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.     

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.     

Embryonic assembly of a central pattern generator without sensory input

Locomotion depends on the integration of sensory information with the activity of central circuitry, which generates patterned discharges in motor nerves to appropriate muscles. Isolated central networks generate fictive locomotor rhythms (recorded in the absence of movement), indicating that the fundamental pattern of motor output depends on the intrinsic connectivity and electrical properties of these central circuits. Sensory inputs are required to modify the pattern of motor activity in response to the actual circumstances of real movement. A central issue for our understanding of how locomotor circuits are specified and assembled is the extent to which sensory inputs are required as such systems develop. Here we describe the effects of eliminating sensory function and structure on the development of the peristaltic motor pattern of Drosophila embryos and larvae. We infer that the circuitry for peristaltic crawling develops in the complete absence of sensory input; however, the integration of this circuitry into actual patterns of locomotion requires additional information from the sensory system. In the absence of sensory inputs, the polarity of movement is deranged, and backward peristaltic waves predominate at the expense of forward peristalsis.     

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.     

基于听觉通路的盲人无损视觉补偿系统

针对盲人群体的视觉补偿问题,提出了一种基于听觉通路的盲人无损视觉补偿系统.该系统采集周围的环境信息,先利用带优化截断的嵌入式方块编码(embedded block coding with optimized truncation,EBCOT)方法对环境信息编码,再利用小波变换对感兴趣区域(region of interest,ROI)编码.编码后的环境信息经传输、解码,得到重建的图像数据.按照极坐标扫描重建的图像数据,将图像中像素点的坐标信息和灰度值映射成声音信号的时间、频率及幅度,按正弦波模型合成声音信号.结果表明,采用EBCOT,图像编码速度快,能获得较多的信息量,提高传输速率;用极坐标方...     

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.     

基于ICA与PSD的ERD／ERS信号检测

介绍一种基于独立分量分析（ICA）空间滤波结合功率谱密度（PSD）曲线分析法用于提取大脑在想象动作时产生事件相关去同步／同步（ERD／ERS）信号的方法．其检测流程为：先对想象动作诱发的脑电（EEG）信号进行ICA分解得到独立分量与相应的解混矩阵,再按特征频段取其主要分量得到滤波后数据,然后采用短时傅里叶变换计算相关导联EEG信号在特征时段与频段的PSD曲线,引入ERD／ERS系数作为量化指标以进行想象动作的识别．计算结果表明,上述方法能够显著增强运动想象脑电信号的ERD／ERS特征信息,且通过实际分类验证,采用该方法可以获得更高的识别正确率,较传统信息检测方法平均提高8％以上．     

Multiple dynamic representations in the motor cortex during sensorimotor learning

The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning.     

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.     

The perception of heading during eye movements.

When a person walks through a rigid environment while holding eyes and head fixed, the pattern of retinal motion flows radially away from a point, the focus of expansion (Fig. 1a). Under such conditions of translation, heading corresponds to the focus of expansion and people identify it readily. But when making an eye/head movement to track an object off to the side, retinal motion is no longer radial (Fig. 1b). Heading perception in such situations has been modelled in two ways. Extra-retinal models monitor the velocity of rotational movements through proprioceptive or efference information from the extraocular and neck muscles and use that information to discount rotation effects. Retinal-image models determine (and eliminate) rotational components from the retinal image alone. These models have been tested by measuring heading perception under two conditions. First, observers judged heading while tracking a point on a simulated ground plane. Second, they fixated a stationary point and the flow field simulated the effects of a tracking eye movement. Extra-retinal models predict poorer performance in the simulated condition because the eyes do not move. Retinal-image models predict no difference in performance because the two conditions produce identical patterns of retinal motion. Warren and Hannon observed similar performance and concluded that people do not require extra-retinal information to judge heading with eye/head movements present, but they used extremely slow tracking eye movements of 0.2-1.2 deg s-1; a moving observer frequently tracks objects at much higher rates (L. Stark, personal communication). Here we examine heading judgements at higher, more typical eye movement velocities and find that people require extra-retinal information about eye position to perceive heading accurately under many viewing conditions.     

