebellar GMv and WMv and grip strength, right cerebellar WMv and right-hand tapping speed, right cerebellar WMv and dexterity, M1v and grip strength, and right M1v and left-hand dexterity, though effect sizes were small. Conclusions Our results show that cerebellar GMv and WMv are differently associated with manual motor performance. These associations partly overlap with the brain-behavior associations between M1 and manual motor performance. Not all observed associations were lateralized (i.e., ipsilateral cerebellar and contralateral M1v associations with motor performance), which could point to age-related neural dedifferentiation. The current study provides new insights in the role of the cerebellum in manual motor performance. In consideration of the small effect sizes replication studies are needed to validate these results. Hum Brain Mapp 36:2352–2363, 2015. © 2015 Wiley Periodicals, Inc.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children that often continues into adulthood. It has been suggested that motor impairments in ADHD are associated with underlying cerebellar pathology. If such is the case, individuals with ADHD should be impaired on motor tasks requiring healthy cerebellar function. To test this, we compared performance of individuals with ADHD and ADHD-like symptoms with non-ADHD controls on a visuomotor adaptation task known to be impaired following cerebellar lesions. Participants adapted reaching movements to a visual representation that was rotated by 30°. Individuals with ADHD and those with ADHD-like symptoms took longer to correct the angle of movement once the rotation was applied relative to controls. However, post-adaptation residual effect did not differ for individuals with ADHD and ADHD-like symptoms compared to the control group. These results are consistent with the hypothesis that mild cerebellar deficits are evident in the motor performance of adults with ADHD.

Stress-related psychiatric conditions are one of the main causes of disability in developed countries. They account for a large portion of resource investment in stress-related disorders, become chronic, and remain difficult to treat. Research on the neurobehavioral effects of stress reveals how changes in certain brain areas, mediated by a number of neurochemical messengers, markedly alter behavior. The cerebellum is connected with stress-related brain areas and expresses the machinery required to process stress-related neurochemical mediators. Surprisingly, it is not regarded as a substrate of stress-related behavioral alterations, despite numerous studies that show cerebellar responsivity to stress. Therefore, this review compiles those studies and proposes a hypothesis for cerebellar function in stressful conditions, relating it to stress-induced psychopathologies. It aims to provide a clearer picture of stress-related neural circuitry and stimulate cerebellum-stress research. Consequently, it might contribute to the development of improved treatment strategies for stress-related disorders.

Understanding the contribution of cerebellar dysfunction to complex neurological diseases such as autism spectrum disorders (ASD) is an ongoing topic of investigation. In a recent paper, Tsai et al. (Nature 488:647-651, 2012) used a powerful combination of conditional mouse genetics, electrophysiology, behavioral tests, and pharmacological manipulations to address the role of Tuberous sclerosis complex 1 (Tsc1) in Purkinje cells and cerebellar function. The authors make the staggering discovery that morphological and electrophysiological defects in Purkinje cells are linked to system-wide ASD-like behavioral deficits. In this journal club, I discuss the major findings of this paper and critically assess the implications of this seminal work.

In the late 1970s, Wally Welker and his colleagues published a series of papers describing the first high-resolution physiological maps of tactile mossy fiber projections to the granule cell layer of the rat. Over the subsequent decade, his laboratory continued to explore the implications of these results for cerebellar connectivity and function while also extending the basic mapping results to a number of additional mammalian species. In each case, the maps revealed several surprising features, including a dominance of tactile (cutaneous inputs), robust short latency responses from the sensory periphery, and a fractured patchy somatotopic organization of receptive fields. This paper summarizes the major results of these micromapping experiments and reconsiders their implications for cerebellar function in light of more recent experimental data. The paper also explores the relationship between these fundamental discoveries and Wally Welker's theory-neutral approach to experimental science.

Complex spike synchrony is thought to be a key feature of how inferior olive climbing fibre afferents make their vital contribution to cerebellar function. However, little is known about whether the other major cerebellar input, the mossy fibres (which generate simple spikes within Purkinje cells, PCs), exhibit a similar synchrony in impulse timing. We have used a multi-microelectrode system to record simultaneously from two or more PCs in the posterior lobe of the ketamine/xylazine-anaesthetized rat to examine the relationship between complex spike and simple spike synchrony in PC pairs located mainly in the A2 and C1 zones in crus II and the paramedian lobule. PC pairs displaying correlations in the occurrence of their complex spikes (coupled PCs) were usually located in the same zone and were also more likely to exhibit correlations in the timing of their spontaneous simple spikes and associated pauses in activity. In coupled PCs, synchrony in both complex spike and simple spike activity was enhanced and the relative timing in the occurrence of complex spikes could be altered by peripheral stimulation. We conclude that the functional coupling between PC pairs in their complex spike and simple spike activity can be significantly modified by sensory inputs, and that mechanisms besides electrotonic coupling are involved in generating PC synchrony. Synchronous activity in multiple PCs converging onto the same cerebellar nuclear cells is likely to have a significant impact on cerebellar output that could form important timing signals to orchestrate coordinated movements.

