Investigation into a new denervation model of the sciatic nerve zones in rats: Selective motor or sensorial denervation.

OBJECTIVE: This study aimed to introduce a reliable and useful model of selective sensorial or motor denervations of the sciatic nerve in rats with clinical and laboratory outcomes. METHODS: The surgical technique was determined via detailed cadaveric dissections of rat sciatic nerve roots and cross-sectional histoanatomy. Forty animals were divided into the sham, sensorial denervation (SD), motor denervation (MD), and combined denervation (CD) groups and evaluated clinically via the pinch test and observation. Electrophysiological tests, retrograde neuronal labeling, and histologic and radiographic studies were performed. The weights of the muscles innervated by the sciatic nerve were measured. RESULTS: The nerve root topography at the L4 level was consistent. Hemilaminectomy satisfactorily exposed all the roots contributing to the sciatic nerve and selectively denervated its sensorial and motor zones. Sensorial denervation caused foot deformities and wound problems, which were more severe in SD than in MD and CD. Nerve histomorphometry, electrophysiological tests, retrograde neuronal labeling studies, and measurements of the muscle weights also verified the denervations. CONCLUSION: This study has shown the feasibility of selective (sensory or motor) sciatic nerve denervation through a single-level hemilaminectomy. The surgical technique is reliable and has a confounding effect on gait. Sensorial denervation had more severe foot problems than motor and combined denervation in rats.

Differential control of sympathetic outflow to muscle and skin during physical and cognitive stressors.

PURPOSE: Sympathetic nerve activity towards muscle (MSNA) and skin (SSNA) regulates various physiological parameters. MSNA primarily functions in blood pressure and flow, while SSNA operates in thermoregulation. Physical and cognitive stressors have been shown to have effects on both types of sympathetic activity, but there are inconsistencies as to what these effects are. This article aims to address the discrepancies in the literature and compare MSNA and SSNA responses. METHODS: Microelectrode recordings were taken from the common peroneal nerve in 29 participants: MSNA (n = 21), SSNA (n = 16) and both MSNA and SSNA (n = 8). Participants were subjected to four different 2-min stressors: two physical (isometric handgrip task, cold pressor test) and two cognitive (mental arithmetic task, Stroop colour-word conflict test), the latter of which saw participants separated into responders and non-responders to the stressors. It was hypothesised that the physical stressors would have a greater effect on MSNA than SSNA, while the cognitive stressors would operate conversely. RESULTS: Peristimulus time histogram (PSTH) analysis showed the mental arithmetic task to significantly increase both MSNA and SSNA; the isometric handgrip task and cold pressor test to increase MSNA, but not SSNA; and Stroop test to have no significant effects on changing MSNA or SSNA from baseline. Additionally, stress responses did not differ between MSNA and SSNA in participants who had both sets of data recorded. CONCLUSIONS: This study has provided evidence to support the literature which claims cognitive stressors increase sympathetic activity, and provides much needed SSNA data in response to stressors.

Injectable tissue prosthesis for instantaneous closed-loop rehabilitation.

To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces3-5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.

Bridging two insect flight modes in evolution, physiology and robophysics.

Since taking flight, insects have undergone repeated evolutionary transitions between two seemingly distinct flight modes1-3. Some insects neurally activate their muscles synchronously with each wingstroke. However, many insects have achieved wingbeat frequencies beyond the speed limit of typical neuromuscular systems by evolving flight muscles that are asynchronous with neural activation and activate in response to mechanical stretch2-8. These modes reflect the two fundamental ways of generating rhythmic movement: time-periodic forcing versus emergent oscillations from self-excitation8-10. How repeated evolutionary transitions have occurred and what governs the switching between these distinct modes remain unknown. Here we find that, despite widespread asynchronous actuation in insects across the phylogeny3,6, asynchrony probably evolved only once at the order level, with many reversions to the ancestral, synchronous mode. A synchronous moth species, evolved from an asynchronous ancestor, still preserves the stretch-activated muscle physiology. Numerical and robophysical analyses of a unified biophysical framework reveal that rather than a dichotomy, these two modes are two regimes of the same dynamics. Insects can transition between flight modes across a bridge in physiological parameter space. Finally, we integrate these two actuation modes into an insect-scale robot11-13 that enables transitions between modes and unlocks a new self-excited wingstroke strategy for engineered flight. Together, this framework accounts for repeated transitions in insect flight evolution and shows how flight modes can flip with changes in physiological parameters.

