Error detection and correction in intracortical brain-machine interfaces controlling two finger groups.

Objective.While brain-machine interfaces (BMIs) are promising technologies that could provide direct pathways for controlling the external world and thus regaining motor capabilities, their effectiveness is hampered by decoding errors. Previous research has demonstrated the detection and correction of BMI outcome errors, which occur at the end of trials. Here we focus on continuous detection and correction of BMI execution errors, which occur during real-time movements.Approach.Two adult male rhesus macaques were implanted with Utah arrays in the motor cortex. The monkeys performed single or two-finger group BMI tasks where a Kalman filter decoded binned spiking-band power into intended finger kinematics. Neural activity was analyzed to determine how it depends not only on the kinematics of the fingers, but also on the distance of each finger-group to its target. We developed a method to detect erroneous movements, i.e. consistent movements away from the target, from the same neural activity used by the Kalman filter. Detected errors were corrected by a simple stopping strategy, and the effect on performance was evaluated.Mainresults.First we show that including distance to target explains significantly more variance of the recorded neural activity. Then, for the first time, we demonstrate that neural activity in motor cortex can be used to detect execution errors during BMI controlled movements. Keeping false positive rate below5%, it was possible to achieve mean true positive rate of28.1%online. Despite requiring 200 ms to detect and react to suspected errors, we were able to achieve a significant improvement in task performance via reduced orbiting time of one finger group.Significance.Neural activity recorded in motor cortex for BMI control can be used to detect and correct BMI errors and thus to improve performance. Further improvements may be obtained by enhancing classification and correction strategies.

Shifts in Estimated Preferred Directions During Simulated BMI Experiments With No Adaptation.

Experiments with brain-machine interfaces (BMIs) reveal that the estimated preferred direction (EPD) of cortical motor units may shift following the transition to brain control. However, the cause of those shifts, and in particular, whether they imply neural adaptation, is an open issue. Here we address this question in simulations and theoretical analysis. Simulations are based on the assumption that the brain implements optimal state estimation and feedback control and that cortical motor neurons encode the estimated state and control vector. Our simulations successfully reproduce apparent shifts in EPDs observed in BMI experiments with different BMI filters, including linear, Kalman and re-calibrated Kalman filters, even with no neural adaptation. Theoretical analysis identifies the conditions for reducing those shifts. We demonstrate that simulations that better satisfy those conditions result in smaller shifts in EPDs. We conclude that the observed shifts in EPDs may result from experimental conditions, and in particular correlated velocities or tuning weights, even with no adaptation. Under the above assumptions, we show that if neurons are tuned differently to the estimated velocity, estimated position and control signal, the EPD with respect to actual velocity may not capture the real PD in which the neuron encodes the estimated velocity. Our investigation provides theoretical and simulation tools for better understanding shifts in EPD and BMI experiments.

Error related EEG potentials evoked by visuo-motor rotations.

Electroencephalographic (EEG) correlates of errors, known as error-related potentials (ErrPs), provide promising tools to investigate error processing in the brain and to detect and correct errors induced by brain-computer interfaces (BCIs). Visuo-motor rotation (VMR) is a well-known experimental paradigm to introduce visuo-motor errors that closely mimics directional errors induced by BCIs. However, investigations of ErrPs during VMR experiments are limited and reveals different ErrPs depending on task and synchronization. We conducted VMR experiments with 5 randomly selected conditions (no-rotation, small, ±22.5°, or large, ±45° rotations) to hamper adaptation and facilitate investigation of the effect of error size. We tracked eye movements so EEG was synchronized not only to onset of movement correction (OMC) but also to saccadic movement onset (SMO). Kinematic analysis indicated that maximum deviations from a straight line to the target were larger in trials with large rotations compared to small or no rotations, but there was a large overlap. Thus, we also compared ErrPs generated by trials with different maximum deviations. Our results reveal that trials with large rotations and especially trials with large maximum deviations evoke a significant positive ErrP component. The positive peak appeared 380 msec after SMO and 240 msec after OMC. Furthermore, the positive peak was associated with activity in Brodmann areas 5 and 7, in agreement with other studies and with the role of posterior parietal cortex in reaching movements. The observed ErrP may facilitate further investigation of error processing in the brain and error detection and correction in BCIs.

Policy gradient optimization of controllers for natural dynamic mono-pedal gait.

