Distal Effectors Research Articles

The Origin of Movement Biases During Reaching.

Goal-directed movements can fail due to errors in our perceptual and motor systems. While these errors may arise from random noise within these sources, they also reflect systematic motor biases that vary with the location of the target. The origin of these systematic biases remains controversial. Drawing on data from an extensive array of reaching tasks conducted over the past 30 years, we evaluated the merits of various computational models regarding the origin of motor biases. Contrary to previous theories, we show that motor biases do not arise from systematic errors associated with the sensed hand position during motor planning or from the biomechanical constraints imposed during motor execution. Rather, motor biases are primarily caused by a misalignment between eye-centric and the body-centric representations of position. This model can account for motor biases across a wide range of contexts, encompassing movements with the right versus left hand, proximal and distal effectors, visible and occluded starting positions, as well as before and after sensorimotor adaptation.

Osteoporosis GWAS-implicated DNM3 locus contextually regulates osteoblastic and chondrogenic fate of mesenchymal stem/progenitor cells through oscillating miR-199a-5p levels.

Genome wide association study (GWAS)-implicated bone mineral density (BMD) signals have been shown to localize in cis-regulatory regions of distal effector genes using 3D genomic methods. Detailed characterization of such genes can reveal novel causal genes for BMD determination. Here, we elected to characterize the "DNM3" locus on chr1q24, where the long non-coding RNA DNM3OS and the embedded microRNA MIR199A2 (miR-199a-5p) are implicated as effector genes contacted by the region harboring variation in linkage disequilibrium with BMD-associated sentinel single nucleotide polymorphism, rs12041600. During osteoblast differentiation of human mesenchymal stem/progenitor cells (hMSC), miR-199a-5p expression was temporally decreased and correlated with the induction of osteoblastic transcription factors RUNX2 and Osterix. Functional relevance of miR-199a-5p downregulation in osteoblastogenesis was investigated by introducing miR-199a-5p mimic into hMSC. Cells overexpressing miR-199a-5p depicted a cobblestone-like morphological change and failed to produce BMP2-dependent extracellular matrix mineralization. Mechanistically, a miR-199a-5p mimic modified hMSC propagated normal SMAD1/5/9 signaling and expressed osteoblastic transcription factors RUNX2 and Osterix but depicted pronounced upregulation of SOX9 and enhanced expression of essential chondrogenic genes ACAN, COMP, and COL10A1. Mineralization defects, morphological changes, and enhanced chondrogenic gene expression associated with miR-199a-5p mimic over-expression were restored with miR-199a-5p inhibitor suggesting specificity of miR-199a-5p in chondrogenic fate specification. The expression of both the DNM3OS and miR-199a-5p temporally increased and correlated with hMSC chondrogenic differentiation. Although miR-199a-5p overexpression failed to further enhance chondrogenesis, blocking miR-199a-5p activity significantly reduced chondrogenic pellet size, extracellular matrix deposition, and chondrogenic gene expression. Taken together, our results indicate that oscillating miR-199a-5p levels dictate hMSC osteoblast or chondrocyte terminal fate. Our study highlights a functional role of miR-199a-5p as a BMD effector gene at the DNM3 BMD GWAS locus, where patients with cis-regulatory genetic variation which increases miR-199a-5p expression could lead to reduced osteoblast activity.

Abstract 4699: Evaluating extracellular matrix invasion and cytotoxicity of natural killer cells in a novel co-culture assay

