Restoration of grasp following paralysis through brain-controlled stimulation of muscles

Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems.     

Neurobiology: motor control of flexible octopus arms

Animals with rigid skeletons can rely on several mechanisms to simplify motor control--for example, they have skeletal joints that reduce the number of variables and degrees of freedom that need to be controlled. Here we show that when the octopus uses one of its long and highly flexible arms to transfer an object from one place to another, it employs a vertebrate-like strategy, temporarily reconfiguring its arm into a stiffened, articulated, quasi-jointed structure. This indicates that an articulated limb may provide an optimal solution for achieving precise, point-to-point movements.     

Localization of cytoplasmic dynein to mitotic spindles and kinetochores

What is the origin of the forces generating chromosome and spindle movements in mitosis? Both microtubule dynamics and microtubule-dependent motors have been proposed as the source of these motor forces. Cytoplasmic dynein and kinesin are two soluble proteins that power membranous organelle movements on microtubules. Kinesin directs movement of organelles to the 'plus' end of microtubules, and is found at the mitotic spindle in sea urchin embryos, but not in mammalian cells. Cytoplasmic dynein translocates organelles to the 'minus' end of microtubules, and is composed of two heavy chains and several light chains. We report here that monoclonal antibodies to two of these subunits and to another polypeptide that associates with dynein localize the protein to the mitotic spindle and to the kinetochores of isolated chromosomes, suggesting that cytoplasmic dynein is important in powering movements of the spindle and chromosomes in dividing cells.     

Horizontal and vertical components of head movement are controlled by distinct neural circuits in the barn owl

To generate behaviour, the brain must transform sensory information into signals that are appropriate to control movement. Sensory and motor coordinate frames are fundamentally different, however: sensory coordinates are based on the spatiotemporal patterns of activity arising from the various sense organs, whereas motor coordinates are based on the pulling directions of muscles or groups of muscles. Results from psychophysical experiments suggest that in the process of transforming sensory information into motor control signals, the brain encodes movements in abstract or extrinsic coordinate frames, that is ones not closely related to the geometry of the sensory apparatus or of the skeletomusculature. Here we show that an abstract code underlies movements of the head by the barn owl. Specifically, the data show that subsequent to the retinotopic code for space in the optic tectum yet before the motor neuron code for muscle tensions there exists a code for head movement in which upward, downward, leftward and rightward components of movement are controlled by four functionally distinct neural circuits. Such independent coding of orthogonal components of movement may be a common intermediate step in the transformation of sensation into behaviour.     

Overlap of internal models in motor cortex for mechanical loads during reaching

A hallmark of the human motor system is its ability to adapt motor patterns for different environmental conditions, such as when a skilled ice-hockey player accurately shoots a puck with or without protective equipment. Each object (stick, shoulder pad, elbow pad) imparts a distinct load upon the limb, and a key problem in motor neuroscience is to understand how the brain controls movement for different mechanical contexts. We addressed this issue by training non-human primates to make reaching movements with and without viscous loads applied to the shoulder and/or elbow joints, and then examined neural representations in primary motor cortex (MI) for each load condition. Even though the shoulder and elbow loads are mechanically independent, we found that some neurons responded to both of these single-joint loads. Furthermore, changes in activity of individual neurons during multi-joint loads could be predicted from their response to subordinate single-joint loads. These findings suggest that neural representations of different mechanical contexts in MI are organized in a highly structured manner that may provide a neural basis for how complex motor behaviour is learned from simpler motor tasks.     

Force production by disassembling microtubules

Microtubules (MTs) are important components of the eukaryotic cytoskeleton: they contribute to cell shape and movement, as well as to the motions of organelles including mitotic chromosomes. MTs bind motor enzymes that drive many such movements, but MT dynamics can also contribute to organelle motility. Each MT polymer is a store of chemical energy that can be used to do mechanical work, but how this energy is converted to motility remains unknown. Here we show, by conjugating glass microbeads to tubulin polymers through strong inert linkages, such as biotin-avidin, that depolymerizing MTs exert a brief tug on the beads, as measured with laser tweezers. Analysis of these interactions with a molecular-mechanical model of MT structure and force production shows that a single depolymerizing MT can generate about ten times the force that is developed by a motor enzyme; thus, this mechanism might be the primary driving force for chromosome motion. Because even the simple coupler used here slows MT disassembly, physiological couplers may modulate MT dynamics in vivo.     

Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex

Neuronal activity in the motor cortex is understood to be correlated with movements, but the impact of action potentials (APs) in single cortical neurons on the generation of movement has not been fully determined. Here we show that trains of APs in single pyramidal cells of rat motor cortex can evoke long sequences of small whisker movements. For layer-5 pyramids, we find that evoked rhythmic movements have a constant phase relative to the AP train, indicating that single layer-5 pyramids can reset the rhythm of whisker movements. Action potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking, with a variable phase of movements relative to the AP train. An increasing number of APs decreases the latency to onset of movement, whereas AP frequency determines movement direction and amplitude. We find that the efficacy of cortical APs in evoking whisker movements is not dependent on background cortical activity and is greatly enhanced in waking rats. We conclude that in vibrissae motor cortex sparse AP activity can evoke movements.     

Identifying natural images from human brain activity

A challenging goal in neuroscience is to be able to read out, or decode, mental content from brain activity. Recent functional magnetic resonance imaging (fMRI) studies have decoded orientation, position and object category from activity in visual cortex. However, these studies typically used relatively simple stimuli (for example, gratings) or images drawn from fixed categories (for example, faces, houses), and decoding was based on previous measurements of brain activity evoked by those same stimuli or categories. To overcome these limitations, here we develop a decoding method based on quantitative receptive-field models that characterize the relationship between visual stimuli and fMRI activity in early visual areas. These models describe the tuning of individual voxels for space, orientation and spatial frequency, and are estimated directly from responses evoked by natural images. We show that these receptive-field models make it possible to identify, from a large set of completely novel natural images, which specific image was seen by an observer. Identification is not a mere consequence of the retinotopic organization of visual areas; simpler receptive-field models that describe only spatial tuning yield much poorer identification performance. Our results suggest that it may soon be possible to reconstruct a picture of a person's visual experience from measurements of brain activity alone.     

Direct control of paralysed muscles by cortical neurons

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms, and paralysed muscles have been activated by functional electrical stimulation. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.     

ALS相关突变型σ1R的激活促进大鼠施旺细胞RSC96的凋亡

肌萎缩性侧索硬化症(ALS)是一种渐进的致命的神经退行性疾病,症状为运动神经元损失所导致的肌肉萎缩和痉挛,大部分病人最后死于呼吸衰竭.对其致病机理的研究主要集中于对神经元的影响,而对施旺细胞在其中的作用至今仍未有报道.之前研究发现在一个青少年发病的ALS家族中,SIGMAR1基因编码区的一个碱基存在错位突变,该突变使Sigma-1型受体(σ1R)的102位氨基酸由谷氨酸(E)突变为谷氨酰胺(Q).本文通过在大鼠施旺细胞系(RSC96细胞)中过表达野生型及突变型σ1R来研究该突变对RSC96细胞凋亡的影响.实验结果表明在毒胡萝卜素(Thapsigargin)诱导的内质网压力和σ1R激动剂PRE084的刺激下,突变型σ1R使施旺细胞更倾向于凋亡,失去了对胞质Ca~(2+)调节的能力,并且对ADAM10具有更强的抑制作用.本研究提示σ1R突变也可能通过施旺细胞对ALS的病理过程起到作用.     

Energy-Aware GPU Programming at Source-Code Levels

To enhance the energy efficiency and performance of algorithms with Graphics Processing Unit (GPU) accelerators in source-code development, we consider the power efficiency based on data transfer bandwidth and power consumption in key situations. First, a set of primitives is abstracted from program statements. Then, data transfer bandwidth and power consumption in different granularity sizes are considered and mapped into proper primitives. With these mappings, a programmer can intuitively determine the power efficiency and performance in different running states of a thread. Finally, this intuition enables the programmer to tune the algorithm in order to achieve the best energy efficiency and performance. Using these power-aware principles, two Fast Fourier Transform (FFT) methods are compared. The mapping between power consumption and primitives is helpful for algorithm tuning in source-code levels.     

