Our research path toward the restoration of natural sensations in hand prostheses.

The human hand, with its intricate sensory capabilities, plays a pivotal role in our daily interactions with the world. This remarkable organ possesses a wide range of natural sensors that enrich our experiences, enabling us to perceive touch, position, and temperature. These natural sensors work in concert to provide us with a rich sensory experience, enabling us to distinguish between various textures, gauge the force of our grip, determine the position of our fingers without needing to see them, perceive the temperature of objects we come into contact with or detect if a cloth is wet or dry. This complex sensory system is fundamental to our ability to manipulate objects, explore our surroundings, and interact with the world and people around us. In this article, we summarize the research performed in our laboratories over the years and our findings to restore both touch, position, and temperature modalities. The combination of intraneural stimulation, sensory substitution, and wearable technology opens new possibilities for enhancing sensory feedback in prosthetic hands, promising improved functionality and a closer approximation to natural sensory experiences for individuals with limb differences.

Effect of disease, freezing of gait, and dopaminergic medication in the biomechanics of trunk and upper limbs in the gait of Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) causes gait abnormalities that may be associated with an arm swing reduction. Medication and freezing of gait (FoG) may influence gait characteristics. However, these comparisons do not consider differences in gait speed and clinical characteristics in individuals with PD. OBJECTIVE: This study aims to analyze the effect of FoG and medication on the biomechanics of the trunk and upper limbs during gait in PD, controlling for gait speed and clinical differences between groups. METHODS: Twenty-two people with a clinical diagnosis of idiopathic PD in ON and OFF medication (11 FoG), and 35 healthy participants (control) were selected from two open data sets. All participants walked on the floor on a 10-m-long walkway. The joint and linear kinematic variables of gait were compared: (1) Freezers and nonfreezers in the ON condition and control; (2) Freezers and nonfreezers in the OFF condition and control; (3) Group (freezers and nonfreezers) and medication. RESULTS: The disease affects the upper limbs more strongly but not the trunk. The medication does not significantly influence the joint characteristics but rather the linear wrist displacement. The FoG does not affect trunk movement and partially influences the upper limbs. The interaction between medications and FoG suggests that the medication causes more substantial improvement in freezers than in nonfreezers. CONCLUSION: The study shows differences in the biomechanics of the upper limbs of people with PD, FoG, and the absence of medication. The future rehabilitation protocol should consider this aspect.

A Virtual Reality-Based Protocol to Determine the Preferred Control Strategy for Hand Neuroprostheses in People With Paralysis.

Hand neuroprostheses restore voluntary movement in people with paralysis through neuromodulation protocols. There are a variety of strategies to control hand neuroprostheses, which can be based on residual body movements or brain activity. There is no universally superior solution, rather the best approach may vary from patient to patient. Here, we propose a protocol based on an immersive virtual reality (VR) environment that simulates the use of a hand neuroprosthesis to allow patients to experience and familiarize themselves with various control schemes in clinically relevant tasks and choose the preferred one. We used our VR environment to compare two alternative control strategies over 5 days of training in four patients with C6 spinal cord injury: (a) control via the ipsilateral wrist, (b) control via the contralateral shoulder. We did not find a one-fits-all solution but rather a subject-specific preference that could not be predicted based only on a general clinical assessment. The main results were that the VR simulation allowed participants to experience the pros and cons of the proposed strategies and make an educated choice, and that there was a longitudinal improvement. This shows that our VR-based protocol is a useful tool for personalization and training of the control strategy of hand neuroprostheses, which could help to promote user comfort and thus acceptance.

A sensory-motor hand prosthesis with integrated thermal feedback.

BACKGROUND: Recently, we reported the presence of phantom thermal sensations in amputees: thermal stimulation of specific spots on the residual arm elicited thermal sensations in their missing hands. Here, we exploit phantom thermal sensations via a standalone system integrated into a robotic prosthetic hand to provide real-time and natural temperature feedback. METHODS: The subject (a male adult with unilateral transradial amputation) used the sensorized prosthesis to manipulate objects and distinguish their thermal properties. We tested his ability to discriminate between (1) hot, cold, and ambient temperature objects, (2) different materials (copper, glass, and plastic), and (3) artificial versus human hands. We also introduced the thermal box and block test (thermal BBT), a test to evaluate real-time temperature discrimination during standardized pick-and-place tasks. FINDINGS: The subject performed all three discrimination tasks above chance level with similar accuracies as with his intact hand. Additionally, in all 15 sessions of the thermal BBT, he correctly placed more than half of the samples. Finally, the phantom thermal sensation was stable during the 13 recording sessions spread over 400 days. CONCLUSION: Our study paves the way for more natural hand prostheses that restore the full palette of sensations. FUNDING: This work was funded by the Bertarelli Foundation (including the Catalyst program); the Swiss National Science Foundation through the National Centre of Competence in Research (NCCR) Robotics; the European Union's Horizon 2020 research and innovation program; the Horizon Europe Research & Innovation Program; the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP); and the Tuscany Health Ecosystem.

