Participation of the motor cortex in the bimanual unloading task: a study by transcranial magnetic stimulation

Motor potentials of m. biceps brachii evoked by transcranial magnetic stimulation of the contralateral motor cortex have been recorded in postural adjustment during arm unloading in humans. During active unloading, the amplitude of the motor evoked potential decreases simultaneously with the decreasing of the muscle activity. During load keeping, the muscle response changes simultaneously with the load changes. When the other arm has lifted the other load during load keeping, the amplitude of the motor evoked potential decreases in the m. biceps of the keeping arm without muscle activity changes. Passive unloading results in the same changes of the motor evoked potential as active unloading. A possible role of the direct corticospinal volley and the motor command mediated by some subcortical structures in the decrease of the muscle activity preceding active unloading (postural adjustment) is discussed.     

Impairment of vestibular-mediated cardiovascular response and motor coordination in rats born and reared under hypergravity

It is well known that environmental stimulation is important for the proper development of sensory function. The vestibular system senses gravitational acceleration and then alters cardiovascular and motor functions through reflex pathways. The development of vestibular-mediated cardiovascular and motor functions may depend on the gravitational environment present at birth and during subsequent growth. To examine this hypothesis, arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were monitored during horizontal linear acceleration and performance in a motor coordination task in rats born and reared in 1-G or 2-G environments. Linear acceleration of +/-1 G increased AP and RSNA. These responses were attenuated in rats with a vestibular lesion, suggesting that the vestibular system mediated AP and RSNA responses. These responses were also attenuated in rats born in a 2-G environment. AP and RSNA responses were partially restored in these rats when the hypergravity load was removed, and the rats were maintained in a 1-G environment for 1 wk. The AP response to compressed air, which is mediated independently of the vestibular system, did not change in the 2-G environment. Motor coordination was also impaired in the 2-G environment and remained impaired even after 1 wk of unloading. These results indicate that hypergravity impaired both the vestibulo-cardiovascular reflex and motor coordination. The vestibulo-cardiovascular reflex was only impaired temporarily and partially recovered following 1 wk of unloading. In contrast, motor coordination did not return to normal in response to unloading.     

Essential role of satellite cells in the growth of rat soleus muscle fibers

Effects of gravitational loading or unloading on the growth-associated increase in the cross-sectional area and length of fibers, as well as the total fiber number, in soleus muscle were studied in rats. Furthermore, the roles of satellite cells and myonuclei in growth of these properties were also investigated. The hindlimb unloading by tail suspension was performed in newborn rats from postnatal day 4 to month 3 with or without 3-mo reloading. The morphological properties were measured in whole muscle and/or single fibers sampled from tendon to tendon. Growth-associated increases of soleus weight and fiber cross-sectional area in the unloaded group were approximately 68% and 69% less than the age-matched controls. However, the increases of number and length of fibers were not influenced by unloading. Growth-related increases of the number of quiescent satellite cells and myonuclei were inhibited by unloading. And the growth-related decrease of mitotically active satellite cells, seen even in controls (20%, P > 0.05), was also stimulated (80%). The increase of myonuclei during 3-mo unloading was only 40 times vs. 92 times in controls. Inhibited increase of myonuclear number was not related to apoptosis. The size of myonuclear domain in the unloaded group was less and that of single nuclei, which was decreased by growth, was larger than controls. However, all of these parameters, inhibited by unloading, were increased toward the control levels generally by reloading. It is suggested that the satellite cell-related stimulation in response to gravitational loading plays an essential role in the cross-sectional growth of soleus muscle fibers.     

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.     

