General Locomotor Research Articles

Spatial Contraction Based on Velocity Variation for Natural Walking in Virtual Reality.

Virtual Reality (VR) offers an immersive 3D digital environment, but enabling natural walking sensations without the constraints of physical space remains a technological challenge. Previous VR locomotion methods, including game controller, teleportation, treadmills, walking-in-place, and redirected walking (RDW), have made strides towards overcoming this challenge. However, these methods also face limitations such as possible unnaturalness, additional hardware requirements, or motion sickness risks. This paper introduces "Spatial Contraction (SC)", an innovative VR locomotion method inspired by the phenomenon of Lorentz contraction in Special Relativity. Similar to the Lorentz contraction, our SC contracts the virtual space along the user's velocity direction in response to velocity variation. The virtual space contracts more when the user's speed is high, whereas minimal or no contraction happens at low speeds. We provide a virtual space transformation method for spatial contraction and optimize the user experience in smoothness and stability. Through SC, VR users can effectively traverse a longer virtual distance with a shorter physical walking. Different from locomotion gains, the spatial contraction effect is observable by the user and aligns with their intentions, so there is no inconsistency between the user's proprioception and visual perception. SC is a general locomotion method that has no special requirements for VR scenes. The experimental results of our live user studies in various virtual scenarios demonstrate that SC has a significant effect in reducing both the number of resets and the physical walking distance users need to cover. Furthermore, experiments have also demonstrated that SC has the potential for integration with existing locomotion techniques such as RDW.

Organization of spontaneous spatial behaviors under dark conditions is unaffected in adult male and female long-Evans rats after moderate prenatal alcohol exposure.

Prenatal alcohol exposure can produce disruptions in a wide range of cognitive functions, but it is especially detrimental to spatial navigation. In open environments, rodents organize their spatial behaviors around centralized locations, termed home bases, from which they make circuitous and slow locomotor trips (progressions) into the rest of the environment. Open-field behaviors are organized even under darkened test conditions, suggesting a role for self-motion cues (vestibular, motor, etc.). The impact of moderate prenatal alcohol exposure (mPAE) on the organization of spontaneous open-field behaviors under darkened conditions has not been investigated. Here we tested adult female and male rats with mPAE or saccharin control exposure in a circular open field for 30 min in a testing room that was made completely dark. While general locomotion, as measured by reductions in travel distance and increased stop duration, decreased across the test session, the organization of these behaviors, as measured by stop duration, home base establishment, home base stability, progression accuracy, and scaling of peak speeds with progression length, did not differ between mPAE and saccharin control rats. Together, the findings strongly suggest that spontaneous movement organization in relation to self-motion cues remains intact in adult mPAE rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The generalized spring-loaded inverted pendulum model for analysis of various planar reduced-order models and for optimal robot leg design

This paper proposes a generalized spring-loaded inverted pendulum (G-SLIP) model to explore various popular reduced-order dynamic models’ characteristics and suggest a better robot leg design under specified performance indices. The G-SLIP model’s composition can be varied by changing the model’s parameters, such as ground contacting type and spring property. It can be transformed into four widely used models: the spring-loaded inverted pendulum (SLIP) model, the two-segment leg model, the SLIP with rolling foot model, and the rolling SLIP model. The effects of rolling contact and spring configuration on the dynamic behavior and fixed-point distribution of the G-SLIP model were analyzed, and the basins of attraction of the four described models were studied. By varying the parameters of the G-SLIP model, the dynamic behavior of the model can be optimized. Optimized for general locomotion running at various speeds, the model provided leg design guidelines. The leg was empirically fabricated and installed on the hexapod for experimental evaluation. The results indicated that the robot with a designed leg runs faster and is more power-efficient.

Neural Endophenotype Assessment in Zebrafish Larvae Using Optomotor and ZebraBox Locomotion Assessment.

Due to the highly conserved genetics across the central nervous system, the easily probed visual system can act as an endophenotype for assessing neurological function. Here, we describe a psychophysics approach to assess visually driven swimming behavior in the high-throughput zebrafish genetic model system. We use the optomotor response test together with general locomotion behavior to assess neural processing while excluding motor defects related to muscle function.

