Physiological and circuit mechanisms of postural control

The postural system maintains a specific body orientation and equilibrium during standing and during locomotion in the presence of many destabilizing factors (external and internal). Numerous studies in humans have revealed essential features of the functional organization of this system. Recent studies on different animal models have significantly supplemented human studies. They have greatly expanded our knowledge of how the control system operates, how the postural functions are distributed within different parts of CNS, and how these parts interact with each other to produce postural corrections and adjustments. This review outlines recent advances in the studies of postural control in quadrupeds, with special attention given the neuronal postural mechanisms.     

The contribution of animal models to the study of obesity

Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such genetically-engineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy balance. Despite all this work, there are many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of pharmaceuticals to treat obesity. Accordingly, reductions in the use of animal models, while ethically desirable, will not be feasible in the short to medium term, and indeed an expansion in activity using animal models is anticipated as the epidemic continues and spreads geographically.     

A robotic device for understanding neuromechanical interactions during standing balance control

Postural stability in standing balance results from the mechanics of body dynamics as well as active neural feedback control processes. Even when an animal or human has multiple legs on the ground, active neural regulation of balance is required. When the postural configuration, or stance, changes, such as when the feet are placed further apart, the mechanical stability of the organism changes, but the degree to which this alters the demands on neural feedback control for postural stability is unknown. We developed a robotic system that mimics the neuromechanical postural control system of a cat in response to lateral perturbations. This simple robotic system allows us to study the interactions between various parameters that contribute to postural stability and cannot be independently varied in biological systems. The robot is a 'planar', two-legged device that maintains compliant balance control in a variety of stance widths when subject to perturbations of the support surface, and in this sense reveals principles of lateral balance control that are also applicable to bipeds. Here we demonstrate that independent variations in either stance width or delayed neural feedback gains can have profound and often surprisingly detrimental effects on the postural stability of the system. Moreover, we show through experimentation and analysis that changing stance width alters fundamental mechanical relationships important in standing balance control and requires a coordinated adjustment of delayed feedback control to maintain postural stability.     

Estimating metabolic heat loss in birds and mammals by combining infrared thermography with biophysical modelling

Infrared thermography (IRT) is a technique that determines surface temperature based on physical laws of radiative transfer. Thermal imaging cameras have been used since the 1960s to determine the surface temperature patterns of a wide range of birds and mammals and how species regulate their surface temperature in response to different environmental conditions. As a large proportion of metabolic energy is transferred from the body to the environment as heat, biophysical models have been formulated to determine metabolic heat loss. These models are based on heat transfer equations for radiation, convection, conduction and evaporation and therefore surface temperature recorded by IRT can be used to calculate heat loss from different body regions. This approach has successfully demonstrated that in birds and mammals heat loss is regulated from poorly insulated regions of the body which are seen to be thermal windows for the dissipation of body heat. Rather than absolute measurement of metabolic heat loss, IRT and biophysical models have been most useful in estimating the relative heat loss from different body regions. Further calibration studies will improve the accuracy of models but the strength of this approach is that it is a non-invasive method of measuring the relative energy cost of an animal in response to different environments, behaviours and physiological states. It is likely that the increasing availability and portability of thermal imaging systems will lead to many new insights into the thermal physiology of endotherms.     

Spinal Mechanisms May Provide a Combination of Intermittent and Continuous Control of Human Posture: Predictions from a Biologically Based Neuromusculoskeletal Model

Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called “paradoxical” behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the other hand showed that this effect may arise without any anticipatory neural control mechanism.     

Cryptococcus neoformans: the yeast that likes it hot

The ability of fungi to grow well at mammalian body temperatures is a fundamental characteristic of invasive human fungal pathogens. Cryptococcus neoformans, with its genetics, molecular biology, robust animal models and clinical importance, has become a premier fungal model system for molecular fungal pathogenesis studies. There has been over a half century of study into how C. neoformans grows at high temperatures. However, recently the understanding of high-temperature growth at a molecular level has dramatically accelerated. Many strategies have been used to identify genes and over a dozen genes have already been identified to be necessary for high-temperature growth. It is likely that there are many more to discover. It is clear that, as further studies understand how this encapsulated yeast is able to withstand the stresses of high temperature at a genetic and molecular basis, we will also know more about how it and other fungal pathogens have evolved into well-established human pathogens.     