Abstract Background: The complex tumor microenvironment (TME) in solid tumors presents unique challenges for lymphocytes used in cancer immunotherapy. The extracellular matrix (ECM) in TME can limit the recruitment of lymphocytes and restrict access to cancer cells. This study utilized Matrigel to study the kinetics of natural killer cell invasion and cytotoxicity. We hypothesized that the kinetics of tumor cell killing by the NKs would depend on the distance for invasion and rely on matrix-metalloproteinases (MMPs) for remodeling the ECM. Methods: Increasing volumes (50-100 µL/well) of Matrigel (6 mg/mL) representing increasing distance for invasion was layered over MCF7-red target tumor cells expressing nuclear-localized mKate2 (red fluorescent protein). NK92 (Creative Bioarray) or eGFP-NK92 (BPS Bioscience) were seeded over the solidified Matrigel layer at E:T of 3:1. The broad spectrum MMP inhibitor, Ilomostat (GM6001, 2 µM and 10 µM), was added to the wells to investigate to role of MMPs. Label-free impedance and live cell imaging data was collected in real time on xCELLigence RTCA eSight to evaluate NK cell invasion and cytotoxicity. Percent cytolysis was calculated on the RTCA software from normalized cell impedance readings and imaging data using the formula [(1-(treated/untreated)*100]. Results: Impedance reading increases as the MCF7-red cells settle, attach, and proliferate. The readings plateau as the cells reach confluence. The addition of Matrigel modulates the impedance signature of MCF7 cells. Importantly, Matrigel delays cytolysis by NK92 cells added at 24h. The delay increases with increasing volume of Matrigel representing increasing invasion distance. The time to achieve 60% killing with respect to controls (KT60) was 67, 76 and 89 hours for 50, 75 and 100 µL/well, respectively. Consistent with the role of MMPs in invasion, percent cytolysis calculated independently from normalized impedance readings and live cell imaging data confirmed both delayed and reduced target cell killing by GFP-NK92 cells in the presence of Ilomostat. Interestingly, only a few GFP-NK92 were detected by live cell imaging when there was increased target cell death. These included highly active NK cells that made multiple contacts with different MCF7 red targets in clusters suggesting serial killing activity. Conclusions: The observations that only a few NK92 cells are detected during the killing of susceptible target cells and that cytolysis is not abrogated by the inhibition of MMPs suggest a potential role for distal effectors like cytokines, independent of invasion. This is a novel 2.5D assay that demonstrates the potential of RTCA eSight platform for studying the invasion and cytotoxicity function of various immune cells through both real-time impedance recording and live-cell time-lapse imaging simultaneously. (For Research Use Only. Not for use in diagnostic procedures. RA45236.3472453704) Citation Format: Jyothi Thyagabhavan Mony, Xiaoyu Zhang. Evaluating extracellular matrix invasion and cytotoxicity of natural killer cells in a novel co-culture assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4699.

Startle-triggered responses indicate reticulospinal drive is larger for voluntary shoulder versus finger movements

Recent primate studies have implicated a substantial role of reticulospinal pathways in the production of various voluntary movements. A novel way to assess the relative reticulospinal contributions in humans is through the use of a “StartReact” paradigm where a startling acoustic stimulus (SAS) is presented during a simple reaction time (RT) task. The StartReact response is characterized by short-latency triggering of a prepared response, which is attributed to increased reticulospinal drive associated with startle reflex activation. The current study used a StartReact protocol to examine differences in reticulospinal contributions between proximal and distal effectors by examining EMG onset latencies in lateral deltoid and first dorsal interosseous during bilateral shoulder or finger abduction. The magnitude of the StartReact effect, and thus relative reticulospinal drive, was quantified as the difference in RT between startle trials in which startle-reflex related EMG activation in the sternocleidomastoid (SCM) was present (SCM +) versus absent (SCM −). A significantly larger StartReact effect was observed for bilateral shoulder abduction versus bimanual finger abduction and a higher incidence of SCM + trials occurred in the proximal task. Additionally, both startle reflex and response-related EMG measures were larger on SCM + trials for the shoulder versus finger task. These results provide compelling novel evidence for increased reticulospinal activation in bilateral proximal upper-limb movements.

Bilateral Force Deficit in Proximal Effectors Versus Distal Effectors in Lower Extremities

ABSTRACT Purpose: Bilateral force deficit occurs when the maximal generated force during simultaneous bilateral muscle contractions is lower than the sum of forces generated unilaterally. Neural inhibition is stated as the main source for bilateral force deficit. Based on differences in bilateral neural organization, there might be a pronounced neural inhibition for proximal compared to distal effectors. The aim of the present experiment was to evaluate potential differences in bilateral force deficit in proximal compared to distal effectors in lower extremities. Methods: Fifteen young adults performed single-joint maximal voluntary contractions in isometric dorsiflexion of ankle (distal) and knee (proximal) extension unilaterally and bilaterally. Results: Results showed a significant absolute bilateral force deficit for both proximal (123.46 ± 59.51 N) and distal effectors (33.00 ± 35.60 N). Interestingly, the relative bilateral force deficit for knee extension was significantly larger compared to dorsiflexion of ankle, 19.98 ± 10.04% and 10.27 ± 9.57%, respectively. Our results indicate a significantly higher bilateral force deficit for proximal effectors compared to distal effectors. Conclusion: Plausible explanations are related to neuroanatomical and neurophysiological differences between proximal effectors and distal effectors where proximal muscles have a higher potential for bilateral communication compared to distal muscles. In addition, higher forces produced with proximal effectors could cause a higher perceived exertion and cause a more pronounced bilateral force deficit to proximal effectors.

