A structural model of the thoracic cage in the cat

A homogeneous shell model of the mechanical characteristics of the thoracic cage in the cat is presented. The global characterization proposed parallels the characterization--presented elsewhere--of the motor control of the intercostal musculature in terms of a conceptual spatially continuous control function, that underlies the discretely distributed muscular activity and reflects an inferred global dynamic control of the intercostal muscles during breathing. Proposing a static, homogeneous shell characterization of the thoracic cage, which is heterogeneous and composed of an assembly of mobile structures, implies assuming that other elements are indirectly giving this system features that make it resemble, from a structure analysis point of view, a homogeneous, static one. The pattern of the lines of stress along the shell structure proposed as a model compares favourably with the shape of the ribs. In agreement with previous findings, supporting the need for muscular activity to satisfy demands of purely structural character, it is suggested that this global shell-like functional character is achieved by neuromuscular global dynamic integration of the components of the rib cage by the nervous control of the intercostal muscles.     

Role of motor cortex in coordinating multi-joint movements: is it time for a new paradigm?

Reaching movements to spatial targets require motor patterns at the shoulder to be coordinated carefully with those at the elbow to smoothly move the hand through space. While the motor cortex is involved in this volitional task, considerable debate remains about how this cortical region participates in planning and controlling movement. This article reviews two opposing interpretations of motor cortical function during multi-joint movements. On the one hand, studies performed predominantly on single-joint movement generally support the notion that motor cortical activity is intimately involved in generating motor patterns at a given joint. In contrast, studies on reaching demonstrate correlations between motor cortical activity and features of movement related to the hand, suggesting that the motor cortex may be involved in more global features of the task. Although this latter paradigm involves a multi-joint motor task in which neural activity is correlated with features of movement related to the hand, this neural activity is also correlated to other movement variables. Therefore it is difficult to assess if and how the motor cortex contributes to the coordination of motor patterns at different joints. In particular, present paradigms cannot assess whether motor cortical activity contributes to the control of one joint or multiple joints during whole-arm tasks. The final point discussed in this article is the development of a new experimental device (KINARM) that can both monitor and manipulate the mechanics of the shoulder and elbow independently during multi-joint motor tasks. It is hoped that this new device will provide a new approach for examining how the motor cortex is involved in motor coordination.     

Myoelectric activity along human gastrocnemius medialis: Different spatial distributions of postural and electrically elicited surface potentials

It has recently been shown that motor units in human medial gastrocnemius (MG), activated during standing, occupy relatively small territories along the muscle’s longitudinal axis. Such organisation provides potential for different motor tasks to produce differing regional patterns of activity. Here, we investigate whether postural control and nerve electrical stimulation produce equal longitudinal activation patterns in MG. Myoelectric activity, at different proximal–distal locations of MG, was recorded using a linear electrode array. To ensure differences in signal amplitude between channels did not result from local, morphological factors two experimental protocols were completed: (i) quiet standing; (ii) electrical stimulation of the tibial nerve. Averaged, rectified values (ARVs) were calculated for each channel in each condition. The distribution of signals along electrode channels was described using linear regression and differences between protocols at each channel determined as the ratio between mean ARV from standing: stimulation protocols. Ratio values changed systematically across electrode channels in seven (of eight) participants, with larger values in distal channels. The distribution of ARV along MG therefore differed between experimental conditions. Compared to fibres of units activated during MG nerve stimulation, units activated during standing may have a tendency to be more highly represented in the distal muscle portion.     

The Decay of Motor Memories Is Independent of Context Change Detection

When the error signals that guide human motor learning are withheld following training, recently-learned motor memories systematically regress toward untrained performance. It has previously been hypothesized that this regression results from an intrinsic volatility in these memories, resulting in an inevitable decay in the absence of ongoing error signals. However, a recently-proposed alternative posits that even recently-acquired motor memories are intrinsically stable, decaying only if a change in context is detected. This new theory, the context-dependent decay hypothesis, makes two key predictions: (1) after error signals are withheld, decay onset should be systematically delayed until the context change is detected; and (2) manipulations that impair detection by masking context changes should result in prolonged delays in decay onset and reduced decay amplitude at any given time. Here we examine the decay of motor adaptation following the learning of novel environmental dynamics in order to carefully evaluate this hypothesis. To account for potential issues in previous work that supported the context-dependent decay hypothesis, we measured decay using a balanced and baseline-referenced experimental design that allowed for direct comparisons between analogous masked and unmasked context changes. Using both an unbiased variant of the previous decay onset analysis and a novel highly-powered group-level version of this analysis, we found no evidence for systematically delayed decay onset nor for the masked context change affecting decay amplitude or its onset time. We further show how previous estimates of decay onset latency can be substantially biased in the presence of noise, and even more so with correlated noise, explaining the discrepancy between the previous results and our findings. Our results suggest that the decay of motor memories is an intrinsic feature of error-based learning that does not depend on context change detection.     

