History of a model

This paper refers us to the mid-1960s, when mechanisms of the animal rhythmic activity were vividly discussed and the concept of “generator of rhythm” was formulated. Since at that time the device of the generator of rhythm was understood very poorly, Menshutkin, Sviderskii, and Umnov, by the example of an insect (locust), attempted to create the first mathematical model generating rhythm of the flight. Why the interest in such model arose, how the model was created, and what the result of it was has been described in this paper.     

A two compartment model of the stepping generator: Analysis of the roles of a stage-setter and a rhythm generator

Recent studies on locomotion of the mesencephalic cat demonstrated that activation of the spinal stepping generator and the postural control system are dependent phenomena (Mori et al., 1978, 1980). This has motivated the construction of a new model of the stepping generator to account for interactions with the postural control system. The present model consists of two main compartments, the rhythm generator and the stage-setter. The rhythm generator generates rhythmic bursting discharges of extensor and flexor alpha motoneurons. The function of the stage-setter is to set and reset the excitability of extensor alpha motoneuron to a number of desired levels. This study analyzes interactions in this model between rhythm generating and postural control system. By adding a concept of stage-setting to the rhythm generator model, we succeed in simulating a variety of locomotor patterns observed in the mesencephalic cat, including stepping automatism (Mori et al., 1979).     

经颈静脉途径制备Beagle犬心脏记忆模型

目的经颈静脉途径应用心室起搏的方法制备心脏记忆犬模型。方法 8只普通级成年健康Beagle犬经腹腔麻醉后,Seldinger’s法穿刺颈外静脉成功后送入心内膜起搏电极,将电极头端固定于右室心尖部,近端连接于脉冲发生器。起搏频率设置较犬窦性心律时的基础心率快15%,保证起搏器连续起搏。结果连续起搏1周后所有动物均成功制备为心脏记忆模型。建模后犬的心率、呼吸、体重与建模前比较,无明显改变;所有模型组犬起搏前心电图均为窦性心律,起搏1周后出现心脏T波记忆,在下壁导联以及胸前导联均出现T波倒置,停止起搏后,心脏T波记忆逐渐消失;模型组犬与正常组犬心肌病理相比,无明显改变。结论经颈静脉途径应用心室起搏法建立心脏记忆犬模型的方法,具有手术简单,创伤小,诱发方式与临床相似等优点,为深入展开心脏记忆的机制研究奠定基础。     

Theta phase coding in a network model of the entorhinal cortex layer II with entorhinal-hippocampal loop connections

We investigated successive firing of the stellate cells within a theta cycle, which replicates the phase coding of place information, using a network model of the entorhinal cortex layer II with loop connections. Layer II of the entorhinal cortex (ECII) sends signals to the hippocampus, and the hippocampus sends signals back to layer V of the entorhinal cortex (ECV). In addition to this major pathway, projection from ECV to ECII also exists. It is, therefore, inferred that reverberation activity readily appears if projections from ECV to ECII are potentiated. The frequency of the reverberation would be in a gamma range because it takes signals 20–30 ms to go around the entorhinal-hippocampal loop circuits. On the other hand, it has been suggested that ECII is a theta rhythm generator. If the reverberation activity appears in the entorhinal-hippocampal loop circuits, gamma oscillation would be superimposed on a theta rhythm in ECII like a gamma-theta oscillation. This is a reminiscence of the theta phase coding of place information. In this paper, first, a network model of ECII will be developed in order to reproduce a theta rhythm. Secondly, we will show that loop connections from one stellate cell to the other one are selectively potentiated by afferent signals to ECII. Frequencies of those afferent signals are different, and transmission delay of the loop connections is 20 ms. As a result, stellate cells fire successively within one cycle of the theta rhythm. This resembles gamma-theta oscillation underlying the phase coding. Our model also replicates the phase precession of stellate cell firing within a cycle of subthreshold oscillation (theta rhythm).     