Structure-based discovery of a novel small-molecule inhibitor of TEAD palmitoylation with anticancer activity.

The paralogous oncogenic transcriptional coactivators YAP and TAZ are the distal effectors of the Hippo signaling pathway, which plays a critical role in cell proliferation, survival and cell fate specification. They are frequently deregulated in most human cancers, where they contribute to multiple aspects of tumorigenesis including growth, metabolism, metastasis and chemo/immunotherapy resistance. Thus, they provide a critical point for therapeutic intervention. However, due to their intrinsically disordered structure, they are challenging to target directly. Since YAP/TAZ exerts oncogenic activity by associating with the TEAD1-4 transcription factors, to regulate target gene expression, YAP activity can be controlled indirectly by regulating TEAD1-4. Interestingly, TEADs undergo autopalmitoylation, which is essential for their stability and function, and small-molecule inhibitors that prevent this posttranslational modification can render them unstable. In this article we report discovery of a novel small molecule inhibitor of YAP activity. We combined structure-based virtual ligand screening with biochemical and cell biological studies and identified JM7, which inhibits YAP transcriptional reporter activity with an IC50 of 972 nMoles/Ltr. Further, it inhibits YAP target gene expression, without affecting YAP/TEAD localization. Mechanistically, JM7 inhibits TEAD palmitoylation and renders them unstable. Cellular thermal shift assay revealed that JM7 directly binds to TEAD1-4 in cells. Consistent with the inhibitory effect of JM7 on YAP activity, it significantly impairs proliferation, colony-formation and migration of mesothelioma (NCI-H226), breast (MDA-MB-231) and ovarian (OVCAR-8) cancer cells that exhibit increased YAP activity. Collectively, these results establish JM7 as a novel lead compound for development of more potent inhibitors of TEAD palmitoylation for treating cancer.

The influence of distal and proximal muscle activation on neural crosstalk.

Previous research has indicated that neural crosstalk is asymmetric, with the dominant effector exerting a stronger influence on the non-dominant effector than vice versa. Recently, it has been hypothesized that this influence is more substantial for proximal than distal effectors. The current investigation was designed to determine the effects of distal ((First Dorsal Interosseous (FDI)) and proximal (triceps brachii (TBI)) muscle activation on neural crosstalk. Twelve right-limb dominant participants (mean age = 21.9) were required to rhythmically coordinate a 1:2 pattern of isometric force guided by Lissajous displays. Participants performed 10, 30 s trials with both distal and proximal effectors. Coherence between the two effector groups were calculated using EMG-EMG wavelet coherence. The results indicated that participants could effectively coordinate the goal coordination pattern regardless of the effectors used. However, spatiotemporal performance was more accurate when performing the task with distal than proximal effectors. Force distortion, quantified by harmonicity, indicated that more perturbations occurred in the non-dominant effector than in the dominant effector. The results also indicated significantly lower harmonicity for the non-dominant proximal effector compared to the distal effectors. The current results support the notion that neural crosstalk is asymmetric in nature and is greater for proximal than distal effectors. Additionally, the EMG-EMG coherence results indicated significant neural crosstalk was occurring in the Alpha bands (5–13 Hz), with higher values observed in the proximal condition. Significant coherence in the Alpha bands suggest that the influence of neural crosstalk is occurring at a subcortical level.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Supra-threshold vibration applied to the foot soles enhances jump height under maximum effort.

Previous studies have shown that absence or reduction of cutaneous sensory feedback can diminish human motor performance under maximum effort. However, it has not been explored whether any appropriate intervention in the cutaneous sensory input can augment the output motor performance, particularly in motor tasks such as jumping that involve the kinematic chain of the entire body. Using shoes with active vibrating insoles, we applied mechanical vibration to the soles of 20 young and healthy adults and evaluated the change in the jump height and muscle activation using within-participants repeated measures. The noise-like vibration having an amplitude of 130% of the sensory threshold of each participant led to an average increase of 0.38 cm in the jump height (p = 0.008) and activation of the rectus femoris of the dominant leg (p = 0.011). These results indicate that application of a properly designed cutaneous stimulus to the soles, the distal end effectors of motor tasks, can augment the output performance by involving the prime movers distant from the end effector.

