Measuring instability in chronic human intracortical neural recordings towards stable, long-term brain-computer interfaces.

Intracortical brain-computer interfaces (iBCIs) enable people with tetraplegia to gain intuitive cursor control from movement intentions. To translate to practical use, iBCIs should provide reliable performance for extended periods of time. However, performance begins to degrade as the relationship between kinematic intention and recorded neural activity shifts compared to when the decoder was initially trained. In addition to developing decoders to better handle long-term instability, identifying when to recalibrate will also optimize performance. We propose a method to measure instability in neural data without needing to label user intentions. Longitudinal data were analyzed from two BrainGate2 participants with tetraplegia as they used fixed decoders to control a computer cursor spanning 142 days and 28 days, respectively. We demonstrate a measure of instability that correlates with changes in closed-loop cursor performance solely based on the recorded neural activity (Pearson r = 0.93 and 0.72, respectively). This result suggests a strategy to infer online iBCI performance from neural data alone and to determine when recalibration should take place for practical long-term use.

Low frequency independent components: Internal neuromarkers linking cortical LFPs to behavior.

Local field potentials (LFPs) in the primate motor cortex have been shown to reflect information related to volitional movements. However, LFPs are composite signals that receive contributions from multiple neural sources, producing a complex mix of component signals. Using a blind source separation approach, we examined the components of neural activity recorded using multielectrode arrays in motor areas of macaque monkeys during a grasping and lifting task. We found a set of independent components in the low-frequency LFP with high temporal and spatial consistency associated with each task stage. We observed that ICs often arise from electrodes distributed across multiple cortical areas and provide complementary information to external behavioral markers, specifically in task stage detection and trial alignment. Taken together, our results show that it is possible to separate useful independent components of the LFP associated with specific task-related events, potentially representing internal markers of transition between cortical network states.

The Neural Representation of Force across Grasp Types in Motor Cortex of Humans with Tetraplegia.

Intracortical brain-computer interfaces (iBCIs) have the potential to restore hand grasping and object interaction to individuals with tetraplegia. Optimal grasping and object interaction require simultaneous production of both force and grasp outputs. However, since overlapping neural populations are modulated by both parameters, grasp type could affect how well forces are decoded from motor cortex in a closed-loop force iBCI. Therefore, this work quantified the neural representation and offline decoding performance of discrete hand grasps and force levels in two human participants with tetraplegia. Participants attempted to produce three discrete forces (light, medium, hard) using up to five hand grasp configurations. A two-way Welch ANOVA was implemented on multiunit neural features to assess their modulation to force and grasp Demixed principal component analysis (dPCA) was used to assess for population-level tuning to force and grasp and to predict these parameters from neural activity. Three major findings emerged from this work: (1) force information was neurally represented and could be decoded across multiple hand grasps (and, in one participant, across attempted elbow extension as well); (2) grasp type affected force representation within multiunit neural features and offline force classification accuracy; and (3) grasp was classified more accurately and had greater population-level representation than force. These findings suggest that force and grasp have both independent and interacting representations within cortex, and that incorporating force control into real-time iBCI systems is feasible across multiple hand grasps if the decoder also accounts for grasp type.

Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia.

Intracortical brain-computer interfaces (iBCIs) allow people with paralysis to directly control assistive devices using neural activity associated with the intent to move. Realizing the full potential of iBCIs critically depends on continued progress in understanding how different cortical areas contribute to movement control. Here we present the first comparison between neuronal ensemble recordings from the left middle frontal gyrus (MFG) and precentral gyrus (PCG) of a person with tetraplegia using an iBCI. As expected, PCG was more engaged in selecting and generating intended movements than in earlier perceptual stages of action planning. By contrast, MFG displayed movement-related information during the sensorimotor processing steps preceding the appearance of the action plan in PCG, but only when the actions were instructed using auditory cues. These results describe a previously unreported function for neurons in the human left MFG in auditory processing contributing to motor control.

Big brown bats are challenged by acoustically-guided flights through a circular tunnel of hoops.

