Signal quality of endovascular electroencephalography.

UNLABELLED: Objective, Approach. A growing number of prototypes for diagnosing and treating neurological and psychiatric diseases are predicated on access to high-quality brain signals, which typically requires surgically opening the skull. Where endovascular navigation previously transformed the treatment of cerebral vascular malformations, we now show that it can provide access to brain signals with substantially higher signal quality than scalp recordings. MAIN RESULTS: While endovascular signals were known to be larger in amplitude than scalp signals, our analysis in rabbits borrows a standard technique from communication theory to show endovascular signals also have up to 100× better signal-to-noise ratio. SIGNIFICANCE: With a viable minimally-invasive path to high-quality brain signals, patients with brain diseases could one day receive potent electroceuticals through the bloodstream, in the course of a brief outpatient procedure.

Generalized analog thresholding for spike acquisition at ultralow sampling rates.

Efficient spike acquisition techniques are needed to bridge the divide from creating large multielectrode arrays (MEA) to achieving whole-cortex electrophysiology. In this paper, we introduce generalized analog thresholding (gAT), which achieves millisecond temporal resolution with sampling rates as low as 10 Hz. Consider the torrent of data from a single 1,000-channel MEA, which would generate more than 3 GB/min using standard 30-kHz Nyquist sampling. Recent neural signal processing methods based on compressive sensing still require Nyquist sampling as a first step and use iterative methods to reconstruct spikes. Analog thresholding (AT) remains the best existing alternative, where spike waveforms are passed through an analog comparator and sampled at 1 kHz, with instant spike reconstruction. By generalizing AT, the new method reduces sampling rates another order of magnitude, detects more than one spike per interval, and reconstructs spike width. Unlike compressive sensing, the new method reveals a simple closed-form solution to achieve instant (noniterative) spike reconstruction. The base method is already robust to hardware nonidealities, including realistic quantization error and integration noise. Because it achieves these considerable specifications using hardware-friendly components like integrators and comparators, generalized AT could translate large-scale MEAs into implantable devices for scientific investigation and medical technology.

Smoothness as a failure mode of Bayesian mixture models in brain-machine interfaces.

Various recursive Bayesian filters based on reach state equations (RSE) have been proposed to convert neural signals into reaching movements in brain-machine interfaces. When the target is known, RSE produce exquisitely smooth trajectories relative to the random walk prior in the basic Kalman filter. More realistically, the target is unknown, and gaze analysis or other side information is expected to provide a discrete set of potential targets. In anticipation of this scenario, various groups have implemented RSE-based mixture (hybrid) models, which define a discrete random variable to represent target identity. While principled, this approach sacrifices the smoothness of RSE with known targets. This paper combines empirical spiking data from primary motor cortex and mathematical analysis to explain this loss in performance. We focus on angular velocity as a meaningful and convenient measure of smoothness. Our results demonstrate that angular velocity in the trajectory is approximately proportional to change in target probability. The constant of proportionality equals the difference in heading between parallel filters from the two most probable targets, suggesting a smoothness benefit to more narrowly spaced targets. Simulation confirms that measures to smooth the data likelihood also improve the smoothness of hybrid trajectories, including increased ensemble size and uniformity in preferred directions. We speculate that closed-loop training or neuronal subset selection could be used to shape the user's tuning curves towards this end.

Dynamic analysis of naive adaptive brain-machine interfaces.

The closed-loop operation of brain-machine interfaces (BMI) provides a context to discover foundational principles behind human-computer interaction, with emerging clinical applications to stroke, neuromuscular diseases, and trauma. In the canonical BMI, a user controls a prosthetic limb through neural signals that are recorded by electrodes and processed by a decoder into limb movements. In laboratory demonstrations with able-bodied test subjects, parameters of the decoder are commonly tuned using training data that include neural signals and corresponding overt arm movements. In the application of BMI to paralysis or amputation, arm movements are not feasible, and imagined movements create weaker, partially unrelated patterns of neural activity. BMI training must begin naive, without access to these prototypical methods for parameter initialization used in most laboratory BMI demonstrations. Naive adaptive BMI refer to a class of methods recently introduced to address this problem. We first identify the basic elements of existing approaches based on adaptive filtering and define a decoder, ReFIT-PPF to represent these existing approaches. We then present Joint RSE, a novel approach that logically extends prior approaches. Using recently developed human- and synthetic-subjects closed-loop BMI simulation platforms, we show that Joint RSE significantly outperforms ReFIT-PPF and nonadaptive (static) decoders. Control experiments demonstrate the critical role of jointly estimating neural parameters and user intent. In addition, we show that nonzero sensorimotor delay in the user significantly degrades ReFIT-PPF but not Joint RSE, owing to differences in the prior on intended velocity. Paradoxically, substantial differences in the nature of sensory feedback between these methods do not contribute to differences in performance between Joint RSE and ReFIT-PPF. Instead, BMI performance improvement is driven by machine learning, which outpaces rates of human learning in the human-subjects simulation platform. In this regime, nuances of error-related feedback to the human user are less relevant to rapid BMI mastery.

