Neuronal activity patterns in microcircuits of the cerebellar cortical C3 zone during reaching.

The cerebellum is the largest sensorimotor structure in the brain. A fundamental organizational feature of its cortex is its division into a series of rostrocaudally elongated zones. These are defined by their inputs from specific parts of the inferior olive and Purkinje cell output to specific cerebellar and vestibular nuclei. However, little is known about how patterns of neuronal activity in zones, and their microcircuit subdivisions, microzones, are related to behaviour in awake animals. In the present study, we investigated the organization of microzones within the C3 zone and their activity during a skilled forelimb reaching task in cats. Neurons in different microzones of the C3 zone, functionally determined by receptive field characteristics, differed in their patterns of activity during movement. Groups of Purkinje cells belonging to different receptive field classes, and therefore belonging to different microzones, were found to collectively encode different aspects of the reach controlled by the C3 zone. Our results support the hypothesis that the cerebellar C3 zone is organized and operates within a microzonal frame of reference, with a specific relationship between the sensory input to each microzone and its motor output. KEY POINTS: A defining feature of cerebellar organization is its division into a series of zones and smaller subunits termed microzones. Much of how zones and microzones are organized has been determined in anaesthetized preparations, and little is known about their function in awake animals. We recorded from neurons in the forelimb part of the C3 zone 'in action' by recording from single cerebellar cortical neurons located in different microzones defined by their peripheral receptive field properties during a forelimb reach-retrieval task in cats. Neurons from individual microzones had characteristic patterns of activity during movement, indicating that function is organized in relation to microcomplexes.

Combined exercise and visual gaze training improves stepping accuracy in people with diabetic peripheral neuropathy.

INTRODUCTION: Patients with diabetes and diabetic peripheral neuropathy (DPN) place their feet with less accuracy whilst walking, which may contribute to the increased falls-risk. This study examines the effects of a multi-faceted intervention on stepping accuracy, in patients with diabetes and DPN. METHODS: Forty participants began the study, of which 29 completed both the pre and post-intervention tests, 8 patients with DPN, 11 patients with diabetes but no neuropathy (D) and 10 healthy controls (C). Accuracy of stepping was measured pre- and post-intervention as participants walked along an irregularly arranged stepping walkway. Participants attended a one-hour session, once a week, for sixteen weeks, involving high-load resistance exercise and visual-motor training. RESULTS: Patients who took part in the intervention improved stepping accuracy (DPN: +45%; D: +36%) (p < 0.05). The diabetic non-intervention (D-NI) group did not display any significant differences in stepping accuracy pre- to post- the intervention period (-7%). DISCUSSION: The improved stepping accuracy observed in patients with diabetes and DPN as a result of this novel intervention, may contribute towards reducing falls-risk. This multi-faceted intervention presents promise for improving the general mobility and safety of patients during walking and could be considered for inclusion as part of clinical treatment programmes.

Cautious gait in relation to knowledge and vision of height: is altered visual information the dominant influence?

For some people, visual exposure creates difficulty with movement and balance, yet the mechanisms causing this are poorly understood. The altered visual environment is an obvious possible cause of degraded balance. We studied locomotion in normal healthy adults along a 22-cm-wide walkway at ground level and at a height of 3.5 m. This produced substantial changes in gait progression (velocity reduced by 0.34 ms(-1), P <0.01), proportion of time spent in double support more than doubled (P <0.01), and galvanic skin conductance, a measure of physiological arousal, increased significantly (P <0.01). Since increasing visual distance is known to destabilize balance, our primary question was whether the disturbing effects of height could be eliminated by replacing sight of the drop with a visual surround comparable to ground level while retaining the danger and knowledge of the risk. Removing visual exposure did not significantly change the gait progression (P = 0.65) or double support duration (P = 0.58) but produced a small, significant reduction in physiological arousal (P = 0.04). In response to postural threat, knowledge of danger rather than current visual environment was the dominant cause of cautious gait and elevated physiological arousal in response to postural threat. We conclude that the mechanisms disturbing locomotion, balance, and autonomic response occur at a high task level which integrates cognition and prior experience with sensory input.

Mechanisms of synchronous activity in cerebellar Purkinje cells.

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.

An internal model of a moving visual target in the lateral cerebellum.

In order to overcome the relatively long delay in processing visual feedback information when pursuing a moving visual target, it is necessary to predict the future trajectory of the target if it is to be tracked with accuracy. Predictive behaviour can be achieved through internal models, and the cerebellum has been implicated as a site for their operation. Purkinje cells in the lateral cerebellum (D zones) respond to visual inputs during visually guided tracking and it has been proposed that their neural activity reflects the operation of an internal model of target motion. Here we provide direct evidence for the existence of such a model in the cerebellum by demonstrating an internal model of a moving external target. Single unit recordings of Purkinje cells in lateral cerebellum (D2 zone) were made in cats trained to perform a predictable visually guided reaching task. For all Purkinje cells that showed tonic simple spike activity during target movement, this tonic activity was maintained during the transient disappearance of the target. Since simple spike activity could not be correlated to eye or limb movements, and the target was familiar and moved in a predictable fashion, we conclude that the Purkinje cell activity reflects the operation of an internal model based on memory of its previous motion. Such a model of the target's motion, reflected in the maintained modulation during the target's absence, could be used in a predictive capacity in the interception of a moving object.

Eye movements drive steering: reduced eye movement distribution impairs steering and driving performance.

