Jeffrey M. Weiss

Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury. In this early feasibility clinical trial (NCT01894802), we evaluated the safety, efficacy, and longevity of ICMS because there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. ICMS was delivered to five participants with spinal cord injury who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann's area 1. Across implant durations spanning 2 to 10 years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. More than 168 million ICMS pulses were delivered across a combined implant duration of 27 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3 to 25 events across participants). ICMS detection thresholds increased slowly over time (about 3.5 microamperes per year), but 64 ± 13% of the electrodes still reliably evoked tactile sensations (about 21% decrease in functional electrodes), including 60% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Delivering ICMS to the somatosensory cortex was safe and effective, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration.

Intracortical brain-computer interfaces (BCIs) are used to decode motor intent from neural population activity; their main clinical application is to restore function for individuals with motor or communication deficits. However, when trying to reconstruct movement trajectories, such as in computer cursor control, even state-of-the-art decoders fall short of able-bodied performance during online BCI control. This calls for alternative approaches to improve the usability of motor BCIs. Here, we leveraged an error signal, i.e. a neural correlate of faulty motor control that can be detected from neural activity. By detecting this error signal in parallel to performing movement decoding, it is possible to perform error modulation, i.e. real-time error detection and correction during a closed-loop motor BCI task. We analyzed data from four individuals with upper limb impairment due to cervical spinal cord injury who each used an intracortical BCI to perform a continuous cursor control task with visual feedback. A classifier was trained to detect the error signal and was used to perform online error detection during BCI control to limit ongoing errors (defined as movement of the controller away from its target) without requiring any specific action from the participants. Our contribution is three-fold. First, we show that the error signal has a pre-error component. Cortical activity was already significantly modulated before the onset of the kinematically-defined error, theoretically allowing for earlier detection. Second, we show that error modulation significantly improves performance during online BCI control of cursor kinematics. Finally, we show that the error signal can be robustly leveraged across contexts, as error modulation improves performance in more complex motor tasks (involving for instance grasp and drag actions) or other environments without task-specific calibration. Overall, our results suggest that the error signal can be robustly disentangled from motor intent in cortical activity, and that even a simple linear classifier can enable error modulation in parallel to a continuous kinematic decoder, yielding more reliable and accurate BCI control.

Background: Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury (SCI). In this early-feasibility clinical trial, we evaluate the safety, efficacy, and longevity of ICMS as there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. Methods: ICMS was delivered to five participants with SCI who were each implanted with two Blackrock NeuroPort microelectrode arrays in the hand representation of Brodmann’s Area 1. Across implant durations spanning two to ten years, we measured single-electrode detection thresholds, projected fields, quality reports, and electrode health characteristics. ICMS-related adverse events were documented throughout. Results: Over 168 million ICMS pulses were delivered across a combined implant duration of 24 years without any serious adverse events or direct negative effects on electrode health. ICMS consistently evoked sensations localized to the hand. Rarely, sensations persisted for brief periods after stimulation offset (3–25 events across participants). ICMS detection thresholds increased slowly over time (∼3.5 μA/year), but 62±15% of the electrodes still reliably evoke tactile sensations (∼25% decrease in functional electrodes), including 55% of the electrodes after 10 years in one participant. The quality and projected field coverage of ICMS-evoked sensations were both consistent. Conclusions: Delivering ICMS to somatosensory cortex was safe and reliable, consistently evoking informative somatosensory percepts as long as 10 years, demonstrating the clinical promise of ICMS for sensory restoration. (Funded by NIH; ClinicalTrials.gov: NCT01894802 ).

Tactile feedback from brain-controlled bionic hands can be partially restored via intracortical microstimulation (ICMS) of the primary somatosensory cortex. In ICMS, the location of percepts depends on the electrode’s location and the percept intensity depends on the stimulation frequency and amplitude. Sensors on a bionic hand can thus be linked to somatotopically appropriate electrodes, and the contact force of each sensor can be used to determine the amplitude of a stimulus. Here we report a systematic investigation of the localization and intensity of ICMS-evoked percepts in three participants with cervical spinal cord injury. A retrospective analysis of projected fields showed that they were typically composed of a focal hotspot with diffuse borders, arrayed somatotopically in keeping with their underlying receptive fields and stable throughout the duration of the study. When testing the participants’ ability to rapidly localize a single ICMS presentation, individual electrodes typically evoked only weak sensations, making object localization and discrimination difficult. However, overlapping projected fields from multiple electrodes produced more localizable and intense sensations and allowed for a more precise use of a bionic hand.

A bstract: 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.

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.

Objective. Intracortical brain–computer interfaces (iBCI) have the potential to restore independence for individuals with significant motor or communication impairments. One of the most realistic avenues for clinical translation of iBCI technology is enabling control of a computer cursor—i.e. movement-related neural activity is interpreted (decoded) and used to drive cursor function. Here we aim to improve cursor click decoding to allow for both point-and-click and click-and-drag control. Approach. Using chronic microelectrode arrays implanted in the motor cortex of two participants with tetraplegia, we identified prominent neural responses related to attempted hand grasp. We then developed a new approach for decoding cursor click (hand grasp) based on the most salient responses. Main results. We found that the population-wide response contained three dominant components related to hand grasp: an onset transient response, a sustained response, and an offset transient response. The transient responses were larger in magnitude—and thus more reliably detected—than the sustained response, and a click decoder based on these transients outperformed the standard approach of binary state classification. Significance. A transient-based approach for identifying hand grasp can provide a high degree of cursor click control for both point-and-click and click-and-drag applications. This generalized click functionality is an important step toward high-performance cursor control and eventual clinical translation of iBCI technology.

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 (>100 µ V 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 31.5 μ A at day 100–10.4 μ A 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.

Microstimulation in the somatosensory cortex can evoke artificial tactile percepts and can be incorporated into bidirectional brain–computer interfaces (BCIs) to restore function after injury or disease. However, little is known about how stimulation parameters themselves affect perception. Here, we stimulated through microelectrode arrays implanted in the somatosensory cortex of two human participants with cervical spinal cord injury and varied the stimulus amplitude, frequency, and train duration. Increasing the amplitude and train duration increased the perceived intensity on all tested electrodes. Surprisingly, we found that increasing the frequency evoked more intense percepts on some electrodes but evoked less-intense percepts on other electrodes. These different frequency–intensity relationships were divided into three groups, which also evoked distinct percept qualities at different stimulus frequencies. Neighboring electrode sites were more likely to belong to the same group. These results support the idea that stimulation frequency directly controls tactile perception and that these different percepts may be related to the organization of somatosensory cortex, which will facilitate principled development of stimulation strategies for bidirectional BCIs.

A boost for brain–computer interfaces: The finely controlled movement of our limbs requires two-way neuronal communication between the brain and the body periphery. This includes afferent information from muscles, joints, and skin, as well as visual feedback to plan, initiate, and execute motor output. In tetraplegia, this neural communication is interrupted in both directions at the level of the spinal cord. Brain–computer interfaces have been developed to produce voluntary motor output controlled by directly recording from brain activity. Flesher et al. added an afferent channel to the brain–computer interface to mimic sensory input from the skin of a hand (see the Perspective by Faisal). The improvements achieved by adding the afferent input were substantial in a battery of motor tasks tested in a human subject. Science , abd0380, this issue p. 831 ; see also abi7262, p. 791