Research on the cerebellum is evolving rapidly. The exquisiteness of the cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach cerebellar functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of cerebellar function are generating an immense amount of knowledge. Simultaneously, a better definition of cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of cerebellar function. Contributions were brought together around five themes: (1) cerebellar development, death, and regeneration; (2) cerebellar circuitry: processing and function; (3) mechanisms of cerebellar plasticity and learning; (4) cerebellar function: timing, prediction, and/or coordination?; (5) anatomical and disease perspectives on cerebellar function.

Hereditary episodic ataxia (EA) syndromes are rare monogenic disorders that are phenotypically and genetically heterogeneous. The number of identified EA phenotypes is expanding. So far, mutations have been identified in four genes, all coding for membrane proteins including ion channels and transporters. The study of EA has illuminated previously unrecognized but important roles of ion channels and transporters in cerebellar function. This review summarizes recent advances and focuses on practical approaches in the diagnosis and treatment of episodic ataxia.

Objective: Structural, biochemical, and functional cerebellar abnormalities occur in individuals with or at-risk for developing bipolar disorder (BD), but the clinical implications of these abnormalities are unknown. The present study examined cerebellar function in youths who were at familial risk for BD by comparing ataxia battery scores of youths with a bipolar parent to those of healthy youths. Methods: Trained raters administered an ataxia battery, consisting of three tasks, to children (aged 8–12 years) with at least one parent with BD type I (BDI) who themselves did not have BDI (at-risk or AR group, n = 21) and healthy comparison children (aged 8–12 years) with parents free of DSM-IV Axis I psychopathology (HC group, n = 23). Results: AR youths performed worse than HC youths on the Sharpened Romberg test (subjects standing heel-to-toe) and standing on one foot with eyes open (p

Children with Developmental Coordination Disorder (DCD) are reported to have high temporal variability in tasks requiring precise timing. The current study examined whether this timing deficit was due to the cerebellar ‘explicit timing’ process in the discontinuous, but not the continuous movement. Ten children with DCD and thirty-one typically developing children performed continuous, discontinuous circle- and line-drawing tasks. Results showed that both children with DCD and their age-matched controls had higher temporal variability in the discontinuous than that in the continuous movements. Individual comparisons between each child with DCD and the performance of typically developing children revealed that two out of ten children with DCD showed limited timing deficit in both types of discontinuous drawing (lines and circles). Additionally, three different children with DCD had timing problems with only discontinuous line drawing. Thus, the possibility of a compromised cerebellar function may exist in a subgroup of children with DCD. This work raises a critical issue with respect to the functional heterogeneity of this population and emphasizes the importance of an individualized analysis in this movement disorder.

The role of the cerebellum in motor control and learning has been largely inferred from the effects of cerebellar damage. Recent work shows that cerebellar damage produces greater impairment of movements that require predictive as opposed to reactive control. This dissociation is consistent across many different types of movement. Predictive control is crucial for fast and ballistic movements, but impaired prediction can also affect slow movements, because of increased reliance on time-delayed feedback signals. The new findings are compatible with theories of cerebellar function, but still do not resolve whether the cerebellum operates by predicting the optimal motor commands or future sensory states. Prediction mechanisms must be learned and maintained through comparisons between predicted and observed outcomes. New results show that not all such error information is equivalent in driving cerebellar learning.

The pathophysiology of autism appears to encompass a number of different brain structures and systems. However, the most consistent site of neural abnormality in autism is the cerebellum. Postmortem investigations have reported a variety of anomalies, most notably a reduction in the number of Purkinje neurons. Additionally, structural neuroimaging studies have shown volumetric changes in the cerebellum, including decreases in gray matter and increases in white matter. Emerging evidence for cerebellar abnormality in autism was paralleled by a revolution in our understanding of normal cerebellar function and cerebellar connectivity, such that the importance of elucidating the contributions of the cerebellum to autism is now clear. In fact, recent brain-behavior correlation studies suggest that cerebellar abnormality may play a more central role in autism than previously thought. At present, it is crucial that we increase our understanding of cerebellar functioning in autism, and functional neuroimaging studies are just beginning to reveal the possible role(s) of cerebellar dysfunction in this disorder. In this review, evidence for cerebellar anatomic and functional abnormality in autism will be delineated. This will be followed by consideration of the implications of cerebellar abnormality in autism. Two major questions will be addressed: (1) how might dysfunction of the cerebellum impact the development of connectivity between the cerebellum and other brain systems, and (2) how might cerebellar dysfunction impact behavior and the symptoms of autism. The paper concludes with a discussion of how cerebellar abnormalities might inform our understanding of the etiology of autism spectrum disorders.

