Thermally and Mechanically Stable Perovskite Artificial Synapse as Tuned by Phase Engineering for Efferent Neuromuscular Control.

The doping of perovskites with mixed cations and mixed halides is an effective strategy to optimize phase stability. In this study, we introduce a cubic black phase perovskite CsyFA(1-y)Pb(BrxI(1-x))3 artificial synapse, using phase engineering by adjusting the cesium-bromide content. Low-bromine mixed perovskites are suitable to improve the electric pulse excitation sensitivity and stability of the device. Specifically, the low-bromine and low-cesium mixed perovskite (x = 0.15, y = 0.22) annealed at 373 K allows the device to maintain logic response even after 1000 mechanical flex/flat cycles. The device also shows good thermal stability up to temperatures of 333 K. We have demonstrated reflex-arc behavior with MCMHP synaptic units, capable of making sensory warnings at high frequency. This compositionally engineered, dual-mixed perovskite synaptic device provides significant potential for perceptual soft neurorobotic systems and prostheses.

Discovery of a Novel Yadav-Kunal Reflex in Context of Upper Motor Neuron Lesions: A Report of Three Cases.

Introduction: Numerous reflexive responses have been documented as alterations to the Babinski sign within upper motor neuron lesions. However, scant attention has been given to reflexes beyond these, which exhibit independence from the extensor plantar response. These reflexes predominantly form polysynaptic arcs, with nociceptive stimuli acting as afferents. Case Report: The reflex was serendipitously discovered in an 18-year-old female patient who presented with spastic paraplegia with bowel and bladder involvement, as a consequence of an aneurysmal bone cyst of the D3 (dorsal) vertebrae, and the same was named after the authors as "Yadav-Kunal reflex" which can be defined as: "In individuals with spastic paraparesis, forcibly plantarflexing the toes will result in sudden jerky flexion of the knee and hip on the same side." This novel reflex was further investigated and validated in two additional patients with spastic paraplegia: one, a 45-year-old female with D9-D10 Pott's spine and bowel and bladder involvement, and the other, a 65-year-old male with D10-D11 compressive myelopathy and bowel and bladder involvement. This reflex was meticulously tracked until the abatement of spasticity following surgical intervention. Notably, its manifestation was evident in individuals experiencing spastic paraparesis, dissipating concomitantly with the resolution of spasticity - a direct clinical correlation. Conversely, the reflex was conspicuously absent in cases of flaccid paraplegia. Conclusion: Spasticity, characterized by an increase in muscle tone on swift stretching movements, is a manifestation of a stretch reflex disorder. This condition is primarily induced by lesions affecting upper motor neurons. The activation of muscle spindles in toe dorsiflexors (primarily governed by the L5 nerve) occurs during forceful elongation caused by plantarflexion.

Paraffin-Enabled Superlattice Customization for a Photostimulated Gradient-Responsive Artificial Reflex Arc.

The development of photostimulated-motion artificial reflex arcs - a neural circuit inspired by light-driven motion reflexes - holds significant promises for advancements in robotic perception, navigation, and motion control. However, the fabrication of such systems, especially those that accommodate multiple actions and exhibit gradient responses, remains challenging. Here, a gradient-responsive photostimulated-motion artificial reflex arc is developed by integrating a programmable and tunable photoreceptor based on folded MoS2 at different twist angles. The twisted folded bilayer MoS2 used as photoreceptors can be customized via the transfer technique using patternable paraffin, where the twist angle and fold-line could be controlled. The photoluminescence (PL) intensity is 3.7 times higher at a twist angle of 29° compared to that at 0°, showing a monotonically decreasing indirect bandgap. Through tunable interlayer carrier transport, photoreceptors fabricated using folded bilayer MoS2 at different twist angles demonstrate gradient response time, enabling the photostimulated-motion artificial reflex arc for multiaction responses. They are transformed to digital command flow and studied via machine learning to control the gestures of a robotic hand, showing a prototype of photostimulated gradient-responsive artificial reflex arcs for the first time. This work provides a unique idea for developing intelligent soft robots and next-generation human-computer interfaces.

Mixed-Dimensional Nanoparticle-Nanowire Channels for Flexible Optoelectronic Artificial Synapse with Enhanced Photoelectric Response and Asymmetric Bidirectional Plasticity.