Human motor augmentation with an extra robotic arm without functional interference.

Extra robotic arms (XRAs) are gaining interest in neuroscience and robotics, offering potential tools for daily activities. However, this compelling opportunity poses new challenges for sensorimotor control strategies and human-machine interfaces (HMIs). A key unsolved challenge is allowing users to proficiently control XRAs without hindering their existing functions. To address this, we propose a pipeline to identify suitable HMIs given a defined task to accomplish with the XRA. Following such a scheme, we assessed a multimodal motor HMI based on gaze detection and diaphragmatic respiration in a purposely designed modular neurorobotic platform integrating virtual reality and a bilateral upper limb exoskeleton. Our results show that the proposed HMI does not interfere with speaking or visual exploration and that it can be used to control an extra virtual arm independently from the biological ones or in coordination with them. Participants showed significant improvements in performance with daily training and retention of learning, with no further improvements when artificial haptic feedback was provided. As a final proof of concept, naïve and experienced participants used a simplified version of the HMI to control a wearable XRA. Our analysis indicates how the presented HMI can be effectively used to control XRAs. The observation that experienced users achieved a success rate 22.2% higher than that of naïve users, combined with the result that naïve users showed average success rates of 74% when they first engaged with the system, endorses the viability of both the virtual reality-based testing and training and the proposed pipeline.

Immediate Effect of Ankle Exoskeleton on Spatiotemporal Parameters and Center of Pressure Trajectory After Stroke.

Gait impairments is a common condition in post-stroke subjects. We recently presented a wearable ankle exoskeleton called G-Exos, which showed that the device assisted in the ankle's dorsiflexion and inversion/reversion movements. The aim of the current pilot study was to explore spatiotemporal gait parameters and center of pressure trajectories associated with the use of the G-Exos in stroke participants. Three post-stroke subjects (52-63 years, 2 female/1 male) walked 160-meter using the G-Exos on the affected limb, on a protocol divided into 4 blocks of 40-meters: (I) without the exoskeleton, (II) with systems hybrid system, (III) active only and (IV) passive only. The results showed that the use of the exoskeleton improved swing and stance phases on both limbs, reduced stride width on the paretic limb, increased stance COP distances, and made single support COP distances more similar between the paretic and non-paretic limb. This suggests that all G-Exos systems contributed to improving body weight bearing on the paretic limb and symmetry in the gait cycle.

Human-machine interface for two-dimensional steering control with the auricular muscles.

Human-machine interfaces (HMIs) can be used to decode a user's motor intention to control an external device. People that suffer from motor disabilities, such as spinal cord injury, can benefit from the uses of these interfaces. While many solutions can be found in this direction, there is still room for improvement both from a decoding, hardware, and subject-motor learning perspective. Here we show, in a series of experiments with non-disabled participants, a novel decoding and training paradigm allowing naïve participants to use their auricular muscles (AM) to control two degrees of freedom with a virtual cursor. AMs are particularly interesting because they are vestigial muscles and are often preserved after neurological diseases. Our method relies on the use of surface electromyographic records and the use of contraction levels of both AMs to modulate the velocity and direction of a cursor in a two-dimensional paradigm. We used a locking mechanism to fix the current position of each axis separately to enable the user to stop the cursor at a certain location. A five-session training procedure (20-30 min per session) with a 2D center-out task was performed by five volunteers. All participants increased their success rate (Initial: 52.78 ± 5.56%; Final: 72.22 ± 6.67%; median ± median absolute deviation) and their trajectory performances throughout the training. We implemented a dual task with visual distractors to assess the mental challenge of controlling while executing another task; our results suggest that the participants could perform the task in cognitively demanding conditions (success rate of 66.67 ± 5.56%). Finally, using the Nasa Task Load Index questionnaire, we found that participants reported lower mental demand and effort in the last two sessions. To summarize, all subjects could learn to control the movement of a cursor with two degrees of freedom using their AM, with a low impact on the cognitive load. Our study is a first step in developing AM-based decoders for HMIs for people with motor disabilities, such as spinal cord injury.

Restoration of natural thermal sensation in upper-limb amputees.

