Synergistic Coding by Cortical Neural Ensembles.

An essential step towards understanding how the brain orchestrates information processing at the cellular and population levels is to simultaneously observe the spiking activity of cortical neurons that mediate perception, learning, and motor processing. In this paper, we formulate an information theoretic approach to determine whether cooperation among neurons may constitute a governing mechanism of information processing when encoding external covariates. Specifically, we show that conditional independence between neuronal outputs may not provide an optimal encoding strategy when the firing probability of a neuron depends on the history of firing of other neurons connected to it. Rather, cooperation among neurons can provide a "message-passing" mechanism that preserves most of the information in the covariates under specific constraints governing their connectivity structure. Using a biologically plausible statistical learning model, we demonstrate the performance of the proposed approach in synergistically encoding a motor task using a subset of neurons drawn randomly from a large population. We demonstrate its superiority in approximating the joint density of the population from limited data compared to a statistically independent model and a maximum entropy (MaxEnt) model.

Corrigendum: Low-Dimensional Motor Cortex Dynamics Preserve Kinematics Information During Unconstrained Locomotion in Nonhuman Primates.

[This corrects the article DOI: 10.3389/fnins.2019.01046.].

Low-Dimensional Motor Cortex Dynamics Preserve Kinematics Information During Unconstrained Locomotion in Nonhuman Primates.

The dynamical systems view of movement generation in motor cortical areas has emerged as an effective way to explain the firing properties of populations of neurons recorded from these regions. Recently, many studies have focused on finding low-dimensional representations of these dynamical systems during voluntary reaching and grasping behaviors carried out by the forelimbs. One such model, the Poisson linear-dynamical-system (PLDS) model, has been shown to extract dynamics which can be used to decode reaching kinematics. However, few have investigated these dynamics, especially in non-human primates, during behaviors such as locomotion, which may involve motor cortex to a lesser degree. Here, we focused on unconstrained quadrupedal locomotion, and investigated whether unsupervised latent state-space models can extract low-dimensional dynamics while preserving information about hind-limb kinematics. Spiking activity from the leg area of primary motor cortex of rhesus macaques was recorded simultaneously with hind-limb joint positions during ambulation across a corridor, ladder, and on a treadmill at various speeds. We found that PLDS models can extract stereotyped low-dimensional neural trajectories from these neurons phase-locked to the gait cycle, and that distinct trajectories emerge depending on the speed and class of behavior. Additionally, it was possible to decode both the hind-limb kinematics and the gait phase from these inferred trajectories just as well or better than from the full neural population (18-80 neurons) with only 12 dimensions. Our results demonstrate that kinematics and gait phase during various locomotion tasks are well represented in low-dimensional latent dynamics inferred from motor cortex population activity.

Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures.

The apparent unpredictability of epileptic seizures has a major impact in the quality of life of people with pharmacologically resistant seizures. Here, we present initial results and a proof-of-concept of how focal seizures can be predicted early in advance based on intracortical signals recorded from small neocortical patches away from identified seizure onset areas. We show that machine learning algorithms can discriminate between interictal and preictal periods based on multiunit activity (i.e. thresholded action potential counts) and multi-frequency band local field potentials recorded via 4 X 4 mm2 microelectrode arrays. Microelectrode arrays were implanted in 5 patients undergoing neuromonitoring for resective surgery. Post-implant analysis revealed arrays were outside the seizure onset areas. Preictal periods were defined as the 1-hour period leading to a seizure. A 5-minute gap between the preictal period and the putative seizure onset was enforced to account for potential errors in the determination of actual seizure onset times. We used extreme gradient boosting and long short-term memory networks for prediction. Prediction accuracy based on the area under the receiver operating characteristic curves reached 90% for at least one feature type in each patient. Importantly, successful prediction could be achieved based exclusively on multiunit activity. This result indicates that preictal activity in the recorded neocortical patches involved not only subthreshold postsynaptic potentials, perhaps driven by the distal seizure onset areas, but also neuronal spiking in distal recurrent neocortical networks. Beyond the commonly identified seizure onset areas, our findings point to the engagement of large-scale neuronal networks in the neural dynamics building up toward a seizure. Our initial results obtained on currently available human intracortical microelectrode array recordings warrant new studies on larger datasets, and open new perspectives for seizure prediction and control by emphasizing the contribution of multiscale neural signals in large-scale neuronal networks.

Inference and Decoding of Motor Cortex Low-Dimensional Dynamics via Latent State-Space Models.

