Selective enhancement of low-gamma activity by tACS improves phonemic processing and reading accuracy in dyslexia.

The phonological deficit in dyslexia is associated with altered low-gamma oscillatory function in left auditory cortex, but a causal relationship between oscillatory function and phonemic processing has never been established. After confirming a deficit at 30 Hz with electroencephalography (EEG), we applied 20 minutes of transcranial alternating current stimulation (tACS) to transiently restore this activity in adults with dyslexia. The intervention significantly improved phonological processing and reading accuracy as measured immediately after tACS. The effect occurred selectively for a 30-Hz stimulation in the dyslexia group. Importantly, we observed that the focal intervention over the left auditory cortex also decreased 30-Hz activity in the right superior temporal cortex, resulting in reinstating a left dominance for the oscillatory response. These findings establish a causal role of neural oscillations in phonological processing and offer solid neurophysiological grounds for a potential correction of low-gamma anomalies and for alleviating the phonological deficit in dyslexia.

Volitional control of single-electrode high gamma local field potentials by people with paralysis.

Intracortical brain-computer interfaces (BCIs) can enable individuals to control effectors, such as a computer cursor, by directly decoding the user's movement intentions from action potentials and local field potentials (LFPs) recorded within the motor cortex. However, the accuracy and complexity of effector control achieved with such "biomimetic" BCIs will depend on the degree to which the intended movements used to elicit control modulate the neural activity. In particular, channels that do not record distinguishable action potentials and only record LFP modulations may be of limited use for BCI control. In contrast, a biofeedback approach may surpass these limitations by letting the participants generate new control signals and learn strategies that improve the volitional control of signals used for effector control. Here, we show that, by using a biofeedback paradigm, three individuals with tetraplegia achieved volitional control of gamma LFPs (40-400 Hz) recorded by a single microelectrode implanted in the precentral gyrus. Control was improved over a pair of consecutive sessions up to 3 days apart. In all but one session, the channel used to achieve control lacked distinguishable action potentials. Our results indicate that biofeedback LFP-based BCIs may potentially contribute to the neural modulation necessary to obtain reliable and useful control of effectors. NEW & NOTEWORTHY Our study demonstrates that people with tetraplegia can volitionally control individual high-gamma local-field potential (LFP) channels recorded from the motor cortex, and that this control can be improved using biofeedback. Motor cortical LFP signals are thought to be both informative and stable intracortical signals and, thus, of importance for future brain-computer interfaces.

Phase reorganization leads to transient ß-LFP spatial wave patterns in motor cortex during steady-state movement preparation.

Previous studies on the origin and properties of spatial patterns in motor cortex ß-local field potential (ß-LFP) oscillations have focused on planar traveling waves. However, it is unclear 1) whether ß-LFP waves are limited to plane waves, or even 2) whether they are propagating waves of excito-excitatory activity, i.e., primarily traveling waves in excitable media; they could reflect, instead, reorganization in the relative phases of transient oscillations at different spatial sites. We addressed these two problems in ß-LFPs recorded via microelectrode arrays implanted in three adjacent motor cortex areas of nonhuman primates during steady-state movement preparation. Our findings are fourfold: 1) ß-LFP wave patterns emerged as transient events, despite stable firing rates of single neurons concurrently recorded during the same periods. 2) ß-LFP waves showed a richer variety of spatial dynamics, including rotating and complex waves. 3) ß-LFP wave patterns showed no characteristic wavelength, presenting instead a range of scales with global zero-lag phase synchrony as a limiting case, features surprising for purely excito-excitatory waves but consistent with waves in coupled oscillator systems. 4) Furthermore, excito-excitatory traveling waves induced by optogenetic stimulation in motor cortex showed, in contrast, a characteristic wavelength and reduced phase synchrony. Overall, ß-LFP wave statistics differed from those of induced traveling waves in excitable media recorded under the same microelectrode array setup. Our findings suggest phase reorganization in neural coupled oscillators contribute significantly to the origin of transient ß-LFP spatial dynamics during preparatory steady states and outline important constraints for spatially extended models of ß-LFP dynamics in motor cortex. NEW & NOTEWORTHY We show that a rich variety of transient ß-local field potential (ß-LFP) wave patterns emerge in motor cortex during preparatory steady states, despite stable neuronal firing rates. Furthermore, unlike optogenetically induced traveling waves, ß-LFP waves showed no characteristic wavelength, presenting instead a range of scales with global phase synchrony as a limiting case. Overall, our statistical analyses suggest that transient phase reorganization in neural coupled oscillators, beyond purely excito-excitatory traveling waves, contribute significantly to the origin of motor cortex ß-LFP wave patterns.

