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Item Contributions of Stepping Intensity and Variability to Mobility in Individuals Poststroke(American Heart Association, 2019-08-22) Hornby, T. George; Henderson, Christopher E.; Plawecki, Abbey; Lucas, Emily; Lotter, Jennifer; Holthus, Molly; Brazg, Gabrielle; Fahey, Meghan; Woodward, Jane; Ardestani, Marzieh; Roth, Elliot J.; Physical Medicine and Rehabilitation, School of MedicineBackground and Purpose: The amount of task-specific stepping practice provided during rehabilitation post-stroke can influence locomotor recovery, and reflects one aspect of exercise “dose” that can affect the efficacy of specific interventions. Emerging data suggest that markedly increasing the intensity and variability of stepping practice may also be critical, although such strategies are discouraged during traditional rehabilitation. The goal of this study was to determine the individual and combined contributions of intensity and variability of stepping practice to improving walking speed and distance in individuals post-stroke. Methods: This Phase 2, randomized, blinded assessor clinical trial was performed between May 2015-November 2018. Individuals between 18-85 years old with hemiparesis post-stroke of >6 months duration were recruited. Of the 152 individuals screened, 97 were randomly assigned to 1 of 3 training groups, with 90 completing >10 sessions. Interventions consisted of either high intensity stepping (70-80% heart rate [HR] reserve) of variable, difficult stepping tasks (high-variable), high intensity stepping performing only forward walking (high-forward), and low intensity stepping in variable contexts at 30-40% HR reserve (low-variable). Participants received up to 30 sessions over 2 months, with testing at baseline, post-training and a 3-month follow-up. Primary outcomes included walking speeds and timed distance, with secondary measures of dynamic balance, transfers, spatiotemporal kinematics and metabolic measures. Results: All walking gains were significantly greater following either high-intensity group vs low-variable training (all p<0.001) with significant correlations with stepping amount and rate (r=0.48-60; p<0.01). Additional gains in spatiotemporal symmetry were observed with high-intensity training, and balance confidence increased only following high-variable training in individuals with severe impairments. Conclusion: High intensity stepping training resulted in greater improvements in walking ability and gait symmetry than low-intensity training in individuals with chronic stroke, with potential greater improvements in balance confidence.Item Mechanisms of Left-Right Coordination in Mammalian Locomotor Pattern Generation Circuits: A Mathematical Modeling View(PLoS, 2015-05) Molkov, Yaroslav I.; Bacak, Bartholomew J.; Talpalar, Adolfo E.; Rybak, Ilya A.; Department of Mathematical Sciences, School of ScienceThe locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed. Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Recent studies demonstrated that genetic elimination of all V0 CINs caused switching from a normal left-right alternating activity to a left-right synchronized “hopping” pattern. Furthermore, ablation of only the inhibitory V0 CINs (V0D subtype) resulted in a lack of left-right alternation at low locomotor frequencies and retaining this alternation at high frequencies, whereas selective ablation of the excitatory V0 neurons (V0V subtype) maintained the left–right alternation at low frequencies and switched to a hopping pattern at high frequencies. To analyze these findings, we developed a simplified mathematical model of neural circuits consisting of four pacemaker neurons representing left and right, flexor and extensor rhythm-generating centers interacting via commissural pathways representing V3, V0D, and V0V CINs. The locomotor frequency was controlled by a parameter defining the excitation of neurons and commissural pathways mimicking the effects of N-methyl-D-aspartate on locomotor frequency in isolated rodent spinal cord preparations. The model demonstrated a typical left-right alternating pattern under control conditions, switching to a hopping activity at any frequency after removing both V0 connections, a synchronized pattern at low frequencies with alternation at high frequencies after removing only V0D connections, and an alternating pattern at low frequencies with hopping at high frequencies after removing only V0V connections. We used bifurcation theory and fast-slow decomposition methods to analyze network behavior in the above regimes and transitions between them. The model reproduced, and suggested explanation for, a series of experimental phenomena and generated predictions available for experimental testing.Item The Need for Speed in Rodent Locomotion Analyses.