From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions.     

Electrophysiological and pharmacological analysis of L-dopa-induced dyskinesia and tardive dyskinesia (author's transl)

Electrophysiological and pharmacological analysis of L-Dopa-induced dyskinesia and tardive dyskinesia (L.DD) due to neuroleptics was performed on 12 patients with Parkinson's disease and on 12 others with psychotic diseases. This analysis included the examination of spinal reflexes, monosynaptic H reflex, polysynaptic cutaneous reflex of the lower limb, muscular responses to passive movement [stretch reflex and shortening reaction (SR)] and the study of the motor response to a dopaminergic stimulus (I.V. injection of Piribedil (PBD), a dopamine agonist). There was no difference in EMG activity between L.DD and TD. Three EMG patterns can be distinguished: anarchic discharge pattern (ADA), tonic grouping discharge pattern (AST) and rhythmic burst pattern (ABR). PBD effects indicate a possible relationship between the EMG patterns and the sensitivity level of the motor dopamine receptors. During L-Dopa dyskinesia and tardive dyskinesia, the same changes in spinal reflexes were observed. Muscle tone tested by muscular responses to passive movement (shortening and myotatic reaction) was normal. Monosynaptic excitability explored by H/M ratio was within the normal range. In contrast, the polysynaptic nociceptive reflex was increased in every case. In Parkinsonian patients with L-Dopa dyskinesia, this pattern of the spinal reflexes was significantly different in comparison to the rigid phase. Intravenous infusion of PBD suppressed tremor and provoked the occurrence of dyskinetic activity in Parkinsonian patients with L-Dopa dyskinesia during the rigid phase. During the dyskinetic phase, as in tardive dyskinesia, PBD increases these phenomena and changes EMG activity in rhythmic pattern. It is suggested that L-Dopa dyskinesia and tardive dyskinesia can be determined by testing EMG activity, spinal reflexes and dopaminergic reactivity. There is evidence to suggest that the various types of involuntary abnormal movement represent a single entity, and that dopamine receptor supersensitivity may be involved.     

Widespread anatomical projections of the serotonergic modulatory neuron,CB1, inAplysia

Although sensitization-related changes in the neural circuitry of withdrawal reflexes inAplysia are well studied, relatively few studies address the organization of the modulatory components of sensitization. In particular, it is not known whether individual modulatory loci can simultaneously influence multiple reflex circuits. There is, however, evidence that a single modulatory transmitter, serotonin, plays a pivotal role in facilitating different reflex circuits during sensitization. Furthermore, it is known that activation of a pair of serotonergic neurons, the CB1s, produces heterosynaptic facilitation of the sensorimotor connections of one of these reflex circuits. These data together raise the possibility that the CB1s may produce sensitizing changes in the neural elements of multiple reflex systems simultaneously. In the present study, we utilized immunocytochemistry and intracellular labeling to obtain anatomical evidence of CB1's possible role in modulating multiple reflex circuits. We found that two distinct neurons satisfy previously published physiological criteria for CB1. One of these, CB1, is immunoreactive to serotonin. The second cell, here named CB2, has a different neuroanatomy and is not serotonin immunoreactive. Focusing on CB1, we found (1) profuse fine processes given off by its axons in the posterior neuropil of the cerebral ganglion, (2) extensive branching and fine processes in the pleural ganglion, and (3) a branch of CB1 that projects into the pedal ganglion. These three observations are consistent with the hypothesis that, in addition to its already established role in modulating the siphon withdrawal circuit, CB1 may also modulate synaptic connections between (1) the sensory and motor neurons of the tentacle withdrawal reflex (2) the sensory neurons and interneurons of the tail and tail-elicited siphon withdrawal reflex, and (3) the sensory and motor neurons of the tail withdrawal reflex. These observations support further physiological investigations of a possible global role of CB1 in modulating the tail and tentacle withdrawal reflexes.     

Effect of immersion in water on the rudimentary reflexes of infants in the 1st months of life

Seizing and myotatic reflexes differ in their intensities in the right and left hands already from the first month of life in babies. It was shown that disappearing seizing and myotatic reflexes together with Moro's and Babinsky's reflexes in 3 1/2-4 months old babies can be elicited again during bathing. In the course of adaptation of babies to the water these reflexes disappear.     

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes, illustrating the reversibility of these synaptic defects. Deafferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention.     