The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?

A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.

Bilateral Interference in Motor Performance in Homologous vs. Non-homologous Proximal and Distal Effectors.

Performance of bimanual motor actions requires coordinated and integrated bilateral communication, but in some bimanual tasks, neural interactions and crosstalk might cause bilateral interference. The level of interference probably depends on the proportions of bilateral interneurons connecting homologous areas of the motor cortex in the two hemispheres. The neuromuscular system for proximal muscles has a higher number of bilateral interneurons connecting homologous areas of the motor cortex compared to distal muscles. Based on the differences in neurophysiological organization for proximal vs. distal effectors in the upper extremities, the purpose of the present experiment was to evaluate how the level of bilateral interference depends on whether the bilateral interference task is performed with homologous or non-homologous effectors as the primary task. Fourteen participants first performed a unilateral primary motor task with the dominant arm with (1) proximal and (2) distal controlled joysticks. Performance in the unilateral condition with the dominant arm was compared to the same effector’s performance when two different bilateral interference tasks were performed simultaneously with the non-dominant arm. The two different bilateral interference tasks were subdivided into (1) homologous and (2) non-homologous effectors. The results showed a significant decrease in performance for both proximal and distal controlled joysticks, and this effect was independent of whether the bilateral interference tasks were introduced with homologous or non-homologous effectors. The overall performance decrease as a result of bilateral interference was larger for proximal compared to distal controlled joysticks. Furthermore, a proximal bilateral interference caused a larger performance decrement independent of whether the primary motor task was controlled by a proximal or distal joystick. A novel finding was that the distal joystick performance equally interfered with either homologous (distal bilateral interference) or non-homologous (proximal bilateral interference) interference tasks performed simultaneously. The results indicate that the proximal–distal distinction is an important organismic constraint on motor control and for understanding bilateral communication and interference in general and, in particular, how bilateral interference caused by homologous vs. non-homologous effectors impacts motor performance for proximal and distal effectors. The results seem to map neuroanatomical and neurophysiological differences for these effectors.

More Pronounced Bimanual Interference in Proximal Compared to Distal Effectors of the Upper Extremities

Bimanual performance depends on effective and modular bilateral communication between the two bodysides. Bilateral neural interactions between the bodysides could cause bimanual interference, and the neuromuscular system for proximal and distal muscles is differently organized, where proximal muscles have more bilateral interneurons at both cortical and spinal level compared to distal muscles. These differences might increase the potential for bimanual interference between proximal arm muscles, because of greater proportions of bilateral interneurons to proximal muscles. The purpose of the present experiment was to evaluate potential differences in bimanual interference between proximal versus distal effectors in the upper extremities. 14 participants first performed a unilateral primary motor task with dominant arm with (1) a proximal and (2) distal controlled joysticks (condition A). Performance in condition A, was compared with the same effector’s performance when a bimanual interference task was performed simultaneously with the non-dominant arm (condition B). The results showed a significant bimanual interference for both the proximal and distal controlled joysticks. Most interestingly, the bimanual interference was larger for the proximal joystick compared to the distal controlled joystick. The increase in spatial accuracy error was higher for the proximal controlled joystick, compared with the distal controlled joystick. These results indicate that the proximal-distal distinction is an important organismic constraint on motor control, and especially for bilateral communication. There seem to be an undesired bilateral interference for both proximal and distal muscles. The interference is higher in the case of proximal effectors compared distal effectors, and the results seem to map the neuroanatomical and neurophysiological differences for these effectors.

Genetic Determinants of Childhood Obesity.

Obesity represents a major health burden to both developed and developing countries. Furthermore, the incidence of obesity is increasing in children. Obesity contributes substantially to mortality in the United States by increasing the risk for type 2 diabetes, cardiovascular-related diseases, and other comorbidities. Despite environmental changes over past decades, including increases in high-calorie foods and sedentary lifestyles, there is very clear evidence of a genetic predisposition to obesity risk. Childhood obesity cases can be categorized in one of two ways: syndromic or non-syndromic. Syndromic obesity includes disorders such as Prader-Willi syndrome, Bardet-Biedl syndrome, and Alström syndrome. Non-syndromic cases of obesity can be further separated into rarer instances of monogenic obesity and much more common forms of polygenic obesity. The advent of genome-wide association studies (GWAS) and next-generation sequencing has driven significant advances in our understanding of the genetic contribution to childhood obesity. Many rare and common genetic variants have been shown to contribute to the heritability in obesity, although the molecular mechanisms underlying most of these variants remain unclear. An important caveat of GWAS efforts is that they do not strictly represent gene target discoveries, rather simply the uncovering of robust genetic signals. One clear example of this is with progress in understanding the key obesity signal harbored within an intronic region of the FTO gene. It has been shown that the non-coding region in which the variant actually resides in fact influences the expression of genes distal to FTO instead, specifically IRX3 and IRX5. Such discoveries suggest that associated non-coding variants can be embedded within or next to one gene, but commonly influence the expression of other, more distal effector genes. Advances in genetics and genomics are therefore contributing to a deeper understanding of childhood obesity, allowing for development of clinical tools and therapeutic agents.