A mixed-dimensional dual-channel synaptic transistor composed of inorganic nanoparticles and organic nanowires was fabricated to expand the photoelectric gain range. The device can actualize the sensitization features of the nociceptor and shows improved responsiveness to visible light. Under electrical pulses with different polarities, the apparatus exhibits reconfigurable asymmetric bidirectional plasticity. Moreover, the devices demonstrate good operational tolerance and mechanical stability, retaining more than 60% of their maximum responsiveness after 100 consecutive/bidirectional and 1000 flex/flat operations. The improved photoelectric response of the device endows a high image recognition accuracy of greater than 80%. Asymmetric bidirectional plasticity is used as punishment/reward in a psychological experiment to emulate the improvement of learning motivation and enables real-time forward and backward deflection (+7 and -25°) of artificial muscle. The mixed-dimensional optoelectronic artificial synapses with switchable behavior and electron/hole transport type have important prospects for neuromorphic processing and artificial somatosensory nerves.

The Importance of Cajal's and Lorente de Nó's Neuroscience to the Birth of Cybernetics.

The beginnings of cybernetics were marked by the publication of two papers in 1943. In the first one, Rosenblueth, Wiener, and Bigelow claimed that purposeful behavior is a circular process controlled by negative feedback. In the second seminal paper, McCulloch and Pitts proposed that neurons are interconnected working as logical operators. Both articles raised human-machine analogies and mathematically formulated cognitive mechanisms. These ideas ignited the interest of von Neumann, who was developing the first stored-program computer. Thus, after a preliminary meeting in 1945, a series of meetings were held between 1946 and 1953. The role of the Spanish neurophysiologist Rafael Lorente de Nó in the beginnings of cybernetics is attested not only by his participation in the core members of these Macy conferences but also for his previous description of reverberating circuits formed by a closed chain of internuncial neurons. This was the first neurobiologic demonstration of a feedback loop. Most researchers considered the central nervous system as a mere reflex organ until then; nevertheless, he demonstrated a self-sustained central activity in the nervous system, supporting the idea of self-regulating mechanisms as a key concept not just in machines but also in the brain.

Cell Differentiation-Inspired, Salt-Induced Multifunctional Gels for an Intelligent Soft Robot with an Artificial Reflex Arc.

To make soft robotics intelligent, dazzling artificial skin and actuators have been created. However, compared to rigid commercial robots, the sophisticated demands of raw materials become a key challenge for autonomous soft actuators to realize manufacturing repeatability and reproducibility. Inspired by the stem cell, which has the potential to differentiate into multifunctional cells with the same original compositions, a potential multifunctional gel is presented. With well-designed polymer chains, the gel has a salt-induced regulating module, conductivity, and other bionic properties. Making use of this advantage, the gel acts as a double-duty electrode for both the actuator and sensor. An artificial reflex arc is therefore formed by their tight integration via an e-brain: a computing unit that specifically responds to organism intervention. This efficient strategy to obtain diverse components with minimal raw materials is promising for effortlessly fabricating fully soft robotics.

Frequency dependent, reversible focused ultrasound suppression of evoked potentials in the reflex arc in an anesthetized animal.

OBJECTIVE: To investigate the potential for noninvasive low frequency, low intensity ultrasound to suppress evoked potentials in the reflex arc neural pathway in anesthetized animal. MATERIAL AND METHODS: Single unit Electromyographic recordings of gastrocnemius muscle activity were obtained in response to electrical activation of the sciatic nerve, in anesthetized animal, with and without US stimulation. Reflex related potentials were evoked via electrical stimulation and low-intensity, low-frequency ultrasound was applied to the sciatic nerve. Electromyogram (EMG) was recorded from the gastrocnemius muscle and amplitude and area under the curve were analyzed to determine the effect of ultrasound stimulation on potentials in the reflex arc. Thermal imaging was used to assess thermal effects of US stimulation and immunohistochemical was performed post-US stimulation assess potential damage to the nerve. RESULTS: Our results show a drop in electromyogram amplitudes as high as 20%, and a drop in areas under the curve as high as 23%, with greater effects at lower frequencies (200 kHz) and lower acoustic intensities. The suppression of EMG scales with the magnitude of the electrical stimuli. Also, our results demonstrated transient reversibility of US suppression and our experiments eliminated thermal effects and mechanical and thermal damage. CONCLUSION: The non-invasiveness of US stimulation and its inhibitory and reversible effects emphasize the potential of US as a therapeutic modality and clinical tool for suppression of neural potentials in the reflex arc such as the case for pain treatments. The study lays the ground for potential applications of US stimulation in pain treatment.

