[Show abstract][Hide abstract] ABSTRACT: Mounting evidence suggests that both α and γ motoneurons are active during movement and posture, but how does the central motor system coordinate the α-γ controls in these tasks remains sketchy due to lack of in vivo data. Here a computational model of α-γ control of muscles and spindles was used to investigate α-γ integration and coordination for movement and posture. The model comprised physiologically realistic spinal circuitry, muscles, proprioceptors, and skeletal biomechanics. In the model, we divided the cortical descending commands into static and dynamic sets, where static commands (α s and γ s ) were for posture maintenance and dynamic commands (α d and γ d ) were responsible for movement. We matched our model to human reaching movement data by straightforward adjustments of descending commands derived from either minimal-jerk trajectories or human EMGs. The matched movement showed smooth reach-to-hold trajectories qualitatively close to human behaviors, and the reproduced EMGs showed the classic tri-phasic patterns. In particular, the function of γ d was to gate the α d command at the propriospinal neurons (PN) such that antagonistic muscles can accelerate or decelerate the limb with proper timing. Independent control of joint position and stiffness could be achieved by adjusting static commands. Deefferentation in the model indicated that accurate static commands of α s and γ s are essential to achieve stable terminal posture precisely, and that the γ d command is as important as the α d command in controlling antagonistic muscles for desired movements. Deafferentation in the model showed that losing proprioceptive afferents mainly affected the terminal position of movement, similar to the abnormal behaviors observed in human and animals. Our results illustrated that tuning the simple forms of α-γ commands can reproduce a range of human reach-to-hold movements, and it is necessary to coordinate the set of α-γ descending commands for accurate and stable control of movement and posture.
[Show abstract][Hide abstract] ABSTRACT: It is widely assumed that neural control of movement is carried out by the a motor system sufficiently. The role of the γ motor system in movement and posture has not been adequately addressed in motor control studies. Here, we propose a modular control model for movement and posture based on propriospinal neuronal (PN) network and spinal α-γ motor system. In the modular control model, the a and γ motor commands are divided into static and dynamic functions. The static commands are specified by the higher center of brain for posture control, and the dynamic commands for movement generation, respectively. Centrally planned kinematics based on the minimal jerk criterion is conveyed to the periphery via the γ motor system, while centrally programmed bi-phasic burst pattern of muscle activation is relayed to a pair of antagonistic muscles through the a motor system via the PN. Results of simulation showed that elbow kinematics and biceps and triceps activations displayed the similar kinematic and EMG features of fast reaching movement in human. This suggests a hypothesis that the α-γ motor systems can achieve modular control of movement and posture in parallel.
[Show abstract][Hide abstract] ABSTRACT: Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson's disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3-C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur.
PLoS ONE 11/2013; 8(11):e79829. DOI:10.1371/journal.pone.0079829 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been hypothesized that propriospinal neurons (PNs) in the C3-C4 spinal cord mediates cortical motor commands to the peripheral muscles during tremor in patients with Parkinson's disease (PD). However, there has been no direct evidence so far to support the role of PN in transmitting tremor commands. In this paper, we report the positive correlation of cutaneous afferents with reduction in tremor amplitude and frequency in PD patients. Resting tremor and EMGs of biceps, triceps, flexor digitorum superficialis (FDS), extensor digitorum (ED), flexor carpi ulnaris (FCU) and extensor carpi radialis (ECR) muscles were recorded while transcutaneous electrical stimulation (TES) was applied to the dorsal hand skin of PD subjects. We observed instant suppression of tremor amplitude and EMGs occurring immediately at the start of electrical stimulation. However at the end of stimulation, the tremor amplitude and EMGs showed a quick recovery to the level prior to stimulation. Spectral analysis indicated that cutaneous afferents also have a long-lasting memory effect on the tremor frequency, i.e. the tremor frequency post stimulation did not recover to the value prior to stimulation. Preliminary results implied that the reduction in tremor amplitude and EMGs could be due to the inhibitory effects of cutaneous afferents to PNs, supporting the hypothesis that the PN network is involved in transmission of cortical tremor commands to peripheral muscles.
Neural Engineering (NER), 2013 6th International IEEE/EMBS Conference on; 01/2013
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to validate a neuromechanical model of the virtual arm (VA) by comparing emerging behaviors of the model to those of experimental observations. Hand stiffness of the VA model was obtained by either theoretical computation, or simulated perturbations. Variability in hand position of the VA was generated by adding signal dependent noise (SDN) to the motoneuron pools of muscles. Reflex circuits of Ia, Ib and Renshaw cells were included to regulate the motoneuron pool outputs. Evaluation of hand stiffness and variability was conducted in simulations with and without afferent feedback under different patterns of muscle activations during postural maintenance. The simulated hand stiffness and variability ellipses captured the experimentally observed features in shape, magnitude and orientation. Steady state afferent feedback contributed significantly to the increase in hand stiffness by in area, and in major and minor axes; and to the reduction of hand variability by in area, and in major and minor axes. The VA model reproduced the neuromechanical behaviors that were consistent with experimental data, and it could be a useful tool for study of neural control of posture and movement, as well as for application to rehabilitation.
