In recent years, quadruped robots have received many attention due to excellent adaptability in complex terrains,and the key to their stable locomotion lies in gait coordination. But,the traditional central pattern generator (CPG) models often face challenges such as high reliance on manual experience for tuning coupling parameters and poor adaptive capability. To address this problem, this study proposes a control method integrating coupling dynamics modeling and intelligent optimization. And,a four-leg coupling dynamics model based on Hopf nonlinear oscillator is constructed, in which coupling matrix describes inter-leg phase relationships. The matrix is automatically optimized by incorporating a genetic algorithm and implementing global search with a phase synchronization stability metric as the fitness function. Simulation results show that the optimized coupling parameters significantly improve the phase coordination ability of the four-leg oscillators. This effective eliminates phase deviations under natural dynamics, and greatly enhances both gait synchrony and stability.And so,the study contributes to the autonomous adaptability of quadruped robots by providing a data-driven global optimization framework for their gait control.\

Objective Spinal cord injury (SCI) is a highly disabling neurological condition that remains a worldwide challenge in healthcare. Our previous studies found that repetitive trans-spinal magnetic stimulation (rTSMS) applied at the L2 spinal segment yielded the most significant improvement in motor function in rats with SCI; however, the underlying mechanism remains unclear. Recent research indicates that disruption of the EphA4 signaling pathway in glutamatergic interneurons within the spinal cord leads to a loss of motor rhythm and a hopping gait in rats. Conversely, activating the locomotor central pattern generator (CPG) located in the L1-2 spinal segments promotes the recovery of motor function. Thus, by examining the effects of rTSMS on proteins associated with the EphA4 signaling pathway, this study provides novel insights for future investigations into its potential mechanisms of action. Methods A multidimensional approach, including behavioral assessments, immunofluorescence, RT-PCR, and Western blotting, was employed to evaluate the effects of rTSMS on motor function in rats with acute SCI. We also assessed its impact on EphA4 mRNA expression levels and the synthesis of related proteins, including VGluT2, EphA4, EphrinB3, and downstream effector molecules Chn1 and Nck1. Results The results showed that rTSMS improved the Basso, Beattie, and Bresnahan (BBB) locomotor scores in rats with acute spinal cord injury. It also exerted positive effects on upregulating the expression level of EphA4 mRNA and promoting the synthesis of proteins, including VGluT2, EphA4, EphrinB3, and the downstream effector molecules Chn1 and Nck1. Conclusion This study suggests that repetitive trans-spinal magnetic stimulation effectively improves motor function after acute spinal cord injury, concomitant with an upregulation of EphA4 pathway-related proteins, thereby providing a new direction for future mechanistic research.

Age-related skeletal muscle deterioration, referred to as sarcopenia, poses significant risks to astronaut health and mission success during spaceflight, yet its multisystem drivers remain poorly understood. While terrestrial sarcopenia manifests gradually through aging, spaceflight induces analogous musculoskeletal decline within weeks, providing an accelerated model to study conserved atrophy mechanisms. Here, we introduced an integrative framework combining cross-species genetic analysis with physiological modeling to understand mechanistic pathways in space-induced sarcopenia. By analyzing rodent and human datasets, we identified conserved molecular pathways underlying spaceflight-induced muscle atrophy, revealing shared regulators of neuromuscular signaling including pathways related to neurotransmitter release and regulation, mitochondrial function, and synaptic integration. Building upon these molecular insights, we developed a physiologically grounded central pattern generator model that reproduced spaceflight-induced locomotion deficits in mice. This multi-scale approach established mechanistic connections between transcriptional changes and impaired movement kinetics while identifying potential therapeutic targets applicable to both spaceflight and terrestrial aging-related muscle loss.

Intraspinal microstimulation (ISMS) is a rehabilitation technology that activates muscle movement by electrically stimulating the spinal cord, thereby restoring the function of paralyzed limbs. In this study, a fuzzy logic-controlled self-tuning proportional-integral-derivative (PID) algorithm was adopted. By simultaneously adjusting three key electrical stimulation parameters-amplitude, pulse width, and frequency of the pulse signal-the distal locomotor central pattern generator (CPG) in rats with spinal cord injury (SCI) was activated, realizing real-time control of hindlimb ankle joint movement in paralyzed rats. To verify the control performance of the intraspinal microstimulation system, animal experiments were conducted. Statistical results showed that the root mean square error (RMSE) of joint angle tracking was 2.50°, and the normalized root mean square error (NRMSE) was 5.78%. The results indicate that the ankle joint of the paralyzed hindlimb in SCI rats can move according to the preset angle trajectory through single-electrode intraspinal electrical stimulation.

