First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Efficacy of functional electrical stimulation in rehabilitating patients with foot drop symptoms after stroke and its correlation with somatosensory evoked potentials-a crossover randomised controlled trial.

OBJECTIVE: The connectivity between somatosensory evoked potentials (SEPs) and cortical plasticity remains elusive due to a lack of supporting data. This study investigates changes in pathological latencies and amplitudes of SEPs caused by an acute stroke after 2 weeks of rehabilitation with functional electrical stimulation (FES). Furthermore, changes in SEPs and the efficacy of FES against foot drop (FD) stroke symptoms were correlated using the 10-m walk test and foot-ankle strength. METHODS: A randomised controlled two-period crossover design plus a control group (group C) was designed. Group A (n = 16) was directly treated with FES, while group B (n = 16) was treated after 2 weeks. The untreated control group of 20 healthy adults underwent repeated SEP measurements for evaluation only. RESULTS: The repeated-measures ANOVA showed a decrease in tibial nerve (TN) P40 and N50 latencies in group A after the intervention, followed by a decline in non-paretic TN SEP in latency N50 (p < 0.05). Moreover, compared to groups B and C from baseline to 4 weeks, group A showed a decrease in paretic TN latency P40 and N50 (p < 0.05). An increase in FD strength and a reduction in step cadence in group B (p < 0.05) and a positive tendency in FD strength (p = 0.12) and step cadence (p = 0.08) in group A were observed after the treatment time. The data showed a moderate (r = 0.50-0.70) correlation between non-paretic TN latency N50 and step cadence in groups A and B after the intervention time. CONCLUSION: The FES intervention modified the pathological gait in association with improved SEP afferent feedback. Registered on 25 February 2021 on ClinicalTrials.gov under identifier number: NCT04767360.

Discriminability of multiple cutaneous and proprioceptive hand percepts evoked by intraneural stimulation with Utah slanted electrode arrays in human amputees.

BACKGROUND: Electrical stimulation of residual afferent nerve fibers can evoke sensations from a missing limb after amputation, and bionic arms endowed with artificial sensory feedback have been shown to confer functional and psychological benefits. Here we explore the extent to which artificial sensations can be discriminated based on location, quality, and intensity. METHODS: We implanted Utah Slanted Electrode Arrays (USEAs) in the arm nerves of three transradial amputees and delivered electrical stimulation via different electrodes and frequencies to produce sensations on the missing hand with various locations, qualities, and intensities. Participants performed blind discrimination trials to discriminate among these artificial sensations. RESULTS: Participants successfully discriminated cutaneous and proprioceptive sensations ranging in location, quality and intensity. Performance was significantly greater than chance for all discrimination tasks, including discrimination among up to ten different cutaneous location-intensity combinations (15/30 successes, p < 0.0001) and seven different proprioceptive location-intensity combinations (21/40 successes, p < 0.0001). Variations in the site of stimulation within the nerve, via electrode selection, enabled discrimination among up to five locations and qualities (35/35 successes, p < 0.0001). Variations in the stimulation frequency enabled discrimination among four different intensities at the same location (13/20 successes, p < 0.0005). One participant also discriminated among individual stimulation of two different USEA electrodes, simultaneous stimulation on both electrodes, and interleaved stimulation on both electrodes (20/24 successes, p < 0.0001). CONCLUSION: Electrode location, stimulation frequency, and stimulation pattern can be modulated to evoke functionally discriminable sensations with a range of locations, qualities, and intensities. This rich source of artificial sensory feedback may enhance functional performance and embodiment of bionic arms endowed with a sense of touch.

Intraneural electrical stimulation of median nerve: a simulation study on sensory and motor fascicles.