Velocity Control of a Bounding Quadruped via Energy Control and Vestibular Reflexes

In this paper a bio-inspired approach of velocity control for a quadruped robot running with a bounding gait on compliant legs is set up. The dynamic properties ofa sagittal plane model of the robot are investigated. By analyzing the stable fixed points based on Poincare map, we find that the energy change of the system is the main source for forward velocity adjustment. Based on the analysis of the dynamics model of the robot, a new simple linear running controller is proposed using the energy control idea, which requires minimal task level feedback and only controls both the leg torque and ending impact angle. On the other hand, the functions of mammalian vestibular reflexes are discussed, and a reflex map between forward velocity and the pitch movement is built through statistical regression analysis. Finally, a velocity controller based on energy control and vestibular reflexes is built, which has the same structure as the mammalian nervous mechanism for body posture control. The new con- troller allows the robot to run autonomously without any other auxiliary equipment and exhibits good speed adjustment capa- bility. A series simulations and experiments were set to show the good movement agility, and the feasibility and validity of the robot system.     

Effect of Inhibition of NO Synthases on Cardiogenic Depressor Reflexes in Different Animal Species

We studied the role of the nitric oxide (NO) system in the realization of cardiogenic depressor reflexes evoked by stimulation of cardiac receptors by veratrine (reproduction of the Bezold–Jarish reflex). Acute experiments were performed on anesthetized dogs and rats: we tested the effects of inhibition of dissimilar isoforms of NO synthase (NOS) and paid special attention to possible species-related differences in realization of the reflex responses. We found that systemic inhibition of NOS by L-nitro-N-arginine (L-NNA, 30 mg/kg, i.v.) significantly decreased the depressor reflex reaction in dogs. Vasomotor dilatatory reactions of the peripheral vessels underwent considerable modifications and in some cases were converted into vasoconstrictory responses. Selective inhibition of neuronal NOS (nNOS) by 7-nitroindazole (7-NI, 25 mg/kg, i.p.) exerted no effect on the development of cardiogenic depressor reflexes in dogs. At the same time, systemic inhibition of NOS in the course of reproduction of cardiogenic depressor reflexes in rats resulted in intensification of depressor responses, while inhibition of nNOS decreased these reactions. Thus, we first demonstrated the role of NO in the realization of cardiogenic depressor reflexes under in vivo conditions and described species-related peculiarities of the involvement of the NO system in the development of these reflexes. We also demonstrated the dependence of formation of cardiogenic depressor reflexes on the predominant involvement of one NOS type or another.     

Long-latency reflexes of the human arm reflect an internal model of limb dynamics

A key feature of successful motor control is the ability to counter unexpected perturbations. This process is complicated in multijoint systems, like the human arm, by the fact that loads applied at one joint will create motion at other joints [1-3]. Here, we test whether our most rapid corrections, i.e., reflexes, address this complexity through an internal model of the limb's mechanical properties. By selectively applying torque perturbations to the subject's shoulder and/or elbow, we revealed a qualitative difference between the arm's short-latency/spinal reflexes and long-latency/cortical reflexes. Short-latency reflexes of shoulder muscles were linked exclusively to shoulder motion, whereas its long-latency reflexes were sensitive to both shoulder and elbow motion, i.e., matching the underlying shoulder torque. In fact, a long-latency reflex could be evoked without even stretching or lengthening the shoulder muscle but by displacing just the elbow joint. Further, the shoulder's long-latency reflexes were appropriately modified across the workspace to account for limb-geometry changes that affect the transformation between joint torque and joint motion. These results provide clear evidence that long-latency reflexes possess an internal model of limb dynamics, a degree of motor intelligence previously reserved for voluntary motor control [3-5]. The use of internal models for both voluntary and reflex control is consistent with substantial overlap in their neural substrates and current notions of intelligent feedback control [6-8].     

Haltere and visual inputs sum linearly to predict wing (but not gaze) motor output in tethered flying Drosophila

In the true flies (Diptera), the hind wings have evolved into specialized mechanosensory organs known as halteres, which are sensitive to gyroscopic and other inertial forces. Together with the fly''s visual system, the halteres direct head and wing movements through a suite of equilibrium reflexes that are crucial to the fly''s ability to maintain stable flight. As in other animals (including humans), this presents challenges to the nervous system as equilibrium reflexes driven by the inertial sensory system must be integrated with those driven by the visual system in order to control an overlapping pool of motor outputs shared between the two of them. Here, we introduce an experimental paradigm for reproducibly altering haltere stroke kinematics and use it to quantify multisensory integration of wing and gaze equilibrium reflexes. We show that multisensory wing-steering responses reflect a linear superposition of haltere-driven and visually driven responses, but that multisensory gaze responses are not well predicted by this framework. These models, based on populations, extend also to the responses of individual flies.     