IEEE transactions on neural systems and rehabilitation engineering: a publication of the IEEE Engineering in Medicine and Biology Society 12/2012; 21(4). DOI:10.1109/TNSRE.2012.2234479 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proprioceptive afferents from muscle spindles encode information about peripheral joint movements for the central nervous system (CNS). The sensitivity of muscle spindle is nonlinearly dependent on the activation of gamma (γ) motoneurons in the spinal cord that receives inputs from the motor cortex. How fusimotor control of spindle sensitivity affects proprioceptive coding of joint position is not clear. Furthermore, what information is carried in the fusimotor signal from the motor cortex to the muscle spindle is largely unknown. In this study, we addressed the issue of communication between the central and peripheral sensorimotor systems using a computational approach based on the virtual arm (VA) model. In simulation experiments within the operational range of joint movements, the gamma static commands (γ(s)) to the spindles of both mono-articular and bi-articular muscles were hypothesized (1) to remain constant, (2) to be modulated with joint angles linearly, and (3) to be modulated with joint angles nonlinearly. Simulation results revealed a nonlinear landscape of Ia afferent with respect to both γ(s) activation and joint angle. Among the three hypotheses, the constant and linear strategies did not yield Ia responses that matched the experimental data, and therefore, were rejected as plausible strategies of spindle sensitivity control. However, if γ(s) commands were quadratically modulated with joint angles, a robust linear relation between Ia afferents and joint angles could be obtained in both mono-articular and bi-articular muscles. With the quadratic strategy of spindle sensitivity control, γ(s) commands may serve as the CNS outputs that inform the periphery of central coding of joint angles. The results suggest that the information of joint angles may be communicated between the CNS and muscles via the descending γ(s) efferent and Ia afferent signals.
[Show abstract][Hide abstract] ABSTRACT: Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX - a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation.
International Journal of Physiology, Pathophysiology and Pharmacology 07/2012; 4(2):108-14.
[Show abstract][Hide abstract] ABSTRACT: Synchrotron radiation (SR) X-ray has great potential for its applications in medical imaging and cancer treatment. In order to apply SR X-ray in clinical settings, it is necessary to elucidate the mechanisms underlying the damaging effects of SR X-ray on normal tissues, and to search for the strategies to reduce the detrimental effects of SR X-ray on normal tissues. However, so far there has been little information on these topics. In this study we used the testes of rats as a model to characterize SR X-ray-induced tissue damage, and to test our hypothesis that NAD(+) administration can prevent SR X-ray-induced injury of the testes. We first determined the effects of SR X-ray at the doses of 0, 0.5, 1.3, 4 and 40 Gy on the biochemical and structural properties of the testes one day after SR X-ray exposures. We found that 40 Gy of SR X-ray induced a massive increase in double-strand DNA damage, as assessed by both immunostaining and Western blot of phosphorylated H2AX levels, which was significantly decreased by intraperitoneally (i.p.) administered NAD(+) at doses of 125 and 625 mg/kg. Forty Gy of SR X-ray can also induce marked increases in abnormal cell nuclei as well as significant decreases in the cell layers of the seminiferous tubules one day after SR X-ray exposures, which were also ameliorated by the NAD(+) administration. In summary, our study has shown that SR X-ray can produce both molecular and structural alterations of the testes, which can be significantly attenuated by NAD(+) administration. These results have provided not only the first evidence that SR X-ray-induced tissue damage can be ameliorated by certain approaches, but also a valuable basis for elucidating the mechanisms underlying SR X-ray-induced tissue injury.
International Journal of Physiology, Pathophysiology and Pharmacology 01/2012; 4(1):1-9.
[Show abstract][Hide abstract] ABSTRACT: Numerous studies have indicated that four interacting factors, including oxidative stress, mitochondrial alterations, calcium dyshomeostasis and inflammation, play crucial pathological roles in multiple major neurological diseases, including stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Increasing evidence has also indicated that NAD(+) plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation. The key NAD(+)-consuming enzyme--poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins--have also been shown to play important roles in cell death and aging, which are two key factors in the pathology of multiple major age-dependent neurological diseases: PARP-1 plays critical roles in both inflammation and oxidative stress-induced cell death; and sirtuins also mediate the process of aging, cell death and inflammation. Thus, it is conceivable that increasing evidence has suggested that NAD(+) metabolism and NAD(+)-dependent enzymes are promising targets for treating a number of neurological illnesses. For examples, the key NAD(+)-dependent enzymes SIRT1 and SIRT2 have been indicated to strongly affect the pathological changes of PD and AD; PARP-1 inhibition can profoundly reduce the brain injury in the animal models of multiple neurological diseases; and administration of either NAD(+) or nicotinamide can also decrease ischemic brain damage. Future studies are necessary to further investigate the roles of NAD+ metabolism and NAD⁺-dependent enzymes in neurological diseases, which may expose novel targets for treating the debilitating illnesses.
