Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations.

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20-30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation.

Developmental coordination disorder: exploration of a cerebellar hypothesis.

This study explored the hypothesis of a specific cerebellar dysfunction in children with developmental coordination disorder (DCD): motor adaptation. The performance of a group of children with DCD (3 girls and 6 boys) was compared to that of a control group (5 girls and 6 boys) on a measure of motor adaptation, the prism adaptation test (PAT). Children were between 6 years 11 months and 11 years 10 months of age. Between-group differences were only found for PAT variables related to throwing accuracy, the DCD group being more variable and less accurate than the control group. While no between-group differences were found for the adaptation variables, individual data analysis revealed that only three children in the DCD group obtained normal adaptation variables. While these findings do not confirm the hypothesis of a cerebellar dysfunction, they also do not refute it. It is possible that the poor throwing accuracy of the DCD group masked the findings for some of the PAT variables. Further exploration of the function of the cerebellum among children with DCD is needed.

Role of the cerebellum in the control and adaptation of gait in health and disease.

In humans, inability to stand and walk is the most limiting of motor disabilities. In humans, upright stance and gait is the most sensitive indicator of cerebellar disease. From animal and human studies, much has been learned about how the cerebellum coordinates normal movement, and how it may play roles in normal motor adaptation and learning. Much of this work suggests that different parts of the cerebellum control stance and gait in different ways, and differently located lesions cause different deficits. What is not known is whether the cerebellum can compensate for stance and gait disorders caused by lesions in other parts of the nervous system, or whether one part of the cerebellum can compensate for deficits caused by lesion of another part. These issues have become increasingly important in rehabilitation research and practice.

Time and frequency characteristics of Purkinje cell complex spikes in the awake monkey performing a nonperiodic task.

A number of studies have been interpreted to support the view that the inferior olive climbing fibers send periodic signals to the cerebellum to time and pace behavior. In a direct test of this hypothesis in macaques performing nonperiodic tasks, we analyzed continuous recordings of complex spikes from the lateral cerebellar hemisphere. We found no periodicity outside of a 100-ms relative refractory period.

Spike firing in the lateral cerebellar cortex correlated with movement and motor parameters irrespective of the effector limb.

Neuronal signals in the lateral aspect of the macaque cerebellar cortex were studied during a visually guided reaching task. During the performance of this task, the firing rate of most neurons was significantly modulated when reaching with either the ipsilateral or the contralateral arm. In some of these reach-modulated cells, we found that spike firing was correlated with the direction and speed of the reach. These correlations with motor parameters were present during reaching with either the ipsilateral or the contralateral arm. Based on these observations we suggest that spike firing in the lateral cerebellum was correlated with movement and motor parameters irrespective of the effector limb.

Dynamic coordination of body parts during prism adaptation.

We studied coordination across body parts in throwing during adaptation to prisms. Human subjects threw balls at a target before, during, and after wearing laterally shifting prism eyeglasses. Positions of head, shoulders, arm, and ball were video-recorded continuously. We computed body angles of eyes-in-head, head-on-trunk, trunk-on-arm, and arm-on-ball. In each subject, the gaze-throw adjustment during adaptation was distributed across all sets of coupled body parts. The distribution of coupling changed unpredictably from throw to throw within a single session. The angular variation among coupled body parts was typically significantly larger than angular variation of on-target hits. Thus coupled body parts changed interdependently to account for the high accuracy of ball-on-target. Principal components and Monte Carlo analyses showed variability in body angles across throws with a wide range of variability/stereotypy across subjects. The data support a model of a dynamic and generalized solution as evidenced by the distribution of the gaze-throw adjustment across body parts.

Purkinje cell spike firing in the posterolateral cerebellum: correlation with visual stimulus, oculomotor response, and error feedback.

Complex (CS)- and simple-spike (SS) discharge from single Purkinje cells (Pc) in the posterolateral cerebellum of two monkeys was recorded during a visually guided reach-touch task. A visual target appeared (TA) off-gaze at a random location on a screen. On initiation of arm reach, the target disappeared, then reappeared (TR) after a fixed delay. TR was either at the same location (baseline condition) or a shifted location at a fixed distance and direction from TA location (shift condition). Across trials, we observed one or two peaks of CS activity, depending on the reach condition. The first CS (T1 CS) peak was tuned to the location of TA on the screen, following TA by approximately 150 ms. The second CS (T2 CS) peak occurred only in the shift condition, was tuned to the shift location of TR, and followed TR by approximately 150 ms. The locational preferences of T1 and T2 CS peaks were the same. T1 and T2 CSs preceded saccades to TA and TR at the preferred location and occurred during reaches with either arm. T1 CSs occurred during trials in which the target appeared, and there was a saccade to target, but no subsequent arm reach followed. SS firing varied with TA/TR in the same preferred location as for the accompanying CS. We conclude that posterolateral Pc CS and SS firing changes following an off-gaze visual target appearance in a preferred location when there is a subsequent saccade to that location.