Aaron P. Batista

Neural constraints on learning

Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain–computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain–computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess.

Single-neuron stability during repeated reaching in macaque premotor cortex.

Some movements that animals and humans make are highly stereotyped, repeated with little variation. The patterns of neural activity associated with repeats of a movement may be highly similar, or the same movement may arise from different patterns of neural activity, if the brain exploits redundancies in the neural projections to muscles. We examined the stability of the relationship between neural activity and behavior. We asked whether the variability in neural activity that we observed during repeated reaching was consistent with a noisy but stable relationship, or with a changing relationship, between neural activity and behavior. Monkeys performed highly similar reaches under tight behavioral control, while many neurons in the dorsal aspect of premotor cortex and the primary motor cortex were simultaneously monitored for several hours. Neural activity was predominantly stable over time in all measured properties: firing rate, directional tuning, and contribution to a decoding model that predicted kinematics from neural activity. The small changes in neural activity that we did observe could be accounted for primarily by subtle changes in behavior. We conclude that the relationship between neural activity and practiced behavior is reasonably stable, at least on timescales of minutes up to 48 h. This finding has significant implications for the design of neural prosthetic systems because it suggests that device recalibration need not be overly frequent, It also has implications for studies of neural plasticity because a stable baseline permits identification of nonstationary shifts.

To sort or not to sort: the impact of spike-sorting on neural decoding performance.

OBJECTIVEnBrain-computer interfaces (BCIs) are a promising technology for restoring motor ability to paralyzed patients. Spiking-based BCIs have successfully been used in clinical trials to control multi-degree-of-freedom robotic devices. Current implementations of these devices require a lengthy spike-sorting step, which is an obstacle to moving this technology from the lab to the clinic. A viable alternative is to avoid spike-sorting, treating all threshold crossings of the voltage waveform on an electrode as coming from one putative neuron. It is not known, however, how much decoding information might be lost by ignoring spike identity.nnnAPPROACHnWe present a full analysis of the effects of spike-sorting schemes on decoding performance. Specifically, we compare how well two common decoders, the optimal linear estimator and the Kalman filter, reconstruct the arm movements of non-human primates performing reaching tasks, when receiving input from various sorting schemes. The schemes we tested included: using threshold crossings without spike-sorting; expert-sorting discarding the noise; expert-sorting, including the noise as if it were another neuron; and automatic spike-sorting using waveform features. We also decoded from a joint statistical model for the waveforms and tuning curves, which does not involve an explicit spike-sorting step.nnnMAIN RESULTSnDiscarding the threshold crossings that cannot be assigned to neurons degrades decoding: no spikes should be discarded. Decoding based on spike-sorted units outperforms decoding based on electrodes voltage crossings: spike-sorting is useful. The four waveform based spike-sorting methods tested here yield similar decoding efficiencies: a fast and simple method is competitive. Decoding using the joint waveform and tuning model shows promise but is not consistently superior.nnnSIGNIFICANCEnOur results indicate that simple automated spike-sorting performs as well as the more computationally or manually intensive methods used here. Even basic spike-sorting adds value to the low-threshold waveform-crossing methods often employed in BCI decoding.

Workshops of the Fifth International Brain-Computer Interface Meeting: Defining the Future

The Fifth International Brain-Computer Interface (BCI) Meeting met June 3-7th, 2013 at the Asilomar Conference Grounds, Pacific Grove, California. The conference included 19 workshops covering topics in brain-computer interface and brain-machine interface research. Topics included translation of BCIs into clinical use, standardization and certification, types of brain activity to use for BCI, recording methods, the effects of plasticity, special interest topics in BCIs applications, and future BCI directions. BCI research is well established and transitioning to practical use to benefit people with physical impairments. At the same time, new applications are being explored, both for people with physical impairments and beyond. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and high-lighting important issues for future research and development.

Single-unit activity, threshold crossings, and local field potentials in motor cortex differentially encode reach kinematics

A diversity of signals can be recorded with extracellular electrodes. It remains unclear whether different signal types convey similar or different information and whether they capture the same or different underlying neural phenomena. Some researchers focus on spiking activity, while others examine local field potentials, and still others posit that these are fundamentally the same signals. We examined the similarities and differences in the information contained in four signal types recorded simultaneously from multielectrode arrays implanted in primary motor cortex: well-isolated action potentials from putative single units, multiunit threshold crossings, and local field potentials (LFPs) at two distinct frequency bands. We quantified the tuning of these signal types to kinematic parameters of reaching movements. We found 1) threshold crossing activity is not a proxy for single-unit activity; 2) when examined on individual electrodes, threshold crossing activity more closely resembles LFP activity at frequencies between 100 and 300 Hz than it does single-unit activity; 3) when examined across multiple electrodes, threshold crossing activity and LFP integrate neural activity at different spatial scales; and 4) LFP power in the beta band (between 10 and 40 Hz) is a reliable indicator of movement onset but does not encode kinematic features on an instant-by-instant basis. These results show that the diverse signals recorded from extracellular electrodes provide somewhat distinct and complementary information. It may be that these signal types arise from biological phenomena that are partially distinct. These results also have practical implications for harnessing richer signals to improve brain-machine interface control.

