This chapter reviews the available data concerning the pharmacological and biophysical properties of transmission, which incorporated in a model that relates these features to the performance of the primary afferent second order neuron pathway during vestibular stimulation. A considerable body of evidence now exists demonstrating that transmission at synapses between vestibular primary afferents and second-order neurons of the medial vestibular nucleus (MVN) is glutamatergic in nature. The existence of recurrent excitatory collaterals between MVN neurons that are modulated by GABAergic inhibition is supported by extracellular single-unit studies of the tonic firing rate of MVN neurons in vitro, which is enhanced by GABAA receptor antagonists. Patch-clamp studies of glutamate receptor-mediated currents have provided a detailed picture of the behavior of the NMDA receptor-channel complex to be utilized in the construction of a kinetic model of the NMDA receptor-mediated EPSC in MVN neurons.

Neural adaptation process needs to balance an ability to distinguish similar patterns (differential sensitivity) and an ability to learn new patterns while keeping old ones intact (incremental learning). In this paper, we used a striatal medium spiny neuron (MSN) model to assess the effects of presynaptic inhibition on the differential sensitivity/incremental learning trade-off problem. Differential sensitivity is positively correlated with the strength of long-term depression (LTD) because it emphasizes pattern difference by eliminating anti-causal weak responses. However, strong LTD interferes with incremental learning. We assumed that presynaptic lateral inhibition could emphasize the pattern difference without losing the previously formed synaptic weight pattern. Then, we applied spike timing dependent plasticity (STDP) rule to a simulation of the corticostriatal pathway with and without presynaptic inhibition of the MSNs. The result confirmed that the trade-off problem could be overcome by presynaptic lateral inhibition.

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions--including prefrontal, parietal and hippocampal cortices--exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or "states" important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures.

The parallelism of neural pathways suffers from destruction by neural plasticity, rendering incremental learning impossible. We demonstrate that pre-synaptic inhibition in the striatum fosters incremental learning and preservation of parallelism. Keywords―Parallelism, PreSynaptic Inhibition, Sparseness, Reproducibility, Differential Sensitivity

Working memory for temporal order is a component of working memory that is especially dependent on striatal systems, but has not been extensively studied in schizophrenia. This study was designed to characterize serial order reproduction by adapting a spatial serial order task developed for nonhuman primate studies, while controlling for working memory load and whether responses were initiated freely (unpaced) or in an externally paced format. Clinically stable schizophrenia patients (n = 27) and psychiatrically healthy individuals (n = 25) were comparable on demographic variables and performance on standardized tests of immediate serial order recall (Digit Span, Spatial Span). No group differences were observed for serial order recall when read sequence reproduction was unpaced. However, schizophrenia patients exhibited significant impairments when responding was paced, regardless of sequence length or retention delay. Intact performance by schizophrenia patients during the unpaced condition indicates that prefrontal storage and striatal output systems are sufficiently intact to learn novel response sequences and hold them in working memory to perform serial order tasks. However, retention for newly learned response sequences was disrupted in schizophrenia patients by paced responding, when read-out of each element in the response sequence was externally controlled. The disruption of memory for serial order in paced read-out condition indicates a deficit in frontostriatal interaction characterized by an inability to update working memory stores and deconstruct ‘chunked’ information.

We investigated the neural processes, with a focus on subcortical circuits, which govern corrective submovements in visually targeted action. During event-related fMRI, subjects moved a cursor to capture targets presented at varying movement amplitudes. Movements were performed in a rehearsed null and a novel viscous (25% random trials) torque field. Movement error feedback was provided after each trial. The viscous field invoked a significantly larger error at the end of the primary movement. Subjects compensated by producing more corrections than they had in the null condition. Corrective submovements were appropriately scaled such that terminal error was similar between the two conditions. Parametric analysis identified two regions where the BOLD signal correlated with the number of submovements per trial: a cerebellar region similar to the one noted in the task contrast and the contralateral dorsal putamen. A separate parametric analysis identified brain regions where activity correlated with movement amplitude. This identified the same cerebellar region as above, bilateral parietal cortex, and left motor and premotor cortex. Our data indicate that the basal ganglia and cerebellum play complementary roles in regulating ongoing actions when precise updating is required. The basal ganglia have a key role in contextually-based motor decision-making, i.e. for deciding if and when to correct a given movement by initiating corrective submovements, and the cerebellum is more generally involved in amplifying and refining the command signals for movements of different amplitudes.