Minimum measured-input models for the assessment of motor ability

The problem of assessing the physical functional limitation of a given individual and establishing the relationship between impairment/s and disability using a biomechanical approach is addressed. This endeavour was pursued with reference to the locomotor system and in order to address the following specific clinical issues: prognosis, eligibility for health services, measure of the outcome of a therapy, and therapeutic programming. A thorough biomechanical analysis of selected motor tasks would be effective but awkward to apply for subject-specific evaluation in clinical practice by reason of the complexity of both instrumentation and experimental protocols. In addition, as illustrated in the paper, the adequacy of the accuracy with which this type of analysis provides relevant information may be argued. Therefore, different methods were devised in the attempt to join objectivity with field applicability. These entailed the measurement of a minimum number of biomechanical variables during the execution of the selected motor task and these quantities were acquired using a low cost experimental apparatus least perceivable to the test subject, that is a dynamometric plate. However, since data thus obtained do not necessarily lend themselves to straightforward interpretation in terms of function assessment, models of the musculo-skeletal system that embodied the invariant aspects of both the modelled system and the specific motor task were devised. Using such "minimum measured-input models", physiology-related, and thus easier to interpret, information was obtained. Two different sets of mathematical models are presented: one deals with the lowest level of detail and normally aims at assessing a global physical performance score, the other discloses joint function and segmental mechanics and therefore contributes to establishing a relationship between impairment and disability. The validation of these models, carried out in the laboratory, has shown that they possess a potential for application in clinical practice.     

Calcium as a counteractive agent to streptomycin induced respiratory depression: an in vivo electrophysiological observation.

Effect of streptomycin on respiratory function in cats was studied. It was observed that streptomycin at a dose of 40 mg/kg body weight intravenously (i.v.) caused respiratory failure or streptomycin induced respiratory depression (SIRD). This respiratory failure is not linked with Herring-Breuer stretch receptors because the effect remained unaltered in artificially ventilated cats. The involvement of central structures in SIRD can be discarded since intracarotid and intraventricular administration of streptomycin failed to produce any change in respiration. Studies on monosynaptic reflex, dorsal and ventral root activities of spinal phrenic and intercostal nerves, and on fusimotor and alpha-motor neuron activities of spinal intercostal and phrenic nerves in decerebrated cats indicated clearly that respiratory depression is not only due to blockade at neuromuscular junction but due to functional depression at the level of muscle receptors and spinal cord motor neurons. The respiratory depression induced by streptomycin was more or less completely reversed when calcium was administered intravenously from external source. It is speculated that streptomycin induced respiratory depression may be mediated through calcium inhibition which can be treated with external calcium in conjunction with artificial respiration.     

Expiratory activity in transferred intercostal nerves in brachial plexus injury patients

Involuntary activity of transferred intercostal motor units was examined in patients with brachial plexus injury. Since the internal intercostal nerves were detached from the thorax to reinnervate the musculus biceps brachii, it was possible to record pure intercostal motor activity in humans. Respiratory activity was seen in the latter part of the expiratory phase, thus dividing the phase into two substages (E1 and E2) by the onset of the activity. CO2 rebreathing prolonged the duration of the intercostal motor activity and increased the tidal activity as determined from the integration curve. There was a close linear correlation between these two variables. These observations indicate that expiratory activity and its duration are actively controlled in humans.     

Recurrent cerebellar architecture solves the motor-error problem

Current views of cerebellar function have been heavily influenced by the models of Marr and Albus, who suggested that the climbing fibre input to the cerebellum acts as a teaching signal for motor learning. It is commonly assumed that this teaching signal must be motor error (the difference between actual and correct motor command), but this approach requires complex neural structures to estimate unobservable motor error from its observed sensory consequences. We have proposed elsewhere a recurrent decorrelation control architecture in which Marr-Albus models learn without requiring motor error. Here, we prove convergence for this architecture and demonstrate important advantages for the modular control of systems with multiple degrees of freedom. These results are illustrated by modelling adaptive plant compensation for the three-dimensional vestibular ocular reflex. This provides a functional role for recurrent cerebellar connectivity, which may be a generic anatomical feature of projections between regions of cerebral and cerebellar cortex.     