Effect Sizes of Cognitive and Locomotive Behavior Tests in the 5XFAD-J Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid β (Aβ) plaques in the brain, leading to cognitive impairment and other clinical symptoms. The 5XFAD mouse model is commonly used in AD research because it expresses five human transgenes that result in the accumulation of Aβ plaques and cognitive decline at a relatively early age. Behavioral experiments are frequently conducted using this model; however, the effect size has not yet been reported. In this study, we examined basic cognition and locomotion in 5XFAD mice with a C57BL6/J background (5XFAD-J) at 6 months of age, a period in which impairments of cognitive function and locomotion are commonly observed. We analyzed the effect sizes of cognitive and locomotive experiments in the 5XFAD mice compared with those in the wild-type mice. Our results suggest that for long-term memory analysis, the novel object recognition test (p = 0.013, effect size 1.24) required a sample size of at least 12 to obtain meaningful results. Moreover, analysis of general locomotion over total distance with the Laboratory Animal Behavior Observation, Registration and Analysis System (LABORAS) test during the dark phase (p = 0.007, effect size -1.37) needed a sample size of 10 for a statistical power (1-β) of 0.8. In conclusion, we can conduct more ethical and scientifically rigorous animal experiments using 5XFAD mice based on the effect and sample sizes suggested in this study.

Enhanced TrkA signaling impairs basal forebrain-dependent behavior.

Basal forebrain cholinergic neurons (BFCNs) modulate cognitive functions such as attention, learning and memory. The NGF/TrkA pathway plays an important role in the development and function of BFCNs, although two mouse models conditionally deleting TrkA expression in the central nervous system (CNS) have shown contradictory results. To shed light into this discrepancy, we used a mouse model with a gain-of-function in TrkA receptor signaling. Our results indicate that enhanced TrkA signaling did not alter hippocampal cholinergic innervation, general locomotion or anxiety-related behaviors, but it increases ChAT expression, the number of cholinergic neurons at early postnatal stages and, mutant mice showed impaired motor learning and memory functions. These data demonstrate that proper functioning of the cholinergic system in CNS requires a balanced NGF/TrkA signaling.

Controlling the Solo12 quadruped robot with deep reinforcement learning.

Quadruped robots require robust and general locomotion skills to exploit their mobility potential in complex and challenging environments. In this work, we present an implementation of a robust end-to-end learning-based controller on the Solo12 quadruped. Our method is based on deep reinforcement learning of joint impedance references. The resulting control policies follow a commanded velocity reference while being efficient in its energy consumption and easy to deploy. We detail the learning procedure and method for transfer on the real robot. We show elaborate experiments. Finally, we present experimental results of the learned locomotion on various grounds indoors and outdoors. These results show that the Solo12 robot is a suitable open-source platform for research combining learning and control because of the easiness in transferring and deploying learned controllers.

There are unique kinematics during locomotor transitions between level ground and stair ambulation that persist with increasing stair grade

Human ambulation is typically characterized during steady-state isolated tasks (e.g., walking, running, stair ambulation). However, general human locomotion comprises continuous adaptation to the varied terrains encountered during activities of daily life. To fill an important gap in knowledge that may lead to improved therapeutic and device interventions for mobility-impaired individuals, it is vital to identify how the mechanics of individuals change as they transition between different ambulatory tasks, and as they encounter terrains of differing severity. In this work, we study lower-limb joint kinematics during the transitions between level walking and stair ascent and descent over a range of stair inclination angles. Using statistical parametric mapping, we identify where and when the kinematics of transitions are unique from the adjacent steady-state tasks. Results show unique transition kinematics primarily in the swing phase, which are sensitive to stair inclination. We also train Gaussian process regression models for each joint to predict joint angles given the gait phase, stair inclination, and ambulation context (transition type, ascent/descent), demonstrating a mathematical modeling approach that successfully incorporates terrain transitions and severity. The results of this work further our understanding of transitory human biomechanics and motivate the incorporation of transition-specific control models into mobility-assistive technology.

Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model.

Disruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model. Female Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet & dry weight and immunohistological analyses were conducted. Substance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters. Intrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery.

Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding

Psilocybin and its active metabolite psilocin have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not in females, as early as 2 days and lasting to 28 days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.