A previous experiment investigating visuomotor adaptation in typically developing children and children with Developmental Coordination Disorder (DCD) suggested poor adaptation to an abruptly induced visuomotor perturbation. In the current study, using a similar center-out drawing task, but administering either an abrupt or a gradual perturbation, and twice as many adaptation trials, we show that typically developing children are well able to successfully update an existing internal model in response to a 60 degrees rotation of the visual feedback, independent of the perturbation condition. Children with DCD, however, updated their internal map more effectively during exposure to an abrupt visuomotor perturbation than to a gradual one. This may suggest that the adaptation process in children with DCD responds differently to small vs. large steps of visuomotor discrepancies. Given the known role of the cerebellum in providing an error signal necessary for updating the internal model in response to a gradual visuomotor distortion, the results of our study add to the growing body of evidence implicating compromised cerebellar function in DCD.

The cerebellum, which has been found to be abnormal in histopathological studies of autism, is important for motor adaptation. We studied controls and children with high functioning autism (HFA) performing a catching adaptation test that is known to be impaired following cerebellar damage. Results showed no differences in adaptation rates or after-effects for HFA subjects versus controls. The findings indicate normal motor adaptation in HFA, suggesting normal or compensated cerebellar function for this task.

The organization of the vertebrate cerebellum has been thoroughly studied over the past century, but the function of this structure remains poorly understood. In elasmobranch fishes, the cerebellum displays tremendous variation in size and development although the basic and conservative nature of cerebellar circuitry as seen in other vertebrate taxa is largely retained. Large and morphologically complex cerebelli have evolved independently in both sharks and batoids, and the relative development of this structure in both taxa parallels those of birds and mammals. There are relatively few studies of the physiological role of the cerebellum in generating or shaping behaviors, however, and a convincing explanation of cerebellar hypertrophy in elasmobranchs is lacking. The purpose of this article is to review the current understanding of the structure of the cerebellum in elasmobranch fishes, the physiological responses of cerebellar neurons and the possible role of the cerebellum in behavior. I will also provide a number of hypotheses for future research directions, based upon models that have been suggested by different investigators. These hypotheses include models of cerebellar function as a sensory coincidence detector, a dynamic state estimator and/or a direct modulator of motor programs. Hypotheses concerning the possible organization of cerebellar microcomplexes, the evolution of afferent and efferent cerebellar connections paralleling those observed in mammals and the role of the cerebellum in learning are also suggested.

The recent demonstration that the human cerebellum is involved in attention operations independent of sensory input or motor output highlights the inadequacy of traditional concepts of cerebellar function, and calls for psychiatrists, neurologists, and neuropsychologists to reconsider the possible contribution of cerebellar abnormalities to disorders characterized by non-motor symptoms.

For decades, cerebellar research has been guided by the central hypothesis that plasticity at synapses in the cerebellar cortex mediates motor learning. This hypothesis has been challenged especially strongly in recent years by data that contradict the original theories of cerebellar motor learning. These data form the basis for strong arguments to the contrary and have inspired new, non-motor theories of cerebellar function. We consider key data that are contrary to the motor learning hypothesis and develop the argument that both old and new data are best explained by extending, rather than rejecting, the basic tenets of the original motor learning theories of cerebellar function. NEUROSCIENTIST 3:303–313, 1997

Neuropathological, neuropsychological, and neuroimaging studies of human alcoholism provide evidence for degradation of frontal, pontine, thalamic, and cerebellar brain sites and disturbed associated functions. Current studies using neuroimaging combined with examination of executive functions, traditionally considered the sole purview of the frontal lobes, have identified a role for the cerebellum serving as a compensatory processing adjunct to enable normal performance on challenging tasks tapping executive functions. This overview proposes that disruption of an executive frontocerebellar network is a major contributor to characteristic behaviors of alcoholism that, on the one hand, enable alcohol use disorders, and on the other hand, lead to compensation for dysfunctions in alcoholism traditionally considered frontally-based.

The cerebellum consists of parasagittal zones that define fundamental modules of neural processing. Each zone receives input from a distinct subdivision of the inferior olive (IO)-activity in one olivary subdivision will affect activity in one cerebellar module. To define functions of the cerebellar modules, we inactivated specific olivary subdivisions in six male cats with a glutamate receptor blocker. Olivary inactivation eliminates Purkinje cell complex spikes, which results in a high rate of Purkinje cell simple spike discharge. The increased simple spike discharge inhibits output from connected regions of the cerebellar nuclei. After inactivation, behavior was evaluated during a reach-to-grasp task and during locomotion. Inactivation of each subdivision produced unique behavioral deficits. Performance of the reach-to-grasp task was affected by inactivation of the rostral dorsal accessory olive (rDAO) and the rostral medial accessory olive (rMAO) and, possibly, the principal olive. rDAO inactivation produced paw drag during locomotion and a deficit in grasping the handle during the reach-to-grasp task. rMAO inactivation caused the cats to reach under the handle and produced severe limb drag during locomotion. Inactivation of the dorsal medial cell column, cell group beta, or caudal medial accessory olive produced little deficit in the reach-to-grasp task, but each produced a different deficit during locomotion. In all cases, the cats appeared to have intact sensation, good spatial awareness, and no change of affect. Normal cerebellar function requires low rates of IO discharge, and each cerebellar module has a specific and unique function in sensory-motor integration.