Planning movements in a simple redundant task

There are infinitely many different combinations of arm postures which will place the hand at the same point in space. Given this abundance, how is one configuration chosen over another? Two main hypotheses have been proposed to solve this problem. Postural models suggest that the posture adopted is purely determined by the desired hand position (known as Donders' law). Transport models suggest that the adopted posture depends on where the hand has moved from. A specific transport model, the minimum work model, has been proposed in which the adopted posture is the one that minimizes the amount of work required to move the hand to the new location. The postural model predicts that the posture will be independent of where the hand has moved from, whereas the transport models predict that the posture will depend on the previous posture. We have devised a simple redundant task-touching a target bar using a hand-held virtual stick-to examine these models. The results show that neither model alone can account for the data. We propose a control planning strategy in which there is a combined cost function that has both a postural term as well as a transport term.     

Comparing internal models of the dynamics of the visual environment

It is well known that the human postural control system responds to motion of the visual scene, but the implicit assumptions it makes about the visual environment and what quantities, if any, it estimates about the visual environment are unknown. This study compares the behavior of four models of the human postural control system to experimental data. Three include internal models that estimate the state of the visual environment, implicitly assuming its dynamics to be that of a linear stochastic process (respectively, a random walk, a general first-order process, and a general second-order process). In each case, all of the coefficients that describe the process are estimated by an adaptive scheme based on maximum likelihood. The fourth model does not estimate the state of the visual environment. It adjusts sensory weights to minimize the mean square of the control signal without making any specific assumptions about the dynamic properties of the environmental motion.We find that both having an internal model of the visual environment and its type make a significant difference in how the postural system responds to motion of the visual scene. Notably, the second-order process model outperforms the human postural system in its response to sinusoidal stimulation. Specifically, the second-order process model can correctly identify the frequency of the stimulus and completely compensate so that the motion of the visual scene has no effect on sway. In this case the postural control system extracts the same information from the visual modality as it does when the visual scene is stationary. The fourth model that does not simulate the motion of the visual environment is the only one that reproduces the experimentally observed result that, across different frequencies of sinusoidal stimulation, the gain with respect to the stimulus drops as the amplitude of the stimulus increases but the phase remains roughly constant. Our results suggest that the human postural control system does not estimate the state of the visual environment to respond to sinusoidal stimuli.     

How performing a repetitive one-legged stance modifies two-legged postural control

The proprioceptive cues in the control of movement is recognized as playing a major role in postural control. However, little is known about its possible increased contribution to postural control consecutive to repetitive muscular activations. To test this, the short-term effects induced by a 1-legged exercise on 2-legged postural control with the eyes closed were assessed in healthy subjects. The center-of-pressure (CP) displacements obtained using a force platform were split into 2 elementary movements: center-of-gravity vertical projection (CGv) and the difference (CP - CGv). These movements assessed the net postural performance and the level of neuromuscular activity, respectively, and were processed afterward (a) through variances, mean velocity, and the average surface covered by the trajectories and (b) a fractional Brownian motion (fBm) modeling. The latter provides further information about how much the subject controls the movements and the spatiotemporal relation between the successive control mechanisms. No difference was found using the classical parameters. In contrast, fBm parameters showed statistically significant changes in postural control after 1-legged exercises: The spatial and temporal coordinates of the transition points for the CG movements along the anteroposterior axis are decreased. Because the body movement control does not rely on visual or vestibular cues, this ability to trigger the corrective process of the CG movements more quickly in the postexercise condition and once a more reduced distance has been covered emphasizes how prior muscular activation improves body movement detection. As a general rule, these data show that the motor systems control body motions better after repetitive stimulation of the sensory cues. These insights should be of interest in physical activities based on a precise muscular length control.     

Evaluation of time-to-contact measures for assessing postural stability

Postural stability has traditionally been examined through spatial measures of the center of mass (CoM) or center of pressure (CoP), where larger amounts of CoM or CoP movements are considered signs of postural instability. However, for stabilization, the postural control system may utilize additional information about the CoM or CoP such as velocity, acceleration, and the temporal margin to a stability boundary. Postural time-to-contact (TtC) is a variable that can take into account this additional information about the CoM or CoP. Postural TtC is the time it would take the CoM or CoP, given its instantaneous trajectory, to contact a stability boundary. This is essentially the time the system has to reverse any perturbation before stance is threatened. Although this measure shows promise in assessing postural stability, the TtC values derived between studies are highly ambiguous due to major differences in how they are calculated. In this study, various methodologies used to assess postural TtC were compared during quiet stance and induced-sway conditions. The effects of the different methodologies on TtC values will be assessed, and issues regarding the interpretation of TtC data will also be discussed.     

