Theories Of Cerebellar Function Research Articles

Facilitation of Fast Backward Priming After Left Cerebellar Continuous Theta-Burst Stimulation

Traditional theories of backward priming account only for the priming effects found at long stimulus onset asynchronies (SOAs). Here, we suggest that the presence of backward priming at short SOAs may be related to the integrative role of the cerebellum. Previous research has shown that the right cerebellum is involved in forward associative priming. Functional magnetic resonance imaging reveals some activation of the left cerebellar hemisphere during backward priming; but what this activation represents is unclear. Here we explore this issue using continuous theta-burst transcranial magnetic stimulation (cTBS) and associative priming in a lexical decision task. We tested the hypothesis that the left cerebellum plays a role in backward priming and that this is dissociated from the role of the right cerebellum in forward priming. Before and after cTBS was applied to their left and right cerebellar hemispheres, participants completed a lexical decision task. Although we did not replicate the forward priming effect reported in the literature, we did find a significant increase in backward priming after left relative to right cerebellar cTBS. We consider how theories of cerebellar function in the motor domain can be extended to language and cognitive models of backward priming.

Bayesian supervised learning and state estimation in a model of the cerebellum

The last decade has seen an explosion of research on the topic of Bayesian inference in neural systems. The cerebral cortex is now widely believed to form predictive internals models of the environment. But what does this mean for the cerebellum, which has historically been attributed just this function? And what might Bayesian inference mean in the cerebellar context? I present a cerebellar model unifying the Bayesian framework with classical cerebellar theories of supervised learning, state estimation, and control theory. This model builds on the dominant supervised learning theory of cerebellar function, which traces to the pioneering work of Marr. This model is extended to account for Bayesian optimal updating of the uncertainties inherent in probabilistic inference. Further, the model is capable of learning about states with little to no supervised input. It also provides theoretical explanation for a wide range of phenomenology observed of the circuit -- most importantly unsupervised synaptic plasticity upstream of cerebellar Purkinje cells. The connectionist architecture of this model is closely based on that of the cerebellum. In the input stage, unsupervised learning in the cerebellar granular layer is seen as essential for subsequent supervised learning in the Purkinje layer. Based on Golgi cell feedback, the granular layer learns to encode supervised learning covariances in a manner akin to the kernel learning of Gaussian processes. This circuit then predicts and filters mossy fiber input, conveying only select signals downstream for supervised learning. This granular representation is further influenced by a global serotonergic signal conveyed by Lugaro cells. In the cerebellar molecular layer, inhibitory interneurons then provide higher-order corrections to these estimates. Finally, learning in the cerebellar nuclei is seen as a parallel, simpler, regression model, allowing for faster, courser adjustments, corrected in time by the cerebellar cortical circuit.

Neural circuits in movement control

Neural circuits in movement control

Feed-forward reduction of motor variability: A theory of cerebellar function

Feed-forward reduction of motor variability: A theory of cerebellar function

Determinants of pattern recognition by cerebellar Purkinje cells

Many theories of cerebellar function assume that longterm depression (LTD) of parallel fiber (PF) synapses enables Purkinje cells (PCs) to learn to recognize PF activity patterns. According to the classic view, a PC can store and learn to distinguish PF activity patterns that have been presented repeatedly together with climbing fibre (CF) input to the cell. The resulting LTD of the PF synapses is often assumed to lead to a decreased rate of PC simple spike firing, a reduction in the inhibition of their target neurons in the deep cerebellar nuclei and thus an increased output from the cerebellum. We have recently shown by combining computer simulations with electrophysiological recordings in slices and in awake behaving mice that the readout of learned patterns in PCs may operate in a fundamentally different way. Our simulations and experiments predict that the best criterion to distinguish between learned and novel patterns is the duration of a pause in firing that occurs after presentation of a pattern, with shorter pauses in response to learned patterns [1].

Stars and stripes in the cerebellar cortex: A voltage sensitive dye study

The lattice-like structure of the cerebellar cortex and its anatomical organization in two perpendicular axes provided the foundations for many theories of cerebellar function. However, the functional organization does not always match the anatomical organization. Thus direct measurement of the functional organization is central to our understanding of cerebellar processing. Here we use voltage sensitive dye imaging in the isolated cerebellar preparation to characterize the spatio-temporal organization of the climbing and mossy fiber (MF) inputs to the cerebellar cortex. Spatial and temporal parameters were used to develop reliable criteria to distinguish climbing fiber (CF) responses from MF responses. CF activation excited postsynaptic neurons along a parasagittal cortical band. These responses were composed of slow (∼25 ms), monophasic depolarizing signals. Neither the duration nor the spatial distribution of CF responses were affected by inhibition. Activation of MF generated responses that were organized in radial patches, and were composed of a fast (∼5 ms) depolarizing phase followed by a prolonged (∼100 ms) negative wave. Application of a GABAA blocker eliminated the hyperpolarizing phase and prolonged the depolarizing phase, but did not affect the spatial distribution of the response, thus suggesting that it is not the inhibitory system that is responsible for the inability of the MF input to generate beams of activity that propagate along the parallel fiber system.

