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.     

Population coding of saccadic eye movements by neurons in the superior colliculus

The deeper layers of the superior colliculus are involved in the initiation and execution of saccadic (high velocity) eye movements. A large population of coarsely tuned collicular neurons is active before each saccade. The mechanisms by which the signals that precisely control the direction and amplitude of a saccade are extracted from the activity of the population are unknown. It has been assumed that the exact trajectory of a saccade is determined by the activity of the entire population and that information is not extracted from only the most active cells in the population at a subsequent stage of neural processing. The trajectory of a saccade could be based on vector summation of the movement tendencies provided by each member of the population of active neurons or be determined by a weighted average of the vector contributions of each neuron in the active population. Here we present the results of experiments in which a small subset of the active population was reversibly deactivated with lidocaine. These results are consistent with the predictions of the latter population-averaging hypothesis and support the general idea that the direction, amplitude and velocity of saccadic eye movements are based on the responses of the entire population of cells active before a saccadic eye movement.     

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.     

The influence of visual motion on fast reaching movements to a stationary object

One of the most important functions of vision is to direct actions to objects. However, every time that vision is used to guide an action, retinal motion signals are produced by the movement of the eye and head as the person looks at the object or by the motion of other objects in the scene. To reach for the object accurately, the visuomotor system must separate information about the position of the stationary target from background retinal motion signals-a long-standing problem that is poorly understood. Here we show that the visuomotor system does not distinguish between these two information sources: when observers made fast reaching movements to a briefly presented stationary target, their hand shifted in a direction consistent with the motion of a distant and unrelated stimulus, a result contrary to most other findings. This can be seen early in the hand's trajectory (approximately 120 ms) and occurs continuously from programming of the movement through to its execution. The visuomotor system might make use of the motion signals arising from eye and head movements to update the positions of targets rapidly and redirect the hand to compensate for body movements.     

A common mammalian plan of accessory optic system organization revealed in all primates

The accessory optic system (AOS), which was described as early as 1870 by Gudden, constitutes a distinct midbrain visual pathway in all classes of vertebrates. In non-primate mammals, retinal fibres of this system project to a set of three nuclei: the dorsal (DTN), the lateral (LTN) and the medial (MTN) terminal nuclei. Whereas all AOS cells respond to the slow motion of large visual stimuli, the neurons are tuned to complementary directions of movement: horizontal temporo-nasal direction for the DTN, vertical up and down for the LTN and vertical down for the MTN. It has thus been suggested that these nuclei establish a system of retinal coordinates for the detection of whole field motion. As the AOS provides direct and indirect pathways to both oculomotor and vestibular structures, each of these nuclei is thought to be an essential link in the co-ordination of eye and head movements in relation to movement within the visual-field. One problem for the generalization of this theory is that the medial terminal nucleus has never been found in primates. In this report we establish both the existence of this nucleus and its afferent input from the retina in all major groups of primates (prosimians, New and Old World monkeys and apes), indicating a common anatomical plan of organization of the AOS in mammals.     

Performance monitoring by the supplementary eye field

Intelligent behaviour requires self-control based on the consequences of actions. The countermanding task is designed to study self-control; it requires subjects to withhold planned movements in response to an imperative stop signal, which they can do with varying success. In humans, the medial frontal cortex has been implicated in the supervisory control of action. In monkeys, the supplementary eye field in the dorsomedial frontal cortex is involved in producing eye movements, but its precise function has not been clarified. To investigate the role of the supplementary eye field in the control of eye movements, we recorded neural activity in macaque monkeys trained to perform an eye movement countermanding task. Distinct groups of neurons were active after errors, after successful withholding of a partially prepared movement, or in association with reinforcement. These three forms of activation could not be explained by sensory or motor factors. Our results lead us to put forward the hypothesis that the supplementary eye field contributes to monitoring the context and consequences of eye movements.     

Genetic dissection of the circuit for hand dexterity in primates

It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex–PN–motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.     