Paleoanthropology could offer valuable insights into neurology by tracing the evolutionary origins of human motor and neural traits. Fossil evidence shows that bipedalism preceded brain expansion, revealing that upright locomotion and encephalization did not evolve in tandem. Early hominins retained ape-like brain organization despite walking upright, suggesting that neural complexity and prolonged childhood development emerged later. This sequence provides a framework for understanding persistent motor circuits in the human nervous system. Central pattern generators, deeply conserved networks producing rhythmic movements, exemplify ancestral continuities whose resilience explains the re-emergence of primitive motor patterns after cortical damage. Interpreting neurological signs through an evolutionary lens raises epistemological challenges, including the need for testable hypotheses and the avoidance of teleological bias. Yet clinically, reframing neurological signs, reflexes, and automatisms as evolutionary echoes could enrich diagnostic reasoning, inform prognosis, and inspire therapeutic strategies that harness ancestral circuits. In this sense, certain neurological signs may represent living traces of evolutionary history, bridging human ancestry with clinical practice.

Awake behaving animal experiments paired with multichannel electrode recordings have advanced motor systems neuroscience in creating models of how the mammalian brain controls move-ments. However, growing theoretical and experimental evidence question the generalizability of such findings from constrained studies to ambulatory behavior, highlighting a limitation in our understanding of how the brain controls movement. To address this question, spiking neural activity during highly-practiced, routine movement (walking) and goal-directed behavior (reach-ing towards food) were compared in an unconstrained setting. Kinematic trajectories of the contralateral arm during reaching and walking were statistically similar, as were the average single-neuron firing rates during these respective movements. However, the dimensionality of reaching was higher than that of walking and existed in largely non-overlapping subspaces. Further, when modeled as dynamical systems, reaching decayed 3-5 times more quickly than walking. Taken together, these findings demonstrate that the low-dimensional structure of motor cortex is more complex for goal-directed reaching than in highly-practiced natural movements. Since this difference is primarily observable at the state and dynamical systems level, these findings suggest behavioral context plays a significant role in the coordination of otherwise kinematically similar movements, providing indirect evidence for non-cortical circuits such as central pattern generators.

Here we investigate the gene regulatory networks responsible for the differentiation of cholinergic neurons in the Ciona larval motor ganglion, which functions as the organism’s central pattern generator for swimming and dispersal. We demonstrate conserved roles motor neuron-enriched transcription factors Neurogenin and Onecut, with Neurogenin likely sitting atop the regulatory cascade. We also identify a key role for the transcription factor Nkx6 in specifying one motor neuron subtype, Motor Neuron 1 (MN1), and show that the secreted Wnt pathway inhibitor Dkk3 is required by MN1 for its unique neuromuscular endplates. We propose that Dkk3 interacts with LRP receptors in target muscle cells, through conserved NxI/V/F motifs shared with another key secreted neuromuscular synapse effector, Agrin. Taken together, our results provide critical insights into the development and evolution of cholinergic neurons involved in chordate locomotion.

In contrast to the central pattern generator hypothesis, which posits that neural networks generate rhythmic motor patterns without sensory feedback, recent robotics studies have demonstrated that independent oscillating agents with load-dependent feedback can organize coordinated gaits in quadrupedal robots. In this study, we develop minimal mathematical models to describe how such coordination emerges from physical interactions through the trunk and environment. By employing active rotators as limb controllers, we demonstrate their capacity to generate distinct gait patterns, including the trot, pace, and bound. We can also predict gait transitions with walking speed. These models provide insight into why different animals with specific physiques have limited gait patterns and offer suggestions for designing quadrupedal robots.

