Browsing by Subject "Locomotion"

Now showing 1 - 10 of 14
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    Chx10+V2a interneurons in spinal motor regulation and spinal cord injury
    (Wolters Kluwer, 2023) Li, Wen-Yuan; Deng, Ling-Xiao; Zhai, Feng-Guo; Wang, Xiao-Yu; Li, Zhi-Gang; Wang, Ying; Neurological Surgery, School of Medicine
    Chx10-expressing V2a (Chx10+V2a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2a interneurons also play an important role in rhythmic patterning maintenance, left-right alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2a interneurons transplanted in spinal cord injury foci.
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    Gains in Daily Stepping Activity in People With Chronic Stroke After High-Intensity Gait Training in Variable Contexts
    (Oxford University Press, 2022) Hornby, T. George; Plawecki, Abbey; Lotter, Jennifer K.; Scofield, Molly E.; Lucas, Emily; Henderson, Christopher E.; Physical Medicine and Rehabilitation, School of Medicine
    Objective: Many physical therapist interventions provided to individuals with chronic stroke can lead to gains in gait speed or endurance (eg, 6-Minute Walk Test [6MWT]), although changes in objective measures of participation are not often observed. The goal of this study was to determine the influence of different walking interventions on daily stepping (steps per day) and the contributions of demographic, training, and clinical measures to these changes. Methods: In this secondary analysis of a randomized clinical trial, steps per day at baseline and changes in steps per day following 1 of 3 locomotor interventions were evaluated in individuals who were ambulatory and >6 months after stroke. Data were collected on 58 individuals who received ≤30 sessions of high-intensity training (HIT) in variable contexts (eg, tasks and environments; n = 19), HIT focused on forward walking (n = 19), or low-intensity variable training (n = 20). Primary outcomes were steps per day at baseline, at post-training, and at a 3-month follow-up, and secondary outcomes were gait speed, 6MWT, balance, and balance confidence. Correlation and regression analyses identified demographic and clinical variables associated with steps per day. Results: Gains in steps per day were observed across all groups combined, with no between-group differences; post hoc within-group analyses revealed significant gains only following HIT in variable contexts. Both HIT groups showed gains in endurance (6MWT), with increases in balance confidence only following HIT in variable contexts. Changes in steps per day were associated primarily with gains in 6MWT, with additional associations with baseline 6MWT, lower-extremity Fugl-Meyer scores, and changes in balance confidence. Conclusion: HIT in variable contexts elicited gains in daily stepping, with changes primarily associated with gains in gait endurance. Impact: Providing HIT in variable contexts appears to improve measures of participation (eg, daily stepping) that may be associated with clinical measures of function. Gains in multiple measures of mobility and participation with HIT in variable contexts may improve the efficiency and value of physical therapy services.
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    High intensity variable stepping training in persons with motor incomplete spinal cord injury: a case series
    (Lippincott, Williams & Wilkins, 2020-04-05) Holleran, Carey L.; Hennessey, Patrick W.; Leddy, Abigail L.; Mahtani, Gordhan B.; Brazg, Gabrielle; Schmit, Brian D.; Hornby, T. George; Physical Medicine and Rehabilitation, School of Medicine
    Background and Purpose: Previous data suggest that large amounts of high intensity stepping training in variable contexts (tasks and environments) may improve locomotor function, aerobic capacity and treadmill gait kinematics in individuals post-stroke. Whether similar training strategies are tolerated and efficacious for patients with other acute-onset neurological diagnoses, such as motor incomplete spinal cord injury (iSCI) is unknown, particularly with potentially greater, bilateral impairments. This case series evaluated the feasibility and preliminary short and long-term efficacy of high intensity variable stepping practice in ambulatory participants >1 year post-iSCI. Case Series Description: Four participants with iSCI (neurological levels C5-T3) completed up to 40 1-hr sessions over 3–4 months. Stepping training in variable contexts was performed at up to 85% maximum predicted heart rate, with feasibility measures of patient tolerance, total steps/session, and intensity of training. Clinical measures of locomotor function, balance, peak metabolic capacity and gait kinematics during graded treadmill assessments were performed at baseline and post-training, with >1 year follow-up. Outcomes: Participants completed 24–40 sessions over 8–15 weeks, averaging 2222±653 steps/session, with primary adverse events of fatigue and muscle soreness. Modest improvements in locomotor capacity where observed at post-training, with variable changes in lower extremity kinematics during treadmill walking. Discussion: High intensity, variable stepping training was feasible and tolerated by participants with iSCI although only modest gains in gait function or quality were observed. The utility of this intervention in patients with more profound impairments may be limited.