Towards In Situ Backlash Estimation of Continuum Robots Using an Endoscopic Camera

Accurate control of continuum robots requires handling non-linear behaviors between actuators and distal effectors. In this letter, we develop a method for estimating the non-linearities of tendon-driven degrees of freedom of flexible endoscopic systems by using a distal endoscopic camera and encoders at the proximal side. The proposed approach separates the non-linearities in two parts, namely a pure non uniform backlash and a non-linear function. The backlash is estimated without relying on any model, while the non-linear function is obtained by a pose estimation process. Experiments realized on a robotic flexible endoscopy platform (STRAS) show the validity of the approach for estimating in situ the quasi-static behavior of the robot and for compensating the non-linearities of the motion transmission.

Targeted tDCS selectively improves motor adaptation with the proximal and distal upper limb

BackgroundThe cerebellum and primary motor cortex (M1) are crucial to coordinated and accurate movements of the upper limbs. There is also appreciable evidence that these two structures exert somewhat divergent influences upon proximal versus distal upper limb control. Here, we aimed to differentially regulate the contribution of the cerebellum and M1 to proximal and distal effectors during motor adaptation, with transcranial direct current stimulation (tDCS). For this, we employed tasks that promote similar motor demands, but isolate whole arm from hand/finger movements, in order to functionally segregate the hierarchy of upper limb control. MethodsBoth young and older adults took part in a visuomotor rotation task; where they adapted to a 60° visuomotor rotation using either a hand-held joystick (requiring finger/hand movements) or a 2D robotic manipulandum (requiring whole-arm reaching movements), while M1, cerebellar or sham tDCS was applied. ResultsWe found that cerebellar stimulation improved adaptation performance when arm movements were required to complete the task, while in contrast stimulation of M1 enhanced adaptation during hand and finger movements only. This double-dissociation was replicated in an independent group of older adults, demonstrating that the behaviour remains intact in ageing. ConclusionsThese results suggest that stimulation of distinct motor areas can selectively improve motor adaptation in the proximal and distal upper limb. This also highlights new ways in which tDCS might be best applied to achieve reliable rehabilitation of upper limb motor deficits.

KAE1 Allelic Variants Affect TORC1 Activation and Fermentation Kinetics in Saccharomyces cerevisiae.

The eukaryotic domain-conserved TORC1 signalling pathway connects growth with nutrient sufficiency, promoting anabolic processes such as ribosomal biogenesis and protein synthesis. In Saccharomyces cerevisiae, TORC1 is activated mainly by the nitrogen sources. Recently, this pathway has gotten renewed attention but now in the context of the alcoholic fermentation, due to its key role in nitrogen metabolism regulation. Although the distal and proximal effectors downstream TORC1 are well characterised in yeast, the mechanism by which TORC1 is activated by nitrogen sources is not fully understood. In this work, we took advantage of a previously developed microculture-based methodology, which indirectly evaluates TORC1 activation in a nitrogen upshift experiment, to identify genetic variants affecting the activation of this pathway. We used this method to phenotype a recombinant population derived from two strains (SA and WE) with different geographic origins, which show opposite phenotypes for TORC1 activation by glutamine. Using this phenotypic information, we performed a QTL mapping that allowed us to identify several QTLs for TORC1 activation. Using a reciprocal hemizygous analysis, we validated GUS1, KAE1, PIB2, and UTH1 as genes responsible for the natural variation in the TORC1 activation. We observed that reciprocal hemizygous strains for KAE1 (ATPase required for t6A tRNA modification) gene showed the greatest phenotypic differences for TORC1 activation, with the hemizygous strain carrying the SA allele (KAE1SA) showing the higher TORC1 activation. In addition, we evaluated the fermentative capacities of the hemizygous strains under low nitrogen conditions, observing an antagonistic effect for KAE1SA allele, where the hemizygous strain containing this allele presented the lower fermentation rate. Altogether, these results highlight the importance of the tRNA processing in TORC1 activation and connects this pathway with the yeasts fermentation kinetics under nitrogen-limited conditions.

