The Sense of Effort and two Models of Single-Joint Motor Control

Two sets of experiments were carried out. In the first set, human subjects were asked to make the same effort with the elbow flexors at different joint angles under isometric conditions. In some experiments, the subjects were standing with the arm in a vertical (parasagittal) plane; in others, they were seated with the arm in a horizontal (transverse) plane. When muscular torque at a given effort level (ordinate) was plotted as a function of elbow joint angle (abscissa), the resulting isoeffort torque-angle profiles tended to be flat or negatively sloping over a range from 45° to 135°, and they were often nonmonotonic. Increases in effort up to near-maximal levels caused the isoeffort torque-angle profiles to shift upward with little alteration in shape. In the second set of experiments, seated subjects with the arm horizontal resisted baseline torques produced by a motor that acted to extend the elbow joint. Unexpected increases and decreases in torque were superimposed on the baseline torque. The subjects either were instructed to intervene and return the elbow to the initial (90°) position, or were told, “Do not intervene voluntarily; let the motor move your arm.” Effort was reported both under baseline conditions and after the changes in torque. It was found that changes in effort were a function of the changes in torque opposed by the elbow flexors, and were similar whether the subject had repositioned the arm or allowed it to be moved by the motor. In the latter case, the arm came to rest after displacements that were a function of the size and direction of the torque change. For individual subjects, the largest angular displacements ranged from ° 10° to °20° for changes in torque of ° 10 N.m. There was no evidence for any angular dependence of the effort judgments at a given torque over this angular range. Depending on whether effort is primarily an efferent perception proportional to voluntary motor activity or also has a significant afferent (involuntary) component, different models of motor control are supported by these data.     

中枢疲劳研究与思考

中枢疲劳既可以作为独立疾病影响人们的日常工作和学习,又可以作为症状出现于多种慢性疾病,其定义和机制国内外说法不尽相同。中枢疲劳是由于中枢神经系统发生退行性或其他不良变化,从而导致躯体、神经、包括心理一系列的疲劳样反应。其机制涉及到中枢神经系统和外周传导系统等多个维度、多个节点的变化,充分把握中枢疲劳的概念本质及潜在生物学机制对其临床防治有着重要理论和实践意义。此外,动物模型作为基础研究的前提和必要工具是中枢疲劳研究过程中又一重要问题。本文在文献整理的基础上,先从定义的角度出发由疲劳引申到中枢疲劳,将现阶段对中枢疲劳的不同概念阐述做一分析,并从机制和动物模型两个方面展开对国外研究进展进行综述。     

Presynaptic and Postsynaptic Cortical Mechanisms of Chronic Pain

Long-term potentiation (LTP) is a cellular model for learning and memory and believed to be critical for plastic changes in the brain. Depending on the central nervous system region, LTP has been proposed to contribute to many key physiological functions and pathological conditions, such as learning/memory, chronic pain, and drug addiction. While the induction of LTP in general requires activation of postsynaptic glutamate receptors, the expression of LTP can be mediated by postsynaptic mechanisms and/or presynaptic enhancement of glutamate release. In this review, we will evaluate recent progress made in the mechanisms of LTP in the anterior cingulate cortex (ACC) and explore its functional significance in synaptic changes after peripheral injury. Recent findings suggest that while ACC LTP in brain slice preparations is postsynaptically induced and expressed, injury triggered synaptic potentiation in the ACC contains both presynaptic enhancement of glutamate release and postsynaptic potentiation of AMPA receptor-mediated responses. Understanding presynaptic and postsynaptic mechanisms for ACC potentiation may help us to treat chronic pain in near future.     

Mechanisms of Zero-Lag Synchronization in Cortical Motifs

Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of “dynamical relaying” – a mechanism that relies on a specific network motif – has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair – a “resonance pair” – plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain.     

Reaching out: Cortical Mechanisms of Directed Action

Recordings from monkey cortex have demonstrated a sophisticated neural mechanism for the complex transformational mapping demanded by visually guided reaching.     

