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.

Interventional- and amputation-stage muscle proteomes in the chronically threatened ischemic limb.

BACKGROUND: Despite improved surgical approaches for chronic limb-threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. The purpose of this study was twofold: (1) to identify differences between the healthy adult and CLTI limb muscle proteome, and (2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation. METHODS AND RESULTS: Gastrocnemius muscle was collected from non-ischemic controls (n = 19) and either pre-interventional surgery (n = 10) or at amputation outcome (n = 29) CLTI patients. All samples were subjected to isobaric tandem-mass-tag-assisted proteomics. The mitochondrion was the primary classification of downregulated proteins (> 70%) in CLTI limb muscles and paralleled robust functional mitochondrial impairment. Upregulated proteins (> 38%) were largely from the extracellular matrix. Across the two independent sites, 39 proteins were downregulated and 12 upregulated uniformly. Pre-interventional CLTI muscles revealed a robust upregulation of mitochondrial proteins but modest functional impairments in fatty acid oxidation as compared with controls. Comparison of pre-intervention and amputation CLTI limb muscles revealed mitochondrial proteome and functional deficits similar to that between amputation and non-ischemic controls. Interestingly, these observed changes occurred despite 62% of the amputation CLTI patients having undergone a prior surgical intervention. CONCLUSIONS: The CLTI proteome supports failing mitochondria as a phenotype that is unique to amputation outcomes. The signature of pre-intervention CLTI muscle reveals stable mitochondrial protein abundance that is insufficient to uniformly prevent functional impairments. Taken together, these findings support the need for future longitudinal investigations aimed to determine whether mitochondrial failure is causally involved in amputation outcomes from CLTI.

Sensory and motor electrophysiological mapping of the cerebellum in humans.

Cerebellar damage during posterior fossa surgery in children can lead to ataxia and risk of cerebellar mutism syndrome. Compartmentalisation of sensorimotor and cognitive functions within the cerebellum have been demonstrated in animal electrophysiology and human imaging studies. Electrophysiological monitoring was carried out under general anaesthesia to assess the limb sensorimotor representation within the human cerebellum for assessment of neurophysiological integrity to reduce the incidence of surgical morbidities. Thirteen adult and paediatric patients undergoing posterior fossa surgery were recruited. Sensory evoked field potentials were recorded in response to mapping (n = 8) to electrical stimulation of limb nerves or muscles. For motor mapping (n = 5), electrical stimulation was applied to the surface of the cerebellum and evoked EMG responses were sought in facial and limb muscles. Sensory evoked potentials were found in two patients (25%). Responses were located on the surface of the right inferior posterior cerebellum to stimulation of the right leg in one patient, and on the left inferior posterior lobe in another patient to stimulation of left forearm. No evoked EMG responses were found for the motor mapping. The present study identifies challenges with using neurophysiological methods to map functional organization within the human cerebellum and considers ways to improve success.

Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat.

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping. Given the ventrolateral location of LAPN axons in the spinal cord white matter, many likely remain intact following incomplete, contusive, thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would disrupt recovered locomotion. Instead, we found that silencing spared LAPNs post-SCI improved locomotor function, including paw placement order and timing, and a decrease in the number of dorsal steps. Silencing also restored left-right hindlimb coordination and normalized spatiotemporal features of gait such as stance and swing time. However, hindlimb-forelimb coordination was not restored. These data indicate that the temporal information carried between the spinal enlargements by the spared LAPNs post-SCI is detrimental to recovered hindlimb locomotor function. These findings are an illustration of a post-SCI neuroanatomical-functional paradox and have implications for the development of neuronal- and axonal-protective therapeutic strategies and the clinical study/implementation of neuromodulation strategies.

Comparing nerve-mediated FGF signalling in the early initiation phase of organ regeneration across mutliple amphibian species.

Amphibians have a very high capacity for regeneration among tetrapods. This superior regeneration capability in amphibians can be observed in limbs, the tail, teeth, external gills, the heart, and some internal organs. The mechanisms underlying the superior organ regeneration capability have been studied for a long time. Limb regeneration has been investigated as the representative phenomenon for organ-level regeneration. In limb regeneration, a prominent difference between regenerative and nonregenerative animals after limb amputation is blastema formation. A regeneration blastema requires the presence of nerves in the stump region. Thus, nerve regulation is responsible for blastema induction, and it has received much attention. Nerve regulation in regeneration has been investigated using the limb regeneration model and newly established alternative experimental model called the accessory limb model. Previous studies have identified some candidate genes that act as neural factors in limb regeneration, and these studies also clarified related events in early limb regeneration. Consistent with the nervous regulation and related events in limb regeneration, similar regeneration mechanisms in other organs have been discovered. This review especially focuses on the role of nerve-mediated fibroblast growth factor in the initiation phase of organ regeneration. Comparison of the initiation mechanisms for regeneration in various amphibian organs allows speculation about a fundamental regenerative process.