Current drug targets 12/2011; 13(2):222-9. DOI:10.2174/138945012799201711 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Synchrotron radiation (SR) X-ray has great potential for its applications in both diagnosis and treatment of diseases, due to its characteristic properties including coherence, collimation, monochromaticity, and exceptional brightness. Great advances have been made regarding potential medical applications of SR X-ray in recent years, particularly with the development of the third generation of SR light sources. However, multiple studies have also suggested damaging effects of SR X-ray on biological samples ranging from protein crystals to cells and biological tissues. It has become increasingly important to conduct comprehensive studies on two closely related topics regarding SR X-ray in medical applications: The safety issues regarding the medical applications of SR X-ray and the fundamental mechanisms underlying the interactions between SR X-ray and biological tissues. In this article, we attempted to provide an overview of the literatures regarding these two increasingly significant topics. We also proposed our hypothesis that there are significant differences between the biological tissue-damaging mechanisms of SR X-ray and those of normal X-ray, due to the characteristic properties of SR X-ray such as high dose rate. Future studies are warranted to test this hypothesis, which may profoundly improve our understanding regarding the fundamental mechanisms underlying the interactions between light and matter. These studies would also constitute an essential basis for establishing the safety standard for the medical applications of SR X-ray.
International Journal of Physiology, Pathophysiology and Pharmacology 12/2011; 3(4):243-8.
[Show abstract][Hide abstract] ABSTRACT: SIRT2 is a tubulin deacetylase, which can play either detrimental or beneficial roles in cell survival under different conditions. While it has been suggested that reduced SIRT2 expression in human gliomas may contribute to development of gliomas, there has been no study that directly determines the effects of decreased SIRT2 activity on the survival of glioma cells. In this study we applied both pharmacological and molecular approaches to determine the roles of SIRT2 in the survival of glioma cells. Our studies, by conducting such assays as flow cytometry-based Annexin V assay and caspase-3 immunostaining, have indicated that decreased SIRT2 activity leads to apoptosis of C6 glioma cells by caspase-3-dependent pathway. Our experiments have further shown that reduced SIRT2 activity produces necrosis of C6 glioma cells. Moreover, our study applying SIRT2 siRNA has also shown that decreased SIRT2 leads to both necrosis and apoptotic changes of C6 glioma cells. Collectively, our study has provided novel evidence indicating that SIRT2 activity plays a key role in maintaining the survival of glioma cells, and that reduced SIRT2 activity can induce both necrosis and caspase-3-dependent apoptosis of C6 glioma cells. These results have also suggested that inhibition of SIRT2 might become a novel therapeutic strategy for gliomas.
Biochemical and Biophysical Research Communications 12/2011; 417(1):468-72. DOI:10.1016/j.bbrc.2011.11.141 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to investigate plausible central and peripheral coding strategies of joint angle by descending γ<sub>s</sub> commands and proprioceptive afferents in humans. Experimental evidence in both human and animal has shown that the firing rate of Ia afferents was linearly correlated to joint angle. Yet, experiments did not elucidate how Ia encoding of joint angle would be affected by α-γ co-activation, and how the peripheral neuromuscular system is informed of central representation of joint configuration. This study is aimed at addressing these issues using a realistic virtual arm (VA) model. In simulated experiments, elbow and shoulder angles of the VA are moved to different angular positions. The γ<sub>s</sub> commands to muscles remain constant, or are adjusted with joint angle in linear and nonlinear fashions. The Ia afferents of muscles are evaluated in each case of γ<sub>s</sub> modulation. Results show that Ia firing rates of mono-articular muscles can be fine-tuned to the characteristics of experimental recordings, while γ<sub>s</sub> commands are nonlinearly modulated with joint angle. This suggests that γ<sub>s</sub> commands could serve as the output of central encoding of joint information for posture and movement, and Ia afferents could be used to decode joint angle information faithfully.
Neural Engineering (NER), 2011 5th International IEEE/EMBS Conference on; 06/2011
[Show abstract][Hide abstract] ABSTRACT: A closed-loop virtual arm (VA) model has been developed in SIMULINK environment by adding spinal reflex circuits and propriospinal neural networks to the open-loop VA model developed in early study . An improved virtual muscle model (VM4.0) is used to speed up simulation and to generate more precise recruitment of muscle force at low levels of muscle activation. Time delays in the reflex loops are determined by their synaptic connections and afferent transmission back to the spinal cord. Reflex gains are properly selected so that closed-loop responses are stable. With the closed-loop VA model, we are developing an approach to evaluate system behaviors by dynamic simulation of perturbation responses. Joint stiffness is calculated based on simulated perturbation responses by a least-squares algorithm in MATLAB. This method of dynamic simulation will be essential for further evaluation of feedforward and reflex control of arm movement and position.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2010; 2010:4866-9. DOI:10.1109/IEMBS.2010.5627281