A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Motor cortex retains and reorients neural dynamics during motor imagery.

The most prominent characteristic of motor cortex is its activation during movement execution, but it is also active when we simply imagine movements in the absence of actual motor output. Despite decades of behavioural and imaging studies, it is unknown how the specific activity patterns and temporal dynamics in motor cortex during covert motor imagery relate to those during motor execution. Here we recorded intracortical activity from the motor cortex of two people who retain some residual wrist function following incomplete spinal cord injury as they performed both actual and imagined isometric wrist extensions. We found that we could decompose the population activity into three orthogonal subspaces, where one was similarly active during both action and imagery, and the others were active only during a single task type-action or imagery. Although they inhabited orthogonal neural dimensions, the action-unique and imagery-unique subspaces contained a strikingly similar set of dynamic features. Our results suggest that during motor imagery, motor cortex maintains the same overall population dynamics as during execution by reorienting the components related to motor output and/or feedback into a unique, output-null imagery subspace.

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.

Benefits of sharing neurophysiology data from the BRAIN Initiative Research Opportunities in Humans Consortium.

Sharing human brain data can yield scientific benefits, but because of various disincentives, only a fraction of these data is currently shared. We profile three successful data-sharing experiences from the NIH BRAIN Initiative Research Opportunities in Humans (ROH) Consortium and demonstrate benefits to data producers and to users.

Neural Data Transformer 2: Multi-context Pretraining for Neural Spiking Activity.

The neural population spiking activity recorded by intracortical brain-computer interfaces (iBCIs) contain rich structure. Current models of such spiking activity are largely prepared for individual experimental contexts, restricting data volume to that collectable within a single session and limiting the effectiveness of deep neural networks (DNNs). The purported challenge in aggregating neural spiking data is the pervasiveness of context-dependent shifts in the neural data distributions. However, large scale unsupervised pretraining by nature spans heterogeneous data, and has proven to be a fundamental recipe for successful representation learning across deep learning. We thus develop Neural Data Transformer 2 (NDT2), a spatiotemporal Transformer for neural spiking activity, and demonstrate that pretraining can leverage motor BCI datasets that span sessions, subjects, and experimental tasks. NDT2 enables rapid adaptation to novel contexts in downstream decoding tasks and opens the path to deployment of pretrained DNNs for iBCI control. Code: https://github.com/joel99/context_general_bci.

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.

Force oscillations underlying precision grip in humans with lesioned corticospinal tracts.

Stability of precision grip depends on the ability to regulate forces applied by the digits. Increased frequency composition and temporal irregularity of oscillations in the force signal are associated with enhanced force stability, which is thought to result from increased voluntary drive along the corticospinal tract (CST). There is limited knowledge of how these oscillations in force output are regulated in the context of dexterous hand movements like precision grip, which are often impaired by CST damage due to stroke. The extent of residual CST volume descending from primary motor cortex may help explain the ability to modulate force oscillations at higher frequencies. Here, stroke survivors with longstanding hand impairment (n = 17) and neurologically-intact controls (n = 14) performed a precision grip task requiring dynamic and isometric muscle contractions to scale and stabilize forces exerted on a sensor by the index finger and thumb. Diffusion spectrum imaging was used to quantify total white matter volume within the residual and intact CSTs of stroke survivors (n = 12) and CSTs of controls (n = 14). White matter volumes within the infarct region and an analogous portion of overlap with the CST, mirrored onto the intact side, were also quantified in stroke survivors. We found reduced ability to stabilize force and more restricted frequency ranges in force oscillations of stroke survivors relative to controls; though, more broadband, irregular output was strongly related to force-stabilizing ability in both groups. The frequency composition and temporal irregularity of force oscillations observed in stroke survivors did not correlate with maximal precision grip force, suggesting that it is not directly related to impaired force-generating capacity. The ratio of residual to intact CST volumes contained within infarct and mirrored compartments was associated with more broadband, irregular force oscillations in stroke survivors. Our findings provide insight into granular aspects of dexterity altered by corticospinal damage and supply preliminary evidence to support that the ability to modulate force oscillations at higher frequencies is explained, at least in part, by residual CST volume in stroke survivors.

Propagating motor cortical patterns of excitability are ubiquitous across human and non-human primate movement initiation.

