Lakshminarayan Srinivasan

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.

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.

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 brains 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.

IterML: A Fast, Robust Algorithm for Estimating Signals With Finite Rate of Innovation

Recently, various methods have emerged for sub- Nyquist sampling and reconstruction of signals with finite rate of innovation (FRI). These methods seek to sample parametric signals at close to their information rate and later reconstruct the parameters of interest. Some proposed reconstruction algorithms are based on annihilating filters and root-finding. Stochastic methods based on Gibbs sampling were subsequently proposed with the intent of improving robustness to noise, but these may run too slowly for some real-time applications. We present a fast maximum-likelihood-based deterministic greedy algorithm, IterML, for reconstructing FRI signals from noisy samples. We show in simulation that it achieves comparable or better performance than previous algorithms at a much lower computational cost. We also uncover a fundamental flaw in the application of MMSE (minimum mean squared error) estimation, a technique employed by some existing methods, to the problem in question.

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.

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.

Feasibility of FRI-based square-wave reconstruction with quantization error and integrator noise

Conventional Nyquist sampling and reconstruction of square waves at a finite rate will always result in aliasing because square waves are not band limited. Based on methods for signals with finite rate of innovation (FRI), generalized Analog Thresholding (gAT-n) is able to sample square waves at a much lower rate under ideal conditions. The target application is efficient, real-time, implantable neurotechnology that extracts spiking neural signals from the brain. This paper studies the effect of integrator noise and quantization error on the accuracy of reconstructed square waves. We explore realistic values for integrator noise and input signal amplitude, using specifications from the Texas Instruments IVC102 integrator chip as a first-pass example because of its readily-available data sheet. ADC resolution is varied from 1 to 16 bits. This analysis indicates that gAT-1 is robust against these hardware non-idealities where gAT-2 degrades less gracefully, which makes gAT-1 a prime target for hardware implementation in a custom integrated circuit.

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 users tuning curves towards this end.

Neural shaping with joint optimization of controller and plant under restricted dynamics

The prototypical brain-computer interface (BCI) algorithm translates brain activity into changes in the states of a computer program, for typing or cursor movement. Most approaches use neural decoding which learns how the user has encoded their intent in their noisy neural signals. Recent adaptive decoders for cursor movement improved BCI performance by modeling the user as a feedback controller; when this model accounts for adaptive control, the neural decoder is termed co-adaptive. This recent collection of control-inspired neural decoding strategies disregards a major antecedent conceptual realization, whereby the user could be induced to adopt an encoding strategy (control policy) such that the encoder-decoder pair (or equivalently, controller-plant pair) is optimal under a desired cost function. We call this alternate conceptual approach neural shaping, in contradistinction to neural decoding. Previous work illuminated the general form of optimal controller-plant pair under a cost representing information gain. For BCI applications requiring the user to issue discrete-valued commands, the information-gain-optimal pair, based on the posterior matching scheme, can be user-friendly. In this paper, we discuss the application of neural shaping to cursor control with continuous-valued states based on continuous-valued user commands. We examine the problem of jointly optimizing controller and plant under quadratic expected cost and restricted linear plant dynamics. This simplification reduces joint controller-plant selection to a static optimization problem, similar to approaches in structural engineering and other areas. This perspective suggests that recent BCI approaches that alternate between adaptive neural decoders and static neural decoders could be local Pareto-optimal, representing a suboptimal iterative-type solution to the optimal joint controller-plant problem.

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.