Central Mechanisms of Frog Galling

The central mechanisms of release calling and mating callingin the Northern leopard frog (Rana pipiens pipiens) and thegreen tree frog (Hyla cinerea) are discussed. The region ofthe ventral magnoceHifl-ar preoptic nucleus is essential formiating calling. This area probably contains androgen receptorsthat project to, and activate, more posterior calling mechanisms.The region of the main sensory nucleus V is involved, in a mannernot yet clearly understood, in calling. Perhaps this area servesas a sensory correlation center that receives and analyzes avariety of sensory inputs, determines what type of call constitutesan appropriate response, and then excites the calling circuitsat more posterior levels. The region of the hypoglossal andvagus motor nuclei is essential for release calling. This areaprobably serves as a motor coordination center that organizesthe motor patterns of calling.     

Central Mechanisms of Pheromone Information Processing

An advantage of using pheromones in olfactory studies is thatthey are chemical signals for which receptor neurons are evolvedand thus elicite biologically relevant odour-information tobe processed in the brain. In many vertebrate and insect species,the olfactory system is separated into a ‘main’and an ‘accessory’ division, the latter mediatingpheromone information. In moths, the pheromone information isfirst processed in the brain in a large and sexually dimorphicstructure, the macroglomerular complex (MGC) of the antennallobe (AL). Also in vertebrates the pheromone information isprocessed in specific or modified glomerular complexes. Oneprinciple question is whether individual olfactory glomeruliare functional units, processing specific information concerningboth the chemical quality and spatiotemporal features of thestimulus, like the pheromone plume. Indeed it has been shownthat the axons of different pheromone-selective receptor neuronsproject into different MGC-glomeruli. Intracellular recordingsfrom the AL projection (output) neurons also show that informationabout single components of the pheromone blend is preservedin some output pathways, whereas other output neurons respondin a unique fashion to the blend. The information about interspecificsignals, which interrupts pheromone attraction, is processedin a specific MGC-glomerulus and is to a large extent kept separatedfrom the pheromone information throughout the AL. Many of theoutput neurons accurately encode changes in the temporal characteristicsof the stimulus. Chem. Senses 21: 269–275, 1996.     

Serotonin and Central Mechanisms Underlying Motor Control

The review considers in a historical aspect the published data on the role of serotonin in brain activity, as well as on the structure and organization of neuronal projections of serotonergic nuclei. In addition, information on the facilitatory and inhibitory effects of serotonin on neurons of various brain regions under both in vivo and in vitro conditions is presented. General characteristics of the main types of central serotonin receptors are also given. It is emphasized that such receptors form a heterogeneous group, and this is the reason for the diversity of the effects when agonists and antagonists are applied. Regularities characteristic of changes in the activity of serotonergic system over the sleep-wakefulness cycle are also analyzed in this review; data on the involvement of serotonin in motor control are cited. Possible reasons for the complexity and multiplicity of the effects evoked by serotonin at different levels of the CNS and within various neuronal structures in the course of motor behavior are discussed.     

Compensatory Effort Parallels Midbrain Deactivation during Mental Fatigue: An fMRI Study

Fatigue reflects the functioning of our physiological negative feedback system, which prevents us from overworking. When fatigued, however, we often try to suppress this system in an effort to compensate for the resulting deterioration in performance. Previous studies have suggested that the effect of fatigue on neurovascular demand may be influenced by this compensatory effort. The primary goal of the present study was to isolate the effect of compensatory effort on neurovascular demand. Healthy male volunteers participated in a series of visual and auditory divided attention tasks that steadily increased fatigue levels for 2 hours. Functional magnetic resonance imaging scans were performed during the first and last quarter of the study (Pre and Post sessions, respectively). Tasks with low and high attentional load (Low and High conditions, respectively) were administrated in alternating blocks. We assumed that compensatory effort would be greater under the High-attentional-load condition compared with the Low-load condition. The difference was assessed during the two sessions. The effect of compensatory effort on neurovascular demand was evaluated by examining the interaction between load (High vs. Low) and time (Pre vs. Post). Significant fatigue-induced deactivation (i.e., Pre>Post) was observed in the frontal, temporal, occipital, and parietal cortices, in the cerebellum, and in the midbrain in both the High and Low conditions. The interaction was significantly greater in the High than in the Low condition in the midbrain. Neither significant fatigue-induced activation (i.e., Pre<Post), nor its interaction with factor Load, was identified. The observed midbrain deactivation ([PreH – PostH]>[PreE– PostE]) may reflect suppression of the negative feedback system that normally triggers recuperative rest to maintain homeostasis.     