Direct visuomotor transformations for reaching

The posterior parietal cortex (PPC) is thought to have a function in the sensorimotor transformations that underlie visually guided reaching, as damage to the PPC can result in difficulty reaching to visual targets in the absence of specific visual or motor deficits. This function is supported by findings that PPC neurons in monkeys are modulated by the direction of hand movement, as well as by visual, eye position and limb position signals. The PPC could transform visual target locations from retinal coordinates to hand-centred coordinates by combining sensory signals in a serial manner to yield a body-centred representation of target location, and then subtracting the body-centred location of the hand. We report here that in dorsal area 5 of the PPC, remembered target locations are coded with respect to both the eye and hand. This suggests that the PPC transforms target locations directly between these two reference frames. Data obtained in the adjacent parietal reach region (PRR) indicate that this transformation may be achieved by vectorially subtracting hand location from target location, with both locations represented in eye-centred coordinates.     

Large adjustments in visually guided reaching do not depend on vision of the hand or perception of target displacement

When we reach towards an object that suddenly appears in our peripheral visual field, not only does our arm extend towards the object, but our eyes, head and body also move in such a way that the image of the object falls on the fovea. Popular models of how reaching movements are programmed have argued that while the first part of the limb movement is ballistic, subsequent corrections to the trajectory are made on the basis of dynamic feedback about the relative positions of the hand and the target provided by central vision. These models have assumed that the adjustments are dependent on seeing the hand moving with respect to the target. Here we present evidence that a change in the position of a visual target during a reaching movement can modify the trajectory even when vision of the hand is prevented. Moreover, these dynamic corrections to the trajectory of the moving limb occur without the subject perceiving the change in target location. These findings demonstrate that visual feedback about the relative position of the hand and target is not necessary for visually driven corrections in reaching to occur, and the mechanisms that maintain the apparent stability of a target in space are dissociable from those that mediate the visuomotor output directed at that target.     

Coding of smooth eye movements in three-dimensional space by frontal cortex

Through the development of a high-acuity fovea, primates with frontal eyes have acquired the ability to use binocular eye movements to track small objects moving in space. The smooth-pursuit system moves both eyes in the same direction to track movement in the frontal plane (frontal pursuit), whereas the vergence system moves left and right eyes in opposite directions to track targets moving towards or away from the observer (vergence tracking). In the cerebral cortex and brainstem, signals related to vergence eye movements--and the retinal disparity and blur signals that elicit them--are coded independently of signals related to frontal pursuit. Here we show that these types of signal are represented in a completely different way in the smooth-pursuit region of the frontal eye fields. Neurons of the frontal eye field modulate strongly during both frontal pursuit and vergence tracking, which results in three-dimensional cartesian representations of eye movements. We propose that the brain creates this distinctly different intermediate representation to allow these neurons to function as part of a system that enables primates to track and manipulate objects moving in three-dimensional space.     

Motion streaks provide a spatial code for motion direction.

Although many neurons in the primary visual cortex (V1) of primates are direction selective, they provide ambiguous information about the direction of motion of a stimulus. There is evidence that one of the ways in which the visual system resolves this ambiguity is by computing, from the responses of V1 neurons, velocity components in two or more spatial orientations and then combining these velocity components. Here I consider another potential neural mechanism for determining motion direction. When a localized image feature moves fast enough, it should become smeared in space owing to temporal integration in the visual system, creating a spatial signal-a 'motion streak'-oriented in the direction of the motion. The orientation masking and adaptation experiments reported here show that these spatial signals for motion direction exist in the human visual system for feature speeds above about 1 feature width per 100 ms. Computer simulations show that this psychophysical finding is consistent with the known response properties of V1 neurons, and that these spatial signals, when appropriately processed, are sufficient to determine motion direction in natural images.     

Dynamic coding of behaviourally relevant stimuli in parietal cortex.