On a winding open road, a driver consistently looks to the inside of each bend before turning the steering wheel. When researchers disrupt this coordination by instructing drivers not to move their eyes, drivers' performance is impaired and their completion time during racing increases. The present authors examined whether changing internal states in a way that also restricts eye movements reduces coordination and affects performance. Participants (N = 24) completed a simulated rally stage under manipulation of their anxiety state through ego threat. Performance decreased under pressure, and the decrement was associated with a narrowing of the range of eye movements and a reduced correlation of eye movements with steering. The authors discuss the possibility that the deterioration in performance is a cost of maintaining steering when eye-movement driving input to the steering controller is reduced.

Alcohol badly affects eye movements linked to steering, providing for automatic in-car detection of drink driving.

Driving is a classic example of visually guided behavior in which the eyes move before some other action. When approaching a bend in the road, a driver looks across to the inside of the curve before turning the steering wheel. Eye and steering movements are tightly linked, with the eyes leading, which allows the parts of the brain that move the eyes to assist the parts of the brain that control the hands on the wheel. We show here that this optimal relationship deteriorates with levels of breath alcohol well within the current UK legal limit for driving. The eyes move later, and coordination reduces. These changes lead to bad performance and can be detected by an automated in-car system, which warns the driver is no longer fit to drive.

A comparison of self-focus versus attentional explanations of choking.

This study examined attentional processes underlying skilled motor performance in threatening situations. Twenty-four trained participants performed a simulated rally driving task under conditions designed either to direct the focus of attention toward the explicit monitoring of driving or a distracting secondary task. Performance (lap time) was compared with a "driving only" control condition. Each condition was completed under nonevaluative and evaluative instructional sets designed to manipulate anxiety. Mental effort was indexed by self-report and dual-task performance measures. The results showed little change in performance in the high-threat explicit monitoring task condition, compared with either the low-threat or the high-threat distraction conditions. Mental effort increased, however, in all high- as opposed to low-threat conditions. Performance effectiveness was therefore maintained under threat although this was at the expense of reduced processing efficiency. The results provide stronger support for the predictions of processing efficiency theory than self-focus theories of choking.

The role of effort in moderating the anxiety-performance relationship: Testing the prediction of processing efficiency theory in simulated rally driving.

We tested some of the key predictions of processing efficiency theory using a simulated rally driving task. Two groups of participants were classified as either dispositionally high or low anxious based on trait anxiety scores and trained on a simulated driving task. Participants then raced individually on two similar courses under counterbalanced experimental conditions designed to manipulate the level of anxiety experienced. The effort exerted on the driving tasks was assessed though self-report (RSME), psychophysiological measures (pupil dilation) and visual gaze data. Efficiency was measured in terms of efficiency of visual processing (search rate) and driving control (variability of wheel and accelerator pedal) indices. Driving performance was measured as the time taken to complete the course. As predicted, increased anxiety had a negative effect on processing efficiency as indexed by the self-report, pupillary response and variability of gaze data. Predicted differences due to dispositional levels of anxiety were also found in the driving control and effort data. Although both groups of drivers performed worse under the threatening condition, the performance of the high trait anxious individuals was affected to a greater extent by the anxiety manipulation than the performance of the low trait anxious drivers. The findings suggest that processing efficiency theory holds promise as a theoretical framework for examining the relationship between anxiety and performance in sport.

Purkinje cells in the lateral cerebellum of the cat encode visual events and target motion during visually guided reaching.

In this study the receipt of visual information by the lateral cerebellum and its contribution to a motor output was studied using single unit recording of cerebellar cortical neurones in cats trained to perform visually guided reaching. The activity of Purkinje cells and other cortical neurones in the lateral cerebellum was investigated in relation to various aspects of the task, such as visual events, parameters of target movement, and limb and eye movements. Two-thirds (66%) of Purkinje cells tested could signal simple visual events, such as a flash of light. Neurones were also capable of detecting other less potent, but behaviourally important visual events, such as a 'GO' signal (LED brightening). Half of the cells tested were responsive to the on-going motion of the visual target, displaying tonically altered discharge rates for as long as it was moving, and a 'preferred' target velocity. A small proportion of cells showed short latency visual modulation that persisted during the forelimb reach. Anatomical tracing studies confirmed that the recordings were obtained from the D1 zone of crus I. In summary, cells in this region of lateral cerebellar cortex perform simple visual functions, such as event detection, but also more complex visual functions, such as encoding parameters of target motion, and their visual responsiveness is appropriate for a role in accurate visually guided reaching to a moving target.

Lateral cerebellum: functional localization within crus I and correspondence to cortical zones.

The present study investigates the functional connections of different parts of the medial-most folium of crus I in the cat cerebellar hemisphere. Three areas were identified physiologically by recording on the cerebellar surface climbing fibre (CF) field potentials evoked by electrical stimulation of different body sites. From medial to lateral in relation to the long axis of the folium, area 1 receives convergent input from all body sites tested (optic chiasm, ipsilateral periorbital region, ipsilateral and contralateral forelimbs), area 2 receives input mainly from the ipsilateral periorbital region, while area 3 receives input mainly from the optic chiasm. These physiological differences were used to guide injections of bi-directional tracer material into individual cortical areas. The inferior olive and cerebellar nuclei were then mapped, revealing a precise topography within the olivo-cerebellar and cortico-nuclear projections for each area. On the basis of their anatomical and physiological characteristics areas 1, 2 and 3 correspond to zones C2, C3 and D1, respectively. CF inputs arise from the rostral medial accessory olive (C2), the interface between the rostral dorsal accessory olive and ventral lamella of the principal olive (vlPO, C3), and from vlPO (D1). The corresponding cortico-nuclear projections are nucleus interpositus posterior (C2), the transitional region between the dentate nucleus and nucleus interpositus anterior (C3), and the dentate nucleus (D1). Overall, the results provide a comprehensive description of the functional localization of different zones within crus I (folium 1), and suggest that a potent source of CF input to the C2 and D1 zones within this region of cortex arises from visual pathways.