The cerebellum and basal ganglia are reciprocally connected with the cerebral cortex, forming many loops that function as distributed processing modules. Here we present a detailed model of one microscopic loop between the motor cortex and the cerebellum, and we show how small arrays of these microscopic loops (CB modules) can be used to generate biologically plausible motor commands for controlling movement. A fundamental feature of CB modules is the presence of positive feedback loops between the cerebellar nucleus and the motor cortex. We use nonlinear dynamics to model one microscopic loop and to investigate its bistable properties. Simulations demonstrate an ability to program a motor command well in advance of command generation and an ability to vary command duration. However, control of command intensity is minimal, which could interfere with the control of movement velocity. To assess these hypotheses, we use a minimal nonlinear model of the neuromuscular (NM) system that translates motor commands into actual movements. Simulations of the combined CB-NM modular model indicate that movement duration is readily controlled, whereas velocity is poorly controlled. We then explore how an array of eight CB-NM modules can be used to control the direction and endpoint of a planar movement. In actuality, thousands of such microscopic loops function together as an array of adjustable pattern generators for programming and regulating the composite motor commands that control limb movements. We discuss the biological plausibility and limitations of the model. We also discuss ways in which an agent-based representation can take advantage of the modularity in order to model this complex system. © 2008 Wiley Periodicals, Inc. Complexity, 2008 This article was submitted as an invited paper following the Understanding Complex Systems conference held at the University of Illinois at Urbana-Champaign, May 2006.

We recorded extracellular single unit discharges of globus pallidus internal segment (GPi) neurons in monkeys performing a visually driven forearm rotation movement task in order to quantify how discharge patterns changed in relation to kinematic parameters. Subjects grasped a handle that rotated about its axis while facing a video screen displaying visual targets. Continuous visual feedback of handle rotation position was provided. Monkeys generated forearm rotation movements of ± 35° and ± 70° amplitude in order to align the cursor and targets. Trial records were aligned to forearm rotation onset in order to compare the discharge patterns that were associated with movements of different amplitudes, velocities, and directions. In addition, we quantified the depth of modulation of neuronal discharge associated with movements generated in two different task phases. Comparisons of discharge patterns were made between the visually guided, rewarded phase ("cued movements") and the self-paced, unrewarded phase that returned the monkey to the task start position ("return movements") by quantifying the goodness of fit between neuronal discharge during cued and return movements. Our analyses revealed no systematic relationship between the depth of modulation of GPi neurons and forearm rotation amplitude, direction, or velocity. Furthermore, comparisons between the two behavioral contexts revealed a systematic attenuation of modulation that could not be attributed to differences in movement velocity. Collectively, these findings suggest that the GPi neurons that we studied were not significantly involved in mediating movement kinematics, but may have instead been instrumental in the processing of information about the behavioral context during which movements were generated.

In [Houk, 2005], the "Agents of the mind" idea is proposed as a suitable framework for studying the dynamics and complexities of mind. "Agents of the mind" is inspired by the society of mind idea of Marvin Minsky [Minsky, 1988]. According to the society of mind, the mind is a complex system. The mind agents are elusive to identify. The mind is proposed as a hierarchy of agents. The higher hierarchy agents compose of lower hierarchy agents. Higher level agents do not command lower level agents but they basically trigger or invoke lower level agents. Agents are functional entities and they interact with each other. One important part of the society of mind idea is that agents at the lowest level are the real workers. Higher level functionalities emerge as a result of the functioning of the lower level agents and the interactions between them. In agents of the mind project, computational distributed processing modules (DPM) are posited for corresponding anatomically defined assemblies and they are referred to as the agents of the mind. M1 is an anatomical area in the cerebral cortex which produces voluntary commands via its loops through basal ganglia and cerebellum. M1-DPM is a computational distributed processing module which simulates M1 area and its loops for voluntary commands production. We use Netlogo 3.1 agent-based programming environment to illuminate the properties of mind. In this work, the attractor network in cerebellar loop and the effects of Purkinje cell on production of motor commands have been studied. The results are reported in this paper.