A general function of cerebral cortex is to allow the flexible association of sensory stimuli with specific behaviours. Many neurons in parietal, prefrontal and motor cortical areas are activated both by particular movements and by sensory cues that trigger these movements, suggesting a role in linking sensation to action. For example, neurons in the lateral intraparietal area (LIP) encode both the location of visual stimuli and the direction of saccadic eye movements. LIP is not believed to encode non-spatial stimulus attributes such as colour. Here we investigated whether LIP would encode colour if colour was behaviourally linked to the eye movement. We trained monkeys to make an eye movement in one of two directions based alternately on the colour or location of a visual cue. When cue colour was relevant for directing eye movement, we found a substantial fraction of LIP neurons selective for cue colour. However, when cue location was relevant, colour selectivity was virtually absent in LIP. These results demonstrate that selectivity of cortical neurons can change as a function of the required behaviour.     

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.     

非人灵长类动物实验中的动物福利

非人灵长类 (Non humanPrimates)实验动物由于它的形态解剖学与生理生化机能方面与人类有相似之处 ,因此在生命科学各个领域的实验研究过程中常用作人类的“替身” ,是不可缺少的支撑条件。在药物毒理学的实验过程中 ,有的药物 ,特别是基因工程药、生物制剂等要求必须使用猴类进行。因此 ,在非人灵长类动物实验中的道德伦理观问题应当引起人们的足够重视 ,因为它也涉及到我国的实验动物科学与国际接轨并获得国际认可的问题。非人灵长类动物实验中的道德伦理问题实质上就是动物福利 (AnimalWelfare)问题。什么是动物福利 ?台湾学者夏良宙 (…     

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.     

A sensory source for motor variation

Suppose that the variability in our movements is caused not by noise in the motor system itself, nor by fluctuations in our intentions or plans, but rather by errors in our sensory estimates of the external parameters that define the appropriate action. For tasks in which precision is at a premium, performance would be optimal if no noise were added in movement planning and execution: motor output would be as accurate as possible given the quality of sensory inputs. Here we use visually guided smooth-pursuit eye movements in primates as a testing ground for this notion of optimality. In response to repeated presentations of identical target motions, nearly 92% of the variance in eye trajectory can be accounted for as a consequence of errors in sensory estimates of the speed, direction and timing of target motion, plus a small background noise that is observed both during eye movements and during fixations. The magnitudes of the inferred sensory errors agree with the observed thresholds for sensory discrimination by perceptual systems, suggesting that the very different neural processes of perception and action are limited by the same sources of noise.     

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.     

Instant neural control of a movement signal

The activity of motor cortex (MI) neurons conveys movement intent sufficiently well to be used as a control signal to operate artificial devices, but until now this has called for extensive training or has been confined to a limited movement repertoire. Here we show how activity from a few (7-30) MI neurons can be decoded into a signal that a monkey is able to use immediately to move a computer cursor to any new position in its workspace (14 degrees x 14 degrees visual angle). Our results, which are based on recordings made by an electrode array that is suitable for human use, indicate that neurally based control of movement may eventually be feasible in paralysed humans.     

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5?years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.     

基于运动相关脑电特征的手运动方向识别

为了研究如何从无创运动相关脑电中提取运动信息作为上肢主动康复训练的控制命令,通过设计实验,使右手完成左、上、右3个方向的运动,同时采集脑电数据和右手运动信息.通过小波时频分析确认与右手运动相关的脑电频带,并提取其小波分解系数作为特征,采用支持向量机进行特征分类,根据方向识别准确率分析提取特征的有效性.结果表明,运动脑电delta和theta频段的小波系数特征可以有效区分右手不同方向的运动,方向识别准确率的均值接近65%,并且用准备阶段特征分类的结果普遍优于运动阶段特征,因此,在手运动之前诱发的脑电活动含有丰富的运动信息,可用于脑-机接口系统提取上肢主动康复训练的控制命令.