Neural sensory stimulation does not interfere with the H-reflex in individuals with lower limb amputation.

Introduction: Individuals with lower limb loss experience an increased risk of falls partly due to the lack of sensory feedback from their missing foot. It is possible to restore plantar sensation perceived as originating from the missing foot by directly interfacing with the peripheral nerves remaining in the residual limb, which in turn has shown promise in improving gait and balance. However, it is yet unclear how these electrically elicited plantar sensation are integrated into the body's natural sensorimotor control reflexes. Historically, the H-reflex has been used as a model for investigating sensorimotor control. Within the spinal cord, an array of inputs, including plantar cutaneous sensation, are integrated to produce inhibitory and excitatory effects on the H-reflex. Methods: In this study, we characterized the interplay between electrically elicited plantar sensations and this intrinsic reflex mechanism. Participants adopted postures mimicking specific phases of the gait cycle. During each posture, we electrically elicited plantar sensation, and subsequently the H-reflex was evoked both in the presence and absence of these sensations. Results: Our findings indicated that electrically elicited plantar sensations did not significantly alter the H-reflex excitability across any of the adopted postures. Conclusion: This suggests that individuals with lower limb loss can directly benefit from electrically elicited plantar sensation during walking without disrupting the existing sensory signaling pathways that modulate reflex responses.

Peripheral nerve stimulation enables somatosensory feedback while suppressing phantom limb pain in transradial amputees.

To simultaneously treat phantom limb pain (PLP) and restore somatic sensations using peripheral nerve stimulation (PNS), two bilateral transradial amputees were implanted with stimulating electrodes in the proximity of the medial, ulnar and radial nerves. Application of PNS evoked tactile and proprioceptive sensations in the phantom hand. Both patients learned to determine the shape of invisible objects by scanning a computer tablet with a stylus while receiving feedback based on PNS or transcutaneous electrical nerve stimulation (TENS). Оne patient learned to use PNS as feedback from the prosthetic hand that grasped objects of different sizes. PNS abolished PLP completely in one patient and reduced it by 40-70% in the other. We suggest incorporating PNS and/or TENS in active tasks to reduce PLP and restore sensations in amputees.

A Haptic Sleeve as a Method of Mechanotactile Feedback Restoration for Myoelectric Hand Prosthesis Users.

Current myoelectric upper limb prostheses do not restore sensory feedback, impairing fine motor control. Mechanotactile feedback restoration with a haptic sleeve may rectify this problem. This randomised crossover within-participant controlled study aimed to assess a prototype haptic sleeve's effect on routine grasping tasks performed by eight able-bodied participants. Each participant completed 15 repetitions of the three tasks: Task 1-normal grasp, Task 2-strong grasp and Task 3-weak grasp, using visual, haptic, or combined feedback All data were collected in April 2021 in the Scottish Microelectronics Centre, Edinburgh, UK. Combined feedback correlated with significantly higher grasp success rates compared to the vision alone in Task 1 (p < 0.0001), Task 2 (p = 0.0057), and Task 3 (p = 0.0170). Similarly, haptic feedback was associated with significantly higher grasp success rates compared to vision in Task 1 (p < 0.0001) and Task 2 (p = 0.0015). Combined feedback correlated with significantly lower energy expenditure compared to visual feedback in Task 1 (p < 0.0001) and Task 3 (p = 0.0003). Likewise, haptic feedback was associated with significantly lower energy expenditure compared to the visual feedback in Task 1 (p < 0.0001), Task 2 (p < 0.0001), and Task 3 (p < 0.0001). These results suggest that mechanotactile feedback provided by the haptic sleeve effectively augments grasping and reduces its energy expenditure.

Effects of stimulus pulse rate on somatosensory adaptation in the human cortex.

