Primate spinal interneurons show pre-movement instructed delay activity.

Preparatory changes in neural activity before the execution of a movement have been documented in tasks that involve an instructed delay period (an interval between a transient instruction cue and a subsequently triggered movement). Such preparatory activity occurs in many motor centres in the brain, including the primary motor cortex, premotor cortex, supplementary motor area and basal ganglia. Activity during the instructed delay period reflects movement planning, as it correlates with parameters of the cue and the subsequent movement (such as direction and extent), although it occurs well before muscle activity. How such delay-period activity shapes the ensuing motor action remains unknown. Here we show that spinal interneurons also exhibit early pre-movement delay activity that often differs from their responses during the subsequent muscle activity. This delay activity resembles the set-related activity found in various supraspinal areas, indicating that movement preparation may occur simultaneously over widely distributed regions, including spinal levels. Our results also suggest that two processes occur in the spinal circuitry during this delay period: the motor network is primed with rate changes in the same direction as subsequent movement-related activity; and a superimposed global inhibition suppresses the expression of this activity in muscles.     

Small modulation of ongoing cortical dynamics by sensory input during natural vision

During vision, it is believed that neural activity in the primary visual cortex is predominantly driven by sensory input from the environment. However, visual cortical neurons respond to repeated presentations of the same stimulus with a high degree of variability. Although this variability has been considered to be noise owing to random spontaneous activity within the cortex, recent studies show that spontaneous activity has a highly coherent spatio-temporal structure. This raises the possibility that the pattern of this spontaneous activity may shape neural responses during natural viewing conditions to a larger extent than previously thought. Here, we examine the relationship between spontaneous activity and the response of primary visual cortical neurons to dynamic natural-scene and random-noise film images in awake, freely viewing ferrets from the time of eye opening to maturity. The correspondence between evoked neural activity and the structure of the input signal was weak in young animals, but systematically improved with age. This improvement was linked to a shift in the dynamics of spontaneous activity. At all ages including the mature animal, correlations in spontaneous neural firing were only slightly modified by visual stimulation, irrespective of the sensory input. These results suggest that in both the developing and mature visual cortex, sensory evoked neural activity represents the modulation and triggering of ongoing circuit dynamics by input signals, rather than directly reflecting the structure of the input signal itself.     

Categorization of behavioural sequences in the prefrontal cortex

Although it has long been thought that the prefrontal cortex of primates is involved in the integrative regulation of behaviours, the neural architecture underlying specific aspects of cognitive behavioural planning has yet to be clarified. If subjects are required to remember a large number of complex motor sequences and plan to execute each of them individually, categorization of the sequences according to the specific temporal structure inherent in each subset of sequences serves to facilitate higher-order planning based on memory. Here we show, using these requirements, that cells in the lateral prefrontal cortex selectively exhibit activity for a specific category of behavioural sequences, and that categories of behaviours, embodied by different types of movement sequences, are represented in prefrontal cells during the process of planning. This cellular activity implies the generation of neural representations capable of storing structured event complexes at an abstract level, exemplifying the development of macro-structured action knowledge in the lateral prefrontal cortex.     

Spatio-temporal correlations and visual signalling in a complete neuronal population

Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies, their origin and importance for neural coding are poorly understood. Here we analyse the functional significance of correlated firing in a complete population of macaque parasol retinal ganglion cells using a model of multi-neuron spike responses. The model, with parameters fit directly to physiological data, simultaneously captures both the stimulus dependence and detailed spatio-temporal correlations in population responses, and provides two insights into the structure of the neural code. First, neural encoding at the population level is less noisy than one would expect from the variability of individual neurons: spike times are more precise, and can be predicted more accurately when the spiking of neighbouring neurons is taken into account. Second, correlations provide additional sensory information: optimal, model-based decoding that exploits the response correlation structure extracts 20% more information about the visual scene than decoding under the assumption of independence, and preserves 40% more visual information than optimal linear decoding. This model-based approach reveals the role of correlated activity in the retinal coding of visual stimuli, and provides a general framework for understanding the importance of correlated activity in populations of neurons.     