Multi-layered multi-pattern CPG for adaptive locomotion of humanoid robots

In this paper, we present an extended mathematical model of the central pattern generator (CPG) in the spinal cord. The proposed CPG model is used as the underlying low-level controller of a humanoid robot to generate various walking patterns. Such biological mechanisms have been demonstrated to be robust in locomotion of animal. Our model is supported by two neurophysiological studies. The first study identified a neural circuitry consisting of a two-layered CPG, in which pattern formation and rhythm generation are produced at different levels. The second study focused on a specific neural model that can generate different patterns, including oscillation. This neural model was employed in the pattern generation layer of our CPG, which enables it to produce different motion patterns—rhythmic as well as non-rhythmic motions. Due to the pattern-formation layer, the CPG is able to produce behaviors related to the dominating rhythm (extension/flexion) and rhythm deletion without rhythm resetting. The proposed multi-layered multi-pattern CPG model (MLMP-CPG) has been deployed in a 3D humanoid robot (NAO) while it performs locomotion tasks. The effectiveness of our model is demonstrated in simulations and through experimental results.     

Diurnal changes in the rabbit's visual evoked potential

Rabbits that have been exposed to the natural cycles of day and night exhibit marked diurnal changes in the shape of their Visual Evoked Potential in constant environmental conditions. The results of exposure to artificial 24 hr light-dark cycles strongly suggest that it is the regular alternation of daylight and darkness which acts as the synchronizing "Zeitgeber" for the V.E.P. rhythm which exists after exposure to the natural cycles of day and night. It would seem further that the V.E.P. changes reflect a square-wave like rhythm in the sensitivity of the visual system to photic stimuli, in which the sensitivity is much higher at night than in the day-time. The probable importance of the diurnal V.E.P. rhythm for the occurrence of daily fluctuations in behaviour is discussed.     

Electrophysiological study of serotoninergic neuron Cl in the pteropod mollusk Clione

Functional characteristics of cerebral serotoninergic neuron Cl, axons of which terminate at the buccal ganglia [7], were investigated in the pteropod molluskClione. Stimulating neuron Cl induced activation of the feeding rhythm generator located in the buccal ganglia — an effect arising after a long latency and persisting for some tens of seconds once stimulation had ended. Neuron Cl receives feedback from buccal ganglion cells and this brings about periodic modulation in ganglia activity during the generation of feeding rhythm. Activity of neuron Cl is correlated with operation of the locomotor rhythm generator located in the pedal ganglia. The firing rate of Cl neurons increased upon activation of the locomotor generator (whether spontaneous or induced by stimulating certain command neurons). The correlation found between workings of the locomotor generator and activity of Cl neurons is thought to be one of the manifestations of feeding synergy involving simultaneous activation of the locomotor and buccal apparatus.Institute for Research on Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov State University, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 18–25, January–February, 1991.     

Respiratory pattern generation in adult lampreys (Lampetra fluviatilis): interneurons and burst resetting

The central pattern generator for the respiratory rhythm in adult lampreys was studied in isolated brain preparations. At least three different types of respiratory units were found in intra- and extracellular recordings near the trigeminal nucleus (Fig. 1), including: units that start firing before the motorneurons, recorded from the ventral surface (Figs. 2 and 3), follower cells near rostral nucleus V (Fig. 4), units bursting after the motorneurons, found in the sulcus limitans (Figs. 5 and 6). Transections of the medulla indicated that the rostral half of nucleus V could be removed without reducing the respiratory frequency (Fig. 8). The earliest respiratory events that could be recorded from the ependymal surface or the cranial nerves were observed near nuclei IX-VII-caudal V during quiet breathing. There was a rostrocaudal delay in the onset of bursts of more caudal motorneurons (Figs. 9, 10, and 12). The rostrocaudal delay became reversed, such that bursts started earlier in n.X than n.IX, during episodes of intense breathing that were accompanied by prolonged discharges in the medial reticular formation (Fig. 11). Stimulation of the medulla surface, near the base of nerve V, could trigger bursts prematurely and reset the timing of the respiratory rhythm, yielding a discontinuous phase response curve (Fig. 14). In sum, 6 types of respiratory interneurons can presently be distinguished (Fig. 15). The sulcus limitans near nucleus V is a candidate location for components of the pattern generator.     