The use of hands for gathering rich sensory information is essential for proper interaction with the environment; therefore, the restoration of sensation is critical for reestablishing the sense of embodiment in hand amputees. Here, we show that a noninvasive wearable device can be used to provide thermal sensations on amputees' phantom hands. The device delivers thermal stimuli to specific regions of skin on their residual limb. These sensations were phenomenologically similar to those on the intact limbs and were stable over time. Using the device, the subjects could successfully exploit the thermal phantom hand maps to detect and discriminate different thermal stimuli. The use of a wearable device that provides thermal sensation can increase the sense of embodiment and improve life quality in hand amputees.

Effect of freezing of gait and dopaminergic medication in the biomechanics of lower limbs in the gait of patients with Parkinson's disease compared to neurologically healthy.

INTRODUCTION: This study aims to evaluate the effects of medication, and the freezing of gait (FoG) on the kinematic and kinetic parameters of gait in people with Parkinson's disease (pwPD) compared to neurologically healthy. METHODS: Twenty-two people with a clinical diagnosis of idiopathic PD in ON and OFF medication (11 FoG), and 18 healthy participants (control) were selected from two open data sets. All participants walked on the floor on a 10-meter-long walkway. The joint kinematic and ground reaction forces (GRF) variables of gait and the clinical characteristics were compared: (1) PD with FoG (pwFoG) and PD without FoG (pwoFoG) in the ON condition and control; (2) PD with FoG and PD without FoG in the OFF condition and control; (3) Group (PD with FoG and PD without FoG) and Medication. RESULTS: (1) FoG mainly affects distal joints, such as the ankle and knee; (2) PD ON showed changes in the range of motion of both distal and proximal joints, which may explain the increase in step length and gait speed expected with the use of L-Dopa; and (3) the medication showed improvements in the kinematic and kinetic parameters of the gait of people with pwFoG and pwoFoG equally; (4) pwPD showed a smaller second peak of the vertical component of the GRF than the control. CONCLUSION: The presence of FoG mainly affects distal joints, such as the ankle and knee. PD presents a lower application of GRF during the impulse period than healthy people, causing lower gait performances.

Training with noninvasive brain-machine interface, tactile feedback, and locomotion to enhance neurological recovery in individuals with complete paraplegia: a randomized pilot study.

In recent years, our group and others have reported multiple cases of consistent neurological recovery in people with spinal cord injury (SCI) following a protocol that integrates locomotion training with brain machine interfaces (BMI). The primary objective of this pilot study was to compare the neurological outcomes (motor, tactile, nociception, proprioception, and vibration) in both an intensive assisted locomotion training (LOC) and a neurorehabilitation protocol integrating assisted locomotion with a noninvasive brain-machine interface (L + BMI), virtual reality, and tactile feedback. We also investigated whether individuals with chronic-complete SCI could learn to perform leg motor imagery. We ran a parallel two-arm randomized pilot study; the experiments took place in São Paulo, Brazil. Eight adults sensorimotor-complete (AIS A) (all male) with chronic (> 6 months) traumatic spinal SCI participated in the protocol that was organized in two blocks of 14 weeks of training and an 8-week follow-up. The participants were allocated to either the LOC group (n = 4) or L + BMI group (n = 4) using block randomization (blinded outcome assessment). We show three important results: (i) locomotion training alone can induce some level of neurological recovery in sensorimotor-complete SCI, and (ii) the recovery rate is enhanced when such locomotion training is associated with BMI and tactile feedback (∆Mean Lower Extremity Motor score improvement for LOC = + 2.5, L + B = + 3.5; ∆Pinprick score: LOC = + 3.75, L + B = + 4.75 and ∆Tactile score LOC = + 4.75, L + B = + 9.5). (iii) Furthermore, we report that the BMI classifier accuracy was significantly above the chance level for all participants in L + B group. Our study shows potential for sensory and motor improvement in individuals with chronic complete SCI following a protocol with BMIs and locomotion therapy. We report no dropouts nor adverse events in both subgroups participating in the study, opening the possibility for a more definitive clinical trial with a larger cohort of people with SCI.Trial registration: http://www.ensaiosclinicos.gov.br/ identifier RBR-2pb8gq.

Kinematics predictors of spatiotemporal parameters during gait differ by age in healthy individuals.