Regulation of the Nuclear–Cytoplasmic Traffic of Class IIa Histone Deacethylases in Rat Soleus Muscle at the Early Stage of Gravitational Unloading

The negative regulation of expression of genes involved in various metabolic pathways in a skeletal muscle is the main function of histone deacetylases 4 and 5 (HDAC4/HDAC5). HDAC4 and HDAC5 seem to be the targets of the AMP-activated protein kinase (AMPK). Earlier, an essential decrease in the level of Thr172-phosphorylated-AMPK in a rat soleus muscle at the first day of gravitational unloading was shown. Possibility of a protein kinase D (PKD) to phosphorylate histone deacetylases 4/5 has been shown, too. We supposed that under the conditions of gravitational unloading, alterations in AMPK phosphorylation level can affect regulation of nuclear-cytoplasmic traffic of class II histone deacetylases and of various skeletal muscle genes expression. To verify the hypothesis, we used administration of an AMPK activator, AICAR, before and during a day-long hindlimb suspension. It was shown that at an early stage of gravitational unloading, HDAC4 is not a PKD target, and its nuclear import is realized due to decrease in AMPK activity. We were the first to show reciprocal relations between AMPK and PKD in a skeletal muscle at early gravitational unloading.     

Influence of repetitive Gz acceleration on structural and metabolic profile of m. vastus lateralis in monkeys exposed to 30 day bedrest

It was shown that changes in structural and metabolic indices of extensor muscles of the lower extremities were usually found in man after exposure to space flight or to bed rest. Similar changes were also observed in monkeys, space-flown on "Kosmos" biosatellites. Response to weightlessness and to restraint was found to be different in m. soleus and in m. vastus lateralis. Therefore, it is important to study structural and metabolic changes of m. vastus lateralis fibers under conditions of gravitational unloading in monkeys, who have motor apparatus similar to that of man, and are much more fruitful object of research. It is assumed that artificial gravity can serve as a countermeasure, aimed at diminishing effects of gravitational unloading. We have studied the effect of repeated gravity overloading, created by means of a centrifuge, on structural and metabolic indices of monkey m. vastus lateralis at the background of 30 day head down tilt bed rest (BR).     

Effects of 9 weeks hindlimb suspension on neuromuscular activity patterns in rat

It is well known that gravitational unloading induces muscle atrophy associated with a shift of fiber type in slow-twitch muscle. Ishihara et al. (1996 & 1997) reported that 2 weeks of spaceflight caused a decrease in succinate dehydrogenase activities of ventral horn and dorsal root ganglion neurons in rats. Significant effects on motor performance are also induced in both human (Kozlovskaya et al., 1981) and rats (Canu and Falempin, 1997), but these changes are reversible. However, it is not known how neuromuscular function respond to long-term gravitational unloading. Therefore, the current study was carried out to investigate the effects of 9 weeks of hindlimb suspension on the neuromuscular function and mass in hindlimb muscles in rats.     

Parameters of fiber cell respiration and desmin content in rat soleus muscle at early stages of gravitational unloading

The aim of the work was to study the parameters of fiber cell respiration and desmin content in Wistar rat soleus muscle after 1, 3, 7 and 14 days of gravitational unloading. Gravitational unloading was simulated by antiorthostatic hindlimb suspension. The parameters of cell respiration were determined using polarography, and desmin content was assessed by means of Western blotting. The results showed that the intensity of cell respiration is reduced after three days of gravitational unloading, reaches a minimum level after seven days and slightly increases by the fourteenth day of hindlimb unloading, as well as the content of desmin, which, however, to the fourteenth day returns to the control level. Taking into account that mitochondrial function depends on the state of cytoskeleton, the data allow us to assume that early reduction of the intensity of cell respiration under unloading could be caused by degradation of the protein desmin that determines the intracellular localization of mitochondria.     

Parameters of fibers cell respiration and desmin content in rat soleus muscle at early stages of gravitational unloading

The aim of the work was to study the parameters of fibers cell respiration and desmin content in Wistar rat soleus muscle after 1, 3, 7 and 14 days of gravitational unloading. Gravitational unloading was simulated by antiorthostatic hindlimb suspension. The parameters of cell respiration were determined using the polarography, and desmin content was assessed by means of Western blotting. The results showed that the intensity of cell respiration is reduced after three days of gravitational unloading, reaches a minimum level after seven days and slightly increases by the fourteenth day of hindlimb unloading, as well as the content of desmin, which, however, to the fourteenth day returns to the control level. Taking into account that mitochondrial function depends on the state of cytoskeleton the data allow us to assume that early reduction of the intensity of cell respiration under unloading could be caused by degradation of the protein desmin that determines intracellular localization of mitochondria.     