We have previously suggested a biologically-inspired natural dynamic controller for biped locomotion, which applies torque pulses to the different joints at particular phases of an internal phase variable. The parameters of the controller, including the timing and magnitude of the torque pulses and the dynamics of the phase variable, can be kept constant in open loop or adapted to the environment in closed loop. Here we demonstrate the implementation of this approach to a mono-ped robot and the optimization of the controller parameters to enhance robustness via policy gradient. Policy gradient was applied in simulations rather than the actual robot due to safety and hardware considerations. A grounded action transformation (GAT) was learned and used to facilitate the transfer of the learned policy from simulation to hardware. We demonstrate how GAT improves the match between simulations and experiments and how learning enhances the performance and robustness of the mono-ped robot.

Effects of model inaccuracies on reaching movements with intermittent control.

BACKGROUND AND OBJECTIVES: Human motor control (HMC) has been hypothesized to involve state estimation, prediction and feedback control to overcome noise, delays and disturbances. However, the nature of communication between these processes, and, in particular, whether it is continuous or intermittent, is still an open issue. Depending on the nature of communication, the resulting control is referred to as continuous control (CC) or intermittent control (IC). While standard HMC theories are based on CC, IC has been argued to be more viable since it reduces computational and communication burden and agrees better with some experimental results. However, to be a feasible model for HMC, IC has to cope well with inaccurately modeled plants, which are common in daily life, as when lifting lighter than expected loads. While IC may involve event-driven triggering, it is generally assumed that refractory mechanisms in HMC set a lower limit on the interval between triggers. Hence, we focus on periodic IC, which addresses this lower limit and also facilitates analysis. THEORETICAL METHODS AND RESULTS: Theoretical stability criteria are derived for CC and IC of inaccurately modeled linear time-invariant systems with and without delays. Considering a simple muscle-actuated hand model with inaccurately modeled load, both CC and IC remain stable over most of the investigated range, and may become unstable only when the actual load is much smaller than expected, usually smaller than the minimum set by the actual mass of the forearm and hand. Neither CC nor IC is consistently superior to the other in terms of the range of loads over which the system remains stable. NUMERICAL METHODS AND RESULTS: Numerical simulations of time-delayed reaching movements are presented and analyzed to evaluate the effects of model inaccuracies when the control and observer gains are time-dependent, as is assumed to occur in HMC. Both IC and CC agree qualitatively with previously published experimental results with inaccurately modeled plants. Thus, our study suggests that IC copes well with inaccurately modeled plants and is indeed a viable model for HMC.

Vib-bracelet: a passive absorber for attenuating forearm tremor.

Tremor is a rhythmic, involuntary, oscillatory movement of a limb produced by alternating contractions of reciprocally innervated muscles. More than 4% of the population over 40 years old suffer from tremor. There is no cure for most tremors, and while psychological therapy is sometimes helpful, tremors are usually treated with either medication or invasive surgery including thalamotomy and deep brain stimulation. Both medications and surgery may have adverse effects, and thus, there is a growing interest in developing non-invasive vibration attenuation devices. This paper presents a passive absorber device for attenuating pronation/supination tremor, dubbed Vib-bracelet. It is based on the principles of dynamic vibration absorption and is tuned to the frequency of the tremor. Prototypes were manufactured and tested on a mechanical model of the human forearm. Simulations and experiments demonstrate the efficiency of the device in attenuating vibrations in the range of 4-6 Hz, which is the range of frequency of observed tremor, with maximum amplitude attenuation of 85%.

Attenuating Tremor Using Passive Devices.

Limb tremor is treated with either medication or surgery, both of which may have adverse effects. This paper presents two passive devices for tremor attenuation: One for attenuating pronation/supination tremor of the forearm using a dynamic vibration absorber, and the other for attenuating flexion/extension tremor of the hand using a rotational damper.

Identification of cell proliferation, immune response and cell migration as critical pathways in a prognostic signature for HER2+:ERα- breast cancer.

BACKGROUND: Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS) for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs) versus non-TICs from MMTV-Her2/neu mammary tumors. Here we probed the pathways and genes that underlie the prognostic power of HTICS. METHODS: We used Leave-One Out, Data Combination Test, Gene Set Enrichment Analysis (GSEA), Correlation and Substitution analyses together with Receiver Operating Characteristic (ROC) and Kaplan-Meier survival analysis to identify critical biological pathways within HTICS. Publically available cohorts with gene expression and clinical outcome were used to assess prognosis. NanoString technology was used to detect gene expression in formalin-fixed paraffin embedded (FFPE) tissues. RESULTS: We show that three major biological pathways: cell proliferation, immune response, and cell migration, drive the prognostic power of HTICS, which is further tuned by Homeostatic and Glycan metabolic signalling. A 6-gene minimal Core that retained a significant prognostic power, albeit less than HTICS, also comprised the proliferation/immune/migration pathways. Finally, we developed NanoString probes that could detect expression of HTICS genes and their substitutions in FFPE samples. CONCLUSION: Our results demonstrate that the prognostic power of a signature is driven by the biological processes it monitors, identify cell proliferation, immune response and cell migration as critical pathways for HER2+:ERα- cancer progression, and defines substitutes and Core genes that should facilitate clinical application of HTICS.