Peripheral nerve adaptations to 10 days of horizontal bed rest in healthy young adult males.

Space analogs, such as bed rest, are used to reproduce microgravity-induced morphological and physiological changes and can be used as clinical models of prolonged inactivity. Nevertheless, nonuniform decreases in muscle mass and function have been frequently reported, and peripheral nerve adaptations have been poorly studied, although some of these mechanisms may be explained. Ten young healthy males (18-33 yr) underwent 10 days of horizontal bed rest. Peripheral neurophysiological assessments were performed bilaterally for the dominant (DL) and nondominant upper and lower limbs (N-DL) on the 1st and 10th day of bed rest, including ultrasound of the median, deep peroneal nerve (DPN), and common fibular nerve (CFN) , as well as a complete nerve conduction study (NCS) of the upper and lower limbs. Consistently, reduced F waves, suggesting peripheral nerve dysfunction, of both the peroneal (DL: P = 0.005, N-DL: P = 0.013) and tibial nerves (DL: P = 0.037, N-DL: P = 0.005) were found bilaterally, whereas no changes were observed in nerve ultrasound or other parameters of the NCS of both the upper and lower limbs. In these young healthy males, only the F waves, known to respond to postural changes, were significantly affected by short-term bed rest. These preliminary results suggest that during simulated microgravity, most changes occur at the muscle or central nervous system level. Since the assessment of F waves is common in clinical neurophysiological examinations, caution should be used when testing individuals after prolonged immobility.

The CPGs for Limbed Locomotion-Facts and Fiction.

The neuronal networks that generate locomotion are well understood in swimming animals such as the lamprey, zebrafish and tadpole. The networks controlling locomotion in tetrapods remain, however, still enigmatic with an intricate motor pattern required for the control of the entire limb during the support, lift off, and flexion phase, and most demandingly when the limb makes contact with ground again. It is clear that the inhibition that occurs between bursts in each step cycle is produced by V2b and V1 interneurons, and that a deletion of these interneurons leads to synchronous flexor-extensor bursting. The ability to generate rhythmic bursting is distributed over all segments comprising part of the central pattern generator network (CPG). It is unclear how the rhythmic bursting is generated; however, Shox2, V2a and HB9 interneurons do contribute. To deduce a possible organization of the locomotor CPG, simulations have been elaborated. The motor pattern has been simulated in considerable detail with a network composed of unit burst generators; one for each group of close synergistic muscle groups at each joint. This unit burst generator model can reproduce the complex burst pattern with a constant flexion phase and a shortened extensor phase as the speed increases. Moreover, the unit burst generator model is versatile and can generate both forward and backward locomotion.

Severe Unilateral Proprioceptive Loss in Medullary- Rostral Spinal Cord Infarction. A Posterior Spinal Artery Syndrome.

We draw attention to a unique presentation, severe unilateral loss of limb proprioception, in patients with medullary and rostral spinal cord infarction. Two patients developed acute severe proprioceptive loss in the limbs ipsilateral to infarcts that involved the caudal medulla and rostral spinal cord. They also had symptoms and signs often found in lateral medullary infarction. The proprioceptive loss is attributable to injury to the gracile and cuneate nuclei and/or their projections to the medial lemniscus. The infarct territory is supplied by the posterior spinal branches of the vertebral artery near its penetration into the posterior fossa. The presence of severe ipsilateral proprioceptive loss in a patient with features of lateral medullary infarction indicates involvement of the rostral spinal cord.

Prediction of Motor Function in Stroke Patients Using Machine Learning Algorithm: Development of Practical Models.

