Less is more: selection from a small set of options improves BCI velocity control.

We designed the discrete direction selection (DDS) decoder for intracortical brain computer interface (iBCI) cursor control and showed that it outperformed currently used decoders in a human-operated real-time iBCI simulator and in monkey iBCI use. Unlike virtually all existing decoders that map between neural activity and continuous velocity commands, DDS uses neural activity to select among a small menu of preset cursor velocities. We compared closed-loop cursor control across four visits by each of 48 naïve, able-bodied human subjects using either DDS or one of three common continuous velocity decoders: direct regression with assist (an affine map from neural activity to cursor velocity), ReFIT, and the velocity Kalman Filter. DDS outperformed all three by a substantial margin. Subsequently, a monkey using an iBCI also had substantially better performance with DDS than with the Wiener filter decoder (direct regression decoder that includes time history). Discretizing the decoded velocity with DDS effectively traded high resolution velocity commands for less tortuous and lower noise trajectories, highlighting the potential benefits of simplifying online iBCI control.

De novo motor learning creates structure in neural activity that shapes adaptation.

Animals can quickly adapt learned movements to external perturbations, and their existing motor repertoire likely influences their ease of adaptation. Long-term learning causes lasting changes in neural connectivity, which shapes the activity patterns that can be produced during adaptation. Here, we examined how a neural population's existing activity patterns, acquired through de novo learning, affect subsequent adaptation by modeling motor cortical neural population dynamics with recurrent neural networks. We trained networks on different motor repertoires comprising varying numbers of movements, which they acquired following various learning experiences. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization in the available population activity patterns. This structure facilitated adaptation, but only when the changes imposed by the perturbation were congruent with the organization of the inputs and the structure in neural activity acquired during de novo learning. These results highlight trade-offs in skill acquisition and demonstrate how different learning experiences can shape the geometrical properties of neural population activity and subsequent adaptation.

Topology of surface electromyogram signals: hand gesture decoding on Riemannian manifolds.

Objective. Decoding gestures from the upper limb using noninvasive surface electromyogram (sEMG) signals is of keen interest for the rehabilitation of amputees, artificial supernumerary limb augmentation, gestural control of computers, and virtual/augmented realities. We show that sEMG signals recorded across an array of sensor electrodes in multiple spatial locations around the forearm evince a rich geometric pattern of global motor unit (MU) activity that can be leveraged to distinguish different hand gestures.Approach. We demonstrate a simple technique to analyze spatial patterns of muscle MU activity within a temporal window and show that distinct gestures can be classified in both supervised and unsupervised manners. Specifically, we construct symmetric positive definite covariance matrices to represent the spatial distribution of MU activity in a time window of interest, calculated as pairwise covariance of electrical signals measured across different electrodes.Main results. This allows us to understand and manipulate multivariate sEMG timeseries on a more natural subspace-the Riemannian manifold. Furthermore, it directly addresses signal variability across individuals and sessions, which remains a major challenge in the field. sEMG signals measured at a single electrode lack contextual information such as how various anatomical and physiological factors influence the signals and how their combined effect alters the evident interaction among neighboring muscles.Significance. As we show here, analyzing spatial patterns using covariance matrices on Riemannian manifolds allows us to robustly model complex interactions across spatially distributed MUs and provides a flexible and transparent framework to quantify differences in sEMG signals across individuals. The proposed method is novel in the study of sEMG signals and its performance exceeds the current benchmarks while being computationally efficient.

BRAND: a platform for closed-loop experiments with deep network models.

Objective.Artificial neural networks (ANNs) are state-of-the-art tools for modeling and decoding neural activity, but deploying them in closed-loop experiments with tight timing constraints is challenging due to their limited support in existing real-time frameworks. Researchers need a platform that fully supports high-level languages for running ANNs (e.g. Python and Julia) while maintaining support for languages that are critical for low-latency data acquisition and processing (e.g. C and C++).Approach.To address these needs, we introduce the Backend for Realtime Asynchronous Neural Decoding (BRAND). BRAND comprises Linux processes, termednodes, which communicate with each other in agraphvia streams of data. Its asynchronous design allows for acquisition, control, and analysis to be executed in parallel on streams of data that may operate at different timescales. BRAND uses Redis, an in-memory database, to send data between nodes, which enables fast inter-process communication and supports 54 different programming languages. Thus, developers can easily deploy existing ANN models in BRAND with minimal implementation changes.Main results.In our tests, BRAND achieved <600 microsecond latency between processes when sending large quantities of data (1024 channels of 30 kHz neural data in 1 ms chunks). BRAND runs a brain-computer interface with a recurrent neural network (RNN) decoder with less than 8 ms of latency from neural data input to decoder prediction. In a real-world demonstration of the system, participant T11 in the BrainGate2 clinical trial (ClinicalTrials.gov Identifier: NCT00912041) performed a standard cursor control task, in which 30 kHz signal processing, RNN decoding, task control, and graphics were all executed in BRAND. This system also supports real-time inference with complex latent variable models like Latent Factor Analysis via Dynamical Systems.Significance.By providing a framework that is fast, modular, and language-agnostic, BRAND lowers the barriers to integrating the latest tools in neuroscience and machine learning into closed-loop experiments.