Cerebellar function: Coordination, learning or timing?

Theories of cerebellar function have largely involved three ideas: movement coordination, motor learning or timing. New evidence indicates these distinctions are not particularly meaningful, as the cerebellum influences movement execution by feedforward use of sensory information via temporally specific learning.

Cerebellar involvement in movement timing on a variety of timescales

The cerebellum has been hypothesized to play a role in a variety of movement timing tasks that involve the processing of temporal information on a variety of timescales. Braitenberg, Heck & Sultan propose a new theory of cerebellar function that is able to account for movement timing on the order of a couple of hundred milliseconds. However, this theory does not account for the rôle the cerebellum plays in the acquisition and retention of adaptively timed discrete movements that are on the order of 200 to 1000 milliseconds, and therefore does not account for the entire temporal range of cerebellar dependent processing.

Chapter 27 Is the cerebellum sensory for motor's sake, or motor for sensory's sake: the view from the whiskers of a rat?

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 but instead facilitates the efficiency with which other structures perform their own functions. In this way the cerebellum may, in fact, be useful but not necessary for brain function as a whole. The idea that the cerebellum controls sensory data acquisition has emerged over the past years from the detailed study of a very small region of crus IIA in the lateral hemispheres of the cerebellum of the albino rat. Perhaps the best evidence that the cerebellum is involved in sensory data acquisition control is its involvement in eye movements system. By definition, anything affecting the position of the eyes is directly related to sensory data acquisition, as acquiring visual data is the only thing an animal does with its eyes.

One cannot build theories of cerebellar function on shaky foundations: Induction properties of long-term depression have to be taken into account

The theories of cerebellar function presented in this BBS special issue cannot be reconciled with the established induction properties of cerebellar LTD. At the same time, the authors presenting their research on cerebellar LTD do not appear very interested in function.

Resilient cerebellar theory complies with stiff opposition

In response to several requests from commentators, an unambiguous definition of time-varying joint stiffness is provided. However, since a variety of different operations can be used to measure stiffness, a problem for quantification admittedly still exists. Several commentaries pointed out the advantage of controlling joint stiffness in optimizing the speed-accuracy trade-off known as Fittss law. The deficit in rapid reciprocal movements and the impact on joint stiffness inhibition caused by cerebellar lesions is clarified here, as the target article was apparently misinterpreted by some readers. In response to the challenge that there is little consensus among cerebellar physiologists, several areas of tacit agreement with other theories of cerebellar function are enumerated. An alternative interpretation of studies showing a transient activation of the cerebellum in motor learning is suggested. Finally, the relationship between the command signals generated by supraspinal centers such as the cerebellum and spinal interneuron networks controlling muscle synergies is discussed.

A New Theory of Cerebellar Function

A new theory of cerebellar function is proposed. It is suggested that the cerebellum works according to a hitherto unknown principle of motor control. A simple learning process in the cerebellum, the 'coupling operation', seems powerful enough to explain the role of this brain part in training and performance ofcomplex motor skills. The coupling operation greatly enhances the capability to perform fast, accurate and highly coordinated motions. These motions can be executed by many different paths, while being well adapted to changing intentions and situations. However, the cerebellar 'coupling machine' does not control movements by itself ; rather, it is a supportive device. In the case of skilled motions, for instance, the control is always left to the forebrain. A network model of the cerebellum demonstrates how the coupling operation might be carried out in cellular detail in a biologically plausible way. According to the theory, the cerebellum only influences complex voluntary movements, and not simple ones. This theory explains a great deal of physiological, anatomical and clinical data, producing a coherent picture.

A new theory of cerebellar function: Movement control through phase‐independent recognition of identities between time‐based neural information symbols

A new theory designed to explain the functions of the cerebellum in the control of movement and the unique anatomy of that structure is presented. The heart of this proposed explanation is that the cerebellum generates increased numbers of outputs from particular Purkinje cells whenever the same pattern of pulses in time is presented both to its mossy fiber and its climbing fiber input systems. The postulated function of the unusual anatomy of the cerebellum is to permit it instantly to recognize and respond to identical patterns presented through these two channels regardless of the phase differences between these two signal sources, where phase differences are defined as differences in times of arrival of patterns of inputs from these two sources. The first means putatively used involves the summation of pulses comprising a given pattern of inputs simultaneously at many different Purkinje cells by virtue of the different speeds of conduction of the parallel fiber axons of granule cells. The second means is the addition of an input from the climbing fiber system that, together with the simultaneous parallel fiber inputs, leads to a discharge of particular Purkinje cells, which discharge temporarily increases the size of EPSP's generated by the parallel fiber synapses involved in the cell's discharge. This specific synaptic potentiation, in turn, makes it possible for the cell to respond by generating closely consecutive additional discharges provided that the same patterns of discharge are presented both to the climbing fiber system and the mossy fiber system. This happens because later pulses in identical patterns will arrive simultaneously at previously facilitated synapses via parallel fibers and at synapses of the climbing fibers, thereby causing additional spatial summations and discharges to occur. According to this explanation the patterns that are compared in the above manner are symbols (patterns of pulses) produced by sensors of current positions and symbols derived from memory and also representing these same positions. When patterns from these two sources are identical, the multiple outputs of specific Purkinje cells inhibit an automatic feedback loop and thereby indirectly cause the attenuation and arrest of movement. The evolution of these concepts resulted in very specific "predictions" of particular connections involving the olive, pons, red nucleus, dentate, thalamus, and sensory-motor cortex. All of these predictions were found to be consistent with evidence in the literature. Points of difference between this theory and all prior ones are discussed as are several critical tests of its validity, and the putative evolution of cerebellar structure and function.(ABSTRACT TRUNCATED AT 400 WORDS)