Postanoxic myoclonus is a well-recognized phenomenon after cardiac arrest and often indicates poor prognosis. Other spontaneous movements, such as tonic eyelid opening, have also been documented, but spontaneous chewing movements remain poorly characterized. The aim of this study was to systematically analyze the electrophysiologic features of postanoxic chewing movements, propose a standardized nomenclature, discuss potential pathophysiology, and evaluate their prognostic significance. We retrospectively reviewed clinical data from post-cardiac arrest patients who exhibited suspicious chewing movements during continuous video-EEG (vEEG) monitoring between January 2021 and December 2024. Chewing movements were analyzed for duration, frequency, and correlation with EEG findings. Demographic, clinical, management, and outcome data were also collected. A thorough literature review was conducted. Twelve patients (mean age: 62.3 ± 10.5 years) who experienced out-of-hospital cardiac arrest exhibited repetitive chewing movements. Detailed analysis of video recordings and bedside observations identified these movements as rhythmic tongue elevations against the upper palate with minimal jaw activity, producing chewing artifacts on EEG. These episodes lasted 4-5 seconds and were periodic in 2 patients. Video-EEG revealed that in 8 patients, the movements followed EEG bursts by 1-1.5 seconds, whereas in 4 patients, they occurred spontaneously without corresponding cortical activity. The movements were transient, with a median duration of 24 hours, and resolved within 72 hours despite persistent burst-suppression patterns. Brain MRI in 3 patients demonstrated diffuse anoxic/hypoxic cortical injury with relative brainstem preservation. All patients died after cardiac arrest, with a median survival of 5 days. We propose the term postanoxic oral automatism (PAOA) to describe a distinct, transient oral motor phenomenon characterized by repetitive, chewing-like tongue movements in comatose patients after cardiac arrest. Unlike previous reports confined to burst-suppression EEG patterns, our findings show that PAOA can occur in both burst-suppression and background-suppression EEG backgrounds. These movements likely result from disinhibition of brainstem central pattern generators responsible for rhythmic orofacial activity and may signify severe cortical dysfunction. Although PAOA is associated with poor prognosis, its independent predictive value remains unclear.

At the core of any rhythmic movement, including walking, lies the function of Central Pattern Generators (CPGs) - neuronal circuits in the spinal cord. Spastic forms of cerebral palsy (CP) hinder full locomotion. CPGs, in the absence of supraspinal control, can generate locomotor patterns independently, which can affect the ability to move both positively and negatively. In rehabilitation, we aim to increase the afferent flow of impulses in patients with CP, which is possible when combining botulinum toxin therapy and providing patients with compressive orthoses. These orthoses can improve the performance of motor tasks in children with CP. Walking, running, and swimming lead to rhythmic arm movements along with the legs through coordination between the central pattern generators of the upper and lower extremities. The absence of coordination or increased spasticity in the upper and lower extremities can be the cause of activation of pathological motor patterns. Thus, spinal cord neuronal circuits become generators of pathologically increased excitation, shaped as a result of a focal organic lesion of the central nervous system. Injections of Botulinum Toxin A (BTX-A) in the upper extremity allow modifying the formation of dominant synergy. Wearing compressive orthoses (corsets, leggings, or long-sleeved shirts) helps create the correct locomotion. Based on the analysis of modern research, a range of botulinum toxins has registered an effective and favorable safety profile for BTX-A (incobotulinumtoxin A) use in children with CP. The combination of botulinum toxin therapy, orthoses, and physical therapy is a dominant factor in rehabilitation.

Legged bio-inspired robots have emerged as a promising solution for locomotion in unstructured and complex environments. By drawing inspiration from animal morphology and biomechanics, researchers have developed robotic systems capable of achieving agility, adaptability, and energy efficiency beyond the limits of traditional wheeled and tracked platforms. Advances in structural design, such as compliant spines and segmented legs, have enhanced gait stability and natural motion. At the same time, progress in control strategies—including model predictive control, central pattern generators, and reinforcement learning—has significantly improved adaptability and robustness. This paper presents recent developments in legged bio-inspired robotics, focusing on structural innovations, control approaches, and perception-driven adaptability. It also discusses the growing application domains of these systems, including disaster response, industrial inspection, and agricultural monitoring. Finally, the paper outlines current challenges and future research directions, highlighting the path toward intelligent, efficient, and reliable legged robots capable of operating in real-world environments.

The swallowing reflex is a highly coordinated process that is essential for safe bolus transit and airway protection. Although its neurophysiological framework has been extensively studied, the molecular mechanisms underlying reflex initiation remain incompletely understood, limiting targeted therapies for oropharyngeal dysphagia. Recent evidence implicates purinergic signaling as a key mediator of swallowing initiation, particularly through ATP release from taste buds and neuroendocrine cells in the hypopharyngeal and laryngeal mucosa. Experimental studies in mice demonstrate that water, acidic, and bitter chemical stimuli induce ATP release, activating purinergic receptors (P2X2, P2X3, heteromeric P2X2/P2X3, and P2Y1) on afferent sensory fibers. This receptor activation enhances input to the brainstem swallowing central pattern generator, initiating reflexive swallowing. Genetic ablation of purinergic receptor-expressing neurons or epithelial sentinel cells, as well as pharmacological antagonism of P2X or P2X3 receptors, markedly attenuates these responses. Furthermore, exogenous ATP or selective P2X3 agonists applied to swallowing-related mucosa evoke swallowing reflexes in an animal model, underscoring translational potential. While the precise upstream receptor mechanisms for water- and acid-induced ATP release, as well as species-specific differences, remain to be clarified, targeting purinergic pathways may represent a novel physiologically grounded therapeutic strategy for restoring swallowing function in patients with oropharyngeal dysphagia.