Mathematical model of activity of spinal generators producing rhythmic movement

Different organizational arrangements of scratching and locomotor rhythm generators were simulated by a computer-aided mathematical model. A functional group of neurons (a hemicenter constructed on the basis of a stochastically arranged neuronal network) served as the basis for the generator. Several organizational arrangements of scratching and locomotor rhythm generators are considered: two hemicenters with reciprocal inhibitory connections and tonic excitatory influences on both; two hemicenters with inhibitory-excitatory connections and tonic excitatory influences on only one of these; circular structures consisting of more than two functional groups of neurons with excitatory and inhibitory connections between them. All these arrangements would allow for generation of rhythmic activity with a similar time course to that of scratching and locomotor rhythm. It was found that the transition from locomotor to scratching rhythm could be based on fairly simply organized effects on generator neurons. Principles possibly guiding the construction of spinal generators of scratching and locomotor movements are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 586–597, September–October, 1988.     

The variability of respiratory pattern and gas exchange

It is known, that spectral analysis of heart rate and respiratory variability allows to find out the very low frequency (VLF) rhythm. However it is not known, it is necessary to carry this rhythm to what type of wave processes. The purpose of the present researches was to study the respiratory variability and the variability of gas exchange parameters. 10 healthy subjects have been surveyed. The pneumogramms within 30 minutes spent record, and then a method "breath-by-breath" within 30 minutes registered gas exchange parameters (Ve--lung ventilation, V(O2) -O2 consumption and other parameters). Fast Fourier transform method has found out two groups of the basic peaks. The first--in a range 0.2-0.3 Hz (a time cycle--3-5 s), that corresponds respiratory frequency which size at subjects varied from 12 to 20 per minute. The second--in a range 0.002-0.0075 Hz, that corresponds VLF diapason (a time cycle--1-3.5 minutes). At the analysis pneumogramms rhythms in the same ranges have been established. The carried out researches allow to draw a conclusion on steady character of wave process in a VLF-range. It can be carried to quasi-periodic oscillations type. First oscillator or respiratory frequency it is formed by means of mechanisms of chemoreception. Considering, that V(O2) and V(CO2) are function energy exchange, it is possible to believe, what exactly energy demand define the second oscillator.     

Influence of the pteropod mollusk pedal ganglia locomoter system on anatomically isolated neurons

It was established during experiments on pedal ganglia generating locomotor rhythm isolated fromClione limacina, a pteropod mollusk, that this rhythm was irregular in 30% of preparations; i.e., the locomotor generator worked in bursts which alternated with periods of regular activity. Locomotor bursts were produced by excitation in command neurons located within the pedal ganglia. Single neurons were extracted from the ganglia in these preparations generating locomotor bursts by means of an intracellular microelectrode; their somata were then placed in their original sites amongst the ganglia cells. A total of 35 neurons were isolated showing changed activity during bursts. Nine of these cells renewed their erratic activity (linked to locomotor bursts) following reinsertion into the ganglion. Neurons which had initially shown an excitatory pattern during bursts continued to be excited; the same was true for inhibitory types. These observations indicate that the command neurons governing generator operation can act on target cells when morphological contact with them has been suppressed.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow; M. V. Lomonosov State University. Moscow. Translated from Neirofiziologiya, Vol. 18, No. 6, pp. 756–763, November–December, 1986.     

The effect of intracerebroventricular administration of substance P fragment and met-enkephalin on the transmission of nervous impulses between the midbrain reticular formation and two generators of the hippocampal theta rhythm in rabbits

The effect of intracerebroventricular administration of Substance P fragment and met-enkephalin on the excitability of two generators of hippocampal theta rhythm was investigated in the experiments performed on chronic rabbits. Substance P had a strong facilitatory effect on the threshold of the generator of the hippocampal theta rhythm of the frequency 4-7 c/s and an inhibitory effect on the threshold of the generator of the 7-12 c/s frequency evoked by stimulation of the midbrain reticular formation. These effects were dose dependent. The effects of met-enkephalin were opposite. They increased the threshold of the 4-7 c/s hippocampal generator and decreased the threshold of the other generator. The effect of these two compounds was evaluated according to the energy of electrical trains of pulses maintaining the continuous arousal pattern in the hippocampus.     