Polarity-Differentiated Dielectric Materials in Monolayer Graphene Charge-Regulated Field-Effect Transistors for an Artificial Reflex Arc and Pain-Modulation System of the Spinal Cord.

The nervous system is a vital part of organisms to survive and it endows them with remarkable abilities, such as perception, recognition, regulation, learning, and decision-making, by intertwining myriad neurons. To realize such outstanding efficacies and functions, many artificial devices and systems have been investigated to emulate the operating principles of the nervous system. Here, an artificial reflex arc (ARA) and artificial pain modulation system (APMS) are proposed to imitate the unconscious behaviors of the spinal cord. Gdx Oy - and Alx Oy -based charge-regulated field-effect transistors (CRFETs) with a monolayer graphene channel are fabricated and adopted as inhibitory and excitatory synapses, respectively, under the same pulse signals to mimic the biological reflex arc through a connection with a poly(vinylidene fluoride-co-trifluoroethylene)-based actuator. Additionally, a memristor is integrated with a CRFET as the interneuron to regulate the Dirac point by controlling the voltage drop on the graphene channel, analogous to the descending pain-inhibition system in the spinal cord, to prevent excessive pain perception. The proposed ARA and APMS provide a significant step forward to realizing the functions of the nervous system, giving promising potential for developing future intelligent alarm systems, neuroprosthetics, and neurorobotics.

Morphological and electrophysiological evidences of synaptic switching in vestibular nerve of land snail Helix lucorum L.

It is well known that the initiation of the reflex arcs of the vertebrate vestibular system occurs in the receptors of the labyrinthine organs which transmit the sensory signals via the ribbon synapses to the vestibular nerve afferents (an interneuron). In invertebrate species, and in particular, the statocyst of pulmonate mollusks, it is thought that the receptors send their axons out of the statocyst in the vestibular connective and establish the first synapse onto cerebral ganglia neurons, thereby bypassing the interneuron in the reflex arc. Morphological and electrophysiological techniques were used in this study to identify the first synapse in the vestibular arc of the mollusk Helix is actually within the vestibular connective on its way from the statocyst to cerebral ganglia. Cerebral interneurons were found that sent their neurites to the vestibular nerve, and thus have the potential to respond to the statocyst output or send efferent input to the statocyst.

Monosynaptic facilitation mediated by group Ia afferents from deltoid to biceps brachii motoneurons in humans.

Effects of low-threshold afferents from the anterior (DA), middle (DM) and posterior parts of the deltoid (DP) on the excitability of biceps brachii (BB) motoneurons in humans were studied. We evaluated the effects on individual motor units and motoneuron pool using a post-stimulus time-histogram (PSTH) and an electromyogram-averaging (EMG-A) methods, respectively, in 11 healthy human subjects. Electrical conditioning stimulation was delivered to the axillary nerve branch innervating DA (DA nerve), DM (DM nerve) and DP (DP nerve) with the intensity below the motor threshold. In the PSTH study, stimulation to the DA, DM and DP nerves produced a significant peak (facilitation) in 26/40 (65%), 28/47 (59%) and 0/32 (0%) of BB motor units, respectively. Since the central latency of the facilitation from the DA and DM nerves was 0.1 ± 0.3 and 0.1 ± 0.2 ms (mean ± S.D.) longer than that of the homonymous monosynaptic Ia facilitation of BB, respectively, the facilitation thus being compatible with monosynaptic path. In the EMG-A study, stimulation to the DA and DM nerves produced a significant peak (facilitation) for the BB motoneuron pool in all the subjects, whereas stimulation to the DP nerve produced no effect on BB. The facilitation diminished by vibration stimulation, and the suppression lasted for 30-40 min after removal of the vibration. Therefore, group Ia afferents should be responsible for the facilitation. These findings suggest that monosynaptic facilitation mediated by group Ia afferents from the DA and DM nerves to BB motoneurons exists in humans.

Sperm-Force: Naturphilosophie and George Newport's Quest to Discover the Secret of Fertilization.