Mammals exhibit robust walking across diverse environments, a capability largely attributed to central pattern generators (CPGs) in the spinal cord. Afferent feedback modulates CPG output and plays a critical role in adaptive locomotion, yet its specific contributions remain poorly understood. To investigate this, we used a neuromusculoskeletal model to simulate hindlimb locomotion in spinalized cats encountering a hole and experiencing a sudden loss of ground support, as described in prior experimental studies. The model couples a trunk-and-hindlimb musculoskeletal system to a pair of two-level, half-center CPGs—one for each hindlimb. The model reproduced the observed adaptive interlimb coordination that allows cats to maintain walking after the sudden loss of ground support. Notably, the adaptive response emerged without re-optimizing parameters, which were tuned for steady walking in an environment without holes. Nullcline analysis based on dynamical systems theory revealed that afferent feedback mechanisms controlling the transitions between fast and slow neuronal dynamics facilitated adaptive interlimb coordination. These findings provide mechanistic insight into how spinal feedback circuits support robust locomotion through dynamic interactions between the nervous system, the musculoskeletal system, and the environment.

The unique, hypnotic pulsation behavior of certain soft corals of the Xeniidae family, the result of rhythmic opening and closing of their tentacles, has fascinated scientists since the 18th century. Repetitive motion is regulated by autonomous neural circuits known as pacemakers or central pattern generators. However, little is known about such circuits in nonbilaterian organisms like corals. In this report, Xenia umbellata, a fast-growing octocoral, served as a model organism to study the muscular and neural mechanisms of pulsation. Leveraging this coral's rapid regeneration ability, we tested somatic regrowth and pulsation recovery following oral disc amputation. Transcriptomic analysis upon transitioning from nonpulsation to intermediate and synchronized pulsation during regeneration demonstrated shared pulsation-related genes in X. umbellata and bilaterians, suggesting an evolutionarily conserved rhythmic machinery. Pharmacological interference experiments supported transcriptomic findings, showing that acetylcholine regulates pulsation and anoctamin channels affect pacemaker rhythm. Interestingly, in the intermediate pulsation phase tentacles could pulsate individually without synchronization, suggesting the development of separate pacemakers. At the synchronized pulsation phase a dense nerve net developed around the mouth opening and overlapping muscle fibers between tentacles, providing the mechanisms for tentacle synchronization. However, when polyp tentacles were cut into small pieces, the fragments remained alive and each retained independent pulsation, revealing a unique pacemaker system driven by a diffuse nerve network lacking any centralized control. This finding uncovers a mechanism of rhythmic behavior generation in nonbilaterian animals, which could represent either a lineage-specific innovation or an ancient origin for more centralized control.

A multi-Layered neural control framework: Combining central pattern generators utilizing muscle synergy Theory and incorporating proprioceptors

Periodic signals propagating along chains are common in biology, for example in locomotion and peristalsis, and are also of interest for continuum robots. In a previous work, we constructed such networks as “feedforward lifts” of a Central Pattern Generator (CPG). When the CPG undergoes periodic oscillations, created by Hopf bifurcation or other mechanisms, it can then transmit periodic signals along one or more feedforward chains in a synchronous or phase-synchronous manner. We proved necessary and sufficient conditions for the stability of these lifted periodic orbits, in several senses. Here we examine the implications of the resulting theory for chains of neurons, using several standard neuron models: FitzHugh–Nagumo, Morris–Lecar, Hindmarsh–Rose, and Hodgkin–Huxley. We compare different notions of transverse stability, and summarize some numerical simulations showing that for all these neuron models, the propagating signal can be transversely Floquet stable. Finally, we discuss implications for less idealized models.