Neural Correlates of Central Inhibition during Physical Fatigue

Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.     

八肽胆囊收缩素对吗啡成瘾大鼠中枢痛觉的调制

目的:观察八肽胆囊收缩素(CCK-8)对正常及吗啡成瘾大鼠尾核中痛兴奋神经元(PEN)电活动的影响,从而进一步探讨中枢CCK-8和尾核在吗啡成瘾大鼠痛觉调制中的作用.方法:70只Wistar大鼠随机分为2组:正常对照组35只(又分为生理盐水组巧只和CCK-8组20只)及吗啡成瘾组35只、(又分为生理盐水组15只和CCK-8组20只).大鼠背部皮下注射递增剂量吗啡,依次为5、10、20、40、50、60mg/kg,3次/d(8:00,12:00,16:00),连续给药6d,建立吗啡成瘾大鼠的模型.正常对照组大鼠背部皮下注射生理盐水,时间、剂量均与吗啡成瘾组相同.第7天8:00观察大鼠的自然戒断症状30min后开始实验.实验以电脉冲刺激大鼠的坐骨神经作为伤害性痛刺激,用玻璃微电极记录尾核中PEN的放电,观察尾核内注入CCK-8对PEN电活动的影响.结果:实验结果表明:①CCK-8可提高正常大鼠尾核中PEN的兴奋性,即25个PEN平均秒净增值由注射CCK-8前(100%)增加到(224.34±10.81)5,潜伏期缩短到(54.69±5.62)%.②CCK-8使吗啡成瘾大鼠尾核中PEN的兴奋性也增高,22个PEN的平均秒净增值比注药前(100%)提高了(118.93±8.50)%,潜伏期缩短了(33.96±7.23)%.结论:CCK-8可使吗啡成瘾与正常大鼠尾核中PEN对电刺激的兴奋性增强,均呈易化疼痛作用,证明中枢CCK-8系统和尾核在吗啡成瘾过程和疼痛的调节中都起到了一定的作用.     

Effect of Hyperoxia on Cortical Neuronal Nuclear Function and Programmed Cell Death Mechanisms

There is growing concern over detrimental neurologic effects to human newborns caused by increased inspired oxygen concentrations. We hypothesize that hyperoxia (FiO₂ > 0.95) results in increased high-affinity Ca²⁺-ATPase activity, Ca²⁺-influx, and proapoptotic protein expression in cortical neuronal nuclei of newborn piglets. Neuronal cerebral energy metabolism was documented by determining ATP and phosphocreatine levels. Neuronal nuclear conjugated dienes and fluorescent compounds were measured as indices of lipid peroxidation. High-affinity Ca²⁺-ATPase activity and ATP-dependent Ca²⁺-influx were determined to document neuronal nuclear membrane function. Hyperoxia resulted in increases in lipid peroxidation, high-affinity Ca²⁺-ATPase activity, ATP-dependent Ca²⁺-influx, and Bax/Bcl-2 ratio in the cortical neuronal nuclei of newborn piglets. We conclude that hyperoxia results in modification of neuronal nuclear membrane function leading to increased nuclear Ca²⁺-influx, and propose that hyperoxia-induced increases in intranuclear Ca²⁺ activates the Ca²⁺/calmodulin-dependent protein kinase pathway, triggering increased CREB protein-mediated apoptotic protein expression in hyperoxic neurons.     