BACKGROUND: Intracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of stimulation on percept intensity over time. OBJECTIVE: Here, we evaluate how tactile percepts evoked by ICMS in the somatosensory cortex of a human participant adapt over time. METHODS: We delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted over approximately one year and linear mixed effects models were used to assess significance. RESULTS: Continuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within 1 min. Intermittent stimulation paradigms with several seconds between stimulus trains evoked intermittent percepts and also led to decreases in intensity on many electrodes, but never resulted in extinction of the sensation after over 3 min of stimulation. Longer breaks between each pulse train resulted in some recovery in the intensity of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity. CONCLUSIONS: Intermittent ICMS paradigms were more effective at maintaining percepts. Given that transient neural activity dominates the response in somatosensory cortex during mechanical contact onsets and offsets, providing brief stimulation trains at these times may more closely represent natural cortical activity and have the additional benefit of prolonging the ability to evoke sensations over longer time periods.

Self-powered smart patch promotes skin nerve regeneration and sensation restoration by delivering biological-electrical signals in program.

Skin wound is always accompanied with nerve destruction. Due to the limited clinical treatment option, loss of skin sensation with unsatisfactory nerve regeneration is remained to be a challenge for wound therapy. Endogenous mesenchymal stem cells (MSCs) based in situ regeneration, of which, MSCs recruited by chemokines and directed for neuronal differentiation by biological and electrical signals have been thought a novel strategy with potential to accelerate the nerve regeneration and sensory functions recovery. However, most current therapeutic systems usually deliver the chemokines, biological and electrical signals separately and statically, resulting in limited nerve regeneration and sensory functions recovery. Moreover, most of the devices for providing electrical signals need external energy input and complicated practice, leading to poor compliance in patients. To address these issues, we propose a self-powered smart patch (PRG-G-C) to provide chemokine and biological-electrical cues in program. PRG-G-C was composed of a flexible piezoelectric generator to supply electrical stimulation and a conductive gel, which served as the reservoir of chemokine and neural directing exosomes as well as the electrode to transfer electric cue. PRG-G-C was shown to efficiently accelerate rapid nerve regeneration and sensation restoration at the wound site within 23 days. This study demonstrates a proof-to-concept in organizing chemokine, neural directing biological-electrical heterogeneous cues within a self-powered smart patch for accelarating nerve regeneration and sensation restoration, possessing great potential in neural repair applications.

Evoking highly focal percepts in the fingertips through targeted stimulation of sulcal regions of the brain for sensory restoration.

BACKGROUND: Paralysis and neuropathy, affecting millions of people worldwide, can be accompanied by significant loss of somatosensation. With tactile sensation being central to achieving dexterous movement, brain-computer interface (BCI) researchers have used intracortical and cortical surface electrical stimulation to restore somatotopically-relevant sensation to the hand. However, these approaches are restricted to stimulating the gyral areas of the brain. Since representation of distal regions of the hand extends into the sulcal regions of human primary somatosensory cortex (S1), it has been challenging to evoke sensory percepts localized to the fingertips. OBJECTIVE/HYPOTHESIS: Targeted stimulation of sulcal regions of S1, using stereoelectroencephalography (SEEG) depth electrodes, can evoke focal sensory percepts in the fingertips. METHODS: Two participants with intractable epilepsy received cortical stimulation both at the gyri via high-density electrocorticography (HD-ECoG) grids and in the sulci via SEEG depth electrode leads. We characterized the evoked sensory percepts localized to the hand. RESULTS: We show that highly focal percepts can be evoked in the fingertips of the hand through sulcal stimulation. fMRI, myelin content, and cortical thickness maps from the Human Connectome Project elucidated specific cortical areas and sub-regions within S1 that evoked these focal percepts. Within-participant comparisons showed that percepts evoked by sulcal stimulation via SEEG electrodes were significantly more focal (80% less area; p = 0.02) and localized to the fingertips more often, than by gyral stimulation via HD-ECoG electrodes. Finally, sulcal locations with consistent modulation of high-frequency neural activity during mechanical tactile stimulation of the fingertips showed the same somatotopic correspondence as cortical stimulation. CONCLUSIONS: Our findings indicate minimally invasive sulcal stimulation via SEEG electrodes could be a clinically viable approach to restoring sensation.

A machine learning framework to optimize optic nerve electrical stimulation for vision restoration.