Mines and caves provide essential roosting places for bats, but often they are obstructed to prevent entry by humans. To allow bats to access their roosts, metal corrugated culvert pipes are sometimes installed. Wildlife surveys indicate, however, that bats may abandon caves having corrugated culvert entrances. Culverts may be confusing to bats due to the complex patterns of echoes returned by the regular, ring-like corrugations. We tested the hypothesis that a circular tunnel composed of successive hoops is difficult for big brown bats (Eptesicus fuscus) to navigate. Experiments challenged bats with flights through a tunnel of round plastic hoops or a corridor flanked left and right by rows of plastic hanging chains. The bats swerved sideways and left the pathway on more flights in the hoop tunnel compared to only rarely in the chain corridor. Even during successful flights through the hoops, bats changed the temporal patterning of their echolocation pulses to compress them into more sonar sound groups. From prior research, this active reaction is an indicator of a perceptually more difficult task. To allow bats access to mines through culverts without affecting their echolocation behavior, smoothing or masking the regular corrugations inside with concrete may be effective.

Neural Representation of Observed, Imagined, and Attempted Grasping Force in Motor Cortex of Individuals with Chronic Tetraplegia.

Hybrid kinetic and kinematic intracortical brain-computer interfaces (iBCIs) have the potential to restore functional grasping and object interaction capabilities in individuals with tetraplegia. This requires an understanding of how kinetic information is represented in neural activity, and how this representation is affected by non-motor parameters such as volitional state (VoS), namely, whether one observes, imagines, or attempts an action. To this end, this work investigates how motor cortical neural activity changes when three human participants with tetraplegia observe, imagine, and attempt to produce three discrete hand grasping forces with the dominant hand. We show that force representation follows the same VoS-related trends as previously shown for directional arm movements; namely, that attempted force production recruits more neural activity compared to observed or imagined force production. Additionally, VoS-modulated neural activity to a greater extent than grasping force. Neural representation of forces was lower than expected, possibly due to compromised somatosensory pathways in individuals with tetraplegia, which have been shown to influence motor cortical activity. Nevertheless, attempted forces (but not always observed or imagined forces) could be decoded significantly above chance, thereby potentially providing relevant information towards the development of a hybrid kinetic and kinematic iBCI.

Watch, Imagine, Attempt: Motor Cortex Single-Unit Activity Reveals Context-Dependent Movement Encoding in Humans With Tetraplegia.

Planning and performing volitional movement engages widespread networks in the human brain, with motor cortex considered critical to the performance of skilled limb actions. Motor cortex is also engaged when actions are observed or imagined, but the manner in which ensembles of neurons represent these volitional states (VoSs) is unknown. Here we provide direct demonstration that observing, imagining or attempting action activates shared neural ensembles in human motor cortex. Two individuals with tetraplegia (due to brainstem stroke or amyotrophic lateral sclerosis, ALS) were verbally instructed to watch, imagine, or attempt reaching actions displayed on a computer screen. Neural activity in the precentral gyrus incorporated information about both cognitive state and movement kinematics; the three conditions presented overlapping but unique, statistically distinct activity patterns. These findings demonstrate that individual neurons in human motor cortex reflect information related to sensory inputs and VoS in addition to movement features, and are a key part of a broader network linking perception and cognition to action.

Spike Train Similarity Space (SSIMS) Method Detects Effects of Obstacle Proximity and Experience on Temporal Patterning of Bat Biosonar.

Bats emit biosonar pulses in complex temporal patterns that change to accommodate dynamic surroundings. Efforts to quantify these patterns have included analyses of inter-pulse intervals, sonar sound groups, and changes in individual signal parameters such as duration or frequency. Here, the similarity in temporal structure between trains of biosonar pulses is assessed. The spike train similarity space (SSIMS) algorithm, originally designed for neural activity pattern analysis, was applied to determine which features of the environment influence temporal patterning of pulses emitted by flying big brown bats, Eptesicus fuscus. In these laboratory experiments, bats flew down a flight corridor through an obstacle array. The corridor varied in width (100, 70, or 40 cm) and shape (straight or curved). Using a relational point-process framework, SSIMS was able to discriminate between echolocation call sequences recorded from flights in each of the corridor widths. SSIMS was also able to tell the difference between pulse trains recorded during flights where corridor shape through the obstacle array matched the previous trials (fixed, or expected) as opposed to those recorded from flights with randomized corridor shape (variable, or unexpected), but only for the flight path shape in which the bats had previous training. The results show that experience influences the temporal patterns with which bats emit their echolocation calls. It is demonstrated that obstacle proximity to the bat affects call patterns more dramatically than flight path shape.

