Evaluating Skilled Prehension in Mice Using an Auto-Trainer.

We describe a method to introduce naïve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to encourage the mice to perform the food retrieval from the slot. As the mice begin to associate coming to the slot for food, the pellets are manually pulled away to stimulate extension and pronation of their paw to grasp and retrieve the pellet through the frontal slot. When the mice begin to reach for the pellets as they arrive at the slot, the behavioral assay can be performed by measuring the rate at which they successfully grasp and retrieve the desired pellet. They are then introduced to an auto-trainer that automates both the process of providing food pellets for the mouse to grasp, and the recording of successful and failed reaching and grasping attempts. This allows for the collection of reaching data for multiple mice with minimal effort, to be used in experimental analysis as appropriate.

Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions.

Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection.

Diversity in the magnitude of hind limb unloading occurs with similar forms of lameness in dairy cows.

The objective of the study was to evaluate the relationship of veterinary clinical assessments of lameness to probability estimates of lameness predicted from vertical kinetic measures. We hypothesized that algorithm-derived probability estimates of lameness would accurately reflect vertical measures in lame limbs even though vertical changes may not inevitably occur in all lameness. Kinetic data were collected from sound (n=179) and unilaterally lame (n=167) dairy cattle with a 1-dimensional, parallel force plate system that registered vertical ground reaction force signatures of all four limbs as cows freely exited the milking parlour. Locomotion was scored for each hind limb using a 1-5 locomotion score system (1=sound, 5=severely lame). Pain response in the interdigital space was quantified with an algometer and pain response in the claw was quantified with a hoof tester fitted with a pressure gage. Lesions were assigned severity scores (1=minimal pathology to 5=severe pathology). Lameness diminished the magnitude of peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses in the lame limbs of unilaterally lame cows. The only effect of lameness on the opposite sound limb was increased magnitude of stance times and vertical impulses in unilaterally lame cows. Symmetry measures of the peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses between the left and right hind limbs were also affected in unilateral lameness. Paradoxically, limbs with clinically similar lesion and locomotion scores and pain responses were associated with a broad range of load-transfer off the limb. Substantial unloading and changes in the vertical limb variables occurred in some lameness while minimal unloading and changes in vertical limb variables occurred in other lameness. Corresponding probability estimates of lameness accurately reflected changes in the vertical parameters of limbs and generated low probability estimates of lameness when minimal unloading occurred. Failure to transfer load off limbs with pain reactions, locomotion abnormalities and lesions explained much of the limited sensitivity in lameness detection with vertical limb variables.

Locomotion analysis of Sprague-Dawley rats before and after injecting 6-OHDA.

The hypothesis that changes in measured ground reaction forces and time parameters during locomotion can noninvasively detect Parkinsonism in unilateral 6-OH dopamine (6-OHDA) lesioned rats is tested. It was found that changes of seven locomotion parameters can be used to construct a logistic regression model with a detection sensitivity and specificity of over 90% as compared to non-lesioned rats. Comparisons between this model and other neurological and neuromuscular disorders are presented.

Gait analysis of locomotory impairment in rats before and after neuromuscular injury.

We used a gait analysis system (GAS) to measure the changes in locomotion parameters of adult Sprague-Dawley rats after neuromuscular injury, induced by repeated large-strain lengthening contractions of the dorsiflexors muscles. We developed a logistic regression model from test runs of control and permanently impaired (denervation of the dorsiflexor muscles) rats and used this model to predict the probabilities of locomotory impairment in rats injured by lengthening contractions. The data showed that GAS predicts the probability of locomotory impairment with very high reliability, with values close to 100% immediately after injury and close to 0% after several weeks of recovery from injury. The six transformed locomotion parameters most effective in the model were in three domains: frequency, force, and time. We conclude that application of the GAS instrument with our predictive model accurately identifies locomotory changes due to neuromuscular deficits. Use of this technology should be valuable for monitoring the progression of a neuromuscular disease and the effects of therapeutic interventions.

Measuring early pre-symptomatic changes in locomotion of SOD1-G93A rats--a rodent model of amyotrophic lateral sclerosis.

A locomotion analysis system for laboratory rats is presented. The system produces locomotion parameters (LPs) in 4 different domains: force, space, time and frequency. Video images of the walking rats are used to associate the system signals with individual limbs. Numerous LPs can be derived for every test run when the rat walks through the system on the way to sweets and a personal toy placed at the exit. This manuscript demonstrates that in order to differentiate SOD1-G93A mutant rat, a model of amyotrophic lateral sclerosis (ALS), from a Sprague Dawley (SD) control rat at a pre-symptomatic stage, one has only to use 8 key parameters. These 8 parameters are the bio-markers of ALS. The spline-based transformed values of these parameters are used as explanatory variables of a logistic regression model. This model predicts the probability that the examined rat belongs to the SOD1-G93A group. The model differentiates faultlessly between the SOD1 and control groups from the very first time the rats walked through the system at 51 days old. This system provides a new paradigm for ALS diagnosis, and it can have a significant impact on the development of new therapeutic procedures for ALS. The methodology presented in this manuscript can further address the development and validation of therapeutic procedures for other neurological diseases that affect locomotion.