Representation of a perceptual decision in developing oculomotor commands

Behaviour often depends on the ability to make categorical judgements about sensory information acquired over time. Such judgements require a comparison of the evidence favouring the alternatives, but how the brain forms these comparisons is unknown. Here we show that in a visual discrimination task, the accumulating balance of sensory evidence favouring one interpretation over another is evident in the neural circuits that generate the behavioural response. We trained monkeys to make a direction judgement about dynamic random-dot motions and to indicate their judgement with an eye movement to a visual target. We interrupted motion viewing with electrical microstimulation of the frontal eye field and analysed the resulting, evoked eye movements for evidence of ongoing activity associated with the oculomotor response. Evoked eye movements deviated in the direction of the monkey's judgement. The magnitude of the deviation depended on motion strength and viewing time. The oculomotor signals responsible for these deviations reflected the accumulated motion information that informed the monkey's choices on the discrimination task. Thus, for this task, decision formation and motor preparation appear to share a common level of neural organization.     

小脑经颅直流电刺激技术提升运动表现的应用

小脑是脑皮层下的一个重要运动调节中枢,它与大脑不同皮层区域在解剖和功能上紧密连接,配合大脑皮层完成机体的运动功能和运动学习。经颅直流电刺激(transcranial direct current stimulation, tDCS)是一种非侵入性的脑刺激技术,通过电极将微弱的电流作用于小脑能有效地提升皮层脊髓兴奋性和调控小脑与大脑皮层间的功能连接。本文系统梳理近20年国内外关于tDCS刺激小脑对提升人类运动表现影响的相关文献,研究结果表明tDCS刺激小脑可以改善人体的运动表现,如姿势控制、运动适应与运动学习、肌肉力量表现等。然而,tDCS刺激小脑的生理机制和刺激强度、刺激时间、刺激时间间隔等参数的选择有待进一步研究。未来的体育科学研究中,如何将tDCS刺激小脑的技术应用于运动训练,帮助运动员突破现有的运动能力仍有待深入探究。     

New advances in the neural correlates of insight: A decade in review of the insightful brain

The first neuroimaging study of real-time brain activity during insight problem solving was conducted almost ten years ago. Many subsequent studies have used high-resolution event-related potentials (ERPs) and event-related functional magnetic resonance imaging (fMRI) to investigate the temporal dynamics and neural correlates of insight. Recent results on the neural underpinnings of insight have led researchers to propose a neural framework referred to as the "insightful brain". This putative framework represents the neural basis of the cognitive and affective processes that are involved in insight. The insightful brain may involve numerous brain regions, including the lateral prefrontal cortex, cingulate cortex, hippocampus, superior temporal gyrus, fusiform gyrus, precuneus, cuneus, insula and cerebellum. Functional studies have demonstrated that the lateral prefrontal cortex is responsible for mental set shifting and breaking during insight problem solving. The cingulate cortex is involved in the cognitive conflict between new and old ideas and progress monitoring. The hippocampus, superior temporal gyrus and fusiform gyrus form an integrated functional network that specializes in the formation of novel and effective associations. The effective transformation of problem representations depends on a non-verbal visuospatial information-processing network that comprises the precuneus and cuneus. The insula reflects cognitive flexibility and the emotional experience that is associated with insight. The cortical control of finger movements relies on the cerebellum.     

Human cerebellar activity reflecting an acquired internal model of a new tool

Theories of motor control postulate that the brain uses internal models of the body to control movements accurately. Internal models are neural representations of how, for instance, the arm would respond to a neural command, given its current position and velocity. Previous studies have shown that the cerebellar cortex can acquire internal models through motor learning. Because the human cerebellum is involved in higher cognitive function as well as in motor control, we propose a coherent computational theory in which the phylogenetically newer part of the cerebellum similarly acquires internal models of objects in the external world. While human subjects learned to use a new tool (a computer mouse with a novel rotational transformation), cerebellar activity was measured by functional magnetic resonance imaging. As predicted by our theory, two types of activity were observed. One was spread over wide areas of the cerebellum and was precisely proportional to the error signal that guides the acquisition of internal models during learning. The other was confined to the area near the posterior superior fissure and remained even after learning, when the error levels had been equalized, thus probably reflecting an acquired internal model of the new tool.     