Evaluating functional roles of phase resetting in generation of adaptive human bipedal walking with a physiologically based model of the spinal pattern generator

The central pattern generators (CPGs) in the spinal cord strongly contribute to locomotor behavior. To achieve adaptive locomotion, locomotor rhythm generated by the CPGs is suggested to be functionally modulated by phase resetting based on sensory afferent or perturbations. Although phase resetting has been investigated during fictive locomotion in cats, its functional roles in actual locomotion have not been clarified. Recently, simulation studies have been conducted to examine the roles of phase resetting during human bipedal walking, assuming that locomotion is generated based on prescribed kinematics and feedback control. However, such kinematically based modeling cannot be used to fully elucidate the mechanisms of adaptation. In this article we proposed a more physiologically based mathematical model of the neural system for locomotion and investigated the functional roles of phase resetting. We constructed a locomotor CPG model based on a two-layered hierarchical network model of the rhythm generator (RG) and pattern formation (PF) networks. The RG model produces rhythm information using phase oscillators and regulates it by phase resetting based on foot-contact information. The PF model creates feedforward command signals based on rhythm information, which consists of the combination of five rectangular pulses based on previous analyses of muscle synergy. Simulation results showed that our model establishes adaptive walking against perturbing forces and variations in the environment, with phase resetting playing important roles in increasing the robustness of responses, suggesting that this mechanism of regulation may contribute to the generation of adaptive human bipedal locomotion.     

Adherence to cardioprotective medications and mortality among patients with diabetes and ischemic heart disease

Background

Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies. The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF.

Methods

Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion.

Results

32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04).

Conclusion

In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion.     

Centrally patterned rhythmic activity integrated by a peripheral circuit linking multiple oscillators

The central pattern generator for heartbeat in the medicinal leech, Hirudo generates rhythmic activity conveyed by heart excitor motor neurons in segments 3-18 to coordinate the bilateral tubular hearts and side vessels. We focus on behavior and the influence of previously un-described peripheral nerve circuitry. Extracellular recordings from the valve junction (VJ) where afferent vessels join the heart tube were combined with optical recording of contractions. Action potential bursts at VJs occurred in advance of heart tube and afferent vessel contractions. Transections of nerves were performed to reduce the output of the central pattern generator reaching the heart tube. Muscle contractions persisted but with a less regular rhythm despite normal central pattern generator rhythmicity. With no connections between the central pattern generator and heart tube, a much slower rhythm became manifest. Heart excitor neuron recordings showed that peripheral activity might contribute to the disruption of centrally entrained contractions. In the model presented, peripheral activity would normally modify the activity actually reaching the muscle. We also propose that the fundamental efferent unit is not a single heart excitor neuron, but rather is a functionally defined unit of about three adjacent motor neurons and the peripheral assembly of coupled peripheral oscillators.     

A model of the neuro-musculo-skeletal system for human locomotion

The generation of human locomotion was examined by linking computational neuroscience with biomechanics from the perspective of nonlinear dynamical theory. We constructed a model of human locomotion, which includes a musculo-skeletal system with 8 segments and 20 muscles, a neural rhythm generator composed of 7 pairs of neural oscillators, and mechanisms for processing and transporting sensory and motor signals. Using a computer simulation, we found that locomotion emerged as a stable limit cycle that was generated by the global entrainment between the musculo-skeletal system, the neural system, and the environment. Moreover, the walking movements of the model could be compared quantitatively with those of experimental studies in humans.Part of this paper was presented to IVth International Symposium on Computer Simulation in Biomechanics, Paris, France, July 1, 1993     