Stable long-term BCI-enabled communication in ALS and locked-in syndrome using LFP signals.

Restoring communication for people with locked-in syndrome remains a challenging clinical problem without a reliable solution. Recent studies have shown that people with paralysis can use brain-computer interfaces (BCIs) based on intracortical spiking activity to efficiently type messages. However, due to neuronal signal instability, most intracortical BCIs have required frequent calibration and continuous assistance of skilled engineers to maintain performance. Here, an individual with locked-in syndrome due to brain stem stroke and an individual with tetraplegia secondary to amyotrophic lateral sclerosis (ALS) used a simple communication BCI based on intracortical local field potentials (LFPs) for 76 and 138 days, respectively, without recalibration and without significant loss of performance. BCI spelling rates of 3.07 and 6.88 correct characters/minute allowed the participants to type messages and write emails. Our results indicate that people with locked-in syndrome could soon use a slow but reliable LFP-based BCI for everyday communication without ongoing intervention from a technician or caregiver. NEW & NOTEWORTHY This study demonstrates, for the first time, stable repeated use of an intracortical brain-computer interface by people with tetraplegia over up to four and a half months. The approach uses local field potentials (LFPs), signals that may be more stable than neuronal action potentials, to decode participants' commands. Throughout the several months of evaluation, the decoder remained unchanged; thus no technical interventions were required to maintain consistent brain-computer interface operation.

Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.

BACKGROUND: People with chronic tetraplegia, due to high-cervical spinal cord injury, can regain limb movements through coordinated electrical stimulation of peripheral muscles and nerves, known as functional electrical stimulation (FES). Users typically command FES systems through other preserved, but unrelated and limited in number, volitional movements (eg, facial muscle activity, head movements, shoulder shrugs). We report the findings of an individual with traumatic high-cervical spinal cord injury who coordinated reaching and grasping movements using his own paralysed arm and hand, reanimated through implanted FES, and commanded using his own cortical signals through an intracortical brain-computer interface (iBCI). METHODS: We recruited a participant into the BrainGate2 clinical trial, an ongoing study that obtains safety information regarding an intracortical neural interface device, and investigates the feasibility of people with tetraplegia controlling assistive devices using their cortical signals. Surgical procedures were performed at University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Study procedures and data analyses were performed at Case Western Reserve University (Cleveland, OH, USA) and the US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center (Cleveland, OH, USA). The study participant was a 53-year-old man with a spinal cord injury (cervical level 4, American Spinal Injury Association Impairment Scale category A). He received two intracortical microelectrode arrays in the hand area of his motor cortex, and 4 months and 9 months later received a total of 36 implanted percutaneous electrodes in his right upper and lower arm to electrically stimulate his hand, elbow, and shoulder muscles. The participant used a motorised mobile arm support for gravitational assistance and to provide humeral abduction and adduction under cortical control. We assessed the participant's ability to cortically command his paralysed arm to perform simple single-joint arm and hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralysed arm with that of a virtual three-dimensional arm. This study is registered with ClinicalTrials.gov, number NCT00912041. FINDINGS: The intracortical implant occurred on Dec 1, 2014, and we are continuing to study the participant. The last session included in this report was Nov 7, 2016. The point-to-point target acquisition sessions began on Oct 8, 2015 (311 days after implant). The participant successfully cortically commanded single-joint and coordinated multi-joint arm movements for point-to-point target acquisitions (80-100% accuracy), using first a virtual arm and second his own arm animated by FES. Using his paralysed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session 463 days after implant) and feed himself (717 days after implant). INTERPRETATION: To our knowledge, this is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoration of reaching and grasping after paralysis. FUNDING: National Institutes of Health, Department of Veterans Affairs.

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm.

Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5 years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.

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.

The science of neural interface systems.

The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.

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.

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.

Cue to action processing in motor cortex populations.