Motor cortex neuronal ensemble spiking activity exhibits strong low-dimensional collective dynamics (i.e., coordinated modes of activity) during behavior. Here, we demonstrate that these low-dimensional dynamics, revealed by unsupervised latent state-space models, can provide as accurate or better reconstruction of movement kinematics as direct decoding from the entire recorded ensemble. Ensembles of single neurons were recorded with triple microelectrode arrays (MEAs) implanted in ventral and dorsal premotor (PMv, PMd) and primary motor (M1) cortices while nonhuman primates performed 3-D reach-to-grasp actions. Low-dimensional dynamics were estimated via various types of latent state-space models including, for example, Poisson linear dynamic system (PLDS) models. Decoding from low-dimensional dynamics was implemented via point process and Kalman filters coupled in series. We also examined decoding based on a predictive subsampling of the recorded population. In this case, a supervised greedy procedure selected neuronal subsets that optimized decoding performance. When comparing decoding based on predictive subsampling and latent state-space models, the size of the neuronal subset was set to the same number of latent state dimensions. Overall, our findings suggest that information about naturalistic reach kinematics present in the recorded population is preserved in the inferred low-dimensional motor cortex dynamics. Furthermore, decoding based on unsupervised PLDS models may also outperform previous approaches based on direct decoding from the recorded population or on predictive subsampling.

Predicting seizures from local field potentials recorded via intracortical microelectrode arrays.

The need for new therapeutic interventions to treat pharmacologically resistant focal epileptic seizures has led recently to the development of closed-loop systems for seizure control. Once a seizure is predicted/detected by the system, electrical stimulation is delivered to prevent seizure initiation or spread. So far, seizure prediction/detection has been limited to tracking non-invasive electroencephalogram (EEG) or intracranial EEG (iEEG) signals. Here, we examine seizure prediction based on local field potentials (LFPs) from a small neocortical patch recorded via a 10×10 microelectrode array implanted in a patient with focal seizures. We formulate the seizure (ictal) prediction problem in terms of discriminating between interictal and preictal neural activity. Using deep Convolutional Neural Networks (CNNs), we show that periods of preictal activity can be successfully discriminated (80% detection; no false positives) from periods of interictal activity several (2-18) minutes prior to seizure onset. CNN input features consisted of the spectral power of LFP channels (1-second time windows) computed in 50 frequency bands (0-100 Hz; 2 Hz steps). Our preliminary results show that intracortical LFPs may be a promising neural signal for seizure prediction in focal epilepsy.

Latent state-space models for neural decoding.

Ensembles of single-neurons in motor cortex can show strong low-dimensional collective dynamics. In this study, we explore an approach where neural decoding is applied to estimated low-dimensional dynamics instead of to the full recorded neuronal population. A latent state-space model (SSM) approach is used to estimate the low-dimensional neural dynamics from the measured spiking activity in population of neurons. A second state-space model representation is then used to decode kinematics, via a Kalman filter, from the estimated low-dimensional dynamics. The latent SSM-based decoding approach is illustrated on neuronal activity recorded from primary motor cortex in a monkey performing naturalistic 3-D reach and grasp movements. Our analysis show that 3-D reach decoding performance based on estimated low-dimensional dynamics is comparable to the decoding performance based on the full recorded neuronal population.

Sorting and tracking neuronal spikes via simple thresholding.

A fundamental goal in systems neuroscience is to assess the individual as well as the synergistic roles of single neurons in a recorded ensemble as they relate to an observed behavior. A mandatory step to achieve this goal is to sort spikes in an extracellularly recorded mixture that belong to individual neurons through feature extraction and clustering techniques. Here, we propose an approach for approximating the often nonlinear and time varying decision boundaries between spike-derived feature classes based on a simple, yet optimal thresholding mechanism. Because thresholding is a binary classifier, we show that the complex nonlinear decision boundaries required for spike class discrimination can be achieved by adequately fusing a set of weak binary classifiers. The thresholds for these binary classifiers are adaptively estimated through a learning algorithm that maximizes the separability between the sparsely represented classes. Based on our previous work, the approach substantially reduces the computational complexity of extracting, aligning and sorting multiple single unit activity early in the data stream. Here, we also show its ability to track changes in spike features over extended periods of time, making it highly suitable for basic neuroscience studies as well as for implementation in miniaturized, fully implantable electronics in brain-machine interface applications.

A Fully Implantable, Programmable and Multimodal Neuroprocessor for Wireless, Cortically Controlled Brain-Machine Interface Applications.

Reliability, scalability and clinical viability are of utmost importance in the design of wireless Brain Machine Interface systems (BMIs). This paper reports on the design and implementation of a neuroprocessor for conditioning raw extracellular neural signals recorded through microelectrode arrays chronically implanted in the brain of awake behaving rats. The neuroprocessor design exploits a sparse representation of the neural signals to combat the limited wireless telemetry bandwidth. We demonstrate a multimodal processing capability (monitoring, compression, and spike sorting) inherent in the neuroprocessor to support a wide range of scenarios in real experimental conditions. A wireless transmission link with rate-dependent compression strategy is shown to preserve information fidelity in the neural data. At 32 channels, the neuroprocessor has been fully implemented on a 5mm×5mm nano-FPGA, and the prototyping resulted in 5.19 mW power consumption, bringing its performance within the power-size constraints for clinical use. The optimal design for compression and sorting performance was evaluated for multiple sampling frequencies, wavelet basis choice and power consumption.

Optimal space-time precoding of artificial sensory feedback through mutichannel microstimulation in bi-directional brain-machine interfaces.