BACKGROUND: Machine learning (ML) techniques are being increasingly adopted in the medical field. OBJECTIVE: We developed a deep neural network (DNN) model and applied 2 well-known ML algorithms, logistic regression and random forest, in predicting motor outcome at 6 months after stroke. METHODS: In the present study, by using 14 input variables which are easily measured by clinicians, we developed ML models and investigated their applicability to predicting motor outcome in hemiplegic stroke patients. We retrospectively analyzed data of 1,056 consecutive stroke patients. Favorable outcomes of the upper and lower limbs were defined as a modified Brunnstrom classification (MBC) score of ≥5 (able to perform activities of daily living with the affected upper limb) and a functional ambulation category (FAC) score of ≥4 (able to walk without guardian's assistance), respectively. Poor outcomes of the upper and lower limbs were defined as MBC and FAC scores of <5 and <4, respectively. We developed 3 ML algorithms, namely the DNN, logistic regression, and random forest. RESULTS: Regarding the prediction of upper limb function, for the DNN model, the area under the curve (AUC) was 0.906. For the logistic regression and random forest models, the AUC were 0.874 and 0.882, respectively. For the prediction of lower limb function, for the DNN, logistic regression, and random forest models, the AUCs were 0.822, 0.768, and 0.802, respectively. CONCLUSIONS: We demonstrated that the ML algorithms, particularly the DNN, can be useful for predicting motor outcomes in the upper and lower limbs at 6 months after stroke.

Encoding of limb state by single neurons in the cuneate nucleus of awake monkeys.

The cuneate nucleus (CN) is among the first sites along the neuraxis where proprioceptive signals can be integrated, transformed, and modulated. The objective of the study was to characterize the proprioceptive representations in CN. To this end, we recorded from single CN neurons in three monkeys during active reaching and passive limb perturbation. We found that many neurons exhibited responses that were tuned approximately sinusoidally to limb movement direction, as has been found for other sensorimotor neurons. The distribution of their preferred directions (PDs) was highly nonuniform and resembled that of muscle spindles within individual muscles, suggesting that CN neurons typically receive inputs from only a single muscle. We also found that the responses of proprioceptive CN neurons tended to be modestly amplified during active reaching movements compared to passive limb perturbations, in contrast to cutaneous CN neurons whose responses were not systematically different in the active and passive conditions. Somatosensory signals thus seem to be subject to a "spotlighting" of relevant sensory information rather than uniform suppression as has been suggested previously.NEW & NOTEWORTHY The cuneate nucleus (CN) is the somatosensory gateway into the brain, and only recently has it been possible to record these signals from an awake animal. We recorded single CN neurons in monkeys. Proprioceptive CN neurons appear to receive input from very few muscles, and their sensitivity to movement changes reliably during reaching relative to passive arm perturbations. Sensitivity is generally increased, but not exclusively so, as though CN "spotlights" critical proprioceptive information during reaching.

Rehabilitation training combined acupuncture for limb hemiplegia caused by cerebral infarction: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Previous studies have reported that rehabilitation training combined acupuncture (RTA) can be used for the treatment of limb hemiplegia (LH) caused by cerebral infarction (CI). However, its effectiveness is still unclear. In this systematic review study, we aim to evaluate the effectiveness and safety of RTA for LH following CI. METHODS: We will retrieve the databases of CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, CBM, PUBMED, and CNKI from inception to June 1, 2020 with no language restrictions. The randomized controlled trials of RTA for evaluating effectiveness and safety in patients with LH following CI will be included. Cochrane risk of bias tool will be used to measure the methodological quality for all included studies. Two authors will independently select the studies, extract the data, and assess the methodological quality of included studies. A third author will be invited to discuss if any disagreements exist between 2 authors. We will perform heterogeneity assessment before carrying out meta-analysis. According to the heterogeneity, we select random effect model or fixed effect model for meta-analysis of the included cohort studies. Cochrane risk of bias tool will be used to determine the methodological quality for included studies. RevMan 5.3 software (Cochrane Community, London, UK) will be utilized to perform statistical analysis. RESULTS: This systematic review will assess the effectiveness and safety of RTA for LH caused by CI. The primary outcome includes limbs function, as measured by the Wolf Motor Function Test (WMFT) Assessment scale, or other associated scales. The secondary outcomes consist of muscle strength, muscle tone, quality of life, and any adverse events. CONCLUSION: The findings of this study will summarize the current evidence of RTA for LH caused by CI, and may provide helpful evidence for the clinical treatment. DISSEMINATION AND ETHICS: The findings of this study are expected to be published in peer-reviewed journals. It does not require ethical approval, because no individual data will be utilized in this study. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070114.

Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy.