A spatiotemporal pattern of excitability propagates across the primary motor cortex prior to the onset of a reaching movement in non-human primates. If this pattern is a necessary component of voluntary movement initiation, it should be present across a variety of motor tasks, end-effectors, and even species. Here, we show that propagating patterns of excitability occur during the initiation of precision grip force and tongue protrusion in non-human primates, and even isometric wrist extension in a human participant. In all tasks, the directions of propagation across the cortical sheet were bimodally distributed across trials with modes oriented roughly opposite to one another. Propagation speed was unimodally distributed with similar mean speeds across tasks and species. Additionally, propagation direction and speed did not vary systematically with any behavioral measures except response times indicating that this propagating pattern is invariant to kinematic or kinetic details and may be a generic movement initiation signal.

Lifting as we climb: Experiences and recommendations from women in neural engineering.

Neural engineering is an emerging and multidisciplinary field in which engineering approaches are applied to neuroscience problems. Women are underrepresented in engineering fields, and indeed in science, technology, engineering, and mathematics (STEM) fields generally. Underrepresentation of women is particularly notable at later academic career stages, suggesting that even though women are interested in the field, barriers exist that ultimately cause them to leave. Here, we investigate many of the obstacles to women's success in the field of neural engineering and provide recommendations and materials to overcome them. We conducted a review of the literature from the past 15 years regarding the experiences of women in academic careers, as well as reports on the number of women in fields closely related to neural engineering from the National Science Foundation (NSF) and the American Society for Engineering Education (ASEE). Additionally, we interviewed six women in neural engineering who are involved in initiatives and outreach concerning the inclusion and experiences of women in engineering. Throughout the literature and interviews, we identified common themes spanning the role of identity and confidence, professional relationships, career-related hurdles, and personal and professional expectations. We explore each of these themes in detail and provide resources to support the growth of women as they climb within the field of neural engineering.

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.

Motor cortex retains and reorients neural dynamics during motor imagery.

The most prominent role of motor cortex is generating patterns of neural activity that lead to movement, but it is also active when we simply imagine movements in the absence of actual motor output. Despite decades of behavioral and imaging studies, it is unknown how the specific activity patterns and temporal dynamics within motor cortex during covert motor imagery relate to those during motor execution. Here we recorded intracortical activity from the motor cortex of two people with residual wrist function following incomplete spinal cord injury as they performed both actual and imagined isometric wrist extensions. We found that we could decompose the population-level activity into orthogonal subspaces such that one set of components was similarly active during both action and imagery, and others were only active during a single task typeâ€"action or imagery. Although they inhabited orthogonal neural dimensions, the action-unique and imagery-unique subspaces contained a strikingly similar set of dynamical features. Our results suggest that during motor imagery, motor cortex maintains the same overall population dynamics as during execution by recreating the missing components related to motor output and/or feedback within a unique imagery-only subspace.

Amputee, clinician, and regulator perspectives on current and prospective upper extremity prosthetic technologies.

Existing prosthetic technologies for people with upper limb amputation are being adopted at moderate rates. Once fitted for these devices, many upper limb amputees report not using them regularly or at all. The primary aim of this study was to solicit feedback about prosthetic technology and important device design criteria from amputees, clinicians, and device regulators. We compare these perspectives to identify common or divergent priorities. Twenty-one adults with upper limb loss, 35 clinicians, and 3 regulators completed a survey on existing prosthetic technologies and a conceptual sensorimotor prosthesis driven by implanted myoelectric electrodes with sensory feedback via spinal root stimulation. The survey included questions from the Trinity Amputation and Prosthesis Experience Scale, the Disabilities of the Arm, Shoulder, and Hand, and novel questions about technology acceptance and neuroprosthetic design. User and clinician ratings of satisfaction with existing devices were similar. Amputees were most accepting of the proposed sensorimotor prosthesis (75.5% vs clinicians (68.8%), regulators (67.8%)). Stakeholders valued user-centered outcomes like individualized task goals, improved quality of life, device reliability, and user safety; regulators emphasized these last two. The results of this study provide insight into amputee, clinician, and regulator priorities to inform future upper-limb prosthetic design and clinical trial protocol development.

Limb accelerations during sleep are related to measures of strength, sensation, and spasticity among individuals with spinal cord injury.

