An Analysis of Variability in “CatWalk” Locomotor Measurements to Aid Experimental Design and Interpretation
Open Access
- 9 July 2020
- journal article
- research article
- Published by Society for Neuroscience in eneuro
- Vol. 7 (4)
Abstract
Preclinical studies in models of neurologic injury and disease rely on behavioral outcomes to measure intervention efficacy. For spinal cord injury, the CatWalk system provides unbiased quantitative assessment of subtle aspects of locomotor function in rodents and so can powerfully detect significant differences between experimental and control groups. Although clearly of key importance, summary group-level data can obscure the variability within and between individual subjects and therefore make it difficult to understand the magnitude of effect in individual animals and the proportion of a group that may show benefit. Here, we calculate reference change intervals (RCIs) that define boundaries of normal variability for measures of rat locomotion on the CatWalk. Our results indicate that many commonly-used outcome measures are highly variable, such that differences of up to 70% from baseline value must be considered normal variation. Many CatWalk outcome variables are also highly correlated and dependent on run speed. Application of calculated RCIs to open access data (https://scicrunch.org/odc-sci) on hindlimb stride length in spinal cord-injured rats illustrates the complementarity between group-level (16 mm change;p = 0.0009) and individual-level (5/32 animals show change outside RCI boundaries) analysis between week 3 and week 6 after injury. We also conclude that interdependence among CatWalk variables implies that test “batteries” require careful composition to ensure that different aspects of defective gait are analyzed. Calculation of RCIs aids in experimental design by quantifying variability and enriches overall data analysis by providing details of change at an individual level that complement group-level analysis.Keywords
This publication has 31 references indexed in Scilit:
- Derivation of Multivariate Syndromic Outcome Metrics for Consistent Testing across Multiple Models of Cervical Spinal Cord Injury in RatsPLOS ONE, 2013
- Confidence Intervals and Power Calculations for Within-Person Biological Variation: Effect of Analytical Imprecision, Number of Replicates, Number of Samples, and Number of IndividualsClinical Chemistry, 2012
- Outcome Measures for Acute/Subacute Cervical Sensorimotor Complete (AIS-A) Spinal Cord Injury During a Phase 2 Clinical TrialTopics in Spinal Cord Injury Rehabilitation, 2012
- Reference Change Values for Brain Natriuretic Peptides RevisitedClinical Chemistry, 2006
- The Assessment of Locomotor Function in Spinal Cord Injured Rats: The Importance of Objective Analysis of CoordinationJournal of Neurotrauma, 2005
- The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variationScandinavian Journal of Clinical and Laboratory Investigation, 2004
- Designing a research project: randomised controlled trials and their principlesEmergency Medicine Journal, 2003
- Automated Quantitative Gait Analysis During Overground Locomotion in the Rat: Its Application to Spinal Cord Contusion and Transection InjuriesJournal of Neurotrauma, 2001
- A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in RatsJournal of Neurotrauma, 1995
- Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.Stroke, 1986