Brain-machine interfaces (BMIs) aim to restore lost sensorimotor and cognitive function in subjects with severe neurological deficits. In particular, lost somatosensory function may be restored by artificially evoking patterns of neural activity through microstimulation to induce perception of tactile and proprioceptive feedback to the brain about the state of the limb. Despite an early proof of concept that subjects could learn to discriminate a limited vocabulary of intracortical microstimulation (ICMS) patterns that instruct the subject about the state of the limb, the dynamics of a moving limb are unlikely to be perceived by an arbitrarily-selected, discrete set of static microstimulation patterns, raising questions about the generalization and the scalability of this approach. In this work, we propose a microstimulation protocol intended to activate optimally the ascending somatosensory pathway. The optimization is achieved through a space-time precoder that maximizes the mutual information between the sensory feedback indicating the limb state and the cortical neural response evoked by thalamic microstimulation. Using a simplified multi-input multi-output model of the thalamocortical pathway, we show that this optimal precoder can deliver information more efficiently in the presence of noise compared to suboptimal precoders that do not account for the afferent pathway structure and/or cortical states. These results are expected to enhance the way microstimulation is used to induce somatosensory perception during sensorimotor control of artificial devices or paralyzed limbs.

A programmable and implantable microsystem for multimodal processing of ensemble neural recordings.

Conditioning raw neural signals recorded through microelectrode arrays implanted in the brain is an important first step before information extraction can take place. This paper reports on the design and implementation of a programmable and fully implantable microsystem that fulfills this purpose. The system design builds on our earlier work that relies on a sparse representation of the neural signals to combat the limited telemetry bandwidth when wireless communication with the external world is sought. The system has a multimodal processing capability to support a wide range of scenarios in real experimental conditions. A transmission link with rate-dependent compression and spike sorting strategy is shown to preserve information fidelity. At 32 channels sampled at 25 kHz, the power consumption of the system is 5.19 mW and has been implemented on a 5 mm × 5 mm nano-FPGA, bringing its performance within the implantable power-size constraints for clinical applications.

An implantable VLSI architecture for real time spike sorting in cortically controlled Brain Machine Interfaces.

Brain Machine Interface (BMI) systems demand real-time spike sorting to instantaneously decode the spike trains of simultaneously recorded cortical neurons. Real-time spike sorting, however, requires extensive computational power that is not feasible to implement in implantable BMI architectures, thereby requiring transmission of high-bandwidth raw neural data to an external computer. In this work, we describe a miniaturized, low power, programmable hardware module capable of performing this task within the resource constraints of an implantable chip. The module computes a sparse representation of the spike waveforms followed by "smart" thresholding. This cascade restricts the sparse representation to a subset of projections that preserve the discriminative features of neuron-specific spike waveforms. In addition, it further reduces telemetry bandwidth making it feasible to wirelessly transmit only the important biological information to the outside world, thereby improving the efficiency, practicality and viability of BMI systems in clinical applications.

Compressed and distributed sensing of neuronal activity for real time spike train decoding.

Multivariate point processes are increasingly being used to model neuronal response properties in the cortex. Estimating the conditional intensity functions underlying these processes is important to characterize and decode the firing patterns of cortical neurons. This paper proposes a new approach for estimating these intensity functions directly from a compressed representation of the neurons' extracellular recordings. The approach is based on exploiting a sparse representation of the extracellular spike waveforms, previously demonstrated to yield near-optimal denoising and compression properties. We show that by restricting this sparse representation to a subset of projections that simultaneously preserve features of the spike waveforms in addition to the temporal characteristics of the underlying intensity functions, we can reasonably approximate the instantaneous firing rates of the recorded neurons with variable tuning characteristics across a multitude of time scales. Such feature is highly desirable to detect subtle temporal differences in neuronal firing characteristics from single-trial data. An added advantage of this approach is that it eliminates multiple steps from the typical processing path of neural signals that are customarily performed for instantaneous neural decoding. We demonstrate the decoding performance of the approach using a stochastic cosine tuning model of motor cortical activity during a natural, nongoal-directed 2-D arm movement.

Impact of compressed sensing of motor cortical activity on spike train decoding in Brain Machine Interfaces.

Decoding spike trains is an essential step to translate multiple single unit activity to useful control commands in cortically controlled Brain Machine Interface (BMI) systems. Extracting the spike trains of individual neurons from the recorded mixtures requires spike sorting, a computationally prohibitive step that precludes the development of fully implantable, small size and low power electronics. Previously, we reported on the ability to extract the critical information in these spike trains such as precise spike timing and firing rate of individual neurons using a compressed sensing strategy that overcomes the computational burden of the spike sorting step. Herein, we assess the decoding performance using this method and compare it to the case where classical spike sorting takes place prior to decoding. We use the local average of the sparsely represented data as discriminative features to 'informally' detect and classify spikes in the data stream. We demonstrate that there is a substantial gain in performance assessed under different decoding strategies, while much less computations are needed compared to spike sorting in the traditional sense.