Distinct electroencephalographic responses to disturbances and distractors during continuous reaching movements.

Discrepancies between actual and appropriate motor commands, dubbed low-level errors, have been shown to elicit a P300 like component. P300 has been studied extensively in cognitive tasks using, in particular, the three-stimulus oddball paradigm. This paradigm revealed two sub-components, known as P3a and P3b, whose relative contributions depend on saliency and task-relevance, respectively. However, the existence and roles of these sub-components in response to low-level errors are poorly understood. Here we investigated responses to low level errors generated by disturbances - including target and cursor jumps, versus responses to distractors, i.e., environmental changes that are irrelevant to the reaching task. Additionally, we examined the response to matching cursor and target jumps (dual jumps), which generate estimation errors, and are thus considered task relevant disturbances, but do not generate low level errors. We found that a significant P3a-like component is evoked by both disturbances and distractors, whereas the P3b-like component is significantly stronger in response to disturbances than distractors. The P3b-like component appears also in response to dual jumps, even though there are no low level errors. We conclude that disturbances and distractors elicit distinct responses, and that the P3b-like component reflects estimation errors rather than low-level errors.

Minimal feedback to a rhythm generator improves the robustness to slope variations of a compass biped.

In recent years there has been a growing interest in the field of dynamic walking and bio-inspired robots. However, while walking and running on a flat surface have been studied extensively, walking dynamically over terrains with varying slope remains a challenge. Previously we developed an open loop controller based on a central pattern generator (CPG). The controller applied predefined torque patterns to a compass-gait biped, and achieved stable gaits over a limited range of slopes. In this work, this range is greatly extended by applying a once per cycle feedback to the CPG controller. The terrain's slope is measured and used to modify both the CPG frequency and the torque amplitude once per step. A multi-objective optimization algorithm was used to tune the controller parameters for a simulated CB model. The resulting controller successfully traverses terrains with slopes ranging from +7° to -8°, comparable to most slopes found in human constructed environments. Gait stability was verified by computing the linearized Poincaré Map both numerically and analytically.

Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces.

Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

Signal-independent timescale analysis (SITA) and its application for neural coding during reaching and walking.

What are the relevant timescales of neural encoding in the brain? This question is commonly investigated with respect to well-defined stimuli or actions. However, neurons often encode multiple signals, including hidden or internal, which are not experimentally controlled, and thus excluded from such analysis. Here we consider all rate modulations as the signal, and define the rate-modulations signal-to-noise ratio (RM-SNR) as the ratio between the variance of the rate and the variance of the neuronal noise. As the bin-width increases, RM-SNR increases while the update rate decreases. This tradeoff is captured by the ratio of RM-SNR to bin-width, and its variations with the bin-width reveal the timescales of neural activity. Theoretical analysis and simulations elucidate how the interactions between the recovery properties of the unit and the spectral content of the encoded signals shape this ratio and determine the timescales of neural coding. The resulting signal-independent timescale analysis (SITA) is applied to investigate timescales of neural activity recorded from the motor cortex of monkeys during: (i) reaching experiments with Brain-Machine Interface (BMI), and (ii) locomotion experiments at different speeds. Interestingly, the timescales during BMI experiments did not change significantly with the control mode or training. During locomotion, the analysis identified units whose timescale varied consistently with the experimentally controlled speed of walking, though the specific timescale reflected also the recovery properties of the unit. Thus, the proposed method, SITA, characterizes the timescales of neural encoding and how they are affected by the motor task, while accounting for all rate modulations.

Robust Satisficing Linear Regression: performance/robustness trade-off and consistency criterion.

Linear regression quantifies the linear relationship between paired sets of input and output observations. The well known least-squares regression optimizes the performance criterion defined by the residual error, but is highly sensitive to uncertainties or perturbations in the observations. Robust least-squares algorithms have been developed to optimize the worst case performance for a given limit on the level of uncertainty, but they are applicable only when that limit is known. Herein, we present a robust-satisficing approach that maximizes the robustness to uncertainties in the observations, while satisficing a critical sub-optimal level of performance. The method emphasizes the trade-off between performance and robustness, which are inversely correlated. To resolve the resulting trade-off we introduce a new criterion, which assesses the consistency between the observations and the linear model. The proposed criterion determines a unique robust-satisficing regression and reveals the underlying level of uncertainty in the observations with only weak assumptions. These algorithms are demonstrated for the challenging application of linear regression to neural decoding for brain-machine interfaces. The model-consistent robust-satisfying regression provides superior performance for new observations under both similar and different conditions.