Action initiation in the human dorsal anterior cingulate cortex.

The dorsal anterior cingulate cortex (dACC) has previously been implicated in processes that influence action initiation. In humans however, there has been little direct evidence connecting dACC to the temporal onset of actions. We studied reactive behavior in patients undergoing therapeutic bilateral cingulotomy to determine the immediate effects of dACC ablation on action initiation. In a simple reaction task, three patients were instructed to respond to a specific visual cue with the movement of a joystick. Within minutes of dACC ablation, the frequency of false starts increased, where movements occurred prior to presentation of the visual cue. In a decision making task with three separate patients, the ablation effect on action initiation persisted even when action selection was intact. These findings suggest that human dACC influences action initiation, apart from its role in action selection.

Stochastic optimal control as a theory of brain-machine interface operation.

The closed-loop operation of brain-machine interfaces (BMI) provides a framework to study the mechanisms behind neural control through a restricted output channel, with emerging clinical applications to stroke, degenerative disease, and trauma. Despite significant empirically driven improvements in closed-loop BMI systems, a fundamental, experimentally validated theory of closed-loop BMI operation is lacking. Here we propose a compact model based on stochastic optimal control to describe the brain in skillfully operating canonical decoding algorithms. The model produces goal-directed BMI movements with sensory feedback and intrinsically noisy neural output signals. Various experimentally validated phenomena emerge naturally from this model, including performance deterioration with bin width, compensation of biased decoders, and shifts in tuning curves between arm control and BMI control. Analysis of the model provides insight into possible mechanisms underlying these behaviors, with testable predictions. Spike binning may erode performance in part from intrinsic control-dependent constraints, regardless of decoding accuracy. In compensating decoder bias, the brain may incur an energetic cost associated with action potential production. Tuning curve shifts, seen after the mastery of a BMI-based skill, may reflect the brain's implementation of a new closed-loop control policy. The direction and magnitude of tuning curve shifts may be altered by decoder structure, ensemble size, and the costs of closed-loop control. Looking forward, the model provides a framework for the design and simulated testing of an emerging class of BMI algorithms that seek to directly exploit the presence of a human in the loop.

Breaking the fixed-arrival-time restriction in reaching movements of neural prosthetic devices.

We routinely generate reaching arm movements to function independently. For paralyzed users of upper extremity neural prosthetic devices, flexible, high-performance reaching algorithms will be critical to restoring quality-of-life. Previously, algorithms called real-time reach state equations (RSE) were developed to integrate the user's plan and execution-related neural activity to drive reaching movements to arbitrary targets. Preliminary validation under restricted conditions suggested that RSE might yield dramatic performance improvements. Unfortunately, real-world applications of RSE have been impeded because the RSE assumes a fixed, known arrival time. Recent animal-based prototypes attempted to break the fixed-arrival-time assumption by proposing a standard model (SM) that instead restricted the user's movements to a fixed, known set of targets. Here, we leverage general purpose filter design (GPFD) to break both of these critical restrictions, freeing the paralyzed user to make reaching movements to arbitrary target sets with various arrival times and definitive stopping. In silico validation predicts that the new approach, GPFD-RSE, outperforms the SM while offering greater flexibility. We demonstrate the GPFD-RSE against SM in the simulated control of an overactuated 3-D virtual robotic arm with a real-time inverse kinematics engine.

Variable-arrival-time reaching with the brain-machine interface: performance comparison on empirically-derived movements.