Extracting low-dimensional latent structure from time series in the presence of delays

Noisy, high-dimensional time series observations can often be described by a set of low-dimensional latent variables. Commonly used methods to extract these latent variables typically assume instantaneous relationships between the latent and observed variables. In many physical systems, changes in the latent variables manifest as changes in the observed variables after time delays. Techniques that do not account for these delays can recover a larger number of latent variables than are present in the system, thereby making the latent representation more difficult to interpret. In this work, we introduce a novel probabilistic technique, time-delay gaussian-process factor analysis (TD-GPFA), that performs dimensionality reduction in the presence of a different time delay between each pair of latent and observed variables. We demonstrate how using a gaussian process to model the evolution of each latent variable allows us to tractably learn these delays over a continuous domain. Additionally, we show how TD-GPFA combines temporal smoothing and dimensionality reduction into a common probabilistic framework. We present an expectation/conditional maximization either (ECME) algorithm to learn the model parameters. Our simulations demonstrate that when time delays are present, TD-GPFA is able to correctly identify these delays and recover the latent space. We then applied TD-GPFA to the activity of tens of neurons recorded simultaneously in the macaque motor cortex during a reaching task. TD-GPFA is able to better describe the neural activity using a more parsimonious latent space than GPFA, a method that has been used to interpret motor cortex data but does not account for time delays. More broadly, TD-GPFA can help to unravel the mechanisms underlying high-dimensional time series data by taking into account physical delays in the system.

Comparing temporal aspects of visual, tactile, and microstimulation feedback for motor control

OBJECTIVESnCurrent brain-computer interfaces (BCIs) rely on visual feedback, requiring sustained visual attention to use the device. Improvements to BCIs may stem from the development of an effective way to provide quick feedback independent of vision. Tactile stimuli, either delivered on the skin surface, or directly to the brain via microstimulation in somatosensory cortex, could serve that purpose. We examined the effectiveness of vibrotactile stimuli and microstimulation as a means of non-visual feedback by using a fundamental element of feedback: the ability to react to a stimulus while already in motion.nnnAPPROACHnHuman and monkey subjects performed a center-out reach task which was, on occasion, interrupted with a stimulus cue that instructed a change in reach target.nnnMAIN RESULTSnSubjects generally responded faster to tactile cues than to visual cues. However, when we delivered cues via microstimuation in a monkey, its response was slower on average than for both tactile and visual cues.nnnSIGNIFICANCEnTactile and microstimulation feedback can be used to rapidly adjust movements mid-flight. The relatively slow speed of microstimulation is surprising and warrants further investigation. Overall, these results highlight the importance of considering temporal aspects of feedback when designing alternative forms of feedback for BCIs.

Stable online control of an electrocorticographic brain-computer interface using a static decoder

A brain computer interface (BCI) system was implemented by recording electrocorticographic signals (ECoG) from the motor cortex of a Rhesus macaque. These signals were used to control two-dimensional cursor movements in a standard center-out task, utilizing an optimal linear estimation (OLE) method. We examined the time course over which a monkey could acquire accurate control when operating in a co-adaptive training scheme. Accurate and maintained control was achieved after 4-5 days. We then held the decode parameters constant and observed stable control over the next 28 days. We also investigated the underlying neural strategy employed for control, asking whether neural features that were correlated with a given kinematic output (e.g. velocity in a certain direction) were clustered anatomically, and whether the features were coordinated or conflicting in their contributions to the control signal.

An L1-regularized logistic model for detecting short-term neuronal interactions

Interactions among neurons are a key component of neural signal processing. Rich neural data sets potentially containing evidence of interactions can now be collected readily in the laboratory, but existing analysis methods are often not sufficiently sensitive and specific to reveal these interactions. Generalized linear models offer a platform for analyzing multi-electrode recordings of neuronal spike train data. Here we suggest an L1-regularized logistic regression model (L1L method) to detect short-term (order of 3 ms) neuronal interactions. We estimate the parameters in this model using a coordinate descent algorithm, and determine the optimal tuning parameter using a Bayesian Information Criterion. Simulation studies show that in general the L1L method has better sensitivities and specificities than those of the traditional shuffle-corrected cross-correlogram (covariogram) method. The L1L method is able to detect excitatory interactions with both high sensitivity and specificity with reasonably large recordings, even when the magnitude of the interactions is small; similar results hold for inhibition given sufficiently high baseline firing rates. Our study also suggests that the false positives can be further removed by thresholding, because their magnitudes are typically smaller than true interactions. Simulations also show that the L1L method is somewhat robust to partially observed networks. We apply the method to multi-electrode recordings collected in the monkey dorsal premotor cortex (PMd) while the animal prepares to make reaching arm movements. The results show that some neurons interact differently depending on task conditions. The stronger interactions detected with our L1L method were also visible using the covariogram method.

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate

OBJECTIVEnElectrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue.nnnAPPROACHnWe implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d.nnnMAIN RESULTSnHistological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation.nnnSIGNIFICANCEnThese results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.