Muscle fatigue - from motor units to clinical symptoms

Reductionist approaches have provided little insight on the fatigue experienced by humans during activities of daily living. Some of the reasons for this lack of progress include the persistence of outdated concepts, the misinterpretation of experimental recordings, and a failure to embrace a global perspective on fatigue. This paper summarizes the three examples of these limitations that were discussed in the 2011 Muybridge Award lecture: motor unit types and muscle fatigue, myoelectric manifestations of fatigue, and fatigue and fatigability. Although the motor units in a population do exhibit a range of fatigability values, there are not distinct groups of motor units and the concept that some motor units are resistant to fatigue emerged from protocols in which motor units were activated by electrical stimulation rather than voluntary activation. The concept of distinct motor unit types should be abandoned. The second example discussed in the lecture was the use of surface EMG signals to assess fatigue-related adjustments in motor unit activity. The critical assumption with this approach is that the association between surface EMG amplitude and muscle force remains constant during fatiguing contractions. Unfortunately, the relation does not remain constant and a series of computational studies demonstrate the magnitude of the discrepancy, including the absence of an association with the activation signal emerging from the spinal cord and that received by the muscle. The third example concerned the concepts of fatigue and fatigability. It has long been recognized that fatigue involves both sensations and impairments in motor function, and the final part of the lecture urged the integration of the two constructs into a single scheme in which fatigue can be modulated either independently or by interactions between perceptions of fatigue and the mechanisms that establish levels of fatigability. The expectation is that such critical evaluations of the concepts and approaches to the study of fatigue will provide a more effective foundation from which to identify the factors that contribute to fatigue in health and disease.     

Effects of progressive hypoxia on parasternal, costal, and crural diaphragm activation

The distribution of motor drive to the costal and crural diaphragm and parasternal intercostal muscles was evaluated during progressive isocapnic hypoxia in anesthetized dogs. Bipolar stainless steel wire electrodes were placed unilaterally into the costal and crural portions of the diaphragm and into the parasternal intercostal muscle in the second or third intercostal space. Both peak and rate of rise of electromyographic activity of each chest wall muscle increased in curvilinear fashion in response to progressive hypoxia. Both crural and parasternal intercostal responses, however, were greater than those of the costal diaphragm. The onset of crural activation preceded that of the costal portion of the diaphragm and parasternal intercostal muscle activation. Despite differences in the degree of activation among the various chest wall muscles, the rate of increase in activation for any given muscle was linearly related to the rate of increases for the other two. This suggests that respiratory drive during progressive hypoxia increases in fixed proportion to the different chest wall inspiratory muscles. Our findings lend further support to the concept that the costal and crural diaphragm are governed by separate neural control mechanisms and, therefore, may be considered separate muscles.     

Distribution of motor and sensory fibers in the intercostal nerves. Significance in reconstructive surgery.

If the distribution of the types of nerve fibers in the various intercostal nerves is taken into consideration, an intercostal nerve segment can be an acceptable donor nerve graft for sensory and/or motor nerve replacements. We describe the distribution of motor and sensory axons in various segments of the upper and lower intercostal nerves.     

On the use of distance constraints in protein-protein docking computations

Protein-protein docking (PPD) is a computational process that predicts the structure of a complex of two interacting proteins from their unbound structures. The accuracy of PPD predictions is low, but can be greatly enhanced if experimentally determined distance data are available for incorporation into the prediction. However, the specific effects of distance constraints on PPD predictions are largely uncharacterized. In this study, we systematically simulated the effects of using distance constraints both on a new distance constraint-driven PPD approach, called DPPD, and also, by re-ranking, on a well-established grid-based global search approach. Our results for a PPD benchmark dataset of 84 protein complexes of known structures showed that near 100% docking success rates could be obtained when the number of distance constraints exceeded six, the degrees of freedom of the system, but the success rate was significantly reduced by long distance constraints, large binding-induced conformational changes, and large errors in the distance data. Our results also showed that, under most conditions simulated, even two or three distance constraints were sufficient to achieve a much better success rate than those using a sophisticated physicochemical function to re-rank the results of the global search. Our study provides guidelines for the practical incorporation of experimental distance data to aid PPD predictions.     