Rapid calibration of an intracortical brain-computer interface for people with tetraplegia.

OBJECTIVE: Brain-computer interfaces (BCIs) can enable individuals with tetraplegia to communicate and control external devices. Though much progress has been made in improving the speed and robustness of neural control provided by intracortical BCIs, little research has been devoted to minimizing the amount of time spent on decoder calibration. APPROACH: We investigated the amount of time users needed to calibrate decoders and achieve performance saturation using two markedly different decoding algorithms: the steady-state Kalman filter, and a novel technique using Gaussian process regression (GP-DKF). MAIN RESULTS: Three people with tetraplegia gained rapid closed-loop neural cursor control and peak, plateaued decoder performance within 3 min of initializing calibration. We also show that a BCI-naïve user (T5) was able to rapidly attain closed-loop neural cursor control with the GP-DKF using self-selected movement imagery on his first-ever day of closed-loop BCI use, acquiring a target 37 s after initiating calibration. SIGNIFICANCE: These results demonstrate the potential for an intracortical BCI to be used immediately after deployment by people with paralysis, without the need for user learning or extensive system calibration.

Dissociation between sustained single-neuron spiking and transient ß-LFP oscillations in primate motor cortex.

Determining the relationship between single-neuron spiking and transient (20 Hz) ß-local field potential (ß-LFP) oscillations is an important step for understanding the role of these oscillations in motor cortex. We show that whereas motor cortex firing rates and beta spiking rhythmicity remain sustained during steady-state movement preparation periods, ß-LFP oscillations emerge, in contrast, as short transient events. Single-neuron mean firing rates within and outside transient ß-LFP events showed no differences, and no consistent correlation was found between the beta oscillation amplitude and firing rates, as was the case for movement- and visual cue-related ß-LFP suppression. Importantly, well-isolated single units featuring beta-rhythmic spiking (43%, 125/292) showed no apparent or only weak phase coupling with the transient ß-LFP oscillations. Similar results were obtained for the population spiking. These findings were common in triple microelectrode array recordings from primary motor (M1), ventral (PMv), and dorsal premotor (PMd) cortices in nonhuman primates during movement preparation. Although beta spiking rhythmicity indicates strong membrane potential fluctuations in the beta band, it does not imply strong phase coupling with ß-LFP oscillations. The observed dissociation points to two different sources of variation in motor cortex ß-LFPs: one that impacts single-neuron spiking dynamics and another related to the generation of mesoscopic ß-LFP signals. Furthermore, our findings indicate that rhythmic spiking and diverse neuronal firing rates, which encode planned actions during movement preparation, may naturally limit the ability of different neuronal populations to strongly phase-couple to a single dominant oscillation frequency, leading to the observed spiking and ß-LFP dissociation.NEW & NOTEWORTHY We show that whereas motor cortex spiking rates and beta (~20 Hz) spiking rhythmicity remain sustained during steady-state movement preparation periods, ß-local field potential (ß-LFP) oscillations emerge, in contrast, as transient events. Furthermore, the ß-LFP phase at which neurons spike drifts: phase coupling is typically weak or absent. This dissociation points to two sources of variation in the level of motor cortex beta: one that impacts single-neuron spiking and another related to the generation of measured mesoscopic ß-LFPs.

Linking Objects to Actions: Encoding of Target Object and Grasping Strategy in Primate Ventral Premotor Cortex.

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.

Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex.

Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

Spike train SIMilarity Space (SSIMS): a framework for single neuron and ensemble data analysis.

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.

Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials.