The ability to survive in the world depends critically on the brain's capacity to detect earlier and earlier predictors of reward Or punishment. The dominant theoretical perspective for understanding this capacity has been the temporal difference (TD) algorithm for reinforcement learning. In this issue of Behavioral Neuroscience, R. C. O'Reilly. M.J. Frank. T. E. Hazy. and B. Watz (2007) propose a new model dubbed primary Value and learned value (PVLV) that is simpler than TD, and they claimed that it is biologically more realistic. In this commentary. the author suggests some slight modifications of a previous biological implementation of TD instead of adopting the new PVLV algorithm.

Rapid reaching movements of human and non-human primates are often characterized by irregular multi-peaked velocity profiles. How to interpret these irregularities is still under debate. While some reports assert that these irregularities are the result of a continuous controller interacting with the environment, we and others hold that the velocity irregularities are evidence for a controller that produces discrete movement corrections. Here we analyze rapid pronation/supination wrist movements in monkey during a 1D step-tracking task, where visual perturbations of the target were randomly introduced at movement onset. We use our recently introduced algorithm (Fishbach et al. in Exp Brain Res 164:442–457, 2005) to decompose an irregular movement into a primary movement and one or more discrete, corrective submovements. We first show that the visual perturbation has almost no effect on primary movements. In contrast, this perturbation influences the type and the extent of the corrective submovements that often follow primary movements. Secondly, we show that the highly variable timing of overlapping submovements does not depend directly on the visual perturbation but rather on an estimate of the movement error and on the movement’s extent-to-go at the time of correction initiation. These results are consistent with a forward-model based intermittent controller with a non-linearity that depends both on a prediction of the magnitude and direction of the movement’s error and on its variance. Corrections are initiated only when the predicted error is statistically significant. A simple abstract model that implements these principles accounts for the type and timing of the corrections observed in our data.

Cover Photo. Rows 1 and 2 show left lateral, posterior, and right lateral views of PET activation reflecting brain regions tied to visual-verbal (row 1) and auditory-verbal (row 2) encoding processes. Rows 3 and 4 show left lateral, superior, and right lateral views of PET activation reflecting brain regions mediating working memory processes for visually (row 3) and aurally (row 4) presented verbal material. See the article by Schumacher et al. in this issue. Current models of verbal working memory assume that modality-specific representations are translated into phonological representations before entering the working memory system. We report an experiment that tests this assumption. Positron emission tomogra-phy measures were taken while subjects performed a verbal working memory task. Stimuli were presented either visually or aurally, and a visual or auditory search task, respectively, was used as a control. Results revealed an almost complete overlap between the active memory areas regardless of input modality. These areas included dorsolateral frontal, Broca's area, SMA, and premotor cortex in the left hemisphere; bilateral superior and posterior parietal cortices and anterior cingulate; and right cerebellum. These results correspond well with previous research and suggest that verbal working memory is modality independent and is mediated by a circuit involving frontal, parietal, and cerebellar mechanisms. o 1996Academic Press, Inc.

Limb movement-related neurons in the cerebellar nuclei (CN) typically produce bursts of discharge in association with movement. Consequently, given the inhibitory nature of the Purkinje cell (PC) projection to CN, it is puzzling that only a minority of movement-related PCs pause; the majority burst. Some of the movement-related CN activity may be the result of excitation from collaterals of mossy and climbing fiber projections to the cerebellar cortex. The only other input to CN is diffuse and neuromodulatory, from locus ceruleus and raphe nuclei. To investigate the role of the excitatory mossy fiber input, single units in CN were recorded in macaque monkeys during the performance of reaching and manipulation tasks, before and after blocking the PC input with local microinjections of GABA(A) antagonists (bicuculline or SR95531). After these injections, the movement-related modulation of CN discharge was greater and began earlier, compared with the modulation in the preinjection group of neurons. These observations indicate that an important excitatory drive is provided by extracerebellar inputs to CN, most likely from collaterals of mossy fibers. PCs may serve primarily to regulate this activity, by either pausing or bursting as necessary.