Functions of the LE sensory neurons inAplysia

Mechanosensory neurons which innervate the siphon and have their cell bodies in the LE cluster of the abdominal ganglion ofAplysia have revealed many cellular and molecular processes that may play general roles in learning and memory. It was initially suggested that these cells are largely responsible for triggering the gill-withdrawal reflex evoked by weak siphon stimulation, and that most of this effect is mediated by their monosynaptic connections to gill motor neurons. This implied a simple link between plasticity at these synapses and modifications of the reflex during learning. We review more recent studies from several laboratories showing that the LE cells are not activated by very weak tactile stimuli that elicit the gill-withdrawal reflex, and that an unidentified population of siphon sensory neurons has lower mechanosensory thresholds and produces shorter latency responses. Furthermore, the direct connections between LE cells and gill motor neurons make a minor contribution when the reflex is elicited in pinned siphon preparations by light stimuli that weakly activate the LE cells. Because weak mechanical stimulation of the unrestrained siphon causes little or no LE cell activation, it is unlikely that, under natural conditions, sensitization or conditioning of reflex responses elicited by light siphon touch depends upon plasticity of LE cell synapses onto either motor or interneurons. The LE cells appear to function as nociceptors because they are tuned to noxious stimuli and, like mammalian nociceptors, show peripheral sensitization following nociceptive activation. This sensitization and the profound activity-dependent potentiation of LE synapses indicate that LE cell contributions to defensive reflexes should be largest during and after intense activation of the LE cells by noxious stimulation (with the LE cell plasticity contributing to long-lasting memory of peripheral injury). The LE sensory neurons offer special opportunities for direct tests of this and other hypotheses about specific mnemonic functions of fundamental mechanisms of neural plasticity.     

Peculiarities of modifying influence of the factors forming the functional status of the central nervous system on dynamics of the rat higher nervous activity disturbances totally exposed to electron and gamma-radiation at a dose of 100 Gy

The dynamics of using a stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after the total influence of high energy electrons and gamma-rays at a dose of 100 Gy and a modifying influence of the two most important factors forming the functional status of the central nervous system: the stage of the conditioned reflex consolidation and typological peculiarities of the higher nervous activity have been investigated. The influence of both types of ionizing radiation has been shown to cause far more profound disturbances of non consolidated conditioned reflexes in comparison with the automatized conditioned reflexes and provoke an inverted picture of disturbances in the animals with opposed peculiarities of the higher nervous activity. The qualitative picture of the dynamics of disturbances that are caused by these types of radiation is identical. In summary, the studied conditions that form the functional status of the central nervous system determine the nature of neuroradiation syndrome to a greater extent than differences in the effectiveness of these types of radiation.     

A Neural Network Model of Sensorimotor Transformations in the Local Bending Reflex of the Medicinal Leech

SYNOPSIS. In response to a moderate mechanical stimulus, theleech withdraws by forming a U-shaped local bend beneath thestimulus. Interneurons in the local bending reflex receive multiplesensory inputs, and have outputs to many motor neurons, suggestingthat stimulus location on the body is represented in a distributedfashion. However, it is possible that as yet unidentified interneuronsdedicated to the detection of specific spatial locations arenecessary for the full range of the local bending motor output.Using the backpropagation algorithm to optimize connectionsin a model of the reflex, we showed that the distributed processingmodel of sensorimotor integration was consistent with our knowledgeof the connection strengths between identified neurons in thereflex. The model further showed that the spatial and temporalconstraints on the linkage between sensory representations andmotor output can be satisfied by the appropriate connectivitybetween layers of interneurons and motor neurons in the leech,as well as in other systems with similar circuitry.     

Effect of hypoxia on the excitability of two cranial reflexes in unanaesthetized fetal sheep