Description of the neuroanatomy of the brachial plexus in South American lizards. Phylogenetic implications.

Few studies considered the anatomy of the nerve plexuses and musculature associated with them in ectothermic sauropsids. Based on differentiated Sudan Black B staining and conventional dissections, we describe the neuroanatomy of the brachial plexus, its main associated nerves, and muscles. For that, representatives of the genera Diplolaemus, Liolaemus, Phymaturus, and Tropidurus were selected. Based on this, potentially useful characters for phylogenetic analysis were described. Our results show that the brachial plexus can be formed by four, five, or six nerve branches. The brachial flexor trunk, circumflex, interosseous, median, radial, subscapulocoracoid, supracoracoid, and ulnar nerves were identified. Regarding the muscles innervated by the main nerves, the following muscles were identified: biceps brachii, deltoideus scapularis, latissimus dorsi, levator scapulae, pectoralis, serratus thoracis, trapezius, triceps longus caudalis, and triceps longus lateralis. Phylogenetic analyzes revealed 31 potential synapomorphies. There exists evidence that neuroanatomy studies in a phylogenetic context could provide useful information helping to elucidate the relationships between taxonomic groups.

Biomechanics, motor control and dynamic models of the soft limbs of the octopus and other cephalopods.

Muscular hydrostats are organs composed entirely of packed arrays of incompressible muscles and lacking any skeletal support. Found in both vertebrates and invertebrates, they are of great interest for comparative biomechanics from engineering and evolutionary perspectives. The arms of cephalopods (e.g. octopus and squid) are particularly interesting muscular hydrostats because of their flexibility and ability to generate complex behaviors exploiting elaborate nervous systems. Several lines of evidence from octopus studies point to the use of both brain and arm-embedded motor control strategies that have evolved to simplify the complexities associated with the control of flexible and hyper-redundant limbs and bodies. Here, we review earlier and more recent experimental studies on octopus arm biomechanics and neural motor control. We review several dynamic models used to predict the kinematic characteristics of several basic motion primitives, noting the shortcomings of the current models in accounting for behavioral observations. We also discuss the significance of impedance (stiffness and viscosity) in controlling the octopus's motor behavior. These factors are considered in light of several new models of muscle biomechanics that could be used in future research to gain a better understanding of motor control in the octopus. There is also a need for updated models that encompass stiffness and viscosity for designing and controlling soft robotic arms. The field of soft robotics has boomed over the past 15 years and would benefit significantly from further progress in biomechanical and motor control studies on octopus and other muscular hydrostats.

Volume conduction: Extracellular waveform generation in theory and practice.

The extracellular waveform manifestations of the intracellular action potential are the quintessential diagnostic foundation of electrodiagnostic medicine, and clinical neurophysiology in general. Volume conduction is the extracellular current flow and associated voltage distributions in an ionic conducting media, such as occurs in the human body. Both surface and intramuscular electrodes, in association with contemporary digital electromyographic systems, permit very sensitive detection and visualization of this extracellular spontaneous, voluntary, and evoked nerve/muscle electrical activity. Waveform configuration, with its associated discharge rate/rhythm, permits the identification of normal and abnormal waveforms, thereby assisting in the diagnosis of nerve and muscle pathology. This monograph utilizes a simple model to explain the various waveforms that may be encountered. There are a limited number of waveforms capable of being generated in excitable tissues which conform to well-known volume conductor concepts. Using these principles, such waveforms can be quickly identified in real time during clinical studies.

Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine.

Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87-95. Reprinted with permission. By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.

Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.

AIMS: Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls. METHODS AND RESULTS: We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25 ± 11% [mean ± standard deviation]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18-81 years). In heart failure, MSNA ranged between 7 and 90 bursts·min-1 , proportionate to heart rate (p < 0.0001) and body mass index (BMI) (p = 0.03), but was unrelated to age, blood pressure, or drug therapy. Mean MSNA, adjusted for age, sex, BMI, and heart rate, was greater in heart failure (+14.2 bursts·min-1 ; 95% confidence interval [CI] 12.1-16.3; p < 0.0001), but lower in women (-5.0 bursts·min-1 ; 95% CI 3.4-6.6; p < 0.0001). With spline modeling, LVEF accounted for 9.8% of MSNA variance; MSNA related inversely to LVEF below an inflection point of ∼21% (p < 0.006), but not above. Burst incidence was greater in ischaemic than dilated cardiomyopathy (p = 0.01), and patients with sleep apnoea (p = 0.03). Burst frequency correlated inversely with stroke volume (p < 0.001), cardiac output (p < 0.001), and peak oxygen consumption (p = 0.002), and directly with norepinephrine (p < 0.0001) and peripheral resistance (p < 0.001). CONCLUSION: Burst frequency and incidence exceeded normative values in only ∼53% and ∼33% of patients. Such diversity encourages selective deployment of sympatho-modulatory therapies. Clinical characteristics can highlight individuals who may benefit from future personalized interventions targeting pathological sympathetic activation.

Influence of Obstructive Sleep Apnea Severity on Muscle Sympathetic Nerve Activity and Blood Pressure: a Systematic Review and Meta-Analysis.

BACKGROUND: We conducted meta-analyses to identify relationships between obstructive sleep apnea (OSA) severity, muscle sympathetic nerve activity (MSNA), and blood pressure (BP). We quantified the effect of OSA treatment on MSNA. METHODS: Structured searches of electronic databases were performed until June 2021. All observational designs (except reviews) were included: population (individuals with OSA); exposures (OSA diagnosis and direct measures of MSNA); comparator (individuals without OSA or different severity of OSA); outcomes (MSNA, BP, and heart rate). RESULTS: Fifty-six studies (N=1872) were included. MSNA burst frequency was higher in OSA (27 studies; n=542) versus controls (n=488; mean differences [MDs], +15.95 bursts/min [95% CI, 12.6-17.6 bursts/min]; I2=86%). As was burst incidence (20 studies; n=357 OSA, n=312 Controls; MD, +22.23 bursts/100 hbs [95% CI, 18.49-25.97 bursts/100 hbs]; I2=67%). Meta-regressions indicated relationships between MSNA and OSA severity (burst frequency, R2=0.489; P<0.001; burst incidence, R2=0.573; P<0.001). MSNA burst frequency was related to systolic pressure (R2=0.308; P=0.016). OSA treatment with continuous positive airway pressure reduced MSNA burst frequency (MD, 11.91 bursts/min [95% CI, 9.36-14.47 bursts/min] I2=15%) and systolic (n=49; MD, 10.3 mm Hg [95% CI, 3.5-17.2 mm Hg]; I2=42%) and diastolic (MD, 6.9 mm Hg [95% CI, 2.3-11.6 mm Hg]; I2=37%) BP. CONCLUSIONS: MSNA is higher in individuals with OSA and related to severity. This sympathoexcitation is also related to BP in patients with OSA. Treatment effectively reduces MSNA and BP, but limited data prevents an assessment of the link between these reductions. These data are clinically important for understanding cardiovascular disease risk in patients with OSA. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42021285159.

The myokinetic stimulation interface: activation of proprioceptive neural responses with remotely actuated magnets implanted in rodent forelimb muscle.