Optic nerve electrical stimulation is a promising technique to restore vision in blind subjects. Machine learning methods can be used to select effective stimulation protocols, but they require a model of the stimulated system to generate enough training data. Here, we use a convolutional neural network (CNN) as a model of the ventral visual stream. A genetic algorithm drives the activation of the units in a layer of the CNN representing a cortical region toward a desired pattern, by refining the activation imposed at a layer representing the optic nerve. To simulate the pattern of activation elicited by the sites of an electrode array, a simple point-source model was introduced and its optimization process was investigated for static and dynamic scenes. Psychophysical data confirm that our stimulation evolution framework produces results compatible with natural vision. Machine learning approaches could become a very powerful tool to optimize and personalize neuroprosthetic systems.

Are critical periods reversible in the adult brain? Insights on cortical specializations based on sensory deprivation studies.

We review here studies with visual and auditory deprived/recovery populations to argue for the need of a redefinition of the crucial role of unisensory-specific experiences during critical periods (CPs) on the emergence of sensory specializations. Specifically, we highlight that these studies, with emphasis on results with congenitally blind adults using visual sensory-substitution devices, consistently document that typical specializations (e.g., in visual cortex) could arise also in adulthood via other sensory modalities (e.g., audition), even after relatively short (tailored) trainings. Altogether, these studies suggest that 1) brain specializations are driven by sensory-independent computations rather than by unisensory-specific inputs and that 2) specific computation-oriented trainings, even if executed during adulthood, can guide the sensory brain to display/recover, core properties of brain specializations. We thus introduce here the concept of a reversible plasticity gradient, namely that brain plasticity spontaneously decreases with age in line with CPs theory, but it nonetheless can be reignited across the lifespan, even without any exposure to unisensory (e.g., visual) experiences during childhood, thus diverging dramatically from CPs assumptions.

Utilizing prosthetic technology to improve quality of life: an interview with Ranu Jung and James Abbas.

In this interview, we spoke with Ranu and James at SfN Neuroscience (19-23 October 2019, Chicago, IL, USA) to discover more about their collaboration on a clinical trial aiming to improve the lives of American veterans and service members who have lost limbs. The clinical trial involves the adaptive neural systems neural-enabled prosthetic hand system [1,2].

Long-Term Home-Use of Sensory-Motor-Integrated Bidirectional Bionic Prosthetic Arms Promotes Functional, Perceptual, and Cognitive Changes.

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users' functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred.

Emerging Approaches for Restoration of Hearing and Vision.

Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For a long time, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye and ear has generated hope for a fundamental improvement of vision and hearing restoration. To date, one gene therapy for the restoration of vision has been approved, and ongoing clinical trials will broaden its application including gene replacement, genome editing, and regenerative approaches. Moreover, optogenetics, i.e., controlling the activity of cells by light, offers a more general alternative strategy. Over little more than a decade, optogenetic approaches have been developed and applied to better understand the function of biological systems, while protein engineers have identified and designed new opsin variants with desired physiological features. Considering potential clinical applications of optogenetics, the spotlight is on the sensory systems, particularly the eye and ear. Multiple efforts have been undertaken to restore lost or hampered function in the eye and ear. Optogenetic stimulation promises to overcome fundamental shortcomings of electrical stimulation, namely, poor spatial resolution and cellular specificity, and accordingly to deliver more detailed sensory information. This review aims to provide a comprehensive reference on current gene therapeutic and optogenetic research relevant to the restoration of hearing and vision. We will introduce gene-therapeutic approaches and discuss the biotechnological and optoelectronic aspects of optogenetic hearing and vision restoration.

Merging brain-computer interface and functional electrical stimulation technologies for movement restoration.

BCI (brain-computer interface) and functional electrical stimulation (FES) technologies have advanced significantly over the last several decades. Recent efforts have involved the integration of these technologies with the goal of restoring functional movement in paralyzed patients. Implantable BCIs have provided neural recordings with increased spatial resolution and have been combined with sophisticated neural decoding algorithms and increasingly capable FES systems to advance efforts toward this goal. This chapter reviews historical developments that have occurred as the exciting fields of BCI and FES have evolved and now overlapped to allow new breakthroughs in medicine, targeting restoration of movement and lost function in users with disabilities.