Neural activity in motor cortex during reach and grasp movements shows modulations in a broad range of signals from single-neuron spiking activity (SA) to various frequency bands in broadband local field potentials (LFPs). In particular, spatiotemporal patterns in multiband LFPs are thought to reflect dendritic integration of local and interareal synaptic inputs, attentional and preparatory processes, and multiunit activity (MUA) related to movement representation in the local motor area. Nevertheless, the relationship between multiband LFPs and SA, and their relationship to movement parameters and their relative value as brain-computer interface (BCI) control signals, remain poorly understood. Also, although this broad range of signals may provide complementary information channels in primary (MI) and ventral premotor (PMv) areas, areal differences in information have not been systematically examined. Here, for the first time, the amount of information in SA and multiband LFPs was compared for MI and PMv by recording from dual 96-multielectrode arrays while monkeys made naturalistic reach and grasp actions. Information was assessed as decoding accuracy for 3D arm end point and grip aperture kinematics based on SA or LFPs in MI and PMv, or combinations of signal types across areas. In contrast with previous studies with ≤16 simultaneous electrodes, here ensembles of >16 units (on average) carried more information than multiband, multichannel LFPs. Furthermore, reach and grasp information added by various LFP frequency bands was not independent from that in SA ensembles but rather typically less than and primarily contained within the latter. Notably, MI and PMv did not show a particular bias toward reach or grasp for this task or for a broad range of signal types. For BCIs, our results indicate that neuronal ensemble spiking is the preferred signal for decoding, while LFPs and combined signals from PMv and MI can add robustness to BCI control.

Relationships among low-frequency local field potentials, spiking activity, and three-dimensional reach and grasp kinematics in primary motor and ventral premotor cortices.

A prominent feature of motor cortex field potentials during movement is a distinctive low-frequency local field potential (lf-LFP) (<4 Hz), referred to as the movement event-related potential (mEP). The lf-LFP appears to be a global signal related to regional synaptic input, but its relationship to nearby output signaled by single unit spiking activity (SUA) or to movement remains to be established. Previous studies comparing information in primary motor cortex (MI) lf-LFPs and SUA in the context of planar reaching tasks concluded that lf-LFPs have more information than spikes about movement. However, the relative performance of these signals was based on a small number of simultaneously recorded channels and units, or for data averaged across sessions, which could miss information of larger-scale spiking populations. Here, we simultaneously recorded LFPs and SUA from two 96-microelectrode arrays implanted in two major motor cortical areas, MI and ventral premotor (PMv), while monkeys freely reached for and grasped objects swinging in front of them. We compared arm end point and grip aperture kinematics' decoding accuracy for lf-LFP and SUA ensembles. The results show that lf-LFPs provide enough information to reconstruct kinematics in both areas with little difference in decoding performance between MI and PMv. Individual lf-LFP channels often provided more accurate decoding of single kinematic variables than any one single unit. However, the decoding performance of the best single unit among the large population usually exceeded that of the best single lf-LFP channel. Furthermore, ensembles of SUA outperformed the pool of lf-LFP channels, in disagreement with the previously reported superiority of lf-LFP decoding. Decoding results suggest that information in lf-LFPs recorded from intracortical arrays may allow the reconstruction of reach and grasp for real-time neuroprosthetic applications, thus potentially supplementing the ability to decode these same features from spiking populations.

Decoding complete reach and grasp actions from local primary motor cortex populations.

How the activity of populations of cortical neurons generates coordinated multijoint actions of the arm, wrist, and hand is poorly understood. This study combined multielectrode recording techniques with full arm motion capture to relate neural activity in primary motor cortex (M1) of macaques (Macaca mulatta) to arm, wrist, and hand postures during movement. We find that the firing rate of individual M1 neurons is typically modulated by the kinematics of multiple joints and that small, local ensembles of M1 neurons contain sufficient information to reconstruct 25 measured joint angles (representing an estimated 10 functionally independent degrees of freedom). Beyond showing that the spiking patterns of local M1 ensembles represent a rich set of naturalistic movements involving the entire upper limb, the results also suggest that achieving high-dimensional reach and grasp actions with neuroprosthetic devices may be possible using small intracortical arrays like those already being tested in human pilot clinical trials.