The higher order circuitry of the brain is comprised of a large-scale network of cerebral cortical areas that are individually regulated by loops through subcortical structures, particularly through the basal ganglia and cerebellum. These subcortical loops have powerful computational architectures. Using, as an example, the relatively well-understood processing that occurs in the cortical/basal ganglionic/cerebellar distributed processing module that generates voluntary motor commands, I postulate that a network of analogous agents is an appropriate framework for exploring the dynamics of the mind.

Holdefer, R. N., J. C. Houk, and L. E. Miller. Movement-related discharge in the cerebellar nuclei persists after local injections of GABAA antagonists. J Neurophysiol 93: 35–43, 2005. First published August 25, 2004; doi:10.1152/jn.00603.2004 Limb movement-related neurons in the cerebellar nuclei (CN) typically produce bursts of discharge in association with movement. Consequently, given the inhibitory nature of the Purkinje cell (PC) projection to CN, it is puzzling that only a minority of movement-related PCs pause; the majority burst. Some of the movement-related CN activity may be the result of excitation from collaterals of mossy and climbing fiber projections to the cerebellar cortex. The only other input to CN is diffuse and neuromodulatory, from locus ceruleus and raphe nuclei. To investigate the role of the excitatory mossy fiber input, single units in CN were recorded in macaque monkeys during the performance of reaching and manipulation tasks, before and after blocking the PC input with local microinjections of GABAA antagonists (bicuculline or SR95531). After these injections, the movement-related modulation of CN discharge was greater and began earlier, compared with the modulation in the preinjection group of neurons. These observations indicate that an important excitatory drive is provided by extracerebellar inputs to CN, most likely from collaterals of mossy fibers. PCs may serve primarily to regulate this activity, by either pausing or bursting as necessary.

Abstract The cerebellum is located in the back of the brain, just above the brainstem. Its important function is to regulate neural signals in other parts of the brain. Most is known about its regulatory actions on neurons that control movement and posture.

We studied the synaptic input from the nucleus interpositus of the cerebellum to the magnocellular division of the red nucleus (RNm) in the mouse using combined electrophysiological and neuroanatomical methods. Whole-cell patch-clamp recordings were made from brain slices (125-150 microm) cut in a horizontal plane oriented to pass through both red nucleus and nucleus interpositus. Large cells that were visually selected and patched were injected with Lucifer Yellow and identified as RNm neurons. Using anterograde tracing from nucleus interpositus in vitro, we examined the course of interposito-rubral axons which are dispersed in the superior cerebellar peduncle. In vitro monosynaptic responses in RNm were elicited by an electrode array placed contralaterally in this pathway but near the midline. Mixed excitatory post-synaptic potentials (EPSPs)/inhibitory post-synaptic potentials (IPSPs) were observed in 48 RNm neurons. Excitatory components of the evoked potentials were studied after blocking inhibitory components with picrotoxin (100 microM) and strychnine (5 microM). All RNm neurons examined continued to show monosynaptic EPSPs after non-N-methyl-D-aspartate (NMDA) glutamate receptor components were blocked with 10 microM 6,7-dinitroquinoxaline-2,3-dione or 5 microM 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX; n=12). The residual potentials were identified as NMDA receptor components since they (i) were blocked by the addition of the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV), (ii) were voltage-dependent, and (iii) were enhanced by Mg(2+) removal. Inhibitory components of the evoked potentials were studied after blocking excitatory components with NBQX and APV. Under these conditions, all RNm neurons studied continued to show IPSPs. Blockade of GABA(A) receptors reduced but did not eliminate the IPSPs. These were eliminated when GABA(A) receptor blockade was combined with strychnine to eliminate glycine components of the IPSPs. Thus, IPSPs evoked by midline stimulation of the superior cerebellar peduncle, while blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and NMDA receptors, raise the possibility of direct inhibitory inputs to RNm from the cerebellum. In summary we propose that the special properties of the NMDA receptor components are considered important for the generation of RNm motor commands: their slow time course will contribute a steady driving force for sustained discharge and their voltage dependency will facilitate abrupt transitions from a resting state of quiescence to an active state of intense motor command generation.