The human respiratory Central Pattern Generator (CPG) is a complex and tightly regulated network of neurons responsible for the automatic rhythm of breathing. Among the brain nuclei involved in respiratory control, excitatory neurons within the PreBotzinger Complex (PreBötC) are both necessary and sufficient for generating this rhythmic activity. Although several models of the PreBötC circuit have been proposed, a comprehensive analysis of network behavior in response to physiologically relevant external inputs remains limited. In this study, we present a computational model of the PreBötC consisting of 1000 excitatory neurons, divided into two functional subgroups: the rhythm-generating population and the pattern-forming population. To enable real-time closed-loop simulations, we employed parallelized multi-process computing to accelerate network simulation. The network, composed of asynchronous neurons, could produce bursting activity at a eupneic breathing frequency of 0.22 Hz, which could also reproduce the rapid and stable chemoreception of breathing activated in response to hypercapnia. Additionally, it successfully replicated rapid and stable respiratory responses to elevated carbon dioxide levels (hypercapnia), mediated through simulated chemoreception. External inputs from a carbon dioxide sensor were used to modulate the network activity, allowing the implementation of a real-time respiratory control system. These results demonstrate that a network of asynchronous, non-bursting neurons can emulate the behavior of the respiratory CPG and its modulation by external stimuli. The proposed model represents a step toward developing a closed-loop controller for breathing regulation.

Understanding the hierarchical organization and transmission characteristics of neural signals-from motor intention, through spinal integration, to lower limb joint motions-is critical for developing physiologically plausible, intention-driven motion generation models. Such models not only advance our comprehension of the neurophysiological mechanisms underlying lower limb locomotion but also provide a biological foundation for the direct neural control of lower limb prostheses and rehabilitation robots, offering both theoretical significance and practical utility. This challenge has persisted for decades due to the intricate coupling between spinal integration outputs (i.e., motor patterns) and joint motions. While bionic Central Pattern Generator (CPG) models primarily address the transformation from motor intention to spinal integration, they often neglect the mapping from spinal integration outputs to joint motions. Conversely, other researchers have also adopted the concept of CPG, but have employed black-box modeling approaches to directly map motor intention to joint motions, bypassing spinal integration entirely, which lack physiological interpretability and biological relevance. To address this gap, this study proposes a physiologically inspired computational model in which spinal integration is represented as a dual-layer Meta-Pattern Generator (MPG). The MPG integrates motor intention and joint feedback to generate meta-pattern signals that correspond one-to-one with joint-specific motor primitives, effectively decoupling spinal integration outputs to joint motions. This model successfully replicates the hierarchical transmission of neural signals from motor intention, through spinal processing, to joint-level execution, enabling generation of joint trajectories driven by the motor intention. Experimental validation was conducted with eight subjects performing five distinct locomotion modes. Results demonstrated a clear one-to-one correspondence between meta-patterns derived from electromyographic (EMG) signals and motor primitives extracted from joint angles. Furthermore, the joint angles predicted by the model closely matched the experimentally recorded angles, with an average error of less than 1.7%. This work provides new insights into neuromusculoskeletal modeling and offers promising applications in the design of lower limb prostheses and rehabilitation robots.

Swallowing function is affected in patients with lateral medullary syndrome (LMS) due to impaired swallowing central pattern generator, but it remains unclear whether their cortical function is affected. To determine the level of cortical involvement during swallowing in LMS dysphagia patients. This is a cross-sectional study carried out from May 2023 and January 2024 in China. 21 patients with LMS dysphagia and 20 age-matched healthy controls were recruited. Functional near-infrared spectroscopy with 39 channels was utilized to detect the cortical hemodynamic changes when repeated salivary swallowing. Cortical activation and functional connectivity during swallowing were analyzed. Compared with healthy subjects, patients with LMS demonstrated reduced activation in bilateral dorsolateral prefrontal cortex(DLPFC), left temporopolar area, frontopolar area(PFA), and right pre-motor and supplementary motor cortex(pSMC) (channel 11, P = 0.031; channel 12, P = 0.042; channel 15, P = 0.042; channel 19, P = 0.031; channel 24, P = 0.031; channel 25, P = 0.031). The activation of patients with LMS in right primary somatosensory cortex (PSC), supramarginal gyrus (SMG), FPA and left pars triangularis (PTG) was negatively correlated with the PAS score (channel1, P = 0.019; channel 2, P = 0.005; channel 23, P = 0.017; channel 27, P = 0.047). The activation in right PSC and SMG was negatively correlated with the stroke duration (channel 2, P = 0.026; channel 16, P = 0.018). There is no difference in the mean functional connectivity strength between the channels of patients with LMS and healthy subjects (P = 0.565). The functional connectivity strength between the bilateral temporopolar areas was reduced in patients with LMS compared with healthy subjects(P = 0.015). Although the lesion site of patients with LMS dysphagia is in the medulla oblongata, cortical activation and functional connectivity during swallowing differ from those of healthy subjects, which may be related to damage of the ascending sensory pathways and cortical-medullary diaschisis.

SynergyFF: A single shooting method for simulating crouch gait using muscle synergy feedforward control as a CPG.