A neural-network system for control of eye movements: basic mechanisms

This paper presents a neural-network-based system that can generate and control movements of the eyes. It was inspired by a number of experimental observations on the saccadic and gaze systems of monkeys and cats. Because of the generality of the approach undertaken, the system can be regarded as a demonstration of how parallel distributed processing principles, namely learning and attractor dynamics, can be integrated with experimental findings, as well as a biologically inspired controller for a dexterous robotic orientation device. The system is composed of three parts: a dynamic motor map, a push-pull circuitry, and a plant. The dynamics of the motor map is generated by a multi-layer network that was trained to compute a bidimensional temporal-spatial transformation. Simulation results indicate (1) that the system is able to reproduce some of the properties observed in the biological system at the neural and movement levels and (2) that the dynamics of the motor map remains stereotyped even when the motor map is subject to abnormal stimulation patterns. The latter result emphasizes the role of the topographic projection that connects the motor map to the push-pull circuitry in determining the features of the resulting movements.     

Maximum likelihood estimation of molecular motor kinetics from staircase dwell-time sequences

Molecular motors, such as kinesin, myosin, or dynein, convert chemical energy into mechanical energy by hydrolyzing ATP. The mechanical energy is used for moving in discrete steps along the cytoskeleton and carrying a molecular load. High resolution single molecule recordings of motor steps appear as a stochastic sequence of dwells, resembling a staircase. Staircase data can also be obtained from other molecular machines such as F1 -ATPase, RNA polymerase, or topoisomerase. We developed a maximum likelihood algorithm that estimates the rate constants between different conformational states of the protein, including motor steps. We model the motor with a periodic Markov model that reflects the repetitive chemistry of the motor step. We estimated the kinetics from the idealized dwell-sequence by numerical maximization of the likelihood function for discrete-time Markov models. This approach eliminates the need for missed event correction. The algorithm can fit kinetic models of arbitrary complexity, such as uniform or alternating step chemistry, reversible or irreversible kinetics, ATP concentration and mechanical force-dependent rates, etc. The method allows global fitting across stationary and nonstationary experimental conditions, and user-defined a priori constraints on rate constants. The algorithm was tested with simulated data, and implemented in the free QuB software.     

Cholinergic stimulation of the pons depresses respiration in decerebrate cats

The injection of carbachol into the pontine tegmentum of decerebrate cats evokes a postural motor atonia that has many of the characteristics of the atonia of natural rapid-eye-movement (REM) sleep (Morales et al. J. Neurophysiol. 57: 1118-1129, 1987). We have used the carbachol-injected decerebrate cat to study the changes in respiratory neuronal activity that accompany the atonia. The activities of representative respiratory motor nerves--phrenic, intercostal, and hypoglossal--and that of a motor branch of C4 were recorded in decerebrate, vagotomized, paralyzed, and artificially ventilated cats. After the microinjection of carbachol, there was a profound suppression of activity in all the nerves and a decrease in respiratory rate. This was a consistent stereotyped response in which the magnitude of the suppression of respiratory-related activity was phrenic (to approximately 65% of control) less than inspiratory intercostal (approximately 50%) less than hypoglossal (approximately 10%) less than expiratory intercostal (approximately 5%). The decrease in respiratory rate (to approximately 70% of control) was caused by a prolongation of both inspiratory and expiratory durations. Complete reversal of the carbachol effect was elicited by the microinjection of atropine into the same site as the carbachol injection. This allowed us to produce a second episode of atonia by the injection of carbachol into the contralateral pons. Thus we have demonstrated the existence of neural pathways originating in the cholinoceptive cells of the pons that have the potential to powerfully and differentially depress various respiratory motoneuronal pools and to reduce the respiratory rate. These pathways are likely to be activated along with the atonia of REM sleep.     

Optimal coordination and control of posture and movements

This paper presents a theoretical model of stability and coordination of posture and locomotion, together with algorithms for continuous-time quadratic optimization of motion control. Explicit solutions to the Hamilton–Jacobi equation for optimal control of rigid-body motion are obtained by solving an algebraic matrix equation. The stability is investigated with Lyapunov function theory and it is shown that global asymptotic stability holds. It is also shown how optimal control and adaptive control may act in concert in the case of unknown or uncertain system parameters. The solution describes motion strategies of minimum effort and variance. The proposed optimal control is formulated to be suitable as a posture and movement model for experimental validation and verification. The combination of adaptive and optimal control makes this algorithm a candidate for coordination and control of functional neuromuscular stimulation as well as of prostheses. Validation examples with experimental data are provided.     