Human muscle signaling responses to 3-day head-out dry immersion

To date little is known about catabolic NO-dependent signaling systems in human skeletal muscle during early stages of gravitational unloading. The goal of the study was to analyze signaling pathways that determine the initial development of proteolytic events in human soleus muscle during short-term gravitational unloading (simulated microgravity). Gravitational unloading was simulated by 3-day head-out dry immersion. Before and after the immersion the samples of soleus muscle were taken under local anesthesia, using biopsy technique. The content of desmin, IRS-1, phospho-AMPK, total and phospho-nNOS in soleus of 6 healthy men was determined using Western-blotting before and after the dry-immersion. Three days of the dry immersion resulted in a significant decrease in desmin, phospho-nNOS and phospho-AMPK as compared to the pre-immersion values. The results of the study suggest that proteolytic processes in human soleus at the early stage of gravitational unloading are associated with inactivation of nNOS. Reduction in AMPK phosphorylation could serve as a trigger event for the development of primary atrophic changes in skeletal muscle.     

Control of phloem unloading by action potentials in Mimosa

In the sensitive plant, Mimosa pudica , action potentials arise when the leaves are touched and they trigger a sudden decrease in turgor of the pulvinar motor cells, which causes the leaf to close. These potentials may travel through the phloem and they appear to influence pulvinar phloem unloading after stimulation. Mature leaves were exposed to ¹⁴CO₂ and phloem translocation was observed by autoradiography. In unstimulated pulvini, labeled photoassimilates were restricted to the phloem. However, after stimulation, the ¹⁴C-label appeared to be concentrated in the extensor region of the motor cortex. Since stimulation elicits an action potential, it is suggested that it also triggers phloem unloading of sucrose in the pulvini.     

Irreversible morphological changes in leg bone following chronic gravitational unloading of growing rats

Effects of gravitational unloading or loading on the growth and development of hindlimb bones were studied in rats. Male Wistar rats were hindlimb-unloaded or loaded at 2-G from the postnatal day 4 to month 3. The morphology and mineral content of tibia and fibula, as well as the mobility of ankle joints, were measured at the end of 3-month suspension or loading, and 1, 2, and 3 months after ambulation recovery. Growth-related increases of bone weight and mineral density were inhibited by unloading. But they were gradually recovered toward the control levels, even though they were still less than those in the age-matched controls after 3 months. None of the parameters were influenced by 2-G loading. However, here we report that chronic unloading causes abnormal morphological development in hindlimb bone of growing rats. Irreversible external bend of the shaft and rotation of the distal end of tibia, which limit the dorsiflexion of ankle joints, were induced following chronic gravitational unloading during developing period. It is also suggested that such phenomena are caused by the abnormal mechanical forces imposed by muscle utilization with altered patterns. The activity of ankle dorsiflexor was increased and that of plantarflexor was inhibited during unloading.     

Anticipatory postural adjustment in bimanual unloading: role of the motor cortex in motor learning

The role of the motor cortex was investigated during learning unusual postural adjustment. Healthy subjects held their right (postural) forearm in a horizontal position while supporting a 1-kG load via an electromagnet. The postural forearm position was perturbed by the load release triggered by other elbow voluntary movement. Repetition of the imposed unloading test resulted in a progressive reduction of the maximal forearm rotation, accompanied by the anticipatory decrease in m. biceps brachii activity (learning). Control situation consisted of the voluntary forearm loading. Using the transcranial magnetic stimulation we examined changes in the motor evoked potential of the m. biceps brahii at the beginning and at the end of learning. The evoked potential amplitude did not significantly change in process of the decrease of m. biceps brachii activity. At the end of learning, motor evoked potential / baseline electromyogram ratio increased as compared to the beginning of learning and to the control situation. The results highlight the fundamental role of the motor cortex in suppression of synergies which interfere with formation of a new coordination during motor learning.     

How Thoughts Give Rise to Action - Conscious Motor Intention Increases the Excitability of Target-Specific Motor Circuits

The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS) of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR), and extensor carpi radialis (ECR), induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension), without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an “intention network” in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before any motor execution.     

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans.

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (approximately 1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5-20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for approximately 30 min (P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.     