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.     

Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement

The confinement of neuronal activity to specific subcellular regions is a mechanism for expanding the computational properties of neurons. Although the circuit organization underlying compartmentalized activity has been studied in several systems, its cellular basis is still unknown. Here we characterize compartmentalized activity in Caenorhabditis elegans RIA interneurons, which have multiple reciprocal connections to head motor neurons and receive input from sensory pathways. We show that RIA spatially encodes head movement on a subcellular scale through axonal compartmentalization. This subcellular axonal activity is dependent on acetylcholine release from head motor neurons and is simultaneously present and additive with glutamate-dependent globally synchronized activity evoked by sensory inputs. Postsynaptically, the muscarinic acetylcholine receptor GAR-3 acts in RIA to compartmentalize axonal activity through the mobilization of intracellular calcium stores. The compartmentalized activity functions independently of the synchronized activity to modulate locomotory behaviour.     

Neuronal ensemble control of prosthetic devices by a human with tetraplegia

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.     

Early consolidation in human primary motor cortex.

Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.     

Firing patterns of motor units in normal rats

Skeletal muscles consist of motor units which may differ considerably in contractile properties and types of usage. Some units participate mainly in relatively rare, quick movements and contract rapidly and are easily fatigued (type FF); others contribute to the maintenance of posture and hence contract slowly and are fatigue-resistant (type S), while others are both fast and fatigue-resistant (type FR). Our understanding of motor control mechanisms and the dependence of contractile properties on usage would be enhanced if more quantitative information were available concerning the firing patterns of individual motor units during normal motor behaviour. Therefore, we have made continuous recordings for extended periods from single motor units in the fast extensor digitorum longus (edl) and the slow soleus (sol) muscle of freely moving adult rats. By counting the total number of discharges for each unit, and by determining the distributions of interspike intervals and the duration of the individual impulse trains, we have obtained information about firing rate, amount of use, modulation of muscle force and tonic and phasic behaviour for 16 motor units. We now report that these units fall into three classes apparently corresponding to type FF and FR in the edl muscle and type S in the soleus muscle.     

Predictable eye-head coordination during driving.

Large changes in the direction of gaze are made with a combination of fast saccadic eye movements and rather slower head movements. Since the first study on freely moving subjects, most authors have agreed that the head movement component of gaze is very variable, with a high 'volitional' component. But in some circumstances head and eye movements can be quite predictable, for example when a subject is asked to shift gaze as quickly as possible. Under these conditions, laboratory studies have shown that the eye and head motor-systems both receive gaze-change commands, although they execute them in rather different ways. Here I reconsider the way gaze direction is changed during free movement, but in the performance of a task where the subject is too busy to exert conscious control over head or eye movements. Using a new portable and inexpensive method for recording head and eye movements, I examine the oculomotor behaviour of car drivers, particularly during the large gaze changes made at road junctions. The results show that the pattern of eye and head movements is highly predictable, given only the sequence of gaze targets.     

蟋蟀鸣叫拮抗肌的运动神经形态

蟋蟀的鸣叫运动是通过8对中胸肌肉束的运动来完成的．按照肌肉的机能分组，参与蟋蟀鸣叫运动的中胸肌肉束可被分为相互拮抗的升肌作用组和降肌作用组．其中的一对拮抗肌103a肌(升肌)和M103b肌(降肌)受中胸神经节的第三侧根即N3侧根的c4(N3-c4)分枝支配．采用逆行染色法。结果表明支配103a肌和103b肌的运动神经的细胞体分布于中胸神经节的背侧侧壁上，二者都有一个细胞体位于与前胸神经节相连的纵连合索基部，轴突分为3个主要分枝，树突在同侧的背侧表面广泛分布．     

Brain-wide neuronal dynamics during motor adaptation in zebrafish

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.     

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.