In fetal sheep acute hypoxia causes a decreased incidence of breathing movements and motor activity, and the excitability of polysynaptic reflexes in the hindlimbs is depressed. To determine whether this inhibitory effect extends to other areas in the fetal CNS, we have studied the effect of hypoxia on two reflexes with cranial pathways. The digastric (jaw opening) reflex was elicited by stimulation of the dental nerve through a pair of stainless steel electrodes implanted into the mandible (4 fetuses). The thyroarytenoid muscle of the larynx was reflexly activated by stimulation of the superior laryngeal nerve by a cuff electrode (4 fetuses). Low level stimulation at 1.5-2 X threshold was repeated at approximately 2 min intervals for 3-4 h; the stimulation did not alter the pattern of electrocortical activity, breathing movements, or cause arousal. The amplitude of the digastric reflex was greatest during low voltage electrocortical activity; conversely, the amplitude of the thyroarytenoid reflex was greatest during high voltage electrocortical activity. Isocapnic hypoxia lasting 30-60 min (16 trials), in which the PaO2 was reduced to 12-14 mmHg, did not reduce the amplitude of either reflex. The reduction of thyroarytenoid reflex amplitude which normally occurred during low voltage electrocortical activity was not present during hypoxia. These experiments show that the inhibitory effects of hypoxia on spinal reflexes, breathing movements and motor activity do not include these cranial pathways.     

Changes in stretch reflexes and muscle stiffness with age in prepubescent children.

Musculo-articular stiffness of the triceps surae (TS) increases with age in prepubescent children, under both passive and active conditions. This study investigates whether these changes in muscle stiffness influence the amplitude of the reflex response to muscle stretch. TS stiffness and reflex activities were measured in 46 children (7-11 yr old) and in 9 adults. The TS Hoffmann reflex (H reflex) and T reflex (tendon jerk) in response to taping the Achilles tendon were evaluated at rest and normalized to the maximal motor response (Mmax). Sinusoidal perturbations of passive or activated muscles were used to evoke stretch reflexes and to measure passive and active musculoarticular stiffness. The children's Hmax-to-Mmax ratio did not change with age and did not differ from adult values. The T-to-Mmax ratio increased with age but remained significantly lower than in adults. Passive stiffness also increased with age and was correlated with the T-to-Mmax ratio. Similarly, the children's stretch reflex and active musculoarticular stiffness were significantly correlated and increased with age. We conclude that prepubescent children have smaller T reflexes and stretch reflexes than adults, and the lower musculoarticular stiffness is mainly responsible for these smaller reflexes, as indicated by the parallel increases in reflex and stiffness.     

Haltere-mediated equilibrium reflexes of the fruit fly, Drosophila melanogaster.

Flies display a sophisticated suite of aerial behaviours that require rapid sensory-motor processing. Like all insects, flight control in flies is mediated in part by motion-sensitive visual interneurons that project to steering motor circuitry within the thorax. Flies, however, possess a unique flight control equilibrium sense that is encoded by mechanoreceptors at the base of the halteres, small dumb-bell-shaped organs derived through evolutionary transformation of the hind wings. To study the input of the haltere system onto the flight control system, I constructed a mechanically oscillating flight arena consisting of a cylindrical array of light-emitting diodes that generated the moving image of a 30 degrees vertical stripe. The arena provided closed-loop visual feedback to elicit fixation behaviour, an orientation response in which flies maintain the position of the stripe in the front portion of their visual field by actively adjusting their wing kinematics. While flies orientate towards the stripe, the entire arena was swung back and forth while an optoelectronic device recorded the compensatory changes in wing stroke amplitude and frequency. In order to reduce the background changes in stroke kinematics resulting from the animal's closed-loop visual fixation behaviour, the responses to eight identical mechanical rotations were averaged in each trial. The results indicate that flies possess a robust equilibrium reflex in which angular rotations of the body elicit compensatory changes in both the amplitude and stroke frequency of the wings. The results of uni- and bilateral ablation experiments demonstrate that the halteres are required for these stability reflexes. The results also confirm that halteres encode angular velocity of the body by detecting the Coriolis forces that result from the linear motion of the haltere within the rotating frame of reference of the fly's thorax. By rotating the flight arena at different orientations, it was possible to construct a complete directional tuning map of the haltere-mediated reflexes. The directional tuning of the reflex is quite linear such that the kinematic responses vary as simple trigonometric functions of stimulus orientation. The reflexes function primarily to stabilize pitch and yaw within the horizontal plane.     

Development of motor behaviour

The development of motor behaviour depends on the differentiation of underlying circuitry. Recent work with the zebrafish brings the simple swimming behaviour of lower vertebrates and their embryos into focus as a suitable model to study the development of motor circuitry and its genetic control. Changes in connectivity and excitability contribute to the development of swimming in this simple system. In the chick embryo, limb motor circuitry is spontaneously active before motor axons reach their muscle targets, and it has properties in common with the spontaneously active networks in the retina. The early rhythmic activity responsible for embryonic movement is probably a generalised property of developing spinal networks that precedes, and may be required for, the completion of functional locomotor circuitry.     