Objective. Proprioception is the sense of one's position, orientation, and movement in space, and it is of fundamental importance for motor control. When proprioception is impaired or absent, motor execution becomes error-prone, leading to poorly coordinated movements. The kinaesthetic illusion, which creates perceptions of limb movement in humans through non-invasively applying vibrations to muscles or tendons, provides an avenue for studying and restoring the sense of joint movement (kinaesthesia). This technique, however, leaves ambiguity between proprioceptive percepts that arise from muscles versus those that arise from skin receptors. Here we propose the concept of a stimulation system to activate kinaesthesia through the untethered application of localized vibration through implanted magnets.Approach. In this proof-of-concept study, we use two simplified one-DoF systems to show the feasibility of eliciting muscle-sensory responses in an animal model across multiple frequencies, including those that activate the kinaesthetic illusion (70-115 Hz). Furthermore, we generalized the concept by developing a five-DoF prototype system capable of generating directional, frequency-selective vibrations with desired displacement profiles.Main results. In-vivotests with the one-DoF systems demonstrated the feasibility to elicit muscle sensory neural responses in the median nerve of an animal model. Instead,in-vitrotests with the five-DoF prototype demonstrated high accuracy in producing directional and frequency selective vibrations along different magnet axes.Significance. These results provide evidence for a new technique that interacts with the native neuro-muscular anatomy to study proprioception and eventually pave the way towards the development of advanced limb prostheses or assistive devices for the sensory impaired.

Botulinum toxin in the masseter muscle: Lingering effects of denervation.

Botulinum neurotoxins (BoNTs) are paralytic agents used to treat a variety of conditions in jaw muscles. Although their effect is considered temporary, there are reports of persistent functional changes. Using rabbits that received BoNT injection in one masseter muscle, the recovery of neuromuscular connection was investigated using nerve stimulation to evoke an electromyographic (EMG) response, and the recovery of muscle fibers was investigated using histological morphometry and bromodeoxyuridine (BrdU) immunohistochemistry. One month after treatment, evoked EMG was greatly reduced in both amplitude and duration, indicating that little reinnervation had taken place. Muscle fibers were atrophied and collagenous tissue was increased. Three months after treatment, evoked EMG duration was normal, indicating that at least some neuromuscular junctions were functional. Histologically, some muscle fibers were hypertrophied, some were still atrophied, and some appeared to have died. Fibrosis was still apparent amid slight increases in dividing cells and regenerating fibers. The histological effects of BoNT were evident although attenuated at a distance of about 1 cm from the injection level, but no regional differences could be discerned for the evoked EMGs. In conclusion, there were persistent muscular deficits seen 3 months after BoNT treatment that may have been caused by the failure of some affected muscle fibers to become reinnervated.

Molecular Mechanisms Underlying Motor Axon Guidance in Drosophila.

Decoding the molecular mechanisms underlying axon guidance is key to precise understanding of how complex neural circuits form during neural development. Although substantial progress has been made over the last three decades in identifying numerous axon guidance molecules and their functional roles, little is known about how these guidance molecules collaborate to steer growth cones to their correct targets. Recent studies in Drosophila point to the importance of the combinatorial action of guidance molecules, and further show that selective fasciculation and defasciculation at specific choice points serve as a fundamental strategy for motor axon guidance. Here, I discuss how attractive and repulsive guidance cues cooperate to ensure the recognition of specific choice points that are inextricably linked to selective fasciculation and defasciculation, and correct pathfinding decision-making.

Miniature neurotransmission is required to maintain Drosophila synaptic structures during ageing.

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.

The Sex-Specific VC Neurons Are Mechanically Activated Motor Neurons That Facilitate Serotonin-Induced Egg Laying in C. elegans.

