Neural activity in ventral premotor cortex (PMv) has been associated with the process of matching perceived objects with the motor commands needed to grasp them. It remains unclear how PMv networks can flexibly link percepts of objects affording multiple grasp options into a final desired hand action. Here, we use a relational encoding approach to track the functional state of PMv neuronal ensembles in macaque monkeys through the process of passive viewing, grip planning, and grasping movement execution. We used objects affording multiple possible grip strategies. The task included separate instructed delay periods for object presentation and grip instruction. This approach allowed us to distinguish responses elicited by the visual presentation of the objects from those associated with selecting a given motor plan for grasping. We show that PMv continuously incorporates information related to object shape and grip strategy as it becomes available, revealing a transition from a set of ensemble states initially most closely related to objects, to a new set of ensemble patterns reflecting unique object-grip combinations. These results suggest that PMv dynamically combines percepts, gradually navigating toward activity patterns associated with specific volitional actions, rather than directly mapping perceptual object properties onto categorical grip representations. Our results support the idea that PMv is part of a network that dynamically computes motor plans from perceptual information. Significance Statement: The present work demonstrates that the activity of groups of neurons in primate ventral premotor cortex reflects information related to visually presented objects, as well as the motor strategy used to grasp them, linking individual objects to multiple possible grips. PMv could provide useful control signals for neuroprosthetic assistive devices designed to interact with objects in a flexible way.

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 8-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.

Objective: Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. Approach: We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the excitability and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Main results: Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average ring rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Significance: Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment, and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point-and-click control of a computer interface to an individual with tetraplegia 1000 days after implantation of this sensor.

We present a point-and-click intracortical neural interface system (NIS) that enables humans with tetraplegia to volitionally move a 2D computer cursor in any desired direction on a computer screen, hold it still and click on the area of interest. This direct brain-computer interface extracts both discrete (click) and continuous (cursor velocity) signals from a single small population of neurons in human motor cortex. A key component of this system is a multi-state probabilistic decoding algorithm that simultaneously decodes neural spiking activity and outputs either a click signal or the velocity of the cursor. The algorithm combines a linear classifier, which determines whether the user is intending to click or move the cursor, with a Kalman filter that translates the neural population activity into cursor velocity. We present a paradigm for training the multi-state decoding algorithm using neural activity observed during imagined actions. Two human participants with tetraplegia (paralysis of the four limbs) performed a closed-loop radial target acquisition task using the point-and-click NIS over multiple sessions. We quantified point-and-click performance using various human-computer interaction measurements for pointing devices. We found that participants were able to control the cursor motion accurately and click on specified targets with a small error rate (< 3% in one participant). This study suggests that signals from a small ensemble of motor cortical neurons (~40) can be used for natural point-and-click 2D cursor control of a personal computer.

Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor’s velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding.

Basic neural-prosthetic control of a computer cursor has been recently demonstrated by Hochberg et al. [1] using the BrainGate system (Cyberkinetics Neurotechnology Systems, Inc.). While these results demonstrate the feasibility of intracortically-driven prostheses for humans with paralysis, a practical cursor-based computer interface requires more precise cursor control and the ability to “click” on areas of interest. Here we present a practical point and click device that decodes both continuous states (e.g. cursor kinematics) and discrete states (e.g. click state) from single neural population in human motor cortex. We describe a probabilistic multi-state decoder and the necessary training paradigms that enable point and click cursor control by a human with tetraplegia using an implanted microelectrode array. We present results from multiple recording sessions and quantify the point and click performance.

Article describes a neuromotor prosthesis (NMP), in development at Brown University, that records human brain signals, decodes them, and transforms them into movement commands. An NMP is described as a system consisting of a neural interface, a decoding system, and a user interface, also called an effector; a closed-loop system would be completed by a feedback signal from the effector to the brain. The interface is based on neural spiking, a source of information-rich, rapid, complex control signals from the nervous system. The NMP described, named BrainGate, consists of a match-head sized platform with 100 thread-thin electrodes implanted just into the surface of the motor cortex where commands to move the hand emanate. Neural signals are decoded by a rack of computers that displays the resultant output as the motion of a cursor on a computer monitor. While computer cursor motion represents a form of virtual device control, this same command signal could be routed to a device to command motion of paralyzed muscles or the actions of prosthetic limbs. The researchers’ overall goal is the development of a fully implantable, wireless multi-neuron sensor for broad research, neural prosthetic, and human neurodiagnostic applications.

This review describes the rationale, early stage development, and initial human application of neural interface systems (NISs) for humans with paralysis. NISs are emerging medical devices designed to allowpersonswith paralysis to operate assistive technologies or to reanimatemuscles based upon a command signal that is obtained directly fromthe brain. Such systems require the development of sensors to detect brain signals, decoders to transformneural activity signals into a useful command, and an interface for the user.We review initial pilot trial results of an NIS that is based on an intracortical microelectrode sensor that derives control signals from the motor cortex.We review recent findings showing, first, that neurons engaged by movement intentions persist in motor cortex years after injury or disease to the motor system, and second, that signals derived from motor cortex can be used by persons with paralysis to operate a range of devices. We suggest that, with further development, this form of NIS holds promise as a useful new neurotechnology for those with limited motor function or communication.We also discuss the additional potential for neural sensors to be used in the diagnosis and management of various neurological conditions and as a new way to learn about human brain function.