Task-driven neural network models predict neural dynamics of proprioception.

Proprioception tells the brain the state of the body based on distributed sensory neurons. Yet, the principles that govern proprioceptive processing are poorly understood. Here, we employ a task-driven modeling approach to investigate the neural code of proprioceptive neurons in cuneate nucleus (CN) and somatosensory cortex area 2 (S1). We simulated muscle spindle signals through musculoskeletal modeling and generated a large-scale movement repertoire to train neural networks based on 16 hypotheses, each representing different computational goals. We found that the emerging, task-optimized internal representations generalize from synthetic data to predict neural dynamics in CN and S1 of primates. Computational tasks that aim to predict the limb position and velocity were the best at predicting the neural activity in both areas. Since task optimization develops representations that better predict neural activity during active than passive movements, we postulate that neural activity in the CN and S1 is top-down modulated during goal-directed movements.

Electrophysiological study of visual processing in children with cochlear implants.

Electrophysiological studies of congenitally deaf children and adults have reported atypical visual evoked potentials (VEPs) which have been associated with both behavioral enhancements of visual attention as well as poorer performance and outcomes in tests of spoken language speech processing. This pattern has often been interpreted as a maladaptive consequence of early auditory deprivation, whereby a remapping of auditory cortex by the visual system ultimately reduces resources necessary for optimal rehabilitative outcomes of spoken language acquisition and use. Making use of a novel electrophysiological paradigm, we compare VEPs in children with severe to profound congenital deafness who received a cochlear implant(s) prior to 31 months (n = 28) and typically developing age matched controls (n = 28). We observe amplitude enhancements and in some cases latency differences in occipitally expressed P1 and N1 VEP components in CI-using children as well as an early frontal negativity, N1a. We relate these findings to developmental factors such as chronological age and spoken language understanding. We further evaluate whether VEPs are additionally modulated by auditory stimulation. Collectively, these data provide a means to examine the extent to which atypical VEPs are consistent with prior accounts of maladaptive cross-modal plasticity. Our results support a view that VEP changes reflect alterations to visual-sensory attention and saliency mechanisms rather than a re-mapping of auditory cortex. The present data suggests that early auditory deprivation may have temporally prolonged effects on visual system processing even after activation and use of cochlear implant.

Preserved neural dynamics across animals performing similar behaviour.

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex.

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded - in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands - the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger's movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation.

Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation.

From monkeys to humans: observation-basedEMGbrain-computer interface decoders for humans with paralysis.

Objective. Intracortical brain-computer interfaces (iBCIs) aim to enable individuals with paralysis to control the movement of virtual limbs and robotic arms. Because patients' paralysis prevents training a direct neural activity to limb movement decoder, most iBCIs rely on 'observation-based' decoding in which the patient watches a moving cursor while mentally envisioning making the movement. However, this reliance on observed target motion for decoder development precludes its application to the prediction of unobservable motor output like muscle activity. Here, we ask whether recordings of muscle activity from a surrogate individual performing the same movement as the iBCI patient can be used as target for an iBCI decoder.Approach. We test two possible approaches, each using data from a human iBCI user and a monkey, both performing similar motor actions. In one approach, we trained a decoder to predict the electromyographic (EMG) activity of a monkey from neural signals recorded from a human. We then contrast this to a second approach, based on the hypothesis that the low-dimensional 'latent' neural representations of motor behavior, known to be preserved across time for a given behavior, might also be preserved across individuals. We 'transferred' an EMG decoder trained solely on monkey data to the human iBCI user after using Canonical Correlation Analysis to align the human latent signals to those of the monkey.Main results. We found that both direct and transfer decoding approaches allowed accurate EMG predictions between two monkeys and from a monkey to a human.Significance. Our findings suggest that these latent representations of behavior are consistent across animals and even primate species. These methods are an important initial step in the development of iBCI decoders that generate EMG predictions that could serve as signals for a biomimetic decoder controlling motion and impedance of a prosthetic arm, or even muscle force directly through functional electrical stimulation.