Neuroprostheses can be an innovative solution to improve quality of life of upper limb amputees. In this framework, the recovery of sensory feedback is a property widely requested by amputee subjects. Neural prostheses are based on neural interfaces that allow delivering direct current stimuli to the nerve fibers. The study of the interaction between the nerve and the electrode is fundamental to investigate activation properties in the nerve. Furthermore, the results could provide useful insight into improve the design of the electrodes and to advance and ameliorate tactile sensations, elicited by these interfaces, obtaining tactile feedback more like natural sensations. This work aims at studying, by means of a FEM Neuron computational model, the axon fibers activation by means of neural stimulation provided through the intraneural electrodes DS-file. Three different types of stimulation waveforms (i.e. biphasic charge balanced stimulus with inter-pulse delay, biphasic charge balanced stimulus without inter-pulse delay, biphasic charge unbalanced stimulus with inter-pulse delay), three different nerve fascicles, i.e. two sensory and one motor fascicle, and ten distances from the electrode in the fascicles, are considered. The efficacy of the stimulation expressed as the percentage of activation of the fibers, and the safety, in terms of current intensity and used waveform, are studied in the previously described different conditions and the results are compared. The obtained results show that: i. stimulating a sensory fascicle with implanted active sites can activate a fascicle close to it, but not all the fascicles belonging to the same nerve. In fact, in the nerve considered in this study, a motor fascicle cannot be activated due to the values of the electrical potential which are too low to activate the fibers; ii. the current intensity necessary to activate fibers increases according to the distance from the source of the stimulus; iii. by using a biphasic charge unbalanced stimulus, the threshold to activate the fibers is lower than using the other tested waveforms. It is an important result because the stimulation is efficient and safer since current intensity is lower than the one used for the other two waveforms.

Sum of phase-shifted sinusoids stimulation prolongs paralyzed muscle output.

Neuroprostheses that activate musculature of the lower extremities can enable standing and movement after paralysis. Current systems are functionally limited by rapid muscle fatigue induced by conventional, non-varying stimulus waveforms. Previous work has shown that sum of phase-shifted sinusoids (SOPS) stimulation, which selectively modulates activation of individual motor unit pools (MUPs) to lower the duty cycle of each while maintaining a high net muscle output, improves joint moment maintenance but introduces greater instability over conventional stimulation. In this case study, implementation of SOPS stimulation with a real-time feedback controller successfully decreased joint moment instability and further prolonged joint moment output with increased stimulation efficiency over open-loop approaches in one participant with spinal cord injury. These findings demonstrate the potential for closed-loop SOPS to improve functionality of neuroprosthetic systems.

Future of Neural Interfaces.

The technological ability to capture electrophysiological activity of populations of cortical neurons through chronic implantable devices has led to significant advancements in the field of brain-computer interfaces. Recent progress in the field has been driven by developments in integrated microelectronics, wireless communications, materials science, and computational neuroscience. Here, we review major device development landmarks in the arena of neural interfaces from FDA-approved clinical systems to prototype head-mounted and fully implantable wireless systems for multi-channel neural recording. Additionally, we provide an outlook toward next-generation, highly miniaturized technologies for minimally invasive, vastly parallel neural interfaces for naturalistic, closed-loop neuroprostheses.

On the design of EEG-based movement decoders for completely paralyzed stroke patients.

BACKGROUND: Brain machine interface (BMI) technology has demonstrated its efficacy for rehabilitation of paralyzed chronic stroke patients. The critical component in BMI-training consists of the associative connection (contingency) between the intention and the feedback provided. However, the relationship between the BMI design and its performance in stroke patients is still an open question. METHODS: In this study we compare different methodologies to design a BMI for rehabilitation and evaluate their effects on movement intention decoding performance. We analyze the data of 37 chronic stroke patients who underwent 4 weeks of BMI intervention with different types of association between their brain activity and the proprioceptive feedback. We simulate the pseudo-online performance that a BMI would have under different conditions, varying: (1) the cortical source of activity (i.e., ipsilesional, contralesional, bihemispheric), (2) the type of spatial filter applied, (3) the EEG frequency band, (4) the type of classifier; and also evaluated the use of residual EMG activity to decode the movement intentions. RESULTS: We observed a significant influence of the different BMI designs on the obtained performances. Our results revealed that using bihemispheric beta activity with a common average reference and an adaptive support vector machine led to the best classification results. Furthermore, the decoding results based on brain activity were significantly higher than those based on muscle activity. CONCLUSIONS: This paper underscores the relevance of the different parameters used to decode movement, using EEG in severely paralyzed stroke patients. We demonstrated significant differences in performance for the different designs, which supports further research that should elucidate if those approaches leading to higher accuracies also induce higher motor recovery in paralyzed stroke patients.

Functional remodeling of subtype-specific markers surrounding implanted neuroprostheses.

Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics. In this study, we investigated whether or not device insertion causes alterations in specific subtypes of these cells. We assessed the expression of both excitatory and inhibitory markers of neurotransmission (vesicular glutamate and GABA transporters, VGLUT1 and VGAT, respectively) surrounding single-shank Michigan-style microelectrode arrays implanted in the motor cortex of adult rats by use of quantitative immunohistochemistry. We found a pronounced shift from significantly elevated VGLUT1 within the initial days following implantation to relatively heightened VGAT by the end of the 4-wk observation period. Unexpectedly, we observed VGAT positivity in a subset of reactive astrocytes during the first week of implantation, indicating heterogeneity in early-responding encapsulating glial cells. We coupled our VGLUT1 data with the evaluation of a second marker of excitatory neurons (CamKiiα); the results closely paralleled each other and underscored a progression from initially heightened to subsequently weakened excitatory tone in the neural tissue proximal to the implanted electrode interface (within 40 µm). Our results provide new evidence for subtype-specific remodeling surrounding brain implants that inform observations of suboptimal integration and performance.NEW & NOTEWORTHY We report novel changes in the local expression of excitatory and inhibitory synaptic markers surrounding microelectrode arrays implanted in the motor cortex of rats, where a progressive shift toward increased inhibitory tone was observed over the 4-wk observation period. The result was driven by declining glutamate transporter expression (VGLUT1) in parallel with increasing GABA transporter expression (VGAT) over time, where a reactive VGAT+ astroglial subtype made an unexpected contribution to our findings.

Neurophysiology and neural engineering: a review.

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight.

Simplification of Visual Rendering in Simulated Prosthetic Vision Facilitates Navigation.

Visual neuroprostheses are still limited and simulated prosthetic vision (SPV) is used to evaluate potential and forthcoming functionality of these implants. SPV has been used to evaluate the minimum requirement on visual neuroprosthetic characteristics to restore various functions such as reading, objects and face recognition, object grasping, etc. Some of these studies focused on obstacle avoidance but only a few investigated orientation or navigation abilities with prosthetic vision. The resolution of current arrays of electrodes is not sufficient to allow navigation tasks without additional processing of the visual input. In this study, we simulated a low resolution array (15 × 18 electrodes, similar to a forthcoming generation of arrays) and evaluated the navigation abilities restored when visual information was processed with various computer vision algorithms to enhance the visual rendering. Three main visual rendering strategies were compared to a control rendering in a wayfinding task within an unknown environment. The control rendering corresponded to a resizing of the original image onto the electrode array size, according to the average brightness of the pixels. In the first rendering strategy, vision distance was limited to 3, 6, or 9 m, respectively. In the second strategy, the rendering was not based on the brightness of the image pixels, but on the distance between the user and the elements in the field of view. In the last rendering strategy, only the edges of the environments were displayed, similar to a wireframe rendering. All the tested renderings, except the 3 m limitation of the viewing distance, improved navigation performance and decreased cognitive load. Interestingly, the distance-based and wireframe renderings also improved the cognitive mapping of the unknown environment. These results show that low resolution implants are usable for wayfinding if specific computer vision algorithms are used to select and display appropriate information regarding the environment.

Reactive stepping with functional neuromuscular stimulation in response to forward-directed perturbations.

BACKGROUND: Implanted motor system neuroprostheses can be effective at increasing personal mobility of persons paralyzed by spinal cord injuries. However, currently available neural stimulation systems for standing employ patterns of constant activation and are unreactive to changing postural demands. METHODS: In this work, we developed a closed-loop controller for detecting forward-directed body disturbances and initiating a stabilizing step in a person with spinal cord injury. Forward-directed pulls at the waist were detected with three body-mounted triaxial accelerometers. A finite state machine was designed and tested to trigger a postural response and apply stimulation to appropriate muscles so as to produce a protective step when the simplified jerk signal exceeded predetermined thresholds. RESULTS: The controller effectively initiated steps for all perturbations with magnitude between 10 and 17.5 s body weight, and initiated a postural response with occasional steps at 5% body weight. For perturbations at 15 and 17.5% body weight, the dynamic responses of the subject exhibited very similar component time periods when compared with able-bodied subjects undergoing similar postural perturbations. Additionally, the reactive step occurred faster for stronger perturbations than for weaker ones (p < .005, unequal varience t-test.) CONCLUSIONS: This research marks progress towards a controller which can improve the safety and independence of persons with spinal cord injury using implanted neuroprostheses for standing.

Real-Time Gait Event Detection Based on Kinematic Data Coupled to a Biomechanical Model.