This paper analyses the forgotten concept of "sperm-force" proposed by George Newport (1803-1854). Newport is known for his comprehensive microscopic examinations of sperm and egg interaction in amphibian fertilization between 1850 and 1854. My work with archival sources reveals that Newport believed fertilization was caused by sperm-force, which the Royal Society refused to publish. My reconstruction chronologically traces the philosophical and experimental origins of sperm-force to Newport's 1830s entomological work. Sperm-force is a remnant of Newport's speculations on the creation of the active individual. I argue that sperm-force was rooted in British interpretations of German Naturphilosophie, which demonstrates Continental influences on mid-Victorian embryology, particularly the role of male generative power. This context provides further evidence that British versions of Romantic science fostered sophisticated experimental work. The refusal by Paleyite stalwarts of natural theology to publish Newport's ideas illustrates the institutional resistance to German pantheistic and vitalistic influences. This reconstruction of sperm-force's philosophical foundation and its reception offers new understandings of mid-Victorian attitudes toward the inheritance of mind and body. It situates Newport's work within the nineteenth century's scientific project to assign stereotypical genders to the gametes.

Deep Inspiration-Provoked Cough: A Sign of Cough Reflex Arc Hypersensitivity.

Deep inspiration-provoked cough (DIPC) is a form of allotussia. Allotussia is thought to be a manifestation of cough reflex arc hypersensitivity but objective evidence about this is lacking. 36 subjects with chronic cough and 25 healthy subjects underwent mannitol and citric acid cough provocation tests. DIPC was defined as two or more coughs after deep inhalation of an empty mannitol capsule. Citric acid was administered utilizing a dosimetric nebulizer during controlled tidal breathing. Nine subjects demonstrated DIPC, 8/36 subjects with chronic cough and 1/25 healthy subjects (p = 0.048). The concentration of citric acid to provoke five or more coughs (C5) was 23.4 (63.8) mM among subjects with DIPC and 750 (2941) mM among the subjects without it (p = 0.006). The number of deep inspiration-provoked coughs correlated with the citric acid C5 (Rs -0.38, p = 0.002). In conclusion, DIPC, a form of allotussia, is associated with cough reflex arc hypersensitivity.Trial Registration Number.ClinicalTrials.gov database KUH5801136.

Differentiation of Intrafusal Fibers from Human Induced Pluripotent Stem Cells.

Human-based "body-on-a-chip" technology provides powerful platforms in developing models for drug evaluation and disease evaluations in phenotypic models. Induced pluripotent stem cells (iPSCs) are ideal cell sources for generating different cell types for these in vitro functional systems and recapitulation of the neuromuscular reflex arc would allow for the study of patient specific neuromuscular diseases. Regarding relevant afferent (intrafusal fibers, sensory neurons) and efferent (extrafusal fibers, motoneurons) cells, in vitro differentiation of intrafusal fiber from human iPSCs has not been established. This work demonstrates a protocol for inducing an enrichment of intrafusal bag fibers from iPSCs using morphological analysis and immunocytochemistry. Phosphorylation of the ErbB2 receptors and S46 staining indicated a 3-fold increase of total intrafusal fibers further confirming the efficiency of the protocol. Integration of induced intrafusal fibers would enable more accurate reflex arc models and application of this protocol on patient iPSCs would allow for patient-specific disease modeling.

An Artificial Somatic Reflex Arc.

The emulation of human sensation, perception, and action processes has become a major challenge for bioinspired intelligent robotics, interactive human-machine interfacing, and advanced prosthetics. Reflex actions, enabled through reflex arcs, are important for human and higher animals to respond to stimuli from environment without the brain processing and survive the risks of nature. An artificial reflex arc system that emulates the functions of the reflex arc simplifies the complex circuit design needed for "central-control-only" processes and becomes a basic electronic component in an intelligent soft robotics system. An artificial somatic reflex arc that enables the actuation of electrochemical actuators in response to the stimulation of tactile pressures is reported. Only if the detected pressure by the pressure sensor is above the stimulus threshold, the metal-organic-framework-based threshold controlling unit (TCU) can be activated and triggers the electrochemical actuators to complete the motion. Such responding mechanism mimics the all-or-none law in the human nervous system. As a proof of concept, the artificial somatic reflex arc is successfully integrated into a robot to mimic the infant grasp reflex. This work provides a unique and simplifying strategy for developing intelligent soft robotics, next-generation human-machine interfaces, and neuroprosthetics.