Annals of the New York Academy of SciencesVolume 978, Issue 1 p. 538-539 Neural Control of Discrete Movement Segments: The Role of the Cerebellum in the Control and Learning of Movements KEVIN E. NOVAK, KEVIN E. NOVAK Northwestern University Medical School, Chicago, Illinois 60611, USASearch for more papers by this authorLEE E MILLER, LEE E MILLER Northwestern University Medical School, Chicago, Illinois 60611, USASearch for more papers by this authorJAMES C. HOUK, Corresponding Author JAMES C. HOUK Northwestern University Medical School, Chicago, Illinois 60611, USAAddress for correspondence: James C. Houk, Northwestern School of Medicine, Chicago, IL 60611.Search for more papers by this author KEVIN E. NOVAK, KEVIN E. NOVAK Northwestern University Medical School, Chicago, Illinois 60611, USASearch for more papers by this authorLEE E MILLER, LEE E MILLER Northwestern University Medical School, Chicago, Illinois 60611, USASearch for more papers by this authorJAMES C. HOUK, Corresponding Author JAMES C. HOUK Northwestern University Medical School, Chicago, Illinois 60611, USAAddress for correspondence: James C. Houk, Northwestern School of Medicine, Chicago, IL 60611.Search for more papers by this author First published: 27 January 2006 https://doi.org/10.1111/j.1749-6632.2002.tb07611.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Volume978, Issue1THE CEREBELLUM: RECENT DEVELOPMENTS IN CEREBELLAR RESEARCHDecember 2002Pages 538-539 RelatedInformation

Rapid targeted movements are subject to special control considerations, since there may be inadequate time available for either visual or somatosensory feedback to be effective. In our experiments, subjects rapidly rotated a knob to align a pointer to one of several targets. We recognized three different types of movement segments: the primary movement, and two types of submovement, which frequently followed. The submovements were initiated either before or after the end of the primary movement. The former, or "overlapping" type of submovement altered the kinematics of the overall movement and was consequently difficult to detect. We used a direct, objective test of movement regularity to detect overlapping submovements, namely, examining the number of jerk and snap zero crossings during the second half of a movement. Any overlapping submovements were parsed from the overall movement by subtracting the velocity profile of the primary movement. The velocity profiles of the extracted submovements had near-symmetric bell shapes, similar to the shapes of both pure primary movements and nonoverlapping submovements. This suggests that the same neural control mechanisms may be responsible for producing all three types of movement segments. Overlapping submovements corrected for errors in the amplitude of the primary movement. Furthermore, they may account for the previously observed, speed-dependent asymmetry of the velocity profile. We used a nonlinear model of the musculoskeletal system to explain most of the kinematic features of these rapid hand movements, including how discrete submovements are superimposed on a primary movement. Finally, we present a plausible scheme for how the central nervous system may generate the commands to control these rapid hand movements.

We recorded the activity of cerebellar Purkinje cells (PCs), primary motor cortical (M1) neurons, and limb EMG signals while monkeys executed a sequential reaching and button pressing task. PC simple spike discharge generally correlated well with the activity of one or more forelimb muscles. Surprisingly, given the inhibitory projection of PCs, only about one quarter of the correlations were negative. The largest group of neurons burst during movement and were positively correlated with EMG signals, while another significant group burst and were negatively correlated. Among the PCs that paused during movement most were negatively correlated with EMG. The strength of these various correlations was somewhat weaker, on average, than equivalent correlations between M1 neurons and EMG signals. On the other hand, there were no significant differences in the timing of the onset of movement related discharge among these groups of PCs, or between the PCs and M1 neurons. PC discharge was modulated largely in phase, or directly out of phase, with muscle activity. The nearly synchronous activation of PCs and muscles yielded positive correlations, despite the fact that the synaptic effect of the PC discharge is inhibitory. The apparent function of this inhibition is to restrain activity in the limb premotor network, shaping it into a spatiotemporal pattern that is appropriate for controlling the many muscles that participate in this task. The observed timing suggests that the cerebellar cortex learns to modulate PC discharge predictively. Through the cerebellar nucleus, this PC signal is combined with an underlying cerebral cortical signal. In this manner the cerebellum refines the descending command as compared with the relatively crude version generated when the cerebellum is damaged.