Reciprocal intralimb transfer of skilled isometric force production.

Motor control theories propose that the same motor plans can be employed by different effectors (e.g., the hand and arm). Skills learned with one effector can therefore "transfer" to others, which has potential applications in clinical situations. However, evidence from adaptation suggests this effect is not reciprocal; learning can be generalized from proximal to distal effectors (e.g., arm to hand), but not from distal to proximal effectors (e.g., hand to arm). We propose that skill learning may not follow the same pattern, because it relies on multiple learning processes beyond error detection and correction. Participants learned a skill task involving the production of isometric forces. We assessed their ability to perform the task with the hand and arm. One group then trained to perform the task using only their hand, whereas a second group trained using only their arm. In a final assessment, we found that participants who trained with either effector improved their skill in performing the task with both their hand and arm. There was no change in a control group that did not train between assessments, indicating that gains were related to the training, not the multiple assessments. These results indicate that in contrast to adaptation, motor skills can generalize from both proximal to distal effectors and from distal to proximal effectors. We propose this is due to differences in the processes underlying skill acquisition as compared with adaptation. NEW & NOTEWORTHY Prior research indicates that motor learning transfers from proximal to distal effectors, but not vice versa. However, this work focused on adapting existing behavior; we questioned whether different results would occur during learning of new motor skills. We found that the benefits of training on a skill task with either the hand or arm transferred across both effectors. This highlights important differences between adaptation and skill learning, and may allow therapeutic benefits for patients with impairments in specific effectors.

Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves.

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect (2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.

Safety-Enhanced Model-Free Visual Servoing for Continuum Tubular Robots Through Singularity Avoidance in Confined Environments

Minimally invasive procedures have gained ever-increasing popularity due to their advantages of smaller incisions, faster recoveries, fewer complications, and reduced scarring to name a few. With the force exertion and curvilinear flexibility at their distal end effectors, the continuum tubular robots have the potential to perform robot-assisted trans-orifice minimally invasive surgery, such as transnasal and transoral operations. During these procedures, it is important and challenging for the continuum tubular robot to automatically adjust its pose according to the target surgical sites and compensate for undesired disturbance, such as respiratory motions. In this paper, a singularity-avoidance visual servoing algorithm based on Jacobian Optimization has been proposed to improve safety and control continuum tubular robots based on intra-operative visual feedback in confined environments. Without the prior knowledge of robot kinematics or hand-eye calibration between the robot and the endoscope, the proposed model-free eye-in-hand visual servoing technique is capable of accomplishing the targeting tasks by adopting the safety-enhanced singularity avoidance mechanism and an efficient image-processing algorithm. The multiple experiments, including simulations, experiments conducted in a confined environment, and cadaveric studies, have been implemented and demonstrated to illustrate the superiority of the proposed singularity-avoidance visual servoing method.

Transfer of Motor Learning Is More Pronounced in Proximal Compared to Distal Effectors in Upper Extremities.

The current experiment investigated generalizability of motor learning in proximal versus distal effectors in upper extremities. Twenty-eight participants were divided into three groups: training proximal effectors, training distal effectors, and no training control group (CG). Performance was tested pre- and post-training for specific learning and three learning transfer conditions: (1) bilateral learning transfer between homologous effectors, (2) lateral learning transfer between non-homologous effectors, and (3) bilateral learning transfer between non-homologous effectors. With respect to specific learning, both training groups showed significant, similar improvement for the trained proximal and distal effectors, respectively. In addition, there was significant learning transfer to all three transfer conditions, except for bilateral learning transfer between non-homologous effectors for the distal training group. Interestingly, the proximal training group showed significantly larger learning transfer to other effectors compared to the distal training group. The CG did not show significant improvements from pre- to post-test. These results show that learning is partly effector independent and generalizable to different effectors, even though transfer is suboptimal compared to specific learning. Furthermore, there is a proximal-distal gradient in generalizability, in that learning transfer from trained proximal effectors is larger than from trained distal effectors, which is consistent with neuroanatomical differences in activation of proximal and distal muscles.