Hierarchical path planning for multi-arm spacecraft with general translational and rotational locomotion mode

Hierarchical path planning for multi-arm spacecraft with general translational and rotational locomotion mode

Wrk-1 and rig-5 control pioneer and follower axon navigation in the ventral nerve cord of Caenorhabditis elegans in a nid-1 mutant background.

During nervous system development, neurons send out axons, which must navigate large distances to reach synaptic targets. Axons grow out sequentially. The early outgrowing axons, pioneers, must integrate information from various guidance cues in their environment to determine the correct direction of outgrowth. Later outgrowing follower axons can at least in part navigate by adhering to pioneer axons. In Caenorhabditis elegans, the right side of the largest longitudinal axon tract, the ventral nerve cord, is pioneered by the AVG axon. How the AVG axon navigates is only partially understood. In this study, we describe the role of two members of the IgCAM family, wrk-1 and rig-5, in AVG axon navigation. While wrk-1 and rig-5 single mutants do not show AVG navigation defects, both mutants have highly penetrant pioneer and follower navigation defects in a nid-1 mutant background. Both mutations increase the fraction of follower axons following the misguided pioneer axon. We found that wrk-1 and rig-5 act in different genetic pathways, suggesting that we identified two pioneer-independent guidance pathways used by follower axons. We assessed general locomotion, mechanosensory responsiveness, and habituation to determine whether axonal navigation defects impact nervous system function. In rig-5 nid-1 double mutants, we found no significant defects in free movement behavior; however, a subpopulation of animals shows minor changes in response duration habituation after mechanosensory stimulation. These results suggest that guidance defects of axons in the motor circuit do not necessarily lead to major movement or behavioral defects but impact more complex behavioral modulation.

Analyzing Turning Behavior after Repeated Lithium, Ketamine, or NaCl Injection and Chronic Stress Exposure in Mice

A single chronic stress is often considered a potential reinforcer in psychiatric disorders. Lithium and ketamine both seem to ameliorate the consequences of stress. Here, male mice were either injected with lithium carbonate (LiCl), ketamine hydrochloride (KET), or sodium chloride (NaCl; controls) over nine consecutive days. Treatment was followed by 2 h of restraint stress over the first seven days. On the 9th day, 2 h after injection, all animals were tested in the open field, and novel object tests and behavior were analyzed using the toolbox ‘DeepLabCut’. To exclude an effect of generally altered locomotion activity on turning behavior, further parameters were assessed. Treatment before chronic stress exposure did not influence the total number of turns, nor the direction of turning behavior in the open field and the novel object test. Additionally, general locomotion did not differ. However, mice treated with LiCl showed a stronger turning bias (i.e., larger absolute lateralization quotients) in the novel object test when compared to mice treated with KET. This study underlines the potential of investigating turning behavior as a sensitive and reliable marker of stress reaction. Additionally, analyzing behavioral asymmetries in the context of psychopharmacological treatment can render new insights.

Statins Induce Locomotion and Muscular Phenotypes in Drosophila melanogaster That Are Reminiscent of Human Myopathy: Evidence for the Role of the Chloride Channel Inhibition in the Muscular Phenotypes.

The underlying mechanisms for statin-induced myopathy (SIM) are still equivocal. In this study, we employ Drosophila melanogaster to dissect possible underlying mechanisms for SIM. We observe that chronic fluvastatin treatment causes reduced general locomotion activity and climbing ability. In addition, transmission microscopy of dissected skeletal muscles of fluvastatin-treated flies reveals strong myofibrillar damage, including increased sarcomere lengths and Z-line streaming, which are reminiscent of myopathy, along with fragmented mitochondria of larger sizes, most of which are round-like shapes. Furthermore, chronic fluvastatin treatment is associated with impaired lipid metabolism and insulin signalling. Mechanistically, knockdown of the statin-target Hmgcr in the skeletal muscles recapitulates fluvastatin-induced mitochondrial phenotypes and lowered general locomotion activity; however, it was not sufficient to alter sarcomere length or elicit myofibrillar damage compared to controls or fluvastatin treatment. Moreover, we found that fluvastatin treatment was associated with reduced expression of the skeletal muscle chloride channel, ClC-a (Drosophila homolog of CLCN1), while selective knockdown of skeletal muscle ClC-a also recapitulated fluvastatin-induced myofibril damage and increased sarcomere lengths. Surprisingly, exercising fluvastatin-treated flies restored ClC-a expression and normalized sarcomere lengths, suggesting that fluvastatin-induced myofibrillar phenotypes could be linked to lowered ClC-a expression. Taken together, these results may indicate the potential role of ClC-a inhibition in statin-associated muscular phenotypes. This study underlines the importance of Drosophila melanogaster as a powerful model system for elucidating the locomotion and muscular phenotypes, promoting a better understanding of the molecular mechanisms underlying SIM.

