Cerebellar control of constrained and unconstrained movements. I. Nuclear inactivation

The aim of this study was to determine in monkeys if inactivation of dentate and lateral interposed deep cerebellar nuclei preferentially impairs certain movements relative to others. Constrained movements of the digits were trained with digits, hand, and elbow constrained in a cast. Simple movements were flexion of Thumb or Index. A compound movement was simultaneous flexion of Thumb+Index. An unconstrained movement consisted of a reach to, pinch of, and retrieval of a small food reward (Reach+Pinch). In two monkeys we mapped the dentate and interpositus with 66 injections of muscimol (3 microl of 5 microg/microl). Thirty-two percent of the injections resulted in increased reaction times of Thumb, Index, and Thumb+Index (mean = 24, 24, 28 + 26, respectively). Fifty percent of the injections impaired Reach+Pinch, producing target overshoot, curved reach trajectory, missed target (X and Y errors), and clumsy pinch with dropped fruit bits. Inactivation impaired each and all of Thumb, Index, Thumb+Index, and Reach+Pinch in 27%, only Reach+Pinch in 23%, and only Thumb, Index, Thumb+Index in 5% of injections. In sum, all types of movement were impaired. Thumb+Index was no more impaired than Thumb or Index alone, suggesting that the lateral cerebellar nuclei are not specifically required for combining movements of the two digits when constrained. Reach+Pinch appeared so greatly impaired and Thumb, Index, Thumb+Index so little as to be consistent with the hypothesis that a principal role of the cerebellum is to control those interactions that occur between body segments in natural unconstrained movements. However, the fact that all movements were impaired shows that the cerebellum contributes to the control of all movements.     

Throwing accuracy in the vertical direction during prism adaptation: not simply timing of ball release

In a previous study, others have hypothesized that the variance in vertical errors that occurs while throwing at visual targets is caused by changes in any of three throw parameters: hand location in space, hand translational velocity, and hand orientation. From an analysis of skilled throwers, those authors concluded that vertical error is best correlated with variance in hand orientation, which in turn is related to the timing of ball release. We used a vertical prism adaptation paradigm to investigate which of these throwing parameters subjects use when adapting to external perturbation. Our subjects showed no correlation between hand position or hand translational velocity and ball impact height in normal, over-practiced throwing. However, video-based motion analysis showed that modifications both of position and speed of the hand play an important role when subjects are forced to compensate for a vertically shifting prism perturbation during a dart-like throw (these factors contribute approximately 30% of the adaptation). We concluded that, during adaptation, more degrees of freedom and more sources of potential error are modified to achieve the gaze-throw recalibration required to hit the target than are employed in this type of throw during normal conditions.     

Interferences with potentiometry of CO2 in the Ektachem 400 Analyzer

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.     

Nonstandard Lumbar Region in Predicting Fracture Risk

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1–L2 BMD with standard L2–L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60?yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1–L2, L2–L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11?±?7?yr. L1–L2 BMD T-score was significantly lower than L2–L4 T-score in both genders (p?<?0.0001). L1–L2 and L2–L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68–0.79) vs 0.68 (95% confidence interval, 0.62–0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1–L2 or L2–L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p?<?0.05). In an elderly population, L1–L2 is as good as but not better than L2–L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed.     

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.