Alpha-synuclein and Parkinson's disease: a proteomic view

In this review, we report how proteomic methodologies have been used to investigate cellular and animal models of Parkinson's disease (PD), with a special focus on alpha-synuclein. PD is a complex, multifactorial neurodegenerative disease affecting approximately 2% of the population over 65 years of age, pathologically characterized by alpha-synuclein intraneuronal inclusions. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis; for example, alpha-synuclein aggregation and altered dopamine homeostasis. Proteomic studies on cellular and animal models have not only confirmed existing theories on PD pathogenesis (mitochondrial impairment, oxidative stress, failure of the ubiquitine-proteasome system), but also allowed the discovery of new important common features of presymptomatic (or premotor) stages of PD, such as dysregulation of cytoskeletal proteins that could be involved at the origin of the disorder.     

Postural control system

The postural control system has two main functions: first, to build up posture against gravity and ensure that balance is maintained; and second, to fix the orientation and position of the segments that serve as a reference frame for perception and action with respect to the external world. This dual function of postural control is based on four components: reference values, such as orientation of body segments and position of the center of gravity (an internal representation of the body or postural body scheme); multisensory inputs regulating orientation and stabilization of body segments; and flexible postural reactions or anticipations for balance recovery after disturbance, or postural stabilization during voluntary movement. The recent data related to the organization of this system will be discussed in normal subjects (during ontogenesis), the elderly and in patients with relevant deficits.     

A single muscle's multifunctional control potential of body dynamics for postural control and running

A neuromechanical approach to control requires understanding how mechanics alters the potential of neural feedback to control body dynamics. Here, we rewrite activation of individual motor units of a behaving animal to mimic the effects of neural feedback without concomitant changes in other muscles. We target a putative control muscle in the cockroach, Blaberus discoidalis (L.), and simultaneously capture limb and body dynamics through high-speed videography and a micro-accelerometer backpack. We test four neuromechanical control hypotheses. We supported the hypothesis that mechanics linearly translates neural feedback into accelerations and rotations during static postural control. However, during running, the same neural feedback produced a nonlinear acceleration control potential restricted to the vertical plane. Using this, we reject the hypothesis from previous work that this muscle acts primarily to absorb energy from the body. The conversion of the control potential is paralleled by nonlinear changes in limb kinematics, supporting the hypothesis that significant mechanical feedback filters the graded neural feedback for running control. Finally, we insert the same neural feedback signal but at different phases in the dynamics. In this context, mechanical feedback enables turning by changing the timing and direction of the accelerations produced by the graded neural feedback.     

Stable Isotope Turnover and Half-Life in Animal Tissues: A Literature Synthesis

Stable isotopes of carbon, nitrogen, and sulfur are used as ecological tracers for a variety of applications, such as studies of animal migrations, energy sources, and food web pathways. Yet uncertainty relating to the time period integrated by isotopic measurement of animal tissues can confound the interpretation of isotopic data. There have been a large number of experimental isotopic diet shift studies aimed at quantifying animal tissue isotopic turnover rate λ (%·day^-1, often expressed as isotopic half-life, ln(2)/λ, days). Yet no studies have evaluated or summarized the many individual half-life estimates in an effort to both seek broad-scale patterns and characterize the degree of variability. Here, we collect previously published half-life estimates, examine how half-life is related to body size, and test for tissue- and taxa-varying allometric relationships. Half-life generally increases with animal body mass, and is longer in muscle and blood compared to plasma and internal organs. Half-life was longest in ecotherms, followed by mammals, and finally birds. For ectotherms, different taxa-tissue combinations had similar allometric slopes that generally matched predictions of metabolic theory. Half-life for ectotherms can be approximated as: ln (half-life) = 0.22*ln (body mass) + group-specific intercept; n = 261, p<0.0001, r² = 0.63. For endothermic groups, relationships with body mass were weak and model slopes and intercepts were heterogeneous. While isotopic half-life can be approximated using simple allometric relationships for some taxa and tissue types, there is also a high degree of unexplained variation in our models. Our study highlights several strong and general patterns, though accurate prediction of isotopic half-life from readily available variables such as animal body mass remains elusive.     

Animal models for gastric Helicobacter immunology and vaccine studies

Over the last decade animal models have been used extensively to investigate disease processes and therapy for Helicobacter pylori infections. The H. pylori animal models which have been used in pathogenesis and vaccine studies include the gnotobiotic pig, non-human primates, cats, dogs, and several species of rodents including mice, rats, gerbils and guinea pigs. H. felis infection of mice and H. mustelae infection of ferrets have also been used. Recently, investigators have begun using transgenic mice and gene-targeted 'knock-out' mice to investigate Helicobacter infections. Each of these animal models has distinct advantages and disadvantages which are discussed in this minireview. The choice of an animal model is dictated by factors such as cost and an understanding of how each model will or will not allow fulfillment of experimental objectives.     