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    Increasing the Amount and Intensity of Stepping Training During Inpatient Stroke Rehabilitation Improves Locomotor and Non-Locomotor Outcomes
    (Sage, 2022) Henderson, Christopher E.; Plawecki, Abbey; Lucas, Emily; Lotter, Jennifer K.; Scofield, Molly; Carbone, Angela; Jang, Jeong H.; Hornby, T. George Hornby; FIRST-Indiana team; Baumgartner, Christina; Breuninger, William; England, Emily; Keys, Amanda; Meier, Jennifer; Nobbe, Carolyn; Pylitt, Alison; Shoger, Lindsay; Wilkie, Kelly; Physical Medicine and Rehabilitation, School of Medicine
    Background: The efficacy of traditional rehabilitation interventions to improve locomotion post-stroke, including providing multiple exercises targeting impairments and activity limitations, is uncertain. Emerging evidence rather suggests attempts to prioritize stepping practice at higher cardiovascular intensities may facilitate greater locomotor outcomes. Objective: The present study was designed to evaluate the comparative effectiveness of high-intensity training (HIT) to usual care during inpatient rehabilitation post-stroke. Methods: Changes in stepping activity and functional outcomes were compared over 9 months during usual-care (n = 131 patients < 2 months post-stroke), during an 18-month transition phase with attempts to implement HIT (n = 317), and over 12 months following HIT implementation (n = 208). The transition phase began with didactic and hands-on education, and continued with meetings, mentoring, and audit and feedback. Fidelity metrics included percentage of sessions prioritizing gait interventions and documenting intensity. Demographics, training measures, and outcomes were compared across phases using linear or logistic regression analysis, Kruskal-Wallis tests, or χ2 analysis. Results: Across all phases, admission scores were similar except for balance (usual-care>HIT; P < .02). Efforts to prioritize stepping and achieve targeted intensities during HIT vs transition or usual-care phases led to increased steps/day (P < .01). During HIT, gains in 10-m walk [HIT median = 0.13 m/s (interquartile range: 0-0.35) vs usual-care = 0.07 m/s (0-0.24), P = .01] and 6-min walk [50 (9.3-116) vs 2.1 (0-56) m, P < .01] were observed, with additional improvements in transfers and stair-climbing. Conclusions: Greater efforts to prioritize walking and reach higher intensities during HIT led to increased steps/day, resulting in greater gains in locomotor and non-locomotor outcomes.
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    Influence of skill and exercise training parameters on locomotor recovery during stroke rehabilitation
    (Wolters Kluwer, 2016-12) Hornby, T. George; Moore, Jennifer L.; Lovell, Linda; Roth, Elliot J.; Physical Medicine and Rehabilitation, School of Medicine
    Purpose of review: Research findings from the fields of motor learning and exercise physiology suggest specific training parameters that can be manipulated during physical rehabilitation profoundly influence skilled task performance. This review details the rationale for some of these training variables and their application in selected intervention studies focused on improving walking function in patients poststroke. Recent findings: Basic and applied studies have shown that the amount, intensity, and variability of specific task practice applied during rehabilitation interventions can affect recovery of walking poststroke. Many studies detailing the effects of conventional, therapist, and mechanically assisted interventions may incorporate some of these training parameters but minimize others, and their relative contributions may influence walking outcomes. Specific patient factors, such as the stroke acuity and degree of impairments, appear to influence the relative contributions of these training variables, and different patient subgroups may benefit from greater emphasis on specific parameters. Summary: The present findings suggest these training parameters should be considered when evaluating or implementing physical interventions directed toward improving locomotor function poststroke. More work is needed to understand their optimal combinations to maximize walking outcomes in patients with different levels of impairment poststroke.
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    Inhibition of the dorsomedial hypothalamus, but not the medullary raphe pallidus, decreases hyperthermia and mortality from MDMA given in a warm environment.