Human-like reflex control for an artificial hand

In this paper, we illustrate the low level reflex control used to govern an anthropomorphic artificial hand. The paper develops the position and stiffness control strategy based on dynamic artificial neurons able to simulate the neurons acting in the human reflex control. The controller has a hierarchical structure. At the lowest level there are the receptors able to convert the analogical signal into a neural impulsive signal appropriate to govern the reflex control neurons. Immediately upon it, the artificial motoneurons set the actuators inner pressure to control the finger joint position and moment. Other auxiliary neurons in combination with the motoneurons are able to set the finger stiffness and emulate the inverse myotatic reflex control. Stiffness modulation is important both to save energy during task execution, and to manage objects made of different materials. The inverse myotatic reflex is able to protect the hand from possible harmful external actions. The paper also presents the dynamic model of the joints and of the artificial muscles actuating Blackfingers, our artificial hand. This new type of neural control has been simulated on the Blackfingers model; the results indicate that the developed control is very flexible and efficient for all kind of joints present in the humanoid hand.     

A large-scale model of some spinal reflex circuits

This paper reports the development of a large-scale model of some spinal reflex circuitry, useful for studying the dynamic interactions among neuronal populations during simple behaviors. The included populations and properties of the neurons and terminals were derived from the literature, mainly on cat spinal cord. The model was conceived as a symmetrical controller of a pair of antagonistic muscles, within the behavioral domain of the stretch and Golgi-tendon-organ reflexes, and was scaled to include realistic numbers of motoneurons. Inputs to the model were fiber populations providing random synaptic drive to some of the populations and sensory stimuli appropriate for the reflexes. The resulting model contained roughly 2300 neurons in six pairs of populations. The total number of connections in the model was about 600 000, and individual postsynaptic potentials were small (0.1–0.6 mV). Model responses were calibrated by examination of their ability to reproduce known aspects of the reflexes. Published algorithms were used to construct the environment, which is easily expandable, in terms of membrane channels, neuronal geometry, and synaptic properties. The system was built to combine a system-level perspective of spinal circuitry with the single-unit perspective common in electrophysiological investigation. It provides a computational tool for system-level investigations of spinal cord similar to the tools available at the level of membrane currents. Received: 16 May 1997 / Accepted in revised form: 2 October 1997     

Possible contributions of CPG activity to the control of rhythmic human arm movement

There is extensive modulation of cutaneous and H-reflexes during rhythmic leg movement in humans. Mechanisms controlling reflex modulation (e.g., phase- and task-dependent modulation, and reflex reversal) during leg movements have been ascribed to the activity of spinal central pattern generating (CPG) networks and peripheral feedback. Our working hypothesis has been that neural mechanisms (i.e., CPGs) controlling rhythmic movement are conserved between the human lumbar and cervical spinal cord. Thus reflex modulation during rhythmic arm movement should be similar to that for rhythmic leg movement. This hypothesis has been tested by studying the regulation of reflexes in arm muscles during rhythmic arm cycling and treadmill walking. This paper reviews recent studies that have revealed that reflexes in arm muscles show modulation within the movement cycle (e.g., phase-dependency and reflex reversal) and between static and rhythmic motor tasks (e.g., task-dependency). It is concluded that reflexes are modulated similarly during rhythmic movement of the upper and lower limbs, suggesting similar motor control mechanisms. One notable exception to this pattern is a failure of contralateral arm movement to modulate reflex amplitude, which contrasts directly with observations from the leg. Overall, the data support the hypothesis that CPG activity contributes to the neural control of rhythmic arm movement.     

The effect of DOPA on segmental reflexes in rat pups]

In acute experiments on spinal 5-30-day rat puppies, studies have been made of the effect of DOPA (100 mg/kg intraperitoneally) on monosynaptic reflex in extensors (evaluated by parameters of H-reflex) as well as on polysynaptic segmentary reflexes. In 5-7-day animals, mainly the inhibitory effect was observed with a short phase of facilitation of monosynaptic reflex. From the 10th day, facilitatory effect of DOPA becomes a predominant one reaching maximum to the 16th day. Within first 16 days of postnatal life, DOPA exhibits facilitatory effect on short-latent polysynaptic reflexes and inhibits long-latent ones. To the 30th day, reactions which are typical of adult animals are observed: inhibition of short-latent and facilitation of long-latent polysynaptic discharges. The data obtained indicate that in early postnatal development the effect of DOPA on mono- and polysynaptic reflexes qualitatively differs from that in adult animals.