Motor Cortex Embeds Muscle-like Commands in an Untangled Population Response.

Primate motor cortex projects to spinal interneurons and motoneurons, suggesting that motor cortex activity may be dominated by muscle-like commands. Observations during reaching lend support to this view, but evidence remains ambiguous and much debated. To provide a different perspective, we employed a novel behavioral paradigm that facilitates comparison between time-evolving neural and muscle activity. We found that single motor cortex neurons displayed many muscle-like properties, but the structure of population activity was not muscle-like. Unlike muscle activity, neural activity was structured to avoid "tangling": moments where similar activity patterns led to dissimilar future patterns. Avoidance of tangling was present across tasks and species. Network models revealed a potential reason for this consistent feature: low tangling confers noise robustness. Finally, we were able to predict motor cortex activity from muscle activity by leveraging the hypothesis that muscle-like commands are embedded in additional structure that yields low tangling.

Responses of somatosensory area 2 neurons to actively and passively generated limb movements.

Control of reaching movements requires an accurate estimate of the state of the limb, yet sensory signals are inherently noisy, because of both noise at the receptors themselves and the stochastic nature of the information representation by neural discharge. One way to derive an accurate representation from noisy sensor data is to combine it with the output of a forward model that considers both the previous state estimate and the noisy input. We recorded from primary somatosensory cortex (S1) in macaques (Macaca mulatta) during both active and passive movements to investigate how the proprioceptive representation of movement in S1 may be modified by the motor command (through efference copy). We found neurons in S1 that respond to one or both movement types covering a broad distribution from active movement only, to both, to passive movement only. Those neurons that responded to both active and passive movements responded with similar directional tuning. Confirming earlier results, some, but not all, neurons responded before the onset of volitional movements, possibly as a result of efference copy. Consequently, many of the features necessary to combine the forward model with proprioceptive feedback appear to be present in S1. These features would not be expected from combinations of afferent receptor responses alone.

Functional connectivity and tuning curves in populations of simultaneously recorded neurons.

How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.

Limb-state information encoded by peripheral and central somatosensory neurons: implications for an afferent interface.

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches.

Statistical assessment of the stability of neural movement representations.

In systems neuroscience, neural activity that represents movements or sensory stimuli is often characterized by spatial tuning curves that may change in response to training, attention, altered mechanics, or the passage of time. A vital step in determining whether tuning curves change is accounting for estimation uncertainty due to measurement noise. In this study, we address the issue of tuning curve stability using methods that take uncertainty directly into account. We analyze data recorded from neurons in primary motor cortex using chronically implanted, multielectrode arrays in four monkeys performing center-out reaching. With the use of simulations, we demonstrate that under typical experimental conditions, the effect of neuronal noise on estimated preferred direction can be quite large and is affected by both the amount of data and the modulation depth of the neurons. In experimental data, we find that after taking uncertainty into account using bootstrapping techniques, the majority of neurons appears to be very stable on a timescale of minutes to hours. Lastly, we introduce adaptive filtering methods to explicitly model dynamic tuning curves. In contrast to several previous findings suggesting that tuning curves may be in constant flux, we conclude that the neural representation of limb movement is, on average, quite stable and that impressions to the contrary may be largely the result of measurement noise.

Designing stimulation patterns for an afferent BMI: representation of kinetics in somatosensory cortex.

In recent years, much attention has been focused on developing stimulating strategies for somatosensory prostheses. One application of such a somatosensory prosthesis is to supply proprioceptive feedback in a brain machine interface application. One strategy for the development of such a stimulation regime is to mimic the natural representation of limb state variables. In this paper, we demonstrate that end point force is represented in primary somatosensory cortex of the macaque and force, in addition to velocity, can be decoded from S1 neural recordings. Force is represented in S1 in both a movement and isometric tasks; however, models that predict force in one condition do not generalize to the other. Possible interpretations of these apparently contradictory results are discussed.

Toward a biomimetic, bidirectional, brain machine interface.

The interest in Brain Machine Interface (BMI) systems has increased tremendously in recent times; many groups have become involved in this type of research, and progress has been quite encouraging. However, two fundamental limitations remain: 1) With a few notable exceptions, BMIs extract only kinematic information from the brain, ignoring the wealth of force or kinetic information also present in the primary motor cortex, and 2) most existing BMIs depend exclusively on natural vision to guide movement, lacking the rapid proprioceptive feedback that is critical for normal movement. The work reported here describes our efforts to address both of these limitations.

Electrical stimulation of the proprioceptive cortex (area 3a) used to instruct a behaving monkey.

A growing number of brain-machine interfaces have now been developed that allow movements of an external device to be controlled using recordings from the brain. This work has been undertaken with a number of different animal models, as well as several human patients with quadriplegia. The resulting movements, whether of computer cursors or robotic limbs, remain quite slow and unstable compared to normal limb movements. It is an open question, how much of this instability is the result of the limited forward control path, and how much has to do with the total lack of normal proprioceptive feedback. We have begun preliminary studies of the effectiveness of electrical stimulation in the proprioceptive area of the primary somatosensory cortex (area 3a) as a potential means to deliver an artificial sense of proprioception to a monkey. We have demonstrated that it is possible for the monkey to detect brief stimulus trains at relatively low current levels, and to discriminate between trains of different frequencies. These observations need to be expanded to include more complex, time-varying waveforms that could potentially convey information about the state of the limb.