Method to Measure Tone of Axial and Proximal Muscle

The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention

Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

An ability to produce rhythmic activity is ubiquitous for locomotor pattern generation and modulation. The role that the rhythmogenesis capacity of the spinal cord plays in injured populations has become an area of interest and systematic investigation among researchers in recent years, despite its importance being long recognized by neurophysiologists and clinicians. Given that each individual interneuron, as a rule, receives a broad convergence of various supraspinal and sensory inputs and may contribute to a vast repertoire of motor actions, the importance of assessing the functional state of the spinal locomotor circuits becomes increasingly evident. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by a reduction of external resistance. This article aims to provide a review on current issues related to the ‘locomotor’ state and interactions between spinal and supraspinal influences on the central pattern generator circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries

assessment of blood capillaries and structural proteins localization

The papillary dermis of human skin is responsible for its biomechanical properties and for supply of epidermis with chemicals. Dermis is mainly composed of structural protein molecules, including collagen and elastin, and contains blood capillaries. Connective tissue diseases, as well as cardiovascular complications have manifestations on the molecular level in the papillary dermis (e.g. alteration of collagen I and III content) and in the capillary structure. In this paper we assessed the molecular structure of internal and external regions of skin capillaries using two-photon fluorescence lifetime imaging (FLIM) of endogenous compounds. It was shown that the capillaries are characterized by a fast fluorescence decay, which is originated from red blood cells and blood plasma. Using the second harmonic generation signal, FLIM segmentation was performed, which provided for spatial localization and fluorescence decay parameters distribution of collagen I and elastin in the dermal papillae. It was demonstrated that the lifetime distribution was different for the inner area of dermal papillae around the capillary loop that was suggested to be due to collagen III. Hence, we propose a generalized approach to two-photon imaging of the papillary dermis components, which extends the capabilities of this technique in skin diagnosis

In Vivo Fluorescence Lifetime Imaging Monitors Binding of Specific Probes to Cancer Biomarkers

One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the “image and treat” concept, especially for early evaluation of the efficacy of the therapy

Human Postural Control

From ancient Greece to nowadays, research on posture control was guided and shaped by many concepts. Equilibrium control is often considered part of postural control. However, two different levels have become increasingly apparent in the postural control system, one level sets a distribution of tonic muscle activity (“posture”) and the other is assigned to compensate for internal or external perturbations (“equilibrium”). While the two levels are inherently interrelated, both neurophysiological and functional considerations point toward distinct neuromuscular underpinnings. Disturbances of muscle tone may in turn affect movement performance. The unique structure, specialization and properties of skeletal muscles should also be taken into account for understanding important peripheral contributors to postural regulation. Here, we will consider the neuromechanical basis of habitual posture and various concepts that were rather influential in many experimental studies and mathematical models of human posture control

Motor Coordination Can be Fully Understood Only by Studying Complex Movements

In this chapter, we use the sit-up to illustrate the complexity of coordination in movements that involve many muscles, joints, degrees of freedom, and high levels of muscle activity. Complex movements often involve the body axis. In addition to the intentional, focal part of any voluntary movement, complex movements also include "associated movements" that are not consciously controlled, but are necessary for the movement to succeed. Some associated movements serve a purpose, and others may not. During sitting up, the leg-lift is a purposive associated movement, whereas three-joint flexion is a non-purposive associated movement. The control of complex movements is also likely to be complex and, we argue, is hierarchically controlled. Associated movements may, themselves, be hierarchically organized and triggered by lower brain structures, local changes in neuronal excitability, and sensory feedback. Complex movements typically involve a high level of mobility. Because this mobility can lead to instability, anticipatory postural adjustments, a type of purposive associated movement, are commonly used to regulate posture. Thus, a number of important aspects of motor coordination can only be revealed by the study of complex movements

Trunk orientation, stability and quadrupedalism

Interesting cases of human quadrupedalism described by Uner Tan and colleagues (2005-2012) have attracted the attention of geneticists, neurologists and anthropologists. Since his first publications in 2005, the main attention has focused on the genetic aspects of disorders that lead to quadrupedalism within an evolutionary framework. In recent years this area has undergone a convincing critique (Downey 2010) and ended with a call "... to move in a different direction … away from thinking solely in terms of genetic abnormality and evolutionary atavism". We consider quadrupedalism as a ‘natural experiment’ that may contribute to our knowledge of the physiological mechanisms underlying our balance system and our tendency toward normal (upright) posture. Bipedalism necessitates a number of characteristics that distinguish us from our ancestors and present-day mammals, including: size and shape of the bones of the foot, structure of the axial and proximal musculature, and the orientation of the human body and head. In this review we address the results of experimental studies on the mechanisms that stabilize the body in healthy people, as well as how these mechanisms may be disturbed in various forms of clinical pathology. These disturbances are related primarily to automatic rather than voluntary control of posture and suggest that human quadrupedalism is a behavior that can result from adaptive processes triggered by disorders in postural tone and environmental cues. These results will serve as a starting point for comparing and contrasting bi- and quadrupedalism

Scaling and non-scaling of muscle activity, kinematics, and dynamics in sit-ups with different degrees of difficulty

The purpose of this study was to investigate how the CNS adjusts motor patterns for variants of a complex axial movement-the situp. Adjustments were induced by changing the support surface contact and mass distribution of the body. Healthy adults performed straight-legged sit-ups, 3 s in duration, with support added to or removed from the lumbar trunk, or with mass added to the head or to the legs. Each of these interventions either increased or decreased the difficulty of the task. The study addressed the extent to which changes in sit-up difficulty are compensated by scaling of muscle activity, kinematics, and dynamics versus the extent to which they are compensated by changing discretely the motor pattern. The analysis of muscle activity, kinematics, and dynamics focused on the first 30-40% of the sit-up-the trunk flexion phase-since this is the most critical part of the movement. Our results demonstrate that, in some respects, sit-up kinematics and dynamics scaled with difficulty, but in other respects, they did not. Muscle activity also scaled, in many respects, but in more difficult sit-ups, abdominal flexor activity decreased instead of increased. Non-scaling changes in these parameters suggest that complex movements, such as the sit-up, may require discrete changes in motor pattern in order to deal with large loads, which challenge the available leverage. (C) 2005 Elsevier Ltd. All rights reserved

Tonic and Rhythmic Spinal Activity Underlying Locomotion

Ivanenko YP, Gurfinkel VS, Selionov V, et al. Tonic and Rhythmic Spinal Activity Underlying Locomotion. Current Pharmaceutical Design. 2017;23(12):1753-1763