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation.

The nictitating membrane/eyelid responses of 18 rabbits were classically conditioned using cerebellar mossy-fiber stimulation as a conditioned stimulus (CS) and air puff as an unconditioned stimulus (US). The dorsolateral, lateral, and medial pontine nuclei and the middle cerebellar peduncle were effective stimulation-CS sites for training. In one group of rabbits, robust conditioned eyelid responses were produced with paired trials and subsequently extinguished with CS-alone and explicitly unpaired presentation of the CS and US. In a second group of rabbits, no conditioned responses were evident for 4 days of unpaired CS and US presentations. Conditioned responses did develop, however, after paired training was begun. Lesions of the interpositus nucleus of the cerebellum completely abolished the conditioned responses of a third group of rabbits overtrained with the mossy-fiber CS and air-puff US. These results support previous studies which have demonstrated that the cerebellum is critically involved in acquisition and retention of simple learned responses. In addition, the present results support previous theories of cerebellar function which have proposed that mossy fibers supply critical "learning" input to the cerebellum for acquisition and retention of motor skills.

Increase in Purkinje cell gain associated with naturally activated climbing fiber input.

These experiments were designed to test the hypothesis that climbing fiber inputs evoked by a peripheral stimulus increase the responsiveness of Purkinje cells to mossy fiber inputs. This hypothesis was based on a previous series of observations demonstrating that spontaneous climbing fiber inputs are associated with an accentuation of the Purkinje cell responses to subsequent mossy fiber inputs (10, 12). Furthermore, short-term nonpersistent interactions between climbing and mossy fiber inputs have been an important aspect of many theories of cerebellar function (5, 7, 8, 12, 36). Extracellular unitary recordings were made from Purkinje cells in lobule V of decerebrate, unanesthetized cats. To activate mossy and climbing fiber inputs, the forepaw was passively flexed by a Ling vibrator system. A data analysis was developed to sort the simple spike trials into two groups, based on the presence or absence of complex spikes activated by the stimulus. In addition, during those trials in which complex spikes were activated, the simple spike train was aligned on the occurrence of the complex spike. For each simple spike response to the forepaw input, the average firing rate during the response was compared to background both in those trials in which complex spikes were activated and in those in which they were not. The ratio of the response amplitudes in the histograms constructed from these two groups of trials permitted a quantification of the change in responsiveness when climbing fiber inputs were activated. The results show that both excitatory and inhibitory simple spike responses are accentuated when associated with the activation of a complex spike. Using an arbitrary level of a gain change ratio of 120% as indicating a significant modification, 64% of the response components analyzed increased their amplitude when climbing fiber input was present. Simple spike response components occurring prior to complex spike activation were usually not accentuated, although in a few cells the amplitude of this component of the response increased. In addition, in a small number of cells the occurrence of complex spikes was associated with a new simple spike component. For excitatory responses, the magnitude of the gain change ratio was shown to be inversely related to the amplitude of the simple spike response evoked by the mossy fiber inputs. The data obtained is consistent with the hypothesis that the climbing fiber input is associated with an increase in the responsiveness of Purkinje cells to mossy fiber inputs. The increased responsiveness occurs whether the simple spike modulation evoked by the peripheral stimulus is excitatory or inhibitory. The change in responsiveness is short term and nonpersistent. It is argued that the activation of climbing fiber inputs to the cerebellar cortex is associated with an increase in the gain of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli.

Acquired pendular nystagmus with oscillopsia in multiple sclerosis: a sign of cerebellar nuclei disease.

In an unselected series of 644 cases of multiple sclerosis, 25 cases with acquired pendular nystagmus were found. Ten additional cases of pendular nystagmus in multiple sclerosis were investigated, and four cases from the literature are analysed. Acquired pendular nystagmus is purely sinusoidal in form, ceases with eye closure, is accompanied by oscillopsia, often monocular and vertical in direction, and never accompanied by optokinetic inversion. This is different from congenital nystagmus. Acquired pendular nystagmus in multiple sclerosis shows a high correlation with holding tremor of head and arm and with trunk ataxia, and must therefore be viewed as a result of lesions of cerebellar nuclei or their fibre connections with the brain-stem. Supporting evidence is discussed. The results fit into a theory of cerebellar function according to which the cerebellar nuclei are involved in the maintenance of positions.