Real-time detection of multiple stance events, more specifically initial contact (IC), foot flat (FF), heel off (HO), and toe off (TO), could greatly benefit neurorobotic (NR) and neuroprosthetic (NP) control. Three real-time threshold-based algorithms have been developed, detecting the aforementioned events based on kinematic data in combination with a biomechanical model. Data from seven subjects walking at three speeds on an instrumented treadmill were used to validate the presented algorithms, accumulating to a total of 558 steps. The reference for the gait events was obtained using marker and force plate data. All algorithms had excellent precision and no false positives were observed. Timing delays of the presented algorithms were similar to current state-of-the-art algorithms for the detection of IC and TO, whereas smaller delays were achieved for the detection of FF. Our results indicate that, based on their high precision and low delays, these algorithms can be used for the control of an NR/NP, with the exception of the HO event. Kinematic data is used in most NR/NP control schemes and is thus available at no additional cost, resulting in a minimal computational burden. The presented methods can also be applied for screening pathological gait or gait analysis in general in/outside of the laboratory.

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee.

Brain oscillatory signatures of motor tasks.

Noninvasive brain-computer-interfaces (BCI) coupled with prosthetic devices were recently introduced in the rehabilitation of chronic stroke and other disorders of the motor system. These BCI systems and motor rehabilitation in general involve several motor tasks for training. This study investigates the neurophysiological bases of an EEG-oscillation-driven BCI combined with a neuroprosthetic device to define the specific oscillatory signature of the BCI task. Controlling movements of a hand robotic orthosis with motor imagery of the same movement generates sensorimotor rhythm oscillation changes and involves three elements of tasks also used in stroke motor rehabilitation: passive and active movement, motor imagery, and motor intention. We recorded EEG while nine healthy participants performed five different motor tasks consisting of closing and opening of the hand as follows: 1) motor imagery without any external feedback and without overt hand movement, 2) motor imagery that moves the orthosis proportional to the produced brain oscillation change with online proprioceptive and visual feedback of the hand moving through a neuroprosthetic device (BCI condition), 3) passive and 4) active movement of the hand with feedback (seeing and feeling the hand moving), and 5) rest. During the BCI condition, participants received contingent online feedback of the decrease of power of the sensorimotor rhythm, which induced orthosis movement and therefore proprioceptive and visual information from the moving hand. We analyzed brain activity during the five conditions using time-frequency domain bootstrap-based statistical comparisons and Morlet transforms. Activity during rest was used as a reference. Significant contralateral and ipsilateral event-related desynchronization of sensorimotor rhythm was present during all motor tasks, largest in contralateral-postcentral, medio-central, and ipsilateral-precentral areas identifying the ipsilateral precentral cortex as an integral part of motor regulation. Changes in task-specific frequency power compared with rest were similar between motor tasks, and only significant differences in the time course and some narrow specific frequency bands were observed between motor tasks. We identified EEG features representing active and passive proprioception (with and without muscle contraction) and active intention and passive involvement (with and without voluntary effort) differentiating brain oscillations during motor tasks that could substantially support the design of novel motor BCI-based rehabilitation therapies. The BCI task induced significantly different brain activity compared with the other motor tasks, indicating neural processes unique to the use of body actuators control in a BCI context.

Sensory control of normal movement and of movement aided by neural prostheses.

Signals from sensory receptors in muscles and skin enter the central nervous system (CNS), where they contribute to kinaesthesia and the generation of motor commands. Many lines of evidence indicate that sensory input from skin receptors, muscle spindles and Golgi tendon organs play the predominant role in this regard. Yet in spite of over 100 years of research on this topic, some quite fundamental questions remain unresolved. How does the CNS choose to use the ability to control muscle spindle sensitivity during voluntary movements? Do spinal reflexes contribute usefully to load compensation, given that the feedback gain must be quite low to avoid instability? To what extent do signals from skin stretch receptors contribute? This article provides a brief review of various theories, past and present, that address these questions. To what extent has the knowledge gained resulted in clinical applications? Muscles paralyzed as a result of spinal cord injury or stroke can be activated by electrical stimulation delivered by neuroprostheses. In practice, at most two or three sensors can be deployed on the human body, providing only a small fraction of the information supplied by the tens of thousands of sensory receptors in animals. Most of the neuroprostheses developed so far do not provide continuous feedback control. Instead, they switch from one state to another when signals from their one or two sensors meet pre-set thresholds (finite state control). The inherent springiness of electrically activated muscle provides a crucial form of feedback control that helps smooth the resulting movements. In spite of the dissimilarities, parallels can be found between feedback control in neuroprostheses and in animals and this can provide surprising insights in both directions.

Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses.

Engineered Graphene Material Improves the Performance of Intraneural Peripheral Nerve Electrodes.

Limb neuroprostheses aim to restore motor and sensory functions in amputated or severely nerve-injured patients. These devices use neural interfaces to record and stimulate nerve action potentials, creating a bidirectional connection with the nervous system. Most neural interfaces are based on standard metal microelectrodes. In this work, a new generation of neural interfaces which replaces metals with engineered graphene, called EGNITE, is tested. In vitro and in vivo experiments are conducted to assess EGNITE biocompatibility. In vitro tests show that EGNITE does not impact cell viability. In vivo, no significant functional decrease or harmful effects are observed. Furthermore, the foreign body reaction to the intraneural implant is similar compared to other materials previously used in neural interfaces. Regarding functionality, EGNITE devices are able to stimulate nerve fascicles, during two months of implant, producing selective muscle activation with about three times less current compared to larger microelectrodes of standard materials. CNAP elicited by electrical stimuli and ENG evoked by mechanical stimuli are recorded with high resolution but are more affected by decreased functionality over time. This work constitutes further proof that graphene-derived materials, and specifically EGNITE, is a promising conductive material of neural electrodes for advanced neuroprostheses.

Neural population dynamics in songbird RA and HVC during learned motor-vocal behavior.

Complex, learned motor behaviors involve the coordination of large-scale neural activity across multiple brain regions, but our understanding of the population-level dynamics within different regions tied to the same behavior remains limited. Here, we investigate the neural population dynamics underlying learned vocal production in awake-singing songbirds. We use Neuropixels probes to record the simultaneous extracellular activity of populations of neurons in two regions of the vocal motor pathway. In line with observations made in non-human primates during limb-based motor tasks, we show that the population-level activity in both the premotor nucleus HVC and the motor nucleus RA is organized on low-dimensional neural manifolds upon which coordinated neural activity is well described by temporally structured trajectories during singing behavior. Both the HVC and RA latent trajectories provide relevant information to predict vocal sequence transitions between song syllables. However, the dynamics of these latent trajectories differ between regions. Our state-space models suggest a unique and continuous-over-time correspondence between the latent space of RA and vocal output, whereas the corresponding relationship for HVC exhibits a higher degree of neural variability. We then demonstrate that comparable high-fidelity reconstruction of continuous vocal outputs can be achieved from HVC and RA neural latents and spiking activity. Unlike those that use spiking activity, however, decoding models using neural latents generalize to novel sub-populations in each region, consistent with the existence of preserved manifolds that confine vocal-motor activity in HVC and RA.

Sensory integration for neuroprostheses: from functional benefits to neural correlates.

In the field of sensory neuroprostheses, one ultimate goal is for individuals to perceive artificial somatosensory information and use the prosthesis with high complexity that resembles an intact system. To this end, research has shown that stimulation-elicited somatosensory information improves prosthesis perception and task performance. While studies strive to achieve sensory integration, a crucial phenomenon that entails naturalistic interaction with the environment, this topic has not been commensurately reviewed. Therefore, here we present a perspective for understanding sensory integration in neuroprostheses. First, we review the engineering aspects and functional outcomes in sensory neuroprosthesis studies. In this context, we summarize studies that have suggested sensory integration. We focus on how they have used stimulation-elicited percepts to maximize and improve the reliability of somatosensory information. Next, we review studies that have suggested multisensory integration. These works have demonstrated that congruent and simultaneous multisensory inputs provided cognitive benefits such that an individual experiences a greater sense of authority over prosthesis movements (i.e., agency) and perceives the prosthesis as part of their own (i.e., ownership). Thereafter, we present the theoretical and neuroscience framework of sensory integration. We investigate how behavioral models and neural recordings have been applied in the context of sensory integration. Sensory integration models developed from intact-limb individuals have led the way to sensory neuroprosthesis studies to demonstrate multisensory integration. Neural recordings have been used to show how multisensory inputs are processed across cortical areas. Lastly, we discuss some ongoing research and challenges in achieving and understanding sensory integration in sensory neuroprostheses. Resolving these challenges would help to develop future strategies to improve the sensory feedback of a neuroprosthetic system.