Sensory Nerve Transfer for Lower Roots Brachial Plexus Injury: Superficial Radial Nerve to the Dorsal Cutaneous Branch and the Superficial Branch of the Ulnar Nerve.

In the treatment of brachial plexus injury to lower nerve roots, the priority is to restore motor function to the paralyzed hand. In addition, it is also important to consider sensory reconstruction, which is crucial to the optimal restoration of prehensile function. We report the surgical technique and sensory recovery of a nerve transfer in a case in which the superficial radial nerve was transferred to the dorsal cutaneous branch and the superficial branch of the ulnar nerve in a patient with C7, C8, and T1 roots injury. The nerve transfer successfully restored sensation in the ulnar one and a half digits as well as the ulnar border of the hand, with minimal donor site deficit. This technique provides a useful sensory reconstructive option in patients with brachial plexus injury to lower roots.

Direct Electrical Stimulation in Electrocorticographic Brain-Computer Interfaces: Enabling Technologies for Input to Cortex.

Electrocorticographic brain computer interfaces (ECoG-BCIs) offer tremendous opportunities for restoring function in individuals suffering from neurological damage and for advancing basic neuroscience knowledge. ECoG electrodes are already commonly used clinically for monitoring epilepsy and have greater spatial specificity in recording neuronal activity than techniques such as electroencephalography (EEG). Much work to date in the field has focused on using ECoG signals recorded from cortex as control outputs for driving end effectors. An equally important but less explored application of an ECoG-BCI is directing input into cortex using ECoG electrodes for direct electrical stimulation (DES). Combining DES with ECoG recording enables a truly bidirectional BCI, where information is both read from and written to the brain. We discuss the advantages and opportunities, as well as the barriers and challenges presented by using DES in an ECoG-BCI. In this article, we review ECoG electrodes, the physics and physiology of DES, and the use of electrical stimulation of the brain for the clinical treatment of disorders such as epilepsy and Parkinson's disease. We briefly discuss some of the translational, regulatory, financial, and ethical concerns regarding ECoG-BCIs. Next, we describe the use of ECoG-based DES for providing sensory feedback and for probing and modifying cortical connectivity. We explore future directions, which may draw on invasive animal studies with penetrating and surface electrodes as well as non-invasive stimulation methods such as transcranial magnetic stimulation (TMS). We conclude by describing enabling technologies, such as smaller ECoG electrodes for more precise targeting of cortical areas, signal processing strategies for simultaneous stimulation and recording, and computational modeling and algorithms for tailoring stimulation to each individual brain.

Transfer of the Dorsal Cutaneous Branch of the Ulnar Nerve for Restoration of Median Nerve Sensation: A Cadaveric Study.

The use of dorsal cutaneous branch of the ulnar nerve (DCBUN) transfer for median nerve (MN) sensory restoration has not been evaluated anatomically and histologically in humans. The purpose of this study was to evaluate the feasibility of DCBUN to MN transfer for sensory restoration with respect to nerve branch pattern, length, and fascicle count match.Using seven fresh frozen cadaveric upper limb specimens, the DCBUN and its branch patterns, lengths, and sizes were recorded. The MN was exposed within the carpal tunnel and dissected distally to identify the common digital nerves (CDN). Simulated nerve transfer was performed with palmar coaptation of the DCBUN branches with the CDNs. Histological analysis of each nerve branch was performed. The seven specimens had a mean of 3.57 branches (range 2-4) off the DCBUN. The longest branch innervated the dorsal 4th web space, on average reaching 7.6 cm distal to the wrist crease. Transferring the DCBUN branches palmarly did not substantially change their maximum distance distal to the wrist crease. The MN CDNs and DCBUN branches had mean cross-sectional areas of 6.37 and 1.99 mm2 , respectively, and mean fascicle counts of 10.4 and 4.05, respectively. The DCBUN provides 2-4 branches suitable for tension-free end-to-end transfer to the MN CDNs. The individual size of the DCBUN branch is smaller than CDN; however, combining two or more branches of the DCBUN would overcome the fascicle and size mismatch to reconstruct the 1st web space CDN for critical sensory restoration. Clin. Anat. 31:1006-1012, 2018. © 2018 Wiley Periodicals, Inc.