Reciprocal and coactivation commands for fast wrist movements

Summary According to the equilibriumpoint hypothesis, movements are produced by means of displacement of the invariant torque/angle characteristic (IC) of the joint and change in its slope. Displacement is produced via the central reciprocal (R) command while the coactivation (C) command specifies the slope of the IC. Neurophysiologically, the R command is associated with reciprocal changes in the membrane potentials of agonist and antagonist motoneurons while the C command is associated with their simultaneous depolarisation. These commands were investigated in single joint wrist-movements by perturbation methods. Subjects normally made free flexion movements to a target at 30° but on random trials they were either opposed by a spring-like load or assisted by a load. The former was generated using negative linear position feedback; the latter using positive position feedback to a torque motor. Subjects were instructed not to correct errors arising from perturbations. Both peak velocity and EMG patterns were strongly affected by load conditions. Subjects undershot or overshot the target when opposing or assisting loads were presented, respectively. However, after removing the load (700 ms later), the target position was regained indicating that the IC was stable despite the perturbation. In two other experiments, subjects initially trained to reach the target with opposing or assisting loads, while on random trials, the load was not presented. Depending on training conditions, the subject shifted the IC by different amounts. The slope of the IC varied independently of the magnitude of its positional shift. We conclude that R and C commands can be specified independently. In addition, although kinematics and EMG are strongly dependent on peripheral conditions, the same does not appear to be the case for basic central commands (R and C).     

The relationship between control,kinematic and electromyographic variables in fast single-joint movements in humans

Two versions of the hypothesis that discrete movements are produced by shifts in the system's equilibrium point are considered. The first suggests that shifts are monotonic and end near the peak velocity of movement, and the second presumes that they are nonmonotonic (N-shaped) and proceed until the end of movement. The first version, in contrast to the second, predicts that movement time may be significantly reduced by opposing loads without changes in the control pattern. The purpose of the present study was to test the two hypotheses about the duration and shape of the shift in the equilibrium point based on their respective predictions concerning the effects of perturbations on kinematic and EMG patterns in fast elbow flexor movements. Subjects performed unopposed flexions of about 55–70° (control trials) and, in random test trials, movements were opposed by spring-like loads generated by a torque motor. Subjects had no visual feedback and were instructed not to correct arm deflections in case of perturbations. After the end of the movement, the load was removed leading to a secondary movement to the same final position as that in control trials (equifinality). When the load was varied, the static arm positions before unloading and associated joint torques (ranging from 0 to 80–90% of maximum voluntary contraction) had a monotonic relationship. Test movements opposed by a high load (80–90% of maximal voluntary contraction) ended near the peak velocity of control movements. Phasic and tonic electromyographic patterns were load-dependent. In movements opposed by high loads, the first agonist burst was significantly prolonged and displayed a high level of tonic activity for as long as the load was maintained. In the same load conditions, the antagonist burst was suppressed during the dynamic and static phases of movement. The findings of suppression of the antagonist burst does not support the hypothesis of an Nshaped control signal. Equally, the substantial reduction in movement time by the introduction of an opposing load cannot be reconciled in this model. Instead, our data indicate that the shifts in the equilibrium point underlying fast flexor movements are of short duration, ending near the peak velocity of unopposed movement. This suggests that kinematic and electromyographic patterns represent a long-lasting oscillatory response of the system to the short-duration monotonic control pattern, external forces and proprioceptive feedback.     