BRAND: A platform for closed-loop experiments with deep network models.

Artificial neural networks (ANNs) are state-of-the-art tools for modeling and decoding neural activity, but deploying them in closed-loop experiments with tight timing constraints is challenging due to their limited support in existing real-time frameworks. Researchers need a platform that fully supports high-level languages for running ANNs (e.g., Python and Julia) while maintaining support for languages that are critical for low-latency data acquisition and processing (e.g., C and C++). To address these needs, we introduce the Backend for Realtime Asynchronous Neural Decoding (BRAND). BRAND comprises Linux processes, termed nodes , which communicate with each other in a graph via streams of data. Its asynchronous design allows for acquisition, control, and analysis to be executed in parallel on streams of data that may operate at different timescales. BRAND uses Redis to send data between nodes, which enables fast inter-process communication and supports 54 different programming languages. Thus, developers can easily deploy existing ANN models in BRAND with minimal implementation changes. In our tests, BRAND achieved <600 microsecond latency between processes when sending large quantities of data (1024 channels of 30 kHz neural data in 1-millisecond chunks). BRAND runs a brain-computer interface with a recurrent neural network (RNN) decoder with less than 8 milliseconds of latency from neural data input to decoder prediction. In a real-world demonstration of the system, participant T11 in the BrainGate2 clinical trial performed a standard cursor control task, in which 30 kHz signal processing, RNN decoding, task control, and graphics were all executed in BRAND. This system also supports real-time inference with complex latent variable models like Latent Factor Analysis via Dynamical Systems. By providing a framework that is fast, modular, and language-agnostic, BRAND lowers the barriers to integrating the latest tools in neuroscience and machine learning into closed-loop experiments.

Using adversarial networks to extend brain computer interface decoding accuracy over time.

Existing intracortical brain computer interfaces (iBCIs) transform neural activity into control signals capable of restoring movement to persons with paralysis. However, the accuracy of the 'decoder' at the heart of the iBCI typically degrades over time due to turnover of recorded neurons. To compensate, decoders can be recalibrated, but this requires the user to spend extra time and effort to provide the necessary data, then learn the new dynamics. As the recorded neurons change, one can think of the underlying movement intent signal being expressed in changing coordinates. If a mapping can be computed between the different coordinate systems, it may be possible to stabilize the original decoder's mapping from brain to behavior without recalibration. We previously proposed a method based on Generalized Adversarial Networks (GANs), called 'Adversarial Domain Adaptation Network' (ADAN), which aligns the distributions of latent signals within underlying low-dimensional neural manifolds. However, we tested ADAN on only a very limited dataset. Here we propose a method based on Cycle-Consistent Adversarial Networks (Cycle-GAN), which aligns the distributions of the full-dimensional neural recordings. We tested both Cycle-GAN and ADAN on data from multiple monkeys and behaviors and compared them to a third, quite different method based on Procrustes alignment of axes provided by Factor Analysis. All three methods are unsupervised and require little data, making them practical in real life. Overall, Cycle-GAN had the best performance and was easier to train and more robust than ADAN, making it ideal for stabilizing iBCI systems over time.

Tessellation of artificial touch via microstimulation of human somatosensory cortex.

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant's hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multichannel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

Nonlinear manifolds underlie neural population activity during behaviour.

There is rich variety in the activity of single neurons recorded during behaviour. Yet, these diverse single neuron responses can be well described by relatively few patterns of neural co-modulation. The study of such low-dimensional structure of neural population activity has provided important insights into how the brain generates behaviour. Virtually all of these studies have used linear dimensionality reduction techniques to estimate these population-wide co-modulation patterns, constraining them to a flat "neural manifold". Here, we hypothesised that since neurons have nonlinear responses and make thousands of distributed and recurrent connections that likely amplify such nonlinearities, neural manifolds should be intrinsically nonlinear. Combining neural population recordings from monkey motor cortex, mouse motor cortex, mouse striatum, and human motor cortex, we show that: 1) neural manifolds are intrinsically nonlinear; 2) the degree of their nonlinearity varies across architecturally distinct brain regions; and 3) manifold nonlinearity becomes more evident during complex tasks that require more varied activity patterns. Simulations using recurrent neural network models confirmed the proposed relationship between circuit connectivity and manifold nonlinearity, including the differences across architecturally distinct regions. Thus, neural manifolds underlying the generation of behaviour are inherently nonlinear, and properly accounting for such nonlinearities will be critical as neuroscientists move towards studying numerous brain regions involved in increasingly complex and naturalistic behaviours.