Patients with paralysis will one day rely on clinically-available brain-machine interfaces (BMI) to facilitate activities of daily living. As such, the ability to generate dexterous reaching movements remains a prime target of BMI algorithms research. The Bayesian approach to BMI algorithms requires a statistical model to describe reaching movements. To date, available models have either required fixed targets or fixed arrival times, neither of which can be assumed under natural operating conditions. Recently, we described a generative reach model, GPFD-RSE, that simultaneously breaks both restrictions. This method combines the reach state equation (RSE) with General Purpose Filter Design (GPFD). In the following paper, we further compare GPFD-RSE against standard methods in simulated open-loop decoding using empirically-derived movements, as an adjunct to the idealized movements tested previously. Our results indicate that GPFD-RSE continues to outperform standard methods when reconstructing more realistic arm movements in simulation.

Acquisition of action potentials with ultra-low sampling rates.

We introduce finite rate of innovation (FRI) based spike acquisition, a new approach to the sampling of action potentials. Drawing from emerging theory on sampling FRI signals, our process aims to acquire the precise shape and timing of spikes from electrodes with single or multiunit spiking activity using sampling rates of 1000 Hz or less. The key insight is that action potentials are essentially stereotyped pulses that are generated by neurons at a rate limited by an absolute refractory period. We use this insight to push sampling below the Nyquist rate. Our process is a parametric method distinct from compressed sensing (CS). In its full implementation, this process could improve spike-based devices for neuroscience and medicine by reducing energy consumption, computational complexity, and hardware demands.

General-purpose filter design for neural prosthetic devices.

Brain-driven interfaces depend on estimation procedures to convert neural signals to inputs for prosthetic devices that can assist individuals with severe motor deficits. Previous estimation procedures were developed on an application-specific basis. Here we report a coherent estimation framework that unifies these procedures and motivates new applications of prosthetic devices driven by action potentials, local field potentials (LFPs), electrocorticography (ECoG), electroencephalography (EEG), electromyography (EMG), or optical methods. The brain-driven interface is described as a probabilistic relationship between neural activity and components of a prosthetic device that may take on discrete or continuous values. A new estimation procedure is developed for action potentials, and a corresponding procedure is described for field potentials and optical measurements. We test our framework against dominant approaches in an arm reaching task using simulated traces of ensemble spiking activity from primary motor cortex (MI) and a wheelchair navigation task using simulated traces of EEG-band power. Adaptive filtering is incorporated to demonstrate performance under neuron death and discovery. Finally, we characterize performance under model misspecification using physiologically realistic history dependence in MI spiking. These simulated results predict that the unified framework outperforms previous approaches under various conditions, in the control of position and velocity, based on trajectory and endpoint mean squared errors.

A state-space framework for movement control to dynamic goals through brain-driven interfaces.

State-space estimation is a convenient framework for the design of brain-driven interfaces, where neural activity is used to control assistive devices for individuals with severe motor deficits. Recently, state-space approaches were developed to combine goal planning and trajectory-guiding neural activity in the control of reaching movements of an assistive device to static goals. In this paper, we extend these algorithms to allow for goals that may change over the course of the reach. Performance between static and dynamic goal state equations and a standard free movement state equation is compared in simulation. Simulated trials are also used to explore the possibility of incorporating activity from parietal areas that have previously been associated with dynamic goal position. Performance is quantified using mean-square error (MSE) of trajectory estimates. We also demonstrate the use of goal estimate MSE in evaluating algorithms for the control of goal-directed movements. Finally, we propose a framework to combine sensor data and control algorithms along with neural activity and state equations, to coordinate goal-directed movements through brain-driven interfaces.

A state-space analysis for reconstruction of goal-directed movements using neural signals.

The execution of reaching movements involves the coordinated activity of multiple brain regions that relate variously to the desired target and a path of arm states to achieve that target. These arm states may represent positions, velocities, torques, or other quantities. Estimation has been previously applied to neural activity in reconstructing the target separately from the path. However, the target and path are not independent. Because arm movements are limited by finite muscle contractility, knowledge of the target constrains the path of states that leads to the target. In this letter, we derive and illustrate a state equation to capture this basic dependency between target and path. The solution is described for discrete-time linear systems and gaussian increments with known target arrival time. The resulting analysis enables the use of estimation to study how brain regions that relate variously to target and path together specify a trajectory. The corresponding reconstruction procedure may also be useful in brain-driven prosthetic devices to generate control signals for goal-directed movements.