Increased emphasis on circuit level activity in the brain makes it necessary to have methods to visualize and evaluate large-scale ensemble activity beyond that revealed by raster-histograms or pairwise correlations. We present a method to evaluate the relative similarity of neural spiking patterns by combining spike train distance metrics with dimensionality reduction. Spike train distance metrics provide an estimate of similarity between activity patterns at multiple temporal resolutions. Vectors of pair-wise distances are used to represent the intrinsic relationships between multiple activity patterns at the level of single units or neuronal ensembles. Dimensionality reduction is then used to project the data into concise representations suitable for clustering analysis as well as exploratory visualization. Algorithm performance and robustness are evaluated using multielectrode ensemble activity data recorded in behaving primates. We demonstrate how spike train SIMilarity space (SSIMS) analysis captures the relationship between goal directions for an eight-directional reaching task and successfully segregates grasp types in a 3D grasping task in the absence of kinematic information. The algorithm enables exploration of virtually any type of neural spiking (time series) data, providing similarity-based clustering of neural activity states with minimal assumptions about potential information encoding models.

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature's amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic "brain-interfaces" within the body, a point of special emphasis of this paper.

Statistical nonparametric modeling tools that enable the discovery and approximation of functional forms (e.g., tuning functions) relating neural spiking activity to relevant covariates are desirable tools in neuroscience. In this article, we show how stochastic gradient boosting regression can be successfully extended to the modeling of spiking activity data while preserving their point process nature, thus providing a robust nonparametric modeling tool. We formulate stochastic gradient boosting in terms of approximating the conditional intensity function of a point process in discrete time and use the standard likelihood of the process to derive the loss function for the approximation problem. To illustrate the approach, we apply the algorithm to the modeling of primary motor and parietal spiking activity as a function of spiking history and kinematics during a two-dimensional reaching task. Model selection, goodness of fit via the time rescaling theorem, model interpretation via partial dependence plots, ranking of covariates according to their relative importance, and prediction of peri-event time histograms are illustrated and discussed. Additionally, we use the tenfold cross-validated log likelihood of the modeled neural processes (67 cells) to compare the performance of gradient boosting regression to two alternative approaches: standard generalized linear models (GLMs) and Bayesian P-splines with Markov chain Monte Carlo (MCMC) sampling. In our data set, gradient boosting outperformed both Bayesian P-splines (in approximately 90% of the cells) and GLMs (100%). Because of its good performance and computational efficiency, we propose stochastic gradient boosting regression as an off-the-shelf nonparametric tool for initial analyses of large neural data sets (e.g., more than 50 cells; more than 10(5) samples per cell) with corresponding multidimensional covariate spaces (e.g., more than four covariates). In the cases where a functional form might be amenable to a more compact representation, gradient boosting might also lead to the discovery of simpler, parametric models.

Effective neural motor prostheses require a method for decoding neural activity representing desired movement. In particular, the accurate reconstruction of a continuous motion signal is necessary for the control of devices such as computer cursors, robots, or a patient's own paralyzed limbs. For such applications, we developed a real-time system that uses Bayesian inference techniques to estimate hand motion from the firing rates of multiple neurons. In this study, we used recordings that were previously made in the arm area of primary motor cortex in awake behaving monkeys using a chronically implanted multielectrode microarray. Bayesian inference involves computing the posterior probability of the hand motion conditioned on a sequence of observed firing rates; this is formulated in terms of the product of a likelihood and a prior. The likelihood term models the probability of firing rates given a particular hand motion. We found that a linear gaussian model could be used to approximate this likelihood and could be readily learned from a small amount of training data. The prior term defines a probabilistic model of hand kinematics and was also taken to be a linear gaussian model. Decoding was performed using a Kalman filter, which gives an efficient recursive method for Bayesian inference when the likelihood and prior are linear and gaussian. In off-line experiments, the Kalman filter reconstructions of hand trajectory were more accurate than previously reported results. The resulting decoding algorithm provides a principled probabilistic model of motor-cortical coding, decodes hand motion in real time, provides an estimate of uncertainty, and is straightforward to implement. Additionally the formulation unifies and extends previous models of neural coding while providing insights into the motor-cortical code.

The direct neural control of external devices such as computer displays or prosthetic limbs requires the accurate decoding of neural activity rep- resenting continuous movement. We develop a real-time control system using the spiking activity of approximately 40 neurons recorded with an electrode array implanted in the arm area of primary motor cortex. In contrast to previous work, we develop a control-theoretic approach that explicitly models the motion of the hand and the probabilistic re- lationship between this motion and the mean firing rates of the cells in 70 bins. We focus on a realistic cursor control task in which the sub- ject must move a cursor to “hit” randomly placed targets on a computer monitor. Encoding and decoding of the neural data is achieved with a Kalman filter which has a number of advantages over previous linear filtering techniques. In particular, the Kalman filter reconstructions of hand trajectories in off-line experiments are more accurate than previ- ously reported results and the model provides insights into the nature of the neural coding of movement.  

Statistical learning and probabilistic inference techniques are used to in- fer the hand position of a subject from multi-electrode recordings of neu- ral activity in motor cortex. First, an array of electrodes provides train- ing data of neural firing conditioned on hand kinematics. We learn a non- parametric representation of this firing activity using a Bayesian model and rigorously compare it with previous models using cross-validation. Second, we infer a posterior probability distribution over hand motion conditioned on a sequence of neural test data using Bayesian inference. The learned firing models of multiple cells are used to define a non- Gaussian likelihood term which is combined with a prior probability for the kinematics. A particle filtering method is used to represent, update, and propagate the posterior distribution over time. The approach is com- pared with traditional linear filtering methods; the results suggest that it may be appropriate for neural prosthetic applications.