对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响

摘要 目的：对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响。方法：选择西安交通大学第一附属医院2020年6月至2021年12月收治的脊柱骨折患者96例作为研究对象,根据1:1随机数字表法把患者分为椎旁神经阻滞组与肋间神经阻滞组各48例。所有患者均给予脊柱手术治疗,所有手术操作都由同一组医生完成,椎旁神经阻滞组与肋间神经阻滞组分别给予超声引导下椎旁神经阻滞与肋间神经阻滞,记录两组阻滞效果及对血流动力学的影响。结果：两组通气5 min、通气30 min、恢复双肺通气30 min等时间点的HR、SPO₂值在组内与组间对比无差异（P>0.05）。两组的术中补液量、术中出血量、手术时间、麻醉时间、术中尿量等对比无差异（P>0.05）。椎旁神经阻滞组的坐骨神经运动神经、感觉神经阻滞持续时间都少于肋间神经阻滞组（P<0.05）,两组运动神经、感觉神经阻滞起效时间对比无差异（P>0.05）。椎旁神经阻滞组术后7 d的肺部感染、肺栓塞、呼吸衰竭等肺部并发症发生率2.1 %,低于肋间神经阻滞组的16.7 %（P<0.05）。结论：相对于肋间神经阻滞,超声引导下椎旁神经阻滞在脊柱手术患者并不会影响患者的血流动力学状况,也不会影响手术与麻醉过程,还可缩短坐骨神经运动神经、感觉神经阻滞持续时间,减少术后并发症的发生。     

Systematic perturbation of an artificial neural network: A step towards quantifying causal contributions in the brain

Lesion inference analysis is a fundamental approach for characterizing the causal contributions of neural elements to brain function. This approach has gained new prominence through the arrival of modern perturbation techniques with unprecedented levels of spatiotemporal precision. While inferences drawn from brain perturbations are conceptually powerful, they face methodological difficulties. Particularly, they are challenged to disentangle the true causal contributions of the involved elements, since often functions arise from coalitions of distributed, interacting elements, and localized perturbations have unknown global consequences. To elucidate these limitations, we systematically and exhaustively lesioned a small artificial neural network (ANN) playing a classic arcade game. We determined the functional contributions of all nodes and links, contrasting results from sequential single-element perturbations with simultaneous perturbations of multiple elements. We found that lesioning individual elements, one at a time, produced biased results. By contrast, multi-site lesion analysis captured crucial details that were missed by single-site lesions. We conclude that even small and seemingly simple ANNs show surprising complexity that needs to be addressed by multi-lesioning for a coherent causal characterization.     

The voltage-dependent sodium channel is co-localized with the acetylcholine receptor at the vertebrate neuromuscular junction

Isolated motor endplates from mouse intercostal muscles can be obtained after subcellular fractionation. On these motor endplates, localization of the nicotinic receptor and of the voltage-dependent Na+ channel coincides as demonstrated by double labeling with rhodamine alpha-bungarotoxin and a specific anti-Na+ channel monoclonal antibody. High density of Na+ channel at the motor endplate is confirmed by the enrichment in TTX binding sites as compared to the crude homogenate. In contrast isolated motor endplates are almost completely devoid of Ca2+ channel antagonist binding sites.     

Cooperativity in RNA-protein interactions: global analysis of RNA binding specificity

The control and function of RNA are governed by the specificity of RNA binding proteins. Here, we describe a method for global unbiased analysis of RNA-protein interactions that uses in vitro selection, high-throughput sequencing, and sequence-specificity landscapes. The method yields affinities for a vast array of RNAs in a single experiment, including both low- and high-affinity sites. It is reproducible and accurate. Using this approach,we analyzed members of the PUF (Pumilio and FBF) family of eukaryotic mRNA regulators. Our data identify effects of a specific protein partner on PUF-RNA interactions, reveal subsets of target sites not previously detected, and demonstrate that designer PUF proteins can precisely alter specificity. The approach described here is, in principle, broadly applicable for analysis of any molecule that binds RNA, including proteins, nucleic acids, and small molecules.