Motor cortex latent dynamics encode arm movement direction and urgency independently.

The fluid movement of an arm is controlled by multiple parameters that can be set independently. Recent studies argue that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independently-specifiable dynamics. Using a task where monkeys made sequential, varied arm movements, we show that independent parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity: each movement's direction by a fixed neural trajectory and its urgency by how quickly that trajectory was traversed. Network models show this latent coding allows the direction and urgency of arm movement to be independently controlled. Our results support a key prediction of the dynamical systems view of motor cortex, but also argue that not all parameters of movement are defined by the initial conditions of those dynamics.

De novo motor learning creates structure in neural activity space that shapes adaptation.

Animals can quickly adapt learned movements in response to external perturbations. Motor adaptation is likely influenced by an animal's existing movement repertoire, but the nature of this influence is unclear. Long-term learning causes lasting changes in neural connectivity which determine the activity patterns that can be produced. Here, we sought to understand how a neural population's activity repertoire, acquired through long-term learning, affects short-term adaptation by modeling motor cortical neural population dynamics during de novo learning and subsequent adaptation using recurrent neural networks. We trained these networks on different motor repertoires comprising varying numbers of movements. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization created by the neural population activity patterns corresponding to each movement. This structure facilitated adaptation, but only when small changes in motor output were required, and when the structure of the network inputs, the neural activity space, and the perturbation were congruent. These results highlight trade-offs in skill acquisition and demonstrate how prior experience and external cues during learning can shape the geometrical properties of neural population activity as well as subsequent adaptation.

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands.

Manual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participant's ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

"Unattended, distracting or irrelevant": Theoretical implications of terminological choices in auditory selective attention research.

For seventy years, auditory selective attention research has focused on studying the cognitive mechanisms of prioritizing the processing a 'main' task-relevant stimulus, in the presence of 'other' stimuli. However, a closer look at this body of literature reveals deep empirical inconsistencies and theoretical confusion regarding the extent to which this 'other' stimulus is processed. We argue that many key debates regarding attention arise, at least in part, from inappropriate terminological choices for experimental variables that may not accurately map onto the cognitive constructs they are meant to describe. Here we critically review the more common or disruptive terminological ambiguities, differentiate between methodology-based and theory-derived terms, and unpack the theoretical assumptions underlying different terminological choices. Particularly, we offer an in-depth analysis of the terms 'unattended' and 'distractor' and demonstrate how their use can lead to conflicting theoretical inferences. We also offer a framework for thinking about terminology in a more productive and precise way, in hope of fostering more productive debates and promoting more nuanced and accurate cognitive models of selective attention.

Targeted Modulation of Human Brain Interregional Effective Connectivity With Spike-Timing Dependent Plasticity.

OBJECTIVE: The ability to selectively up- or downregulate interregional brain connectivity would be useful for research and clinical purposes. Toward this aim, cortico-cortical paired associative stimulation (ccPAS) protocols have been developed in which two areas are repeatedly stimulated with a millisecond-level asynchrony. However, ccPAS results in humans using bifocal transcranial magnetic stimulation (TMS) have been variable, and the mechanisms remain unproven. In this study, our goal was to test whether ccPAS mechanism is spike-timing-dependent plasticity (STDP). MATERIALS AND METHODS: Eleven healthy participants received ccPAS to the left primary motor cortex (M1) → right M1 with three different asynchronies (5 milliseconds shorter, equal to, or 5 milliseconds longer than the 9-millisecond transcallosal conduction delay) in separate sessions. To observe the neurophysiological effects, single-pulse TMS was delivered to the left M1 before and after ccPAS while cortico-cortical evoked responses were extracted from the contralateral M1 using source-resolved electroencephalography. RESULTS: Consistent with STDP mechanisms, the effects on synaptic strengths flipped depending on the asynchrony. Further implicating STDP, control experiments suggested that the effects were unidirectional and selective to the targeted connection. CONCLUSION: The results support the idea that ccPAS induces STDP and may selectively up- or downregulate effective connectivity between targeted regions in the human brain.