Mechanisms of Self-Organization of Cortical Microtubules in Plants Revealed by Computational Simulations

Microtubules confined to the two-dimensional cortex of elongating plant cells must form a parallel yet dispersed array transverse to the elongation axis for proper cell wall expansion. Some of these microtubules exhibit free minus-ends, leading to migration at the cortex by hybrid treadmilling. Collisions between microtubules can result in plus-end entrainment (“zippering”) or rapid depolymerization. Here, we present a computational model of cortical microtubule organization. We find that plus-end entrainment leads to self-organization of microtubules into parallel arrays, whereas catastrophe-inducing collisions do not. Catastrophe-inducing boundaries (e.g., upper and lower cross-walls) can tune the orientation of an ordered array to a direction transverse to elongation. We also find that changes in dynamic instability parameters, such as in mor1-1 mutants, can impede self-organization, in agreement with experimental data. Increased entrainment, as seen in clasp-1 mutants, conserves self-organization, but delays its onset and fails to demonstrate increased ordering. We find that branched nucleation at acute angles off existing microtubules results in distinctive sparse arrays and infer either that microtubule-independent or coparallel nucleation must dominate. Our simulations lead to several testable predictions, including the effects of reduced microtubule severing in katanin mutants.     

Role of the Brainstem Reticular Formation in the Mechanisms of Cortical Electrogenesis

In rats, we studied peculiarities of the electrocorticogram (ECoG) and its segments characterized by synchronization and desynchronization phenomena; these periods were differentiated using a segmentation procedure. The electrocorticogram was recorded under conditions of the intact brain (IB) and in animals with the isolated forebrain (IFB) using intercollicular transection. When ECoG was recorded from IFB preparations, it differed from ECoG of the IB in decreased amplitudes of the rhythms and their reorganization with shifts of the frequency characteristics toward lower values, as well as in greater amplitudes of ECoG rhythms in the left hemisphere (lateralization of the ECoG activity toward this hemisphere). Significant differences of the indices of functional asymmetry were observed in the two examined experimental situations. Using calculations of multiple linear regression and subsequent visualization of the results using polycyclic multigraphs, we found a clear specificity in the formation of correlation links between the amplitudes of different ECoG rhythms under conditions of the IB and IFB preparation. We discuss the role of the brainstem structures, in particular that of the reticular formation, in the organization of integral ECoG activity and the possible importance of mutual influences between hypothetical generators of the ECoG rhythmus for this organization.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 39–51, January–February, 2005.     

Giant Cortical Glial Cells in the Central Nervous System of Insects

Biology Bulletin - Cortical glial cells are located in the neuron body layer of the brain and the ganglia of the ventral nerve cord. There are at least two size classes of cortical glia: small-cell...     

Cortical and Spinal Excitability during and after Lengthening Contractions of the Human Plantar Flexor Muscles Performed with Maximal Voluntary Effort

This study was designed to investigate the sites of potential specific modulations in the neural control of lengthening and subsequent isometric maximal voluntary contractions (MVCs) versus purely isometric MVCs of the plantar flexor muscles, when there is enhanced torque during and following stretch. Ankle joint torque during maximum voluntary plantar flexion was measured by a dynamometer when subjects (n = 10) lay prone on a bench with the right ankle tightly strapped to a foot-plate. Neural control was analysed by comparing soleus motor responses to electrical nerve stimulation (M-wave, V-wave), electrical stimulation of the cervicomedullary junction (CMEP) and transcranial magnetic stimulation of the motor cortex (MEP). Enhanced torque of 17±8% and 9±8% was found during and 2.5–3 s after lengthening MVCs, respectively. Cortical and spinal responsiveness was similar to that in isometric conditions during the lengthening MVCs, as shown by unchanged MEPs, CMEPs and V-waves, suggesting that the major voluntary motor pathways are not subject to substantial inhibition. Following the lengthening MVCs, enhanced torque was accompanied by larger MEPs (p≤0.05) and a trend to greater V-waves (p≤0.1). In combination with stable CMEPs, increased MEPs suggest an increase in cortical excitability, and enlarged V-waves indicate greater motoneuronal output or increased stretch reflex excitability. The new results illustrate that neuromotor pathways are altered after lengthening MVCs suggesting that the underlying mechanisms of the enhanced torque are not purely mechanical in nature.