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.

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.

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.

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.

Neural stimulation and recording performance in human sensorimotor cortex over 1500 days.

Objective.Intracortical microstimulation (ICMS) in somatosensory cortex can restore sensation to people with spinal cord injury. However, the recording quality from implanted microelectrodes can degrade over time and limitations in stimulation longevity have been considered a potential barrier to the clinical use of ICMS. Our objective was to evaluate recording stability of intracortical electrodes implanted in the motor and somatosensory cortex of one person. The electrodes in motor cortex had platinum tips and were not stimulated, while the electrodes in somatosensory cortex had sputtered iridium oxide film (SIROF) tips and were stimulated. Additionally, we measured how well ICMS was able to evoke sensations over time.Approach. We implanted microelectrode arrays with SIROF tips in the somatosensory cortex (SIROF-sensory) of a human participant with a cervical spinal cord injury. We regularly stimulated these electrodes to evoke tactile sensations on the hand. Here, we quantify the stability of these electrodes in comparison to non-stimulated platinum electrodes implanted in the motor cortex (platinum-motor) over 1500 days with recorded signal quality and electrode impedances. Additionally, we quantify the stability of ICMS-evoked sensations using detection thresholds.Main results. We found that recording quality, as assessed by the number of electrodes with high-amplitude waveforms (>100µV peak-to-peak), peak-to-peak voltage, noise, and signal-to-noise ratio, decreased over time on SIROF-sensory and platinum-motor electrodes. However, SIROF-sensory electrodes were more likely to continue to record high-amplitude signals than platinum-motor electrodes. Interestingly, the detection thresholds for stimulus-evoked sensations decreased over time from a median of 31.5µA at day 100-10.4µA at day 1500, with the largest changes occurring between day 100 and 500.Significance. These results demonstrate that ICMS in human somatosensory cortex can be provided over long periods of time without deleterious effects on recording or stimulation capabilities. In fact, the sensitivity to stimulation improved over time.

A brain-computer interface that evokes tactile sensations improves robotic arm control.

Prosthetic arms controlled by a brain-computer interface can enable people with tetraplegia to perform functional movements. However, vision provides limited feedback because information about grasping objects is best relayed through tactile feedback. We supplemented vision with tactile percepts evoked using a bidirectional brain-computer interface that records neural activity from the motor cortex and generates tactile sensations through intracortical microstimulation of the somatosensory cortex. This enabled a person with tetraplegia to substantially improve performance with a robotic limb; trial times on a clinical upper-limb assessment were reduced by half, from a median time of 20.9 to 10.2 seconds. Faster times were primarily due to less time spent attempting to grasp objects, revealing that mimicking known biological control principles results in task performance that is closer to able-bodied human abilities.

The Motor Cortex Has Independent Representations for Ipsilateral and Contralateral Arm Movements But Correlated Representations for Grasping.

Motor commands for the arm and hand generally arise from the contralateral motor cortex, where most of the relevant corticospinal tract originates. However, the ipsilateral motor cortex shows activity related to arm movement despite the lack of direct connections. The extent to which the activity related to ipsilateral movement is independent from that related to contralateral movement is unclear based on conflicting conclusions in prior work. Here we investigate bilateral arm and hand movement tasks completed by two human subjects with intracortical microelectrode arrays implanted in the left hand and arm area of the motor cortex. Neural activity was recorded while they attempted to perform arm and hand movements in a virtual environment. This enabled us to quantify the strength and independence of motor cortical activity related to continuous movements of each arm. We also investigated the subjects' ability to control both arms through a brain-computer interface. Through a number of experiments, we found that ipsilateral arm movement was represented independently of, but more weakly than, contralateral arm movement. However, the representation of grasping was correlated between the two hands. This difference between hand and arm representation was unexpected and poses new questions about the different ways the motor cortex controls the hands and arms.

Implicit Grasp Force Representation in Human Motor Cortical Recordings.

In order for brain-computer interface (BCI) systems to maximize functionality, users will need to be able to accurately modulate grasp force to avoid dropping heavy objects while also being able to handle fragile items. We present a case-study consisting of two experiments designed to identify whether intracortical recordings from the motor cortex of a person with tetraplegia could predict intended grasp force. In the first task, we were able classify neural responses to attempted grasps of four objects, each of which required similar grasp kinematics but different implicit grasp force targets, with 69% accuracy. In the second task, the subject attempted to move a virtual robotic arm in space to grasp a simple virtual object. For each trial, the subject was asked to grasp the virtual object with the force appropriate for one of the four objects from the first experiment, with the goal of measuring an implicit representation of grasp force. While the subject knew the grasp force during all phases of the trial, accurate classification was only achieved during active grasping, not while the hand moved to, transported, or released the object. In both tasks, misclassifications were most often to the object with an adjacent force requirement. In addition to the implications for understanding the representation of grasp force in motor cortex, these results are a first step toward creating intelligent algorithms to help BCI users grasp and manipulate a variety of objects that will be encountered in daily life. Clinical Trial Identifier: NCT01894802 https://clinicaltrials.gov/ct2/show/NCT01894802.

Intracortical recording stability in human brain-computer interface users.