Cortical modulations increase in early sessions with brain-machine interface.

BACKGROUND: During planning and execution of reaching movements, the activity of cortical motor neurons is modulated by a diversity of motor, sensory, and cognitive signals. Brain-machine interfaces (BMIs) extract part of these modulations to directly control artificial actuators. However, cortical modulations that emerge in the novel context of operating the BMI are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we analyzed the changes in neuronal modulations that occurred in different cortical motor areas as monkeys learned to use a BMI to control reaching movements. Using spike-train analysis methods we demonstrate that the modulations of the firing-rates of cortical neurons increased abruptly after the monkeys started operating the BMI. Regression analysis revealed that these enhanced modulations were not correlated with the kinematics of the movement. The initial enhancement in firing rate modulations declined gradually with subsequent training in parallel with the improvement in behavioral performance. CONCLUSIONS/SIGNIFICANCE: We conclude that the enhanced modulations are related to computational tasks that are significant especially in novel motor contexts. Although the function and neuronal mechanism of the enhanced cortical modulations are open for further inquiries, we discuss their potential role in processing execution errors and representing corrective or explorative activity. These representations are expected to contribute to the formation of internal models of the external actuator and their decoding may facilitate BMI improvement.

Coordinative structure of manipulative hand-movements facilitates their recognition.

Manipulative hand movements involve coordinated movements of the fingers to manipulate an object within the hand, and are classified as either simultaneous or sequential. Simultaneous hand movements are characterized by single coordinated patterns of digit movements, while sequential hand movements involve sequences of such patterns. Here, we investigate the extent of the coordination among 15 hand-joints during simultaneous hand movements, and demonstrate that it leads to a concise representation that facilitates movement recognition. Principal component analysis (PCA), performed in the 15-dimensional (15-D) joint-space, indicates that the first principal-component captures more than 98% of the variability in individual hand movements. Consequently, the first principal direction provides a 15-D feature-vector that describes the underlying-coordination and can be used for automatic recognition. We evaluated this recognition strategy on a set of nine simultaneous hand-movements using a database of six users, each performing six sessions. A dedicated classifier for each user resulted in recognition rates of 97.0 +/- 4.7% during testing, while a single generic classifier achieved 95.2 +/- 2.5% recognition rates. We conclude that the suggested feature-vector captures the invariant structure of simultaneous hand-movements, facilitates their recognition, and may provide insight into motor planning.

Temporal decoding by phase-locked loops: unique features of circuit-level implementations and their significance for vibrissal information processing.

Rhythmic active touch, such as whisking, evokes a periodic reference spike train along which the timing of a novel stimulus, induced, for example, when the whiskers hit an external object, can be interpreted. Previous work supports the hypothesis that the whisking-induced spike train entrains a neural implementation of a phase-locked loop (NPLL) in the vibrissal system. Here we extend this work and explore how the entrained NPLL decodes the delay of the novel, contact-induced stimulus and facilitates object localization. We consider two implementations of NPLLs, which are based on a single neuron or a neural circuit, respectively, and evaluate the resulting temporal decoding capabilities. Depending on the structure of the NPLL, it can lock in either a phase- or co-phase-sensitive mode, which is sensitive to the timing of the input with respect to the beginning of either the current or the next cycle, respectively. The co-phase-sensitive mode is shown to be unique to circuit-based NPLLs. Concentrating on temporal decoding in the vibrissal system of rats, we conclude that both the nature of the information processing task and the response characteristics suggest that the computation is sensitive to the co-phase. Consequently, we suggest that the underlying thalamocortical loop should implement a circuit-based NPLL.

Cortical ensemble adaptation to represent velocity of an artificial actuator controlled by a brain-machine interface.

Monkeys can learn to directly control the movements of an artificial actuator by using a brain-machine interface (BMI) driven by the activity of a sample of cortical neurons. Eventually, they can do so without moving their limbs. Neuronal adaptations underlying the transition from control of the limb to control of the actuator are poorly understood. Here, we show that rapid modifications in neuronal representation of velocity of the hand and actuator occur in multiple cortical areas during the operation of a BMI. Initially, monkeys controlled the actuator by moving a hand-held pole. During this period, the BMI was trained to predict the actuator velocity. As the monkeys started using their cortical activity to control the actuator, the activity of individual neurons and neuronal populations became less representative of the animal's hand movements while representing the movements of the actuator. As a result of this adaptation, the animals could eventually stop moving their hands yet continue to control the actuator. These results show that, during BMI control, cortical ensembles represent behaviorally significant motor parameters, even if these are not associated with movements of the animal's own limb.