To investigate circuit mechanisms underlying locomotor behavior, we used serial-section electron microscopy (EM) to acquire a synapse-resolution dataset containing the ventral nerve cord (VNC) of an adult female Drosophila melanogaster. To generate this dataset, we developed GridTape, a technology that combines automated serial-section collection with automated high-throughput transmission EM. Using this dataset, we studied neuronal networks that control leg and wing movements by reconstructing all 507 motor neurons that control the limbs. We show that a specific class of leg sensory neurons synapses directly onto motor neurons with the largest-caliber axons on both sides of the body, representing a unique pathway for fast limb control. We provide open access to the dataset and reconstructions registered to a standard atlas to permit matching of cells between EM and light microscopy data. We also provide GridTape instrumentation designs and software to make large-scale EM more accessible and affordable to the scientific community.

[Diffuse cerebral atrophy and reversible polyneuropathy in a patient with chronic Bromvalerylurea intoxication: a case report].

A 37-year-old man who had been on bromvalerylurea (BU) medication for 11 years at a maximum dose of 2,400 mg per day for headache therapy was admitted to our hospital due to gait disturbance. He had weight loss and exanthema all over his body. Cognitive dysfunction, intellectual deterioration, attention disturbance, decreased muscle strength, and decreased vibratory sense in the lower limbs were observed. Brain MRI showed diffuse brain atrophy, and a peripheral nerve conduction examination revealed decreased nerve conduction velocity and action potential amplitude in the extremities. We diagnosed him with chronic BU intoxication based on pseudohyperchloremia, BU detected in the blood, and bromide elevation. By discontinuing BU and performing intravenous infusion, neurological symptoms and exanthema were improved, and peripheral nerve conduction examination findings also improved. There are few reports of peripheral neuropathy cases of chronic BU intoxication; herein we report one such case along with previously reported cases.

Long ascending propriospinal neurons provide flexible, context-specific control of interlimb coordination.

Within the cervical and lumbar spinal enlargements, central pattern generator (CPG) circuitry produces the rhythmic output necessary for limb coordination during locomotion. Long propriospinal neurons that inter-connect these CPGs are thought to secure hindlimb-forelimb coordination, ensuring that diagonal limb pairs move synchronously while the ipsilateral limb pairs move out-of-phase during stepping. Here, we show that silencing long ascending propriospinal neurons (LAPNs) that inter-connect the lumbar and cervical CPGs disrupts left-right limb coupling of each limb pair in the adult rat during overground locomotion on a high-friction surface. These perturbations occurred independent of the locomotor rhythm, intralimb coordination, and speed-dependent (or any other) principal features of locomotion. Strikingly, the functional consequences of silencing LAPNs are highly context-dependent; the phenotype was not expressed during swimming, treadmill stepping, exploratory locomotion, or walking on an uncoated, slick surface. These data reveal surprising flexibility and context-dependence in the control of interlimb coordination during locomotion.

Use of Peripheral Sensory Information for Central Nervous Control of Arm Movement by Octopus vulgaris.

Octopuses are active predators with highly flexible bodies and rich behavioral repertoires [1-3]. They display advanced cognitive abilities, and the size of their large nervous system rivals that of many mammals. However, only one third of the neurons constitute the CNS, while the rest are located in an elaborate PNS, including eight arms, each containing myriad sensory receptors of various modalities [2-4]. This led early workers to question the extent to which the CNS is privy to non-visual sensory input from the periphery and to suggest that it has limited capacity to finely control arm movement [3-5]. This conclusion seemed reasonable considering the size of the PNS and the results of early behavioral tests [3, 6-8]. We recently demonstrated that octopuses use visual information to control goal-directed complex single arm movements [9]. However, that study did not establish whether animals use information from the arm itself [9-12]. We here report on development of two-choice, single-arm mazes that test the ability of octopuses to perform operant learning tasks that mimic normal tactile exploration behavior and require the non-peripheral neural circuitry to use focal sensory information originating in single arms [1, 10]. We show that the CNS of the octopus uses peripheral information about arm motion as well as tactile input to accomplish learning tasks that entail directed control of movement. We conclude that although octopus arms have a great capacity to act independently, they are also subject to central control, allowing well-organized, purposeful behavior of the organism as a whole.

[Hemiplegia cruciata and severe facial pain due to infarction of the cervicomedullary junction: a case report].