OBJECTIVE: Intracortical brain-computer interfaces (BCIs) are being developed to assist people with motor disabilities in communicating and interacting with the world around them. This technology relies on recordings from the primary motor cortex, which may vary from day to day. APPROACH: Here we quantify, in two long-term BCI subjects, the length of time that action potentials from the same neuron, or group of neurons, can be recorded from the motor cortex. MAIN RESULTS: These action potentials are identified by their extracellular waveforms and may change within a single day, although some of these identified units can be identified consistently for weeks and even months. Features of the extracellular waveforms allowed us to predict whether a specific unit was more or less likely to remain stable over a prolonged period. SIGNIFICANCE: A greater understanding of unit stability and instability can aid the development of motor BCIs, where the goal is to maintain a high level of performance despite changes in the recorded population. BCIs should be able to be operated without technician intervention for hours, and hopefully days, to provide the most benefit to the end-users of this technology.

Motor cortical activity changes during neuroprosthetic-controlled object interaction.

Brain-computer interface (BCI) controlled prosthetic arms are being developed to restore function to people with upper-limb paralysis. This work provides an opportunity to analyze human cortical activity during complex tasks. Previously we observed that BCI control became more difficult during interactions with objects, although we did not quantify the neural origins of this phenomena. Here, we investigated how motor cortical activity changed in the presence of an object independently of the kinematics that were being generated using intracortical recordings from two people with tetraplegia. After identifying a population-wide increase in neural firing rates that corresponded with the hand being near an object, we developed an online scaling feature in the BCI system that operated without knowledge of the task. Online scaling increased the ability of two subjects to control the robotic arm when reaching to grasp and transport objects. This work suggests that neural representations of the environment, in this case the presence of an object, are strongly and consistently represented in motor cortex but can be accounted for to improve BCI performance.

Intracortical microstimulation of human somatosensory cortex.

Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation.

Blending of brain-machine interface and vision-guided autonomous robotics improves neuroprosthetic arm performance during grasping.

BACKGROUND: Recent studies have shown that brain-machine interfaces (BMIs) offer great potential for restoring upper limb function. However, grasping objects is a complicated task and the signals extracted from the brain may not always be capable of driving these movements reliably. Vision-guided robotic assistance is one possible way to improve BMI performance. We describe a method of shared control where the user controls a prosthetic arm using a BMI and receives assistance with positioning the hand when it approaches an object. METHODS: Two human subjects with tetraplegia used a robotic arm to complete object transport tasks with and without shared control. The shared control system was designed to provide a balance between BMI-derived intention and computer assistance. An autonomous robotic grasping system identified and tracked objects and defined stable grasp positions for these objects. The system identified when the user intended to interact with an object based on the BMI-controlled movements of the robotic arm. Using shared control, BMI controlled movements and autonomous grasping commands were blended to ensure secure grasps. RESULTS: Both subjects were more successful on object transfer tasks when using shared control compared to BMI control alone. Movements made using shared control were more accurate, more efficient, and less difficult. One participant attempted a task with multiple objects and successfully lifted one of two closely spaced objects in 92 % of trials, demonstrating the potential for users to accurately execute their intention while using shared control. CONCLUSIONS: Integration of BMI control with vision-guided robotic assistance led to improved performance on object transfer tasks. Providing assistance while maintaining generalizability will make BMI systems more attractive to potential users. TRIAL REGISTRATION: NCT01364480 and NCT01894802 .

High-performance neuroprosthetic control by an individual with tetraplegia.

BACKGROUND: Paralysis or amputation of an arm results in the loss of the ability to orient the hand and grasp, manipulate, and carry objects, functions that are essential for activities of daily living. Brain-machine interfaces could provide a solution to restoring many of these lost functions. We therefore tested whether an individual with tetraplegia could rapidly achieve neurological control of a high-performance prosthetic limb using this type of an interface. METHODS: We implanted two 96-channel intracortical microelectrodes in the motor cortex of a 52-year-old individual with tetraplegia. Brain-machine-interface training was done for 13 weeks with the goal of controlling an anthropomorphic prosthetic limb with seven degrees of freedom (three-dimensional translation, three-dimensional orientation, one-dimensional grasping). The participant's ability to control the prosthetic limb was assessed with clinical measures of upper limb function. This study is registered with ClinicalTrials.gov, NCT01364480. FINDINGS: The participant was able to move the prosthetic limb freely in the three-dimensional workspace on the second day of training. After 13 weeks, robust seven-dimensional movements were performed routinely. Mean success rate on target-based reaching tasks was 91·6% (SD 4·4) versus median chance level 6·2% (95% CI 2·0-15·3). Improvements were seen in completion time (decreased from a mean of 148 s [SD 60] to 112 s [6]) and path efficiency (increased from 0·30 [0·04] to 0·38 [0·02]). The participant was also able to use the prosthetic limb to do skilful and coordinated reach and grasp movements that resulted in clinically significant gains in tests of upper limb function. No adverse events were reported. INTERPRETATION: With continued development of neuroprosthetic limbs, individuals with long-term paralysis could recover the natural and intuitive command signals for hand placement, orientation, and reaching, allowing them to perform activities of daily living. FUNDING: Defense Advanced Research Projects Agency, National Institutes of Health, Department of Veterans Affairs, and UPMC Rehabilitation Institute.

Optogenetic-guided cortical plasticity after nerve injury.

Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory interneuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.