Successful execution of behavior requires coordinated activity and communication between multiple cell types. Studies using the relatively simple neural circuits of invertebrates have helped to uncover how conserved molecular and cellular signaling events shape animal behavior. To understand the mechanisms underlying neural circuit activity and behavior, we have been studying a simple circuit that drives egg-laying behavior in the nematode worm Caenorhabditis elegans Here we show that the sex-specific, ventral C (VC) motor neurons are important for vulval muscle contractility and egg laying in response to serotonin. Ca2+ imaging experiments show the VCs are active during times of vulval muscle contraction and vulval opening, and optogenetic stimulation of the VCs promotes vulval muscle Ca2+ activity. Blocking VC neurotransmission inhibits egg laying in response to serotonin and increases the failure rate of egg-laying attempts, indicating that VC signaling facilitates full vulval muscle contraction and opening of the vulva for efficient egg laying. We also find the VCs are mechanically activated in response to vulval opening. Optogenetic stimulation of the vulval muscles is sufficient to drive VC Ca2+ activity and requires muscle contractility, showing the presynaptic VCs and the postsynaptic vulval muscles can mutually excite each other. Together, our results demonstrate that the VC neurons facilitate efficient execution of egg-laying behavior by coordinating postsynaptic muscle contractility in response to serotonin and mechanosensory feedback.SIGNIFICANCE STATEMENT Many animal motor behaviors are modulated by the neurotransmitters, serotonin and ACh. Such motor circuits also respond to mechanosensory feedback, but how neurotransmitters and mechanoreceptors work together to coordinate behavior is not well understood. We address these questions using the egg-laying circuit in Caenorhabditis elegans where we can manipulate presynaptic neuron and postsynaptic muscle activity in behaving animals while recording circuit responses through Ca2+ imaging. We find that the cholinergic VC motoneurons are important for proper vulval muscle contractility and egg laying in response to serotonin. Muscle contraction also activates the VCs, forming a positive feedback loop that promotes full contraction for egg release. In all, mechanosensory feedback provides a parallel form of modulation that shapes circuit responses to neurotransmitters.

Structural and Functional Synaptic Plasticity Induced by Convergent Synapse Loss in the Drosophila Neuromuscular Circuit.

Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other's structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is the Drosophila larval neuromuscular junction (NMJ) where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s MNs; we surveyed multiple muscles for this reason. Here, we identified a cell-specific promoter that allows ablation of 1s MNs postinnervation and measured structural and functional responses of convergent 1b NMJs using microscopy and electrophysiology. For all muscles examined in both sexes, ablation of 1s MNs resulted in NMJ expansion and increased spontaneous neurotransmitter release at corresponding 1b NMJs. This demonstrates that 1b NMJs can compensate for the loss of convergent 1s MNs. However, only a subset of 1b NMJs showed compensatory evoked neurotransmission, suggesting target-specific plasticity. Silencing 1s MNs led to similar plasticity at 1b NMJs, suggesting that evoked neurotransmission from 1s MNs contributes to 1b synaptic plasticity. Finally, we genetically blocked 1s innervation in male larvae and robust 1b synaptic plasticity was eliminated, raising the possibility that 1s NMJ formation is required to set up a reference for subsequent synaptic perturbations.SIGNIFICANCE STATEMENT In complex neural circuits, multiple convergent inputs contribute to the activity of the target cell, but whether synaptic plasticity exists among these inputs has not been thoroughly explored. In this study, we examined synaptic plasticity in the structurally and functionally tractable Drosophila larval neuromuscular system. In this convergent circuit, each muscle is innervated by a unique pair of motor neurons. Removal of one neuron after innervation causes the adjacent neuron to increase neuromuscular junction outgrowth and functional output. However, this is not a general feature as each motor neuron differentially compensates. Further, robust compensation requires initial coinnervation by both neurons. Understanding how neurons respond to perturbations in adjacent neurons will provide insight into nervous system plasticity in both healthy and disease states.

Diabetic thoracic radiculopathy: a case of a young woman with clinical improvement following immunotherapy.

Thoracic radiculopathy is a rare cause of thoracic-abdominal or abdominal pain in subjects with poorly controlled diabetes. We present a case of a young woman with type I diabetes and a severe abdominal pain in both lower quadrants. An extensive diagnostic gastroenterological and gynaecological workup did not disclose abnormalities. Electromyography revealed an initial polyneuropathy and significant neurogenic abnormalities in the T10-T12 paravertebral muscles. Following the hypothesis that the radiculopathy-related abdominal pain might have an immuno-mediated pathogenesis, the patient underwent a complex trial of immunotherapy, which was accompanied by a sustained improvement over months to full recovery. This report would support the hypothesis that immune-mediated mechanisms are still active even months after onset of symptoms.

