Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks.

Author Summary

How is the functional role of a particular neuron established within an ensemble? The concept of a neural tuning curve – the mapping from input variables such as movement direction to output firing rate – has proven useful in investigating neural function. However, prior work shows that tuning curves are not fixed but may be remapped as a function of task demands – presumably via high-level mechanisms of cognitive control. How is this accomplished? Brain rhythms may play a causal role in this process, but the coupling of single cells to network activity remains poorly understood. We investigated the coupling between rhythmic beta activity and spiking as macaques performed two different tasks. This coupling can be described in terms of a function that maps oscillatory amplitude and phase to instantaneous spike rate. Similarly to direction tuning, this “internal” tuning curve also exhibits task-dependent changes. We characterize these changes across a large ensemble of simultaneously-recorded cells, and consider some of the neuro-computational implications presented by cross-level coupling between single cells and large-scale networks. In particular, relative to the slow time-scale of behavior, the observed beta-to-rate mappings may prove useful for modulating winner-take-all dynamics on intermediate time-scales and relative spike timing on fast time-scales.

The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills1, like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills2–4, it remains unclear if similar circuits or processes are required for abstract skill learning. We utilized a novel behavioral paradigm 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, demonstrated that these learned neuroprosthetic actions were intentional and goal-directed, rather than habitual. Striatal neurons changed their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progressed. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerged. Specific deletion of striatal NMDA receptors impaired the development of this corticostriatal plasticity, and disrupted 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.

Brain-Machine Interfaces (BMI) provide a framework to study cortical dynamics and the neural correlates of learning. Neuroprosthetic control has been associated with tuning changes in specific neurons directly projecting to the BMI (hereafter ‘direct neurons’). However, little is known about the larger network dynamics. By monitoring ensembles of neurons that were either causally linked to BMI control or indirectly involved, here we show that proficient neuroprosthetic control is associated with large-scale modifications to the cortical network in macaque monkeys. Specifically, there were changes in the preferred direction of both direct and indirect neurons. Interestingly, with learning, there was a relative decrease in the net modulation of indirect neural activity in comparison to the direct activity. These widespread differential changes in the direct and indirect population activity were remarkably stable from one day to the next and readily coexisted with the long-standing cortical network for upper limb control. Thus, the process of learning BMI control is associated with differential modification of neural populations based on their specific relation to movement control.

A fundamental organizational principle of the primate motor system is cortical control of contralateral limb movements. Motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. Interestingly, this representation was more correlated with joint angles than hand position. Using bilateral EMG recordings, we excluded the possibility that postural or mirror movements could exclusively account for these findings. In addition, linear methods could decode limb position from cortical field potentials in both monkeys. We also found that M1 spiking activity could control a biomimetic brain-machine interface reflecting ipsilateral kinematics. Finally, we recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

Stimulus-evoked oscillations have been observed in the visual, auditory, olfactory and somatosensory systems. To further our understanding of these oscillations, it is essential to study their occurrence and behavioral modulation in alert, awake animals. Here we show that microstimulation in barrel cortex of alert rats evokes 15–18 Hz oscillations that are strongly modulated by motor behavior. In freely whisking rats, we found that the power of the microstimulation-evoked oscillation in the local field potential was inversely correlated to the strength of whisking. This relationship was also present in rats performing a stimulus detection task suggesting that the effect was not due to sleep or drowsiness. Further, we present a computational model of the thalamocortical loop which recreates the observed phenomenon and predicts some of its underlying causes. These findings demonstrate that stimulus-evoked oscillations are strongly influenced by motor modulation of afferent somatosensory circuits.