    (Wiley, 2014-04) Zaretsky, Dmitry V.; Zaretskaia, Maria V.; Durant, Pamela J.; Rusyniak, Daniel E.; Department of Medicine, IU School of Medicine
    The central mechanisms through which MDMA mediates life-threatening hyperthermia when taken in a warm environment are not well described. It is assumed that MDMA alters normal thermoregulatory circuits resulting in increased heat production through interscapular brown adipose tissue (iBAT) and decreased heat dissipation through cutaneous vasoconstriction. We studied the role of the dorsomedial hypothalamus (DMH) and medullary raphe pallidus (mRPa) in mediating iBAT, tail blood flow, and locomotor effects produced by MDMA. Rats were instrumented with guide cannulas targeting either the DMH or the mRPa-brain regions involved in regulating iBAT and cutaneous vascular beds. In all animals, core temperature and locomotion were recorded with surgically implanted telemetric transmitters; and additionally either iBAT temperature (via telemetric transmitter) or tail artery blood flow (via tail artery Doppler cuff) were also recorded. Animals were placed in an environmental chamber at 32°C and microinjected with either control or the GABA agonist muscimol (80pmol) followed by an intravenous injection of saline or MDMA (7.5 mg kg-1). To prevent undue suffering, a core temperature of 41°C was chosen as the surrogate marker of mortality. Inhibition of the DMH, but not the mRPa, prevented mortality and attenuated hyperthermia and locomotion. Inhibition of either the DMH or the mRPa did not affect iBAT temperature increases or tail blood flow decreases. While MDMA increases iBAT thermogenesis and decreases heat dissipation through cutaneous vasoconstriction, thermoregulatory brain regions known to mediate these effects are not involved. Rather, the finding that inhibiting the DMH decreases both locomotion and body temperature suggests that locomotion may be a key central contributor to MDMA-evoked hyperthermia.
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    Rethinking the tools in the toolbox
    (BMC, 2022-06-20) Hornby, T. George; Physical Medicine and Rehabilitation, School of Medicine
    The commentary by Dr. Labruyere on the article by Kuo et al. (J Neuroeng Rehabil. 2021; 18:174) posits that randomized trials evaluating the comparative efficacy of robotic devices for patients with neurological injury may not be needed. The primary argument is that researchers and clinicians do not know how to optimize training parameters to maximize the benefits of this therapy, and studies vary in how they deliver robotic-assisted training. While I concur with the suggestion that additional trials using robotic devices as therapeutic tools are not warranted, an alternative hypothesis is that future studies will yield similar equivocal results regardless of the training parameters used. Attempts are made to detail arguments supporting this premise, including the notion that the original rationale for providing robotic-assisted walking training, particularly with exoskeletal devices, was flawed and that the design of some of the more commonly used devices places inherent limitations on the ability to maximize neuromuscular demands during training. While these devices arrived nearly 20 years ago amid substantial enthusiasm, we have since learned valuable lessons from robotic-assisted and other rehabilitation studies on some of the critical parameters that influence neuromuscular and cardiovascular activity during locomotor training, and different strategies are now needed to optimize rehabilitation outcomes.
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    Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC)
    (Springer Nature, 2018-05) Kasten, Chelsea R.; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L., II; Psychology, School of Science
    Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.
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    Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol
    (Oxford University Press, 2020-08-14) Hauser, Sheketha R.; Smith, Rebecca J.; Toalston, Jamie E.; Rodd, Zachary A.; McBride, William J.; Bell, Richard L.; Psychiatry, School of Medicine
    Aims: Abstinence after chronic alcohol consumption leads to withdrawal symptoms, which are exacerbated after repeated cycles of relapse. This study examined withdrawal-like behaviors after chronic ethanol drinking, with or without repeated cycles of deprivation. Methods: Male alcohol-preferring (P) rats had access to continuous ethanol (CE), chronic ethanol with repeated deprivation (RD), or remained ethanol naïve (EN). The RD group experienced seven cycles of 2 weeks of deprivation and 2 weeks of re-exposure to ethanol after an initial 6 weeks of ethanol access. Withdrawal was measured after an initial 24 h of ethanol re-exposure in the RD group, which coincided with the same day of ethanol access in the CE group. Withdrawal-like behavior was measured by (a) ethanol intake during the initial 24 h of re-exposure, (b) locomotor activity (LMA) in a novel field 9-13 h after removal of ethanol at the beginning of the fifth re-exposure cycle and (c) acoustic startle responding (ASR) 8-15 h after removal of ethanol at the beginning of the sixth re-exposure cycle. Results: The RD rats displayed a 1-h alcohol deprivation effect (ADE) (temporary ethanol increase), relative to CE rats, during the first to fourth and seventh re-exposure cycles. RD and CE rats displayed significant increases in LMA than EN rats. Regarding ASR, RD rats displayed significantly greater ASR relative to EN rats. Conclusion: This study confirms that P rats meet the animal model criterion for ethanol-associated dependence, without a reliance on either behavioral (limited fluid access) or pharmacological (seizure threshold manipulation) challenges.