电动轮刚性环耦合特性模型建模与分析

为进行电动轮高频转矩激励下的振动响应分析,基于刚性环轮胎模型假设,考虑轮辋与轮毂电机弹性连接关系建立了电动轮刚性环耦合特性模型.通过电动轮工作模态试验对模型主要刚度参数进行了识别,并结合胎面参数分析了模型的固有特性.所建立的电动轮模型能够准确描述胎面径向一阶平移频率和周向旋转频率,且考虑轮辋与轮毂电机连接柔性改变了原有的轮胎环、轮辋固有频率分布,可以避开原有峰值频率.根据电动轮轮毂电机实测激励频率特征,对所建立的电动轮刚性环耦合特性模型进行了相应频率的转矩激励.分析表明,考虑轮辋与轮毂电机间弹性连接耦合特性关系,能够减小原有电动轮一阶径向平移频率附近的轮胎与车身的振动加速度响应,为电动轮结构设计提供理论指导意义.     

Involvement of secondary motor areas in externally-triggered single-finger movements of dominant and non-dominant hands

Abstract Whether the secondary motor areas are involved in simple voluntary movements remains controversial. Differences in the neural substrates of movements with the dominant and the non-dominant hands have not been well documented. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the hemodynamic response in the primary motor cortex (M1), supple-mentary motor area (SMA) and premotor cortex (PMC) in six healthy right-handed subjects while performing a visually-guided finger-tapping task with their dominant or non-dominant hands. Significant activation was observed in M1, SMA and PMC during this externally triggered simple voluntary movement task. While dominant hand movements only activated contralateral motor areas, non-domi-nant hand movements also activated ipsilateral SMA and PMC. The results provide strong evidence for the involvement of the secondary motor areas in simple voluntarymovements, and also suggest that movements of the dominant hand primarily engage the contralateral secondary motor areas, whereas movements of the non-dominant hand engage bilateral secondary motor areas.     

双绕组BSRM 定子振动模态有限元分析

针对以往开关磁阻电动机(SRM)模态分析中,仅将绕组以附加质量归于定子铁心,但忽略其刚度影响的局限,基于6/4极结构的SRM三维物理模型,建立了计及绕组、散热筋和底座的SRM定子有限元模型,提出以弹簧来模拟绕组与定子铁心之间柔性连接的建模方法,SRM试验样机的有限元模态计算结果验证了该建模方法的有效性。为了合理计及转矩绕组、悬浮绕组对双绕组无轴承开关磁阻电动机(BSRM)定子质量和刚度的影响,把通过添加弹簧来模拟柔性连接的建模方法推广应用于双绕组BSRM三维有限元模态分析。有限元计算结果表明,采用弹簧模拟绕组与铁心以及转矩绕组与悬浮绕组之间柔性连接是一种有效计及绕组影响的建模方法,具有工程实用价值。     

The corticomotoneurone connection is normal in Parkinson's disease

Voluntary movements in Parkinson's disease are initiated and executed slowly. It is assumed that the motor cortex and its output pathway are intact and that bradykinesia is due to abnormal motor commands delivered to a normal corticospinal system. We have tested this assumption using electrical stimulation of the motor cortex through the scalp in three patients with severe Parkinson's disease, studied during fluctuations from relatively normal mobility when receiving drugs (ON) to severe bradykinesia when not receiving drugs (OFF). Thresholds and latencies for motor cortex stimulation to excite thumb flexor muscles and the resulting fast mechanical responses were the same in both ON and OFF conditions, even though the patients were unable to execute fast thumb flexion movements voluntarily when OFF. We conclude that the excitability and conduction velocity of the corticospinal motor pathways are normal in Parkinson's disease.     

Propulsion of organelles isolated from Acanthamoeba along actin filaments by myosin-I

Eukaryotic cells are dependent on their ability to translocate membraneous elements about the cytoplasm. In many cells long translocations of organelles are associated with microtubules. In other cases, such as the rapid cytoplasmic streaming in some algae, organelles appear to be propelled along actin filaments. It has been assumed, but not proven, that myosin produces these movements. We have tested vesicles from another eukaryotic cell for their ability to move on the exposed actin bundles of Nitella as an indiction that actin-based organelle movements may be a general property of cells. We found that organelles from Acanthamoeba castellanii can move along Nitella actin filaments. Here, we report two different experiments indicating that the single-headed non-polymerizable myosin isozyme myosin-I is responsible for this organelle motility. First, monoclonal antibodies to myosin-I inhibit movement, but antibodies that inhibit double-headed myosin-II do not. Second, approximately 20% of the myosin-I in homogenates co-migrates with motile vesicles during Percoll density-gradient ultracentrifugation. This is the first indication of a role for myosin-I within the cell and supports the suggestion of Albanesi et al. that myosin-I moves vesicles in this way.