We report the case of a 66-year-old female with hemiplegia cruciata and severe facial pain due to infarction of the cervicomedullary junction. She presented to the hospital with complaints of acute-onset left facial pain and gait disturbance. Neurological examination revealed narrow left palpebral fissure, severe left facial pain and hypothermoesthesia, weakness predominantly in the left upper and right lower extremities, decreased pain and temperature sensation in the right lower extremity, decreased vibration sensation in the left lower extremity, hyperreflexia in the left upper extremity, and mild ataxia in the left upper and lower extremities. Brain MRI revealed a high-intensity lesion in the left cervicomedullary junction on diffusion-weighted and fluid-attenuated inversion recovery images. Hemiplegia cruciata due to the pyramidal tract injury at the cervicomedullary junction is an uncommon clinical manifestation. However, in patients with hemiplegia cruciata, identifying the lesion location may be difficult. Clinicians should consider the possibility of pyramidal decussation lesions. Anatomical differences, in the course of pyramidal tract fibers between the upper and lower limbs have been considered in the pyramidal decussation. Hemiplegia cruciata in this case was primarily caused by the impairment of the left upper limb pyramidal fibers after the pyramidal decussation and the right lower limb pyramidal fibers before the pyramidal decussation.

Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury.

OBJECTIVE: The importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans. METHODS: Ulnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants. RESULTS: Potentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones. CONCLUSIONS: Descending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation. SIGNIFICANCE: Evaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..

Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex.

OBJECTIVE: To assess the long-term analgesic effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic pain syndrome. METHODS: The study included 57 patients (orofacial pain, n = 26, pudendal neuralgia, n = 18, and neuropathic limb pain, n = 13) with an "induction phase" of 12 daily rTMS sessions for 3 weeks, followed by a "maintenance phase" of bi-monthly sessions for the next five months. RESULTS: All pain measures significantly decreased from baseline to the end of the induction phase. Analgesic response, defined as pain intensity decrease ≥ 30% compared to baseline, was observed in 39 patients (68%), who could be differentiated from non-responders from the 7th rTMS session. At the end of the maintenance phase (D180), 27 patients (47%) were still responders. Anxio-depressive symptoms and quality of life also improved. The analgesic response at the end of the induction phase was associated with lower pain score at baseline, and the response at the end of the maintenance phase was associated with lower anxio-depressive score at baseline. CONCLUSION: The analgesic efficacy of motor cortex rTMS can be maintained in the long term in various chronic pain conditions. Patients with high pain level and severe anxio-depressive symptoms may have a less favorable profile to respond to the procedure. SIGNIFICANCE: The overall impact of rTMS treatment on daily life requires a multidimensional evaluation that goes beyond the analgesic effect that can be achieved.

Spinal Interneurons With Dual Axon Projections to Knee-Extensor and Hip-Extensor Motor Pools.

The central nervous system (CNS) may simplify control of limb movements by activating certain combinations of muscles together, i.e., muscle synergies. Little is known, however, about the spinal cord interneurons that activate muscle synergies by exciting sets of motoneurons for different muscles. The turtle spinal cord, even without brain inputs and movement-related sensory feedback, can generate the patterns of motoneuron activity underlying forward swimming, three forms of scratching, and limb withdrawal. Spinal interneurons activated during scratching are typically activated during all three forms of scratching, to different degrees, even though each form of scratching has its own knee-hip synergy. Such spinal interneurons are also typically activated rhythmically during scratching motor patterns, with hip-related timing. We proposed a hypothesis that such interneurons that are most active during rostral scratch stimulation project their axons to both knee-extensor and hip-flexor motoneurons, thus generating the rostral scratch knee-hip synergy, while those interneurons most active during pocket scratch stimulation project their axons to both knee-extensor and hip-extensor motoneurons, thus generating the pocket scratch knee-hip synergy. The activity of the entire population would then generate the appropriate synergy, depending on the location of sensory stimulation. Mathematical modeling has demonstrated that this hypothesis is feasible. Here, we provide one test of this hypothesis by injecting two fluorescent retrograde tracers into the regions of knee-extensor motoneurons (more rostrally) and hip-extensor motoneurons (more caudally). We found that there were double-labeled interneurons, which projected their axons to both locations. The dual-projecting interneurons were widely distributed rostrocaudally, dorsoventrally, and mediolaterally within the hindlimb enlargement and pre-enlargement spinal segments examined. The existence of such dual-projecting interneurons is consistent with the hypothesis that they contribute to generating the knee-hip synergy for pocket scratching. The dual-projecting interneurons, however, were only about 1% of the total interneurons projecting to each location, which suggests that they might be one of several contributors to the appropriate knee-hip synergy. Indirect projections to both motor pools and/or knee extensor-dedicated interneurons might also contribute. There is evidence for dual-projecting spinal interneurons in frogs and mice as well, suggesting that they may contribute to limb motor control in a variety of vertebrates.