BACKGROUND: To evaluate the relationship between measures of neuromuscular impairment and limb accelerations (LA) collected during sleep among individuals with chronic spinal cord injury (SCI) to provide evidence of construct and concurrent validity for LA as a clinically meaningful measure. METHODS: The strength (lower extremity motor score), sensation (summed lower limb light touch scores), and spasticity (categorized lower limb Modified Ashworth Scale) were measured from 40 adults with chronic (≥ 1 year) SCI. Demographics, pain, sleep quality, and other covariate or confounding factors were measured using self-report questionnaires. Each participant then wore ActiGraph GT9X Link accelerometers on their ankles and wrist continuously for 1-5 days to measure LA from movements during sleep. Regression models with built-in feature selection were used to determine the most relevant LA features and the association to each measure of impairment. RESULTS: LA features were related to measures of impairment with models explaining 69% and 73% of the variance (R²) in strength and sensation, respectively, and correctly classifying 81.6% (F1-score = 0.814) of the participants into spasticity categories. The most commonly selected LA features included measures of power and frequency (frequency domain), movement direction (correlation between axes), consistency between movements (relation to recent movements), and wavelet energy (signal characteristics). Rolling speed (change in angle of inclination) and movement smoothness (median crossings) were uniquely associated with strength. When LA features were included, an increase of 72% and 222% of the variance was explained for strength and sensation scores, respectively, and there was a 34% increase in spasticity classification accuracy compared to models containing only covariate features such as demographics, sleep quality, and pain. CONCLUSION: LA features have shown evidence of having construct and concurrent validity, thus demonstrating that LA are a clinically-relevant measure related to lower limb strength, sensation, and spasticity after SCI. LA may be useful as a more detailed measure of impairment for applications such as clinical prediction models for ambulation.

Closed-loop stimulation of lateral cervical spinal cord in upper-limb amputees to enable sensory discrimination: a case study.

Modern myoelectric prosthetic hands have multiple independently controllable degrees of freedom, but require constant visual attention to use effectively. Somatosensory feedback provides information not available through vision alone and is essential for fine motor control of our limbs. Similarly, stimulation of the nervous system can potentially provide artificial somatosensory feedback to reduce the reliance on visual cues to efficiently operate prosthetic devices. We have shown previously that epidural stimulation of the lateral cervical spinal cord can evoke tactile sensations perceived as emanating from the missing arm and hand in people with upper-limb amputation. In this case study, two subjects with upper-limb amputation used this somatotopically-matched tactile feedback to discriminate object size and compliance while controlling a prosthetic hand. With less than 30 min of practice each day, both subjects were able to use artificial somatosensory feedback to perform a subset of the discrimination tasks at a success level well above chance. Subject 1 was consistently more adept at determining object size (74% accuracy; chance: 33%) while Subject 2 achieved a higher accuracy level in determining object compliance (60% accuracy; chance 33%). In each subject, discrimination of the other object property was only slightly above or at chance level suggesting that the task design and stimulation encoding scheme are important determinants of which object property could be reliably identified. Our observations suggest that changes in the intensity of artificial somatosensory feedback provided via spinal cord stimulation can be readily used to infer information about object properties with minimal training.

Ethical commitments, principles, and practices guiding intracranial neuroscientific research in humans.

Leveraging firsthand experience, BRAIN-funded investigators conducting intracranial human neuroscience research propose two fundamental ethical commitments: (1) maintaining the integrity of clinical care and (2) ensuring voluntariness. Principles, practices, and uncertainties related to these commitments are offered for future investigation.

Explant Analysis of Utah Electrode Arrays Implanted in Human Cortex for Brain-Computer-Interfaces.

Brain-computer interfaces are being developed to restore movement for people living with paralysis due to injury or disease. Although the therapeutic potential is great, long-term stability of the interface is critical for widespread clinical implementation. While many factors can affect recording and stimulation performance including electrode material stability and host tissue reaction, these factors have not been investigated in human implants. In this clinical study, we sought to characterize the material integrity and biological tissue encapsulation via explant analysis in an effort to identify factors that influence electrophysiological performance. We examined a total of six Utah arrays explanted from two human participants involved in intracortical BCI studies. Two platinum (Pt) arrays were implanted for 980 days in one participant (P1) and two Pt and two iridium oxide (IrOx) arrays were implanted for 182 days in the second participant (P2). We observed that the recording quality followed a similar trend in all six arrays with an initial increase in peak-to-peak voltage during the first 30-40 days and gradual decline thereafter in P1. Using optical and two-photon microscopy we observed a higher degree of tissue encapsulation on both arrays implanted for longer durations in participant P1. We then used scanning electron microscopy and energy dispersive X-ray spectroscopy to assess material degradation. All measures of material degradation for the Pt arrays were found to be more prominent in the participant with a longer implantation time. Two IrOx arrays were subjected to brief survey stimulations, and one of these arrays showed loss of iridium from most of the stimulated sites. Recording performance appeared to be unaffected by this loss of iridium, suggesting that the adhesion of IrOx coating may have been compromised by the stimulation, but the metal layer did not detach until or after array removal. In summary, both tissue encapsulation and material degradation were more pronounced in the arrays that were implanted for a longer duration. Additionally, these arrays also had lower signal amplitude and impedance. New biomaterial strategies that minimize fibrotic encapsulation and enhance material stability should be developed to achieve high quality recording and stimulation for longer implantation periods.