Lung and buccal ventilation in the frog: uncoupling coupled oscillators

The frog, with two distinct ventilatory acts, provides a useful model to investigate the prospective interaction of two oscillators in generating the respiratory rhythm. Building on evidence supporting the existence of separate oscillators generating buccal and lung ventilation, we have attempted to uncouple the two rhythms in the isolated brain stem preparation. Opioid preferentially inhibits the lung rhythm, suggesting an uncoupling of the lung from the buccal oscillator. Reduction of the superfusate chloride concentration alters both the buccal and the lung rhythms. Joint application of opioid and reduced-chloride superfusate leads to an increase in the variability of the buccal burst-to-lung burst intervals. This increase in variability suggests that chloride-mediated mechanisms are involved in coupling the buccal oscillator to the lung oscillator. Given the results from these interventions, we propose a simple schematic model of the frog respiratory rhythm generator, outlining the coupling of the lung and buccal oscillators.     

The circadian rhythm and photosensitivity of small impulses of the Bulla eye

Summary The eye of the mollusk Bulla gouldiana contains a pacemaker that generates a circadian rhythm in compound action potentials (CAPs) in the optic nerve. In this paper, we present evidence of a second circadian rhythm in the optic nerve of the eye maintained in darkness at 15 °C. This is a rhythm in the frequency of small (10–40 V) neural impulses that occurs about 12 h out-of-phase with the rhythm in CAPs. Typically, the small-spike frequency is at a minimum within an hour of the peak in CAP frequency and is maximal during the subjective night. Like the CAP rhythm, the phase of the small-spike rhythm is determined by the prior light/dark cycle. A rebound in small-spike activity following the end of a light pulse and the presence of photoinhibited impulses in surgically reduced eyes suggests that the cells that generate the small-spikes may be photoreceptors that are inhibited by light. In addition, by using isolated nervous system preparations, we have found that smallspikes occur in the two optic nerves in a one-for-one relationship immediately following a light-to-dark transition. This inter-eye communication may be involved in the coupling of the ocular pacemakers.Abbreviations ASW artificial sea water - BRN basal retinal neuron - CAP compound action potential     

A physiological model of a circannual oscillator

Recent evidence based on studies in hypothalamo-pituitary disconnected Soay sheep suggests that the generation of circannual rhythms may be local to specific tissues or physiological systems. Now, the authors present a physiological model of a circannual rhythm generator centered in the pituitary gland based on the interaction between melatonin-responsive cells in the pars tuberalis that act to decode photoperiod, and lactotroph cells of the adjacent pars distalis that secrete prolactin. The model produces a self-sustained, circannual rhythm in endocrine output that the authors explore by mathematical modeling. The circannual oscillation requires a delayed negative feedback mechanism. The authors highlight specific features of the pituitary dynamics as a guide to future research on circannual rhythms.     

Synaptic patterning of left-right alternation in a computational model of the rodent hindlimb central pattern generator

Establishing, maintaining, and modifying the phase relationships between extensor and flexor muscle groups is essential for central pattern generators in the spinal cord to coordinate the hindlimbs well enough to produce the basic walking rhythm. This paper investigates a simplified computational model for the spinal hindlimb central pattern generator (CPG) that is abstracted from experimental data from the rodent spinal cord. This model produces locomotor-like activity with appropriate phase relationships in which right and left muscle groups alternate while extensor and flexor muscle groups alternate. Convergence to this locomotor pattern is slow, however, and the range of parameter values for which the model produces appropriate output is relatively narrow. We examine these aspects of the model’s coordination of left-right activity through investigation of successively more complicated subnetworks, focusing on the role of the synaptic architecture in shaping motoneuron phasing. We find unexpected sensitivity in the phase response properties of individual neurons in response to stimulation and a need for high levels of both inhibition and excitation to achieve the walking rhythm. In the absence of cross-cord excitation, equal levels of ipsilateral and contralateral inhibition result in a strong preference for hopping over walking. Inhibition alone can produce the walking rhythm, but contralateral inhibition must be much stronger than ipsilateral inhibition. Cross-cord excitatory connections significantly enhance convergence to the walking rhythm, which is achieved most rapidly with strong crossed excitation and greater contralateral than ipsilateral inhibition. We discuss the implications of these results for CPG architectures based on unit burst generators.