Dr. Octopus, the villain of the movie "Spiderman 2", is a fusion of man and machine. Neuroscientist Jose Carmena examines the facts behind this fictional account of a brain- machine interface

The growing use of multi-channel neural recording techniques in behaving animals has produced rich datasets that hold immense potential for advancing our understanding of how the brain mediates behavior. One limitation of these techniques is they do not provide important information about the underlying anatomical connections among the recorded neurons within an ensemble. Inferring these connections is often intractable because the set of possible interactions grows exponentially with ensemble size. This is a fundamental challenge one confronts when interpreting these data. Unfortunately, the combination of expert knowledge and ensemble data is often insufficient for selecting a unique model of these interactions. Our approach shifts away from modeling the network diagram of the ensemble toward analyzing changes in the dynamics of the ensemble as they relate to behavior. Our contribution consists of adapting techniques from signal processing and Bayesian statistics to track the dynamics of ensemble data on time-scales comparable with behavior. We employ a Bayesian estimator to weigh prior information against the available ensemble data, and use an adaptive quantization technique to aggregate poorly estimated regions of the ensemble data space. Importantly, our method is capable of detecting changes in both the magnitude and structure of correlations among neurons missed by firing rate metrics. We show that this method is scalable across a wide range of time-scales and ensemble sizes. Lastly, the performance of this method on both simulated and real ensemble data is used to demonstrate its utility.

In this article, the authors show that the neural representation for control of a neuroprosthetic device undergoes a process of consolidation, after which it is stable, readily recalled, and resistant to interference.

Cortical control of neuroprosthetic devices is known to require neuronal adaptations. It remains unclear whether a stable cortical representation for prosthetic function can be stored and recalled in a manner that mimics our natural recall of motor skills. Especially in light of the mixed evidence for a stationary neuron-behavior relationship in cortical motor areas, understanding this relationship during long-term neuroprosthetic control can elucidate principles of neural plasticity as well as improve prosthetic function. Here, we paired stable recordings from ensembles of primary motor cortex neurons in macaque monkeys with a constant decoder that transforms neural activity to prosthetic movements. Proficient control was closely linked to the emergence of a surprisingly stable pattern of ensemble activity, indicating that the motor cortex can consolidate a neural representation for prosthetic control in the presence of a constant decoder. The importance of such a cortical map was evident in that small perturbations to either the size of the neural ensemble or to the decoder could reversibly disrupt function. Moreover, once a cortical map became consolidated, a second map could be learned and stored. Thus, long-term use of a neuroprosthetic device is associated with the formation of a cortical map for prosthetic function that is stable across time, readily recalled, resistant to interference, and resembles a putative memory engram.

Author Summary

Brain–machine interfaces (BMIs) have the potential to revolutionize the care of neurologically impaired patients. Numerous studies have now shown the feasibility of direct “brain control” of a neuroprosthetic device, yet it remains unclear whether the neural representation for prosthetic control can become consolidated and remain stable over time. This question is especially intriguing given the evidence demonstrating that the neural representation for natural movements can be unstable: BMIs provide a window into the plasticity of cortical circuits in awake-behaving subjects. Here, we show that long-term neuroprosthetic control leads to the formation of a remarkably stable cortical map. Interestingly, this map has the putative attributes of a memory trace, namely, it is stable across time, readily recalled, and resistant to the storage of a second map. The demonstration of such a cortical map for prosthetic control indicates that neuroprosthetic devices could eventually be controlled through the effortless recall of motor memory in a manner that mimics natural skill acquisition and motor control.

Background

During planning and execution of reaching movements, the activity of cortical motor neurons is modulated by a diversity of motor, sensory, and cognitive signals. Brain-machine interfaces (BMIs) extract part of these modulations to directly control artificial actuators. However, cortical modulations that emerge in the novel context of operating the BMI are poorly understood.

Methodology/Principal Findings

Here we analyzed the changes in neuronal modulations that occurred in different cortical motor areas as monkeys learned to use a BMI to control reaching movements. Using spike-train analysis methods we demonstrate that the modulations of the firing-rates of cortical neurons increased abruptly after the monkeys started operating the BMI. Regression analysis revealed that these enhanced modulations were not correlated with the kinematics of the movement. The initial enhancement in firing rate modulations declined gradually with subsequent training in parallel with the improvement in behavioral performance.

Conclusions/Significance

We conclude that the enhanced modulations are related to computational tasks that are significant especially in novel motor contexts. Although the function and neuronal mechanism of the enhanced cortical modulations are open for further inquiries, we discuss their potential role in processing execution errors and representing corrective or explorative activity. These representations are expected to contribute to the formation of internal models of the external actuator and their decoding may facilitate BMI improvement.

Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain–machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles) from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.

With visual feedback, macaque monkeys learn to control a robot arm through a neural interface which records activity from multiple cortical areas