Sensing and decoding the neural drive to paralyzed muscles during attempted movements of a person with tetraplegia using a sleeve array.

Motor neurons convey information about motor intent that can be extracted and interpreted to control assistive devices. However, most methods for measuring the firing activity of single neurons rely on implanted microelectrodes. Although intracortical brain-computer interfaces (BCIs) have been shown to be safe and effective, the requirement for surgery poses a barrier to widespread use that can be mitigated by instead using noninvasive interfaces. The objective of this study was to evaluate the feasibility of deriving motor control signals from a wearable sensor that can detect residual motor unit activity in paralyzed muscles after chronic cervical spinal cord injury (SCI). Despite generating no observable hand movement, volitional recruitment of motor units below the level of injury was observed across attempted movements of individual fingers and overt wrist and elbow movements. Subgroups of motor units were coactive during flexion or extension phases of the task. Single digit movement intentions were classified offline from the electromyogram (EMG) power [root-mean-square (RMS)] or motor unit firing rates with median classification accuracies >75% in both cases. Simulated online control of a virtual hand was performed with a binary classifier to test feasibility of real-time extraction and decoding of motor units. The online decomposition algorithm extracted motor units in 1.2 ms, and the firing rates predicted the correct digit motion 88 ± 24% of the time. This study provides the first demonstration of a wearable interface for recording and decoding firing rates of motor units below the level of injury in a person with motor complete SCI.NEW & NOTEWORTHY A wearable electrode array and machine learning methods were used to record and decode myoelectric signals and motor unit firing in paralyzed muscles of a person with motor complete tetraplegia. The myoelectric activity and motor unit firing rates were task specific, even in the absence of visible motion, enabling accurate classification of attempted single-digit movements. This wearable system has the potential to enable people with tetraplegia to control assistive devices through movement intent.

Longevity and reliability of chronic unit recordings using the Utah, intracortical multi-electrode arrays.

Objective.Microelectrode arrays are standard tools for conducting chronic electrophysiological experiments, allowing researchers to simultaneously record from large numbers of neurons. Specifically, Utah electrode arrays (UEAs) have been utilized by scientists in many species, including rodents, rhesus macaques, marmosets, and human participants. The field of clinical human brain-computer interfaces currently relies on the UEA as a number of research groups have clearance from the United States Federal Drug Administration (FDA) for this device through the investigational device exemption pathway. Despite its widespread usage in systems neuroscience, few studies have comprehensively evaluated the reliability and signal quality of the Utah array over long periods of time in a large dataset.Approach.We collected and analyzed over 6000 recorded datasets from various cortical areas spanning almost nine years of experiments, totaling 17 rhesus macaques (Macaca mulatta) and 2 human subjects, and 55 separate microelectrode Utah arrays. The scale of this dataset allowed us to evaluate the average life of these arrays, based primarily on the signal-to-noise ratio of each electrode over time.Main results.Using implants in primary motor, premotor, prefrontal, and somatosensory cortices, we found that the average lifespan of available recordings from UEAs was 622 days, although we provide several examples of these UEAs lasting over 1000 days and one up to 9 years; human implants were also shown to last longer than non-human primate implants. We also found that electrode length did not affect longevity and quality, but iridium oxide metallization on the electrode tip exhibited superior yield as compared to platinum metallization.Significance.Understanding longevity and reliability of microelectrode array recordings allows researchers to set expectations and plan experiments accordingly and maximize the amount of high-quality data gathered. Our results suggest that one can expect chronic unit recordings to last at least two years, with the possibility for arrays to last the better part of a decade.