Experience with moving visual stimuli drives the early development of cortical direction selectivity

The onset of vision occurs when neural circuits in the visual cortex are immature, lacking both the full complement of connections and the response selectivity that defines functional maturity. Direction-selective responses are particularly vulnerable to the effects of early visual deprivation, but it remains unclear how stimulus-driven neural activity guides the emergence of cortical direction selectivity. Here we report observations from a motion training protocol that allowed us to monitor the impact of experience on the development of direction-selective responses in visually naive ferrets. Using intrinsic signal imaging techniques, we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using two-photon calcium imaging techniques, we found that single neurons in visually naive animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction-selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbours. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction-selective responses in the visual cortex.     

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.     

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.     

Numerical representation for action in the parietal cortex of the monkey

The anterior part of the parietal association area in the cerebral cortex of primates has been implicated in the integration of somatosensory signals, which generate neural images of body parts and apposed objects and provide signals for sensorial guidance of movements. Here we show that this area is active in primates performing numerically based behavioural tasks. We required monkeys to select and perform movement A five times, switch to movement B for five repetitions, and return to movement A, in a cyclical fashion. Cellular activity in the superior parietal lobule reflected the number of self-movement executions. For the most part, the number-selective activity was also specific for the type of movement. This type of numerical representation of self-action was seen less often in the inferior parietal lobule, and rarely in the primary somatosensory cortex. Such activity in the superior parietal lobule is useful for processing numerical information, which is necessary to provide a foundation for the forthcoming motor selection.     

Relation of neurons in the nonprimary motor cortex to bilateral hand movement

In the primate cerebral cortex there are at least two somatotopically organized, nonprimary motor fields rostral to the primary motor area. To understand the functions of these multiple motor representations we have compared the neuronal activity in each of these fields while monkeys performed a trained motor task, using right, left or both hands. In the nonprimary motor cortex, activity in a number of neurons was related to the movement the animal chose and performed, whereas in the primary motor cortex, changes in the firing of most neurons were simply related to activity in the contralateral muscles. This result indicates that the nonprimary motor cortex is involved in higher-order coding of the laterality of the motor response, implying that it exerts its motor control function at a higher hierarchical level than its counterpart in the primary motor cortex.     

Development of an invasive brain machine interface with a monkey model

Brain-machine interfaces (BMIs) translate neural activities of the brain into specific instructions that can be carried out by external devices. BMIs have the potential to restore or augment motor functions of paralyzed patients suffering from spinal cord damage. The neural activities have been used to predict the 2D or 3D movement trajectory of monkey’s arm or hand in many studies. However, there are few studies on decoding the wrist movement from neural activities in center-out paradigm. The present study developed an invasive BMI system with a monkey model using a 10×10-microelectrode array in the primary motor cortex. The monkey was trained to perform a two-dimensional forelimb wrist movement paradigm where neural activities and movement signals were simultaneous recorded. Results showed that neuronal firing rates highly correlated with forelimb wrist movement; > 70% (105/149) neurons exhibited specific firing changes during movement and > 36% (54/149) neurons were used to discriminate directional pairs. The neuronal firing rates were also used to predict the wrist moving directions and continuous trajectories of the forelimb wrist. The four directions could be classified with 96% accuracy using a support vector machine, and the correlation coefficients of trajectory prediction using a general regression neural network were above 0.8 for both horizontal and vertical directions. Results showed that this BMI system could predict monkey wrist movements in high accuracy through the use of neuronal firing information.     

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.     

Free choice activates a decision circuit between frontal and parietal cortex

We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.     

Control of visual cortical signals by prefrontal dopamine

The prefrontal cortex is thought to modulate sensory signals in posterior cortices during top-down attention, but little is known about the underlying neural circuitry. Experimental and clinical evidence indicate that prefrontal dopamine has an important role in cognitive functions, acting predominantly through D1 receptors. Here we show that dopamine D1 receptors mediate prefrontal control of signals in the visual cortex of macaques (Macaca mulatta). We pharmacologically altered D1-receptor-mediated activity in the frontal eye field of the prefrontal cortex and measured the effect on the responses of neurons in area V4 of the visual cortex. This manipulation was sufficient to enhance the magnitude, the orientation selectivity and the reliability of V4 visual responses to an extent comparable with the known effects of top-down attention. The enhancement of V4 signals was restricted to neurons with response fields overlapping the part of visual space affected by the D1 receptor manipulation. Altering either D1- or D2-receptor-mediated frontal eye field activity increased saccadic target selection but the D2 receptor manipulation did not enhance V4 signals. Our results identify a role for D1 receptors in mediating the control of visual cortical signals by the prefrontal cortex and suggest how processing in sensory areas could be altered in mental disorders involving prefrontal dopamine.     