Anodal and cathodal transcranial direct current stimulations of prefrontal cortex in a rodent model of Alzheimer's disease.

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly, with no effective treatment currently available. Transcranial direct current stimulation (tDCS), a non-drug and non-invasive therapy, has been testified efficient in cognitive enhancement. This study aims to examine the effects of tDCS on brain function in a mouse model of AD. The amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice (7–8 months old) were subjected to 20-min anodal and cathodal tDCS (atDCS and ctDCS; 300 μA, 3.12 mA/cm2) for continuous five days. tDCS was applied on the left frontal skull of the animals, targeting on their prefrontal cortex (PFC). Behavioral performances were assessed by open-field, Y-maze, Barnes maze and T-maze paradigms; and their PFC electroencephalogram (EEG) activities were recorded under spontaneous state and during Y-maze performance. Behaviorally, atDCS and ctDCS improved spatial learning and/or memory in AD mice without affecting their general locomotion and anxiety-like behaviors, but the effects depended on the testing paradigms. Interestingly, the memory improvements were accompanied by decreased PFC EEG delta (2–4 Hz) and increased EEG gamma (20–100 Hz) activities when the animals needed memory retrieval during task performance. The decreased EEG delta activities could also be observed in animals under spontaneous state. Specifically, atDCS increased PFC EEG activity in the alpha band (8–12 Hz) for spontaneous state, whereas ctDCS increased that in alpha-beta band (8–20 Hz) for task-related state. In addition, some EEG changes after ctDCS could be found in other cortical regions except PFC. These data indicate that tDCS can reverse the situation of slower brain activity in AD mice, which may further lead to cognitive improvement. Our work highlights the potential clinical use of tDCS to restore neural network activity and improve cognition in AD.

A general locomotion control framework for multi-legged locomotors

Serially connected robots are promising candidates for performing tasks in confined spaces such as search and rescue in large-scale disasters. Such robots are typically limbless, and we hypothesize that the addition of limbs could improve mobility. However, a challenge in designing and controlling such devices lies in the coordination of high-dimensional redundant modules in a way that improves mobility. Here we develop a general framework to discover templates to control serially connected multi-legged robots. Specifically, we combine two approaches to build a general shape control scheme which can provide baseline patterns of self-deformation (‘gaits’) for effective locomotion in diverse robot morphologies. First, we take inspiration from a dimensionality reduction and a biological gait classification scheme to generate cyclic patterns of body deformation and foot lifting/lowering, which facilitate the generation of arbitrary substrate contact patterns. Second, we extend geometric mechanics, which was originally introduced to study swimming at low Reynolds numbers, to frictional environments, allowing the identification of optimal body–leg coordination in this common terradynamic regime. Our scheme allows the development of effective gaits on flat terrain with diverse numbers of limbs (4, 6, 16, and even 0 limbs) and backbone actuation. By properly coordinating body undulation and leg placement, our framework combines the advantages of both limbless robots (modularity and narrow profile) and legged robots (mobility). Our framework can provide general control schemes for rapid deployment of general multi-legged robots, paving the way toward machines that can traverse complex environments. In addition, we show that our framework can also offer insights into body–leg coordination in living systems, such as salamanders and centipedes, from a biomechanical perspective.