Alternative Splicing of Titin mRNA in Rat Soleus after Seven-Day Gravitational Unloading

Human Physiology - Changes in titin alternative splicing in the rat soleus after seven-day gravitational unloading (the hindlimb unloading model) were studied by long-fragment PCR and nanopore...     

Influence of Vibration on Motor Responses in the Upper Arm Muscles under Stationary Conditions and during Voluntary and Evoked Arm Movements under Limb Unloading Conditions

Locomotion of mammals, including humans, is based on the rhythmic activity of spinal cord circuitries. The functioning of these circuitries depends on multimodal afferent information and on supraspinal influences from the motor cortex. Using the method of transcranial magnetic stimulation (TMS) of arm muscle areas in the motor cortex, we studied the motor evoked potentials (MEP) in the upper arm muscles in stationary conditions and during voluntary and vibration-evoked arm movements. The study included 13 healthy subjects under arm and leg unloading conditions. In the first series of experiments, with motionless limbs, the effect of vibration of left upper arm muscles on motor responses in these muscles was evaluated. In the second series of experiments, MEP were compared in the same muscles during voluntary and rhythmic movements generated by left arm m. triceps brachii vibration (the right arm was stationary). Motionless left arm vibration led to an increase in MEP values in both vibrated muscle and in most of the non-vibrated muscles. For most target muscles, MEP was greater with voluntary arm movements than with vibration-evoked movements. At the same time, a similar MEP modulation in the cycle of arm movements was observed in the same upper arm muscles during both types of arm movements. TMS of the motor cortex significantly potentiated arm movements generated by vibration, but its effect on voluntary movements was weaker. These results indicate significant differences in the degree of motor cortex involvement in voluntary and evoked arm movements. We suppose that evoked arm movements are largely due to spinal rather than central mechanisms of generation of rhythmic movements.     

The change of HSP47, collagen specific molecular chaperone, expression in rat skeletal muscle may regulate collagen production with gravitational conditions.

It is well known that unloading of skeletal muscle with spaceflight leads skeletal muscle atrophy. However, it remains unclear how the extracellular matrix within the muscle and the connective tissues such as tendon and ligament respond to reduced mechanical load including microgravity, although they have been thought to play important roles in both the transmission of force and the signal transduction between cells and tissues. Type-I collagen and type-IV collagen, both of the major components of extracellular matrix and connective tissues. We focused on change of these collagen synthesis with mechanical load. To obtain an insight into the effects of gravitational changing on the protein metabolism of collagen in skeletal muscle during mechanical unloading, reloading after unloading, we investigated changes in the amount of Heat shock protein 47 (HSP47), has been postulated to be a collagen-specific molecular chaperone localized in the ER (Nagata et al, 1992). Western blot analysis revealed that HSP47 in rat soleus muscle decreases at 5 days after hindlimb suspension (HS). On the other hand, HSP47 in rat soleus muscle increases at 5 days after hypergravity (HG) induced by the centrifugation. RT-PCR analysis showed HSP47 mRNA decreased with HS earlier, as compared with collagen type-I and type-IV mRNA. From these results, the amount of HSP47 changing by gravitational condition may effect on signal transfers in the primary stage of adaptation and the change of HSP47 expression in skeletal muscle may regulate collagen production with gravitational conditions.     

精准定位脑刺激对运动功能调控研究进展

脑刺激是神经科学研究的重要手段,传统的经颅磁刺激和经颅电刺激等脑刺激方法尽管能调控运动功能(包括减轻运动性障碍疾病的运动障碍、提高运动能力等),但存在空间分辨率低且无法刺激深部脑组织的局限性.近年来迅速发展的深部脑刺激(deep brain stimulation,DBS)、光遗传学、经颅超声刺激(transcranial ultrasound stimulation,TUS)、时间干涉(temporal interference,TI)等精准定位脑刺激方法,具有空间分辨率高、可聚焦深部脑组织等优点.本文综述了上述几种脑刺激方法的原理、特点,对运动功能调控的研究进展,以及面临的挑战和发展前景,从而为神经科学研究提供更好的研究工具,为临床实践提供更多的干预治疗手段.