Circadian dysfunction in a rotenone-induced parkinsonian rodent model

Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-quinone reductase), has been used to elicit degeneration of dopaminergic neurons and development of parkinsonian syndrome. The present work addresses alterations induced by rotenone on both locomotor and body temperature circadian rhythms in rats. Rotenone-treated rats exhibited abnormalities in equilibrium, postural instability, and involuntary movements. Long-term subcutaneous administration of rotenone significantly reduced mean daily locomotor activity in most animals. During rotenone administration, mean body temperatures (BTs) and BT rhythm amplitudes were significantly lower than those observed in the control group. After long-term rotenone administration, the circadian rhythms of both locomotor activity (LA) and BT displayed decreased amplitudes, lower interdaily phase stability, and higher rhythm fragmentation, as compared to the control rats. The magnitude of the LA and BT circadian rhythm alterations induced by rotenone positively correlated with degree of motor impairment. These results indicate that rotenone induces circadian dysfunction in rats through some of the same mechanisms as those responsible for the development of motor disturbances.     

Study of age-related changes in postural control during quiet standing through Linear Discriminant Analysis

Background  

The human body adopts a number of strategies to maintain an upright position. The analysis of the human balance allows for the understanding and identification of such strategies. The displacement of the centre of pressure (COP) is a measure that has been successfully employed in studies regarding the postural control. Most of these investigations are related to the analysis of individuals suffering from neuromuscular disorders. Recent studies have shown that the elderly population is growing very fast in many countries all over the world, and therefore, researches that try to understand changes in this group are required. In this context, this study proposes the analysis of the postural control, measured by the displacement of the COP, in groups of young and elderly adults.     

Animal models of neurological deficits: how relevant is the rat?

Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates.     

Meta level concept versus classic reflex concept for the control of posture and movement

Postural reflexes are replaced soon after birth by automatic reactions that allow for volition and cognition. It is still an enigma how this change in postural control is achieved. We suggest that the change involves the formation of a sensory processing level (meta level) that becomes interleaved in between the tight sensor-actuator coupling of the classic reflexes. We assume that the brain applies at this level intersensory interactions to reconstruct the physical stimuli which are causing the physiological stimuli and sensory signals. The thus derived estimates of the physical stimuli are then used as feedback signals in the posture control system. We present this concept on the background of the classic reflex concept and earlier attempts in the literature to overcome it. The earlier attempts were often motivated by the question how the brain prevents voluntary movements from being hampered by reflexive stabilisation of posture (so-called posture-movement problem). We compare our new concept with the classic reflex concept in a theoretical approach, by implementing both concepts into simple postural control models. In simulations of the two models we superimpose external perturbations (the physical stimuli) and a voluntary body lean movement. We show that it is possible to achieve successful stimulus compensation and unperturbed lean movement with both, the model derived from the new concept and the one of the classic reflex concept. With both approaches, the posture-movement problem does not arise. Based on preliminary considerations that include experimental findings from the literature, however, we conclude that the new concept provides more explanatory power than the classic reflex concept.     

Neurodevelopmental animal models of schizophrenia: effects on prepulse inhibition

Epidemiological studies have shown increased incidence of schizophrenia in patients subjected to different forms of pre- or perinatal stress. However, as the onset of schizophrenic illness does not usually occur until adolescence or early adulthood, it is not yet fully understood how disruption of early brain development may ultimately lead to malfunction years later. In order to elucidate a possible role for neurodevelopmental factors in the pathogenesis of schizophrenia and to highlight potential new treatments, animal models are needed. Prepulse inhibition (PPI) is a model of sensorimotor gating mechanisms in the brain. It is disrupted in schizophrenia patients and the disruption can be reversed with atypical antipsychotics. It has been widely used in animal studies to explore central mechanisms possibly involved in schizophrenia. There has been a recent surge of behavioural and neurochemical animal studies on neurodevelopmental models, particularly on the effects of postweaning isolation, maternal separation and neonatal lesions of the hippocampus. In these models, long lasting alterations in behaviour and/or molecular changes in specific brain regions are observed, comparable to those seen in schizophrenia. The aim of this article is to critically review the available literature on such neurodevelopmental animal models with special focus on the effects on PPI and brain regions that are putatively involved in regulation of PPI.