Temporal dissociation of parallel processing in the human subcortical outputs.

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcorticocortical neural circuits, involving the cerebellum and basal ganglia, respectively. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input-output organization, which presents an ideal neuroimaging model for the study of parallel processing at a systems level. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks.     

Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills

The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills, like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills, it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.     

Selective gating of visual signals by microstimulation of frontal cortex

Several decades of psychophysical and neurophysiological studies have established that visual signals are enhanced at the locus of attention. What remains a mystery is the mechanism that initiates biases in the strength of visual representations. Recent evidence argues that, during spatial attention, these biases reflect nascent saccadic eye movement commands. We examined the functional interaction of saccade preparation and visual coding by electrically stimulating sites within the frontal eye fields (FEF) and measuring its effect on the activity of neurons in extrastriate visual cortex. Here we show that visual responses in area V4 could be enhanced after brief stimulation of retinotopically corresponding sites within the FEF using currents below that needed to evoke saccades. The magnitude of the enhancement depended on the effectiveness of receptive field stimuli as well as on the presence of competing stimuli outside the receptive field. Stimulation of non-corresponding FEF representations could suppress V4 responses. The results suggest that the gain of visual signals is modified according to the strength of spatially corresponding eye movement commands.     

Integration of target and body-part information in the premotor cortex when planning action

To plan an action, we must first select an object to act on and the body part (or parts) to use to accomplish our intention. To plan the motor task of reaching, we specify both the target to reach for and the arm to use. In the process of planning and preparing a motor task, information about the motor target and the arm to use must be integrated before a motor program can be formulated to generate the appropriate limb movement. One of the structures in the brain that is probably involved in integrating these two sets of information is the premotor area in the cerebral cortex of primates. The lateral sector of the dorsal premotor cortex is known to receive both visual and somatosensory input, and we show here that neurons in this area gather information about both the target and the body part, while subsequent activity specifies the planned action.     

Neurophysiological investigation of the basis of the fMRI signal.

Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.     

Decoding grasp movement from monkey premotor cortex for real-time prosthetic hand control

Brain machine interfaces (BMIs) have demonstrated lots of successful arm-related reach decoding in past decades, which provide a new hope for restoring the lost motor functions for the disabled. On the other hand, the more sophisticated hand grasp movement, which is more fundamental and crucial for daily life, was less referred. Current state of arts has specified some grasp related brain areas and offline decoding results; however, online decoding grasp movement and real-time neuroprosthetic control have not been systematically investigated. In this study, we obtained neural data from the dorsal premotor cortex (PMd) when monkey reaching and grasping one of four differently shaped objects following visual cues. The four grasp gesture types with an additional resting state were classified asynchronously using a fuzzy k-nearest neighbor model, and an artificial hand was controlled online using a shared control strategy. The results showed that most of the neurons in PMd are tuned by reach and grasp movement, us- ing which we get a high average offline decoding accuracy of 97.1%. In the online demonstration, the instantaneous status of monkey grasping could be extracted successfully to control the artificial hand, with an event-wise accuracy of 85.1%. Overall, our results inspect the neural firing along the time course of grasp and for the first time enables asynchronous neural control of a prosthetic hand, which underline a feasible hand neural prosthesis in BMIs.     

Interocular rivalry revealed in the human cortical blind-spot representation

To understand conscious vision, scientists must elucidate how the brain selects specific visual signals for awareness. When different monocular patterns are presented to the two eyes, they rival for conscious expression such that only one monocular image is perceived at a time. Controversy surrounds whether this binocular rivalry reflects neural competition among pattern representations or monocular channels. Here we show that rivalry arises from interocular competition, using functional magnetic resonance imaging of activity in a monocular region of primary visual cortex corresponding to the blind spot. This cortical region greatly prefers stimulation of the ipsilateral eye to that of the blind-spot eye. Subjects reported their dominant percept while viewing rivalrous orthogonal gratings in the visual location corresponding to the blind spot and its surround. As predicted by interocular rivalry, the monocular blind-spot representation was activated when the ipsilateral grating became perceptually dominant and suppressed when the blind-spot grating became dominant. These responses were as large as those observed during actual alternations between the gratings, indicating that rivalry may be fully resolved in monocular visual cortex. Our findings provide the first physiological evidence, to our knowledge, that interocular competition mediates binocular rivalry, and indicate that V1 may be important in the selection and expression of conscious visual information.