Distributed control of motor circuits for backward walking in Drosophila.

How do descending inputs from the brain control leg motor circuits to change how an animal walks? Conceptually, descending neurons are thought to function either as command-type neurons, in which a single type of descending neuron exerts a high-level control to elicit a coordinated change in motor output, or through a population coding mechanism, whereby a group of neurons, each with local effects, act in combination to elicit a global motor response. The Drosophila Moonwalker Descending Neurons (MDNs), which alter leg motor circuit dynamics so that the fly walks backwards, exemplify the command-type mechanism. Here, we identify several dozen MDN target neurons within the leg motor circuits, and show that two of them mediate distinct and highly-specific changes in leg muscle activity during backward walking: LBL40 neurons provide the hindleg power stroke during stance phase; LUL130 neurons lift the legs at the end of stance to initiate swing. Through these two effector neurons, MDN directly controls both the stance and swing phases of the backward stepping cycle. These findings suggest that command-type descending neurons can also operate through the distributed control of local motor circuits.

Targeted muscle reinnervation following external hemipelvectomy or hip disarticulation: An anatomic description of technique and clinical case correlates.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to decrease or prevent neuropathic pain, including phantom and residual limb pain, after extremity amputation. Currently, a paucity of data and lack of anatomical description exists regarding TMR in the setting of hemipelvectomy and/or hip disarticulations. We elaborate on the technique of TMR, illustrated through cadaveric and clinical correlates. METHODS: Cadaveric dissections of multiple transpelvic exposures were performed. The major mixed motor and sensory nerve branches were identified, dissected, and tagged. Amputated peripheral nerves were transferred to identified, labeled target motor nerves via direct end-to-end nerve coaptations per traditional TMR technique. A retrospective review was completed by our multi-institutional teams to include examples of clinical correlates for TMR performed in the setting of hemipelvectomies and hip disarticulations. RESULTS: A total of 12 TMR hemipelvectomy/hip disarticulation cases were performed over a 2 to 3-year period (2018-2020). Of these 12 cases, 9 were oncologic in nature, 2 were secondary to traumatic injury, and 1 was a failed limb salvage in the setting of chronic refractory osteomyelitis of the femoral shaft. CONCLUSIONS: This manuscript outlines the technical considerations for TMR in the setting of hemipelvectomy and hip disarticulation with supporting clinical case correlates.

Ketamine-induced neuromuscular reactivity is associated with aging in female rhesus macaques.

Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized. Urodynamic recordings and electromyography (EMG) studies were performed in aged (>20 years old) and adult (3.9-14.9 years old) female rhesus macaques under an equal and light plane of sedation by constant rate infusion (CRI) of ketamine. A total of 4 of 41 adult subjects (9.7%) showed clinical signs of ketamine-induced abnormal neuromuscular reactivity, whereas a larger portion of 14 of 26 aged subjects showed similar ketamine-induced neuromuscular reactivity (53.8%; P< 0.001). The ketamine CRI rate was 19.8±0.9 mg/kg/h in adults and lower in aged subjects at 16.5±1.4 mg/kg/h (P<0.05). The ketamine CRI rate was negatively correlated with age (r = -0.30, P<0.05, n = 64). The incidence of ketamine reactivity or CRI rate was not different between aged pre-and post-menopausal females. EMG recordings during neuromuscular reactivity showed coordinated activation of multiple muscles, suggesting a central nervous system (CNS) mechanism for ketamine-associated neuromuscular reactivity. The incidence of ketamine-induced neuromuscular reactivity is age related but not affected by the estrous cycle in female rhesus macaques. A coordinated activation of multiple muscles, innervated by different peripheral nerves, suggests that ketamine-induced neuromuscular reactivity originates in the CNS.