Benzoresorcinol induces developmental neurotoxicity and injures exploratory, learning and memorizing abilities in zebrafish

Benzophenones (BPs) are a class of UV absorber commonly used in skin care products like sunscreens. With its wide range of application, its environmental and human hazards have received much attention in recent days. Previous studies on the toxicity of BPs mainly focused on its endocrine-disrupting effects, but there are limited studies on its neurodevelopment and neurotoxicity. Herein, using the zebrafish model we studied the neurodevelopmental- and neuro-toxicity of benzophenone 1 (BP1) (0.8, 1.0, 1.2, 1.6, and 2.4 μg/mL). As a result, BP1 led to an increase of embryo mortality, a decrease in hatching rate, and an increase in the rate of developmental abnormalities in a concentration-dependent manner. BP1 also caused developmental defects in the central nervous system (CNS) and dopaminergic (DA) neurons. Accordingly, BP1 injured larval zebrafish general locomotion and response to stimuli in light/dark challenge. In adult zebrafish, BP1 exposure (1, 10, 100, 1000 μg/L) caused inhibition of learning and memory abilities in the T-maze tests, and inhibited exploratory behavior and activity in the novel tank diving tests. Further, transcription levels of genes related to neurotoxicity, neurodevelopment, and anxiety revealed that BP1 may affect the development and function of the myelin sheath, inducing structural and functional defects of CNS, manifested as abnormal behaviors such as anxiety. Hence, the current study revealed the neurodevelopmental toxicity and neurotoxicity of BP1, expanded our knowledge about the toxic effects of BP1 on organisms, posing a possible threat to the environment and human health.

Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice.

Helminth neuroinfections represent serious medical conditions, but the diversity of the host-parasite interplay within the nervous tissue often remains poorly understood, partially due to the lack of laboratory models. Here, we investigated the neuroinvasion of the mouse spinal cord by Trichobilharzia regenti (Schistosomatidae). Active migration of T. regenti schistosomula through the mouse spinal cord induced motor deficits in hindlimbs but did not affect the general locomotion or working memory. Histological examination of the infected spinal cord revealed eosinophilic meningomyelitis with eosinophil-rich infiltrates entrapping the schistosomula. Flow cytometry and transcriptomic analysis of the spinal cord confirmed massive activation of the host immune response. Of note, we recorded striking upregulation of the major histocompatibility complex II pathway and M2-associated markers, such as arginase or chitinase-like 3. Arginase also dominated the proteins found in the microdissected tissue from the close vicinity of the migrating schistosomula, which unselectively fed on the host nervous tissue. Next, we evaluated the pathological sequelae of T. regenti neuroinvasion. While no demyelination or blood-brain barrier alterations were noticed, our transcriptomic data revealed a remarkable disruption of neurophysiological functions not yet recorded in helminth neuroinfections. We also detected DNA fragmentation at the host-schistosomulum interface, but schistosomula antigens did not affect the viability of neurons and glial cells in vitro. Collectively, altered locomotion, significant disruption of neurophysiological functions, and strong M2 polarization were the most prominent features of T. regenti neuroinvasion, making it a promising candidate for further neuroinfection research. Indeed, understanding the diversity of pathogen-related neuroinflammatory processes is a prerequisite for developing better protective measures, treatment strategies, and diagnostic tools.

Balance Recoverability and Control of Bipedal Walkers With Foot Slip.

Low-friction foot/ground contacts present a particular challenge for stable bipedal walkers. The slippage of the stance foot introduces complexity in robot dynamics and the general locomotion stability results cannot be applied directly. We relax the commonly used assumption of nonslip contact between the walker foot and the ground and examine bipedal dynamics under foot slip. Using a two-mass linear inverted pendulum model, we introduce the concept of balance recoverability and use it to quantify the balanced or fall-prone walking gaits. Balance recoverability also serves as the basis for the design of the balance recovery controller. We design the within- or multi-step recovery controller to assist the walker to avoid fall. The controller performance is validated through simulation results and robustness is demonstrated in the presence of measurement noises as well as variations of foot/ground friction conditions. In addition, the proposed methods and models are used to analyze the data from human walking experiments. The multiple subject experiments validate and illustrate the balance recoverability concept and analyses.

Splenectomy does not affect mouse behaviors.

The spleen is critical for immunity. It is the largest immune organ and immune center in the peripheral system. While the relationship between behavior and immunity has been demonstrated in physiology and diseases, the role of the spleen in behavior is not clear. To investigate the effects of the spleen on behaviors, we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test, circadian rhythm test, elevated plus maze, sucrose preference test, and Barnes maze test. Splenectomy did not induce changes in general locomotion, circadian rhythms, learning and memory, or depression/anxiety-related behaviors. To further investigate the effects of spleen on stress susceptibility, we established mouse models of depression through chronic unpredictable mild stress. The behavioral performances of mice subjected to splenectomy showed no differences from control animals. These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.