The timing of arm-trunk coordination is deficient and vision-dependent in Parkinson's patients during reaching movements

The role of the basal ganglia in the coordination of different body segments and utilization of motor synergies was investigated by analyzing reaching movements to remembered three-dimensional (3D) targets in patients with Parkinson's disease (PD). Arm movements were produced alone or in combination with a forward bending of the trunk, with or without visual feedback. Movements in PD patients were more temporally segmented, as evidenced by irregular changes in tangential velocity profiles. In addition, the relative timing in the onsets and offsets of fingertip and trunk motions were substantially different in PD patients than in control subjects. While the control subjects synchronized both onsets and offsets, the PD patients had large mean intervals between the onsets and offsets of the fingertip and trunk motions. Moreover, PD patients showed substantially larger trial-to-trial variability in these intervals. The degree of synchronization in PD patients gradually increased during the movement under the influence of visual feedback. The mean and variability of the intersegmental intervals decreased as the fingertip approached the target. This improvement in timing occurred even though the separate variability in the timing of arm and trunk motions was not reduced by vision. In combined movements, even without vision, the PD patients were able to achieve normal accuracy, suggesting they were able to use the same movement synergies as normals to control the multiple degrees of freedom involved in the movements and to compensate for the added trunk movement. However, they were unable to recruit these synergies in the stereotyped manner characteristic of healthy subjects. These results suggest that the basal ganglia are involved in the temporal coordination of movement of different body segments and that related timing abnormalities may be partly compensated by vision. Abnormal intersegmental timing may be a highly sensitive indicator of a deficient ability to assemble complex movements in patients with basal-ganglia dysfunction. This abnormality may be apparent even when the overall movement goal of reaching a target is preserved and normal movement synergies appear to be largely intact.     

Movement reorganization to compensate for fatigue during sawing

Peripheral (muscle) aspects of fatigue are well documented. However, little is known about the central aspects of fatigue that could influence, in particular, multijoint coordination. To investigate the central aspects of fatigue, we compared the multijoint kinematics of non-fatigued and fatigued individuals while sawing. Muscle fatigue was associated with decreases in sawing force and movement amplitude at the elbow whereas the basic characteristics of the saw trajectory, including the movement direction, extent and duration, remained invariant. This invariance was maintained by increasing the movement amplitude at the wrist, shoulder and trunk. The system thus takes advantage of the redundancy of the motor apparatus to maintain the endpoint trajectory despite fatigue.     

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.     

Stretch reflex spatial threshold measure discriminates between spasticity and rigidity

ObjectiveMuscle spasticity following stroke has been shown to result from limitations in the range of regulation of the tonic reflex spatial threshold (ST), i.e., the joint angle at which the stretch reflex begins to act due to descending and segmental influences on motoneurons. The purpose of this study was to determine whether spasticity due to stroke and rigidity due to parkinsonism can be discriminated based on the ST measure.MethodsElbow muscles were stretched at different velocities in healthy, stroke (spasticity) and parkinsonism (rigidity) subjects. The elbow angle at which muscle activation began for each stretch velocity (dynamic ST) and the velocity sensitivity of the ST were measured. Dynamic ST values extrapolated to zero velocity defined the tonic ST.ResultsCompared to healthy subjects, spasticity and rigidity were associated with a decrease in the range of central regulation of tonic STs. STs were hypersensitive in spastic muscles and either hypo- or inversely sensitive to stretch velocity in rigid muscles.ConclusionsST characteristics discriminate between neurological deficits of muscle tone.SignificanceResults suggest that spasticity and rigidity result from deficits in descending facilitatory control combined with deficits in dynamic fusimotor or/and presynaptic control of Ia inputs to motoneurons.     

Large-scale microarray gene expression analysis in discrete electrophysiologically identified neuronal clusters

The normal processes of learning and memory as well as the pathological progress of various neurological diseases may result in changes in gene expression in small, local populations of neurons in any given brain area, leading to the occurrence of specific patterns of electrical activity without easily detectable changes in the morphology of this brain area. One way of identifying these changes might be the comparison of gene expression of areas which generate and areas which do not generate specific patterns of electrical activity. A method for microbiopsy of limited (0.5-1.0 mm3) tissue samples from electrophysiologically identified areas of neurons generating epileptiform activity in the rat brain is described. Here we demonstrate that total RNA isolated from individual microbiopsy samples might be successfully used for microarray based gene expression analysis of any discretely localized neuronal group which can be identified electrophysiologically, including neurons in cortical columns, cell assemblies or other functional units.