The primary motor cortex (MI) commands motor output after kinematics are planned from goals, thought to occur in a larger premotor network. However, there is a growing body of evidence that MI is involved in processes beyond action generation, and neuronal subpopulations may perform computations related to cue-to-action processing. From multielectrode array recordings in awake behaving Macaca mulatta monkeys, our results suggest that early MI ensemble activity during goal-directed reaches is driven by target information when cues are closely linked in time to action. Single-neuron activity spanned cue presentation to movement, with the earliest responses temporally aligned to cue and the later responses better aligned to arm movements. Population decoding revealed that MI's coding of cue direction evolved temporally, likely going from cue to action generation. We confirmed that a portion of MI activity is related to visual target processing by showing changes in MI activity related to the extinguishing of a continuously pursued visual target. These findings support a view that MI is an integral part of a cue-to-action network for immediate responses to environmental stimuli.

Population interactions between parietal and primary motor cortices during reach.

Neural interactions between parietal area 2/5 and primary motor cortex (M1) were examined to determine the timing and behavioral correlates of cortico-cortical interactions. Neural activity in areas 2/5 and M1 was simultaneously recorded with 96-channel microelectrode arrays in three rhesus monkeys performing a center-out reach task. We introduce a new method to reveal parietal-motor interactions at a population level using partial spike-field coherence (PSFC) between ensembles of neurons in one area and a local field potential (LFP) in another. PSFC reflects the extent of phase locking between spike times and LFP, after removing the coherence between LFPs in the two areas. Spectral analysis of M1 LFP revealed three bands: low, medium, and high, differing in power between movement preparation and performance. We focus on PSFC in the 1-10 Hz band, in which coherence was strongest. PSFC was also present in the 10-40 Hz band during movement preparation in many channels but generally nonsignificant in the 60-200 Hz band. Ensemble PSFC revealed stronger interactions than single cell-LFP pairings. PSFC of area 2/5 ensembles with M1 LFP typically rose around movement onset and peaked ∼500 ms afterward. PSFC was typically stronger for subsets of area 2/5 neurons and M1 LFPs with similar directional bias than for those with opposite bias, indicating that area 2/5 contributes movement direction information. Together with linear prediction of M1 LFP by area 2/5 spiking, the ensemble-LFP pairing approach reveals interactions missed by single neuron-LFP pairing, demonstrating that cortico-cortical communication can be more readily observed at the ensemble level.

Sensors and decoding for intracortical brain computer interfaces.

Intracortical brain computer interfaces (iBCIs) are being developed to enable people to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software that decodes the user's intended movement from those signals. Here, we focus on recent advances in these two areas, placing special attention on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology's capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications.

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.

Somatosensory responses in a human motor cortex.

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications.

Simultaneous reconstruction of continuous hand movements from primary motor and posterior parietal cortex.

Primary motor cortex (MI) and parietal area PE both participate in cortical control of reaching actions, but few studies have been able to directly compare the form of kinematic encoding in the two areas simultaneously during hand tracking movements. To directly compare kinematic coding properties in these two areas under identical behavioral conditions, we recorded simultaneously from two chronically implanted multielectrode arrays in areas MI and PE (or areas 2/5) during performance of a continuous manual tracking task. Monkeys manually pursued a continuously moving target that followed a series of straight-line movement segments, arranged in a sequence where the direction (but not length) of the upcoming segment varied unpredictably as each new segment appeared. Based on recordings from populations of MI (31-143 units) and PE (22-87 units), we compared hand position and velocity reconstructions based on linear filters. We successfully reconstructed hand position and velocity from area PE (mean r (2) = 0.751 for position reconstruction, r (2) = 0.614 for velocity), demonstrating trajectory reconstruction from each area. Combing these populations provided no reconstruction improvements, suggesting that kinematic representations in MI and PE encode overlapping hand movement information, rather than complementary or unique representations. These overlapping representations may reflect the areas' common engagement in a sensorimotor feedback loop for error signals and movement goals, as required by a task with continuous, time-evolving demands and feedback. The similarity of information in both areas suggests that either area might provide a suitable target to obtain control signals for brain computer interface applications.

Interim Safety Profile From the Feasibility Study of the BrainGate Neural Interface System.

BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.

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.

Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

Spelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training.

Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state. Here, we implanted two 64 microelectrode arrays in the supplementary and primary motor cortex of a patient in a completely locked-in state with ALS. The patient modulated neural firing rates based on auditory feedback and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides evidence that brain-based volitional communication is possible even in a completely locked-in state.