Short-term resistance training with instability reduces impairment in V wave and H reflex in individuals with Parkinson's disease.

This study had two objectives: 1) to compare the effects of 3 wk of resistance training (RT) and resistance training with instability (RTI) on evoked reflex responses at rest and during maximal voluntary isometric contraction (MVIC) of individuals with Parkinson's disease (PD) and 2) to determine the effectiveness of RT and RTI in moving values of evoked reflex responses of individuals with PD toward values of age-matched healthy control subjects (HCs) (z-score analysis). Ten individuals in the RT group and 10 in the RTI group performed resistance exercises twice a week for 3 wk, but only the RTI group included unstable devices. The HC group (n = 10) were assessed at pretest only. Evoked reflex responses at rest (H reflex and M wave) and during MVIC [supramaximal M-wave amplitude (Msup) and supramaximal V-wave amplitude (Vsup)] of the plantar flexors were assessed before and after the experimental protocol. From pretraining to posttraining, only RTI increased ratio of maximal H-reflex amplitude to maximal M-wave amplitude at rest (Hmax/Mmax), Msup, Vsup/Msup, and peak torque of the plantar flexors (P < 0.05). At posttraining, RTI was more effective than RT in increasing resting Hmax and Vsup and in moving these values to those observed in HCs (P < 0.05). We conclude that short-term RTI is more effective than short-term RT in modulating H-reflex excitability and in increasing efferent neural drive, approaching average values of HCs. Thus short-term RTI may cause positive changes at the spinal and supraspinal levels in individuals with PD. NEW & NOTEWORTHY Maximal H-reflex amplitude (Hmax) at rest and efferent neural drive [i.e., supramaximal V-wave amplitude (Vsup)] to skeletal muscles during maximal contraction are impaired in individuals with Parkinson's disease. Short-term resistance training with instability was more effective than short-term resistance training alone in increasing Hmax and Vsup of individuals with Parkinson's disease, reaching the average values of healthy control subjects.

Two Episodes of Trigeminocardiac Reflex During a Pan facial Fracture Surgery, a Rare Phenomenon - Case Report and Review of Literature.

Trigeminocardiac reflex is a sudden physiologic response due to mechanical manipulation of any of the branches of trigeminal nerve. Trigeminocardiac reflex occurs due to pressure effect or stretching of trigeminal nerve which causes fall in blood pressure and decrease in heart rate. In this reflex arc, the trigeminal nerve serves as afferent pathway and vagus nerve, which is cardio inhibitory in nature, serves as efferent pathway. Two episodes of trigeminocardiac reflex during maxillofacial trauma surgery is not a common phenomenon. The present case report describes a case of 40-year-old male patient, diagnosed with pan facial fracture in which two episodes of trigeminocardiac reflex were seen intraoperatively during fracture reduction and fixation of left zygomaticomaxillary complex fracture and inferior orbital rim fracture. Intraoperative management of trigeminocardiac reflex was done by withholding the stimulus and administration of atropine.

Vagal afferents, sympathetic efferents and the role of the PVN in heart failure.

Sympatho-excitation is a characteristic of cardiovascular disease including heart failure (HF). The paraventricular nucleus of the hypothalamus (PVN) is an important site for central integration of sympathetic outflow. Atrial volume receptors (AVRs) in the wall of the right atrium transduce cardiovascular variables (pressure/volume) into an input that is integrated centrally, in for example, the PVN. Descriptions of the location and structure of the AVRs as well as the molecular mechanism initiating transduction remain scarce, nevertheless preautonomic neurons of the PVN have been consistently identified as making a significant contribution to the sympatho-excitation evident in HF. Furthermore, excitatory and inhibitory interactions within the PVN determine sympathetic tone. A nitric oxide dependent GABAergic inhibition sets the prevailing sympathetic output from the PVN, which in HF becomes dysregulated. Inflammation and oxidative stress have been recognised as possible triggers to the disinhibition. The actions of proinflammatory cytokines and reactive oxygen species in relation to the signalling pathways, which are important in generating sympathetic tone are discussed, as well as the contribution these might make to abnormal control of the sympathetic nervous system in cardiovascular disease.

Altered bulbocavernosus reflex in patients with multiple system atrophy.

OBJECTIVES: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR. METHODS: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses. RESULTS: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively). DISCUSSION: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.