(Wiley, 2014-10) Batka, Richard J.; Brown, Todd J.; Mcmillan, Kathryn P.; Meadows, Rena M.; Jones, Kathryn J.; Haulcomb, Melissa M.; Department of Anatomy & Cell Biology, IU School of MedicineLocomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed.Item Predicting Discharge Walking Function With High-Intensity Stepping Training During Inpatient Rehabilitation in Nonambulatory Patients Poststroke(Elsevier, 2020) Henderson, Christopher E.; Fahey, Megan; Brazg, Gabi; Moore, Jennifer L.; Hornby, T. George; Physical Medicine and Rehabilitation, School of MedicineObjective This cohort investigation identified primary predictors of discharge walking function of nonambulatory individuals poststroke with high-intensity training (HIT) during inpatient rehabilitation. Design Observational cohort investigation. Setting Inpatient rehabilitation. Participants Data were collected from individuals (N=257) <6 months poststroke who required assistance to walk at admission. Intervention Clinical physical therapy interventions attempted to maximize stepping practice at higher intensities. Main Outcome Measures Primary outcomes included the discharge level of assistance required during walking (minimal or no assistance) and attainment of specific gait speed thresholds (0.4 and 0.8 m/s) during the 10-m walk test. Independent predictors were demographics, training interventions (including steps/day), baseline Berg Balance Scale (BBS), and paretic leg strength. Results Participants performed a median (interquartile range) of 1270 (533-2297) steps per day throughout inpatient rehabilitation, with significant differences between those who walked with versus without assistance at discharge. Logistic regressions indicate steps per day was a primary predictor of unassisted walking recovery; removal of steps per day resulted in primary predictors of baseline BBS and strength. Receiver operating characteristic (ROC) analyses indicate significant areas under the curve for BBS and relatively low cutoff scores of 5.5 points at admission to walk without assistance at any speed. ROC analyses performed using 1-week outcomes indicate BBS scores of 5-17 points were needed to achieve locomotor thresholds. Conclusion Stepping activity, BBS, and paretic leg strength were primary predictors of walking outcomes in patients performing HIT, and ROC analyses indicated recovery of independent walking could be achieved in low functioning patients early poststroke.Item Tester and testing procedure influence clinically determined gait speed(Elsevier, 2019-10-01) Warden, Stuart J.; Kemp, Allie C.; Liu, Ziyue; Moe, Sharon M.; Physical Therapy, School of Health and Human SciencesBackground: There is a clinical need to be able to reliably detect meaningful changes (0.1 to 0.2 m/s) in usual gait speed (UGS) considering reduced gait speed is associated with morbidity and mortality. Research question: What is the impact of tester on UGS assessment, and the influence of test repetition (trial 1 vs. 2), timing method (manual stopwatch vs. automated timing), and starting condition (stationary vs. dynamic start) on the ability to detect changes in UGS and fast gait speed (FGS)? Methods: UGS and FGS was assessed in 725 participants on a 8-m course with infrared timing gates positioned at 0, 2, 4 and 6 m. Testing was performed by one of 13 testers trained by a single researcher. Time to walk 4-m from a stationary start (i.e. from 0-m to 4-m) was measured manually using a stopwatch and automatically via the timing gates at 0-m and 4-m. Time taken to walk 4-m with a dynamic start was measured during the same trial by recording the time to walk between the timing gates at 2-m and 6-m (i.e. after 2-m acceleration). Results: Testers differed for UGS measured using manual vs. automated timing (p=0.02), with five and two testers recording slower and faster UGS using manual timing, respectively. 95% limits of agreement for trial 1 vs. 2, manual vs. automated timing, and dynamic vs. stationary start ranged from ±0.15 m/s to ±0.20 m/s, coinciding with the range for a clinically meaningful change. Limits of agreement for FGS were larger ranging from ±0.26 m/s to ±0.35 m/s. Significance: Repeat testing of UGS should performed by the same tester or using an automated timing method to control for tester effects. Test protocol should remain constant both between and within participants as protocol deviations may result in detection of an artificial clinically meaningful change.