Joint biomechanics and spatiotemporal gait parameters change with age or disease and are used in treatment decision-making. RESEARCH QUESTION: To investigate whether kinematic predictors of spatiotemporal parameters during gait differ by age in healthy individuals. METHODS: We used an open dataset with the gait data of 114 young adults (M = 28.0 years, SD = 7.5) and 128 older adults (M = 67.5 years, SD = 3.8) walking at a comfortable self-selected speed. Linear regression models were developed to predict spatiotemporal parameters separately for each group using joint kinematics as independent variables. RESULTS: In young adults, knee flexion loading response and hip flexion/extension were the common predictors of gait speed; hip flexion and hip extension contributed to explaining the stride length; hip flexion contributed to explaining the cadence and stride time. In older adults, ankle plantarflexion, knee flexion loading response, and pelvic rotation were the common predictors of the gait speed; ankle plantarflexion and knee flexion loading response contributed to explaining the stride length; ankle plantarflexion loading response and ankle plantarflexion contributed to explain the cadence, stride width and stride time. SIGNIFICANCE: Our results suggest that the ability of joint kinematic variables to estimate spatiotemporal parameters during gait differs by age in healthy individuals. Particularly in older adults, ankle plantarflexion was the common predictor of the spatiotemporal parameters, suggesting the importance of the ankle for gait parameters in this age group. This provides insight for clinicians into the most effective evaluation and has been used by physical professionals in prescribing the most appropriate exercises to attenuate the effects produced by age-related neuromuscular changes.

Biomechanical aspects that precede freezing episode during gait in individuals with Parkinson's disease: A systematic review.

BACKGROUND: The freezing episode (FE) management during gait in Parkinson's disease is inefficient with current medications, neurosurgery, and physical interventions. Knowing the biomechanical change patients suffer preceding FE would be the ultimate goal to measure, predict, and prevent these events. OBJECTIVE: We performed a systematic review to summarize the kinematic, kinetic, electromyographic, and spatio-temporal characteristics of the events that precede the FE during gait in Parkinson's disease. LITERATURE SURVEY: Databases searched included PubMed, Embase, and Cochrane and between 2001 to August 2021. METHODOLOGY: The present study was a systematic review registered in the PROSPERO database (CRD42021255082). Three reviewers searched and selected studies with methodologies involving biomechanical changes and kinetic, kinematic, electromyography, and spatiotemporal changes before FE in a patient with Parkinson's disease. The relevant articles that show the events preceding FE in patients with PD were identified. We excluded studies that describe or compare methods or algorithms to detect FE. Studies may include participants with all PD severity, time of disease, and age. SYNTHESIS: We selected ten articles for final evaluation. The most consistent results indicate a dramatic reduction of movement excursions with (1) decrease in stride length; (2) decreased gait speed; (3) postural instability with the increased double support phase; (4) incoordination of anterior tibial and gastrocnemius; (5) larger amplitude in the EMG of biceps femoris; (6) decreased range of motion in the sagittal plane at the ankle and hip joints; and (7) anterior pelvic tilt. CONCLUSION: FE is characterized by complex motor patterns than normal gait and mismatched gains in the perception and execution of the ongoing movement.

A modular strategy for next-generation upper-limb sensory-motor neuroprostheses.

Neuroprosthetics is a discipline that aims at restoring lost functions to people affected by a variety of neurological disorders or neurotraumatic lesions. It combines the expertise of computer science and electrical, mechanical, and micro/nanotechnology with cellular, molecular, and systems neuroscience. Rapid breakthroughs in the field during the past decade have brought the hope that neuroprostheses can soon become a clinical reality, in particular-as we will detail in this review-for the restoration of hand functions. We argue that any neuroprosthesis relies on a set of hardware and algorithmic building elements that we call the neurotechnological modules (NTs) used for motor decoding, movement restoration, or sensory feedback. We will show how the modular approach is already present in current neuroprosthetic solutions and how we can further exploit it to imagine the next generation of neuroprosthetics for sensory-motor restoration.

Author Correction: Non-invasive, Brain-controlled Functional Electrical Stimulation for Locomotion Rehabilitation in Individuals with Paraplegia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Creating a neuroprosthesis for active tactile exploration of textures.

Intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1) can produce percepts that mimic somatic sensation and, thus, has potential as an approach to sensorize prosthetic limbs. However, it is not known whether ICMS could recreate active texture exploration-the ability to infer information about object texture by using one's fingertips to scan a surface. Here, we show that ICMS of S1 can convey information about the spatial frequencies of invisible virtual gratings through a process of active tactile exploration. Two rhesus monkeys scanned pairs of visually identical screen objects with the fingertip of a hand avatar-controlled first via a joystick and later via a brain-machine interface-to find the object with denser virtual gratings. The gratings consisted of evenly spaced ridges that were signaled through individual ICMS pulses generated whenever the avatar's fingertip crossed a ridge. The monkeys learned to interpret these ICMS patterns, evoked by the interplay of their voluntary movements and the virtual textures of each object, to perform a sensory discrimination task. Discrimination accuracy followed Weber's law of just-noticeable differences (JND) across a range of grating densities; a finding that matches normal cutaneous sensation. Moreover, 1 monkey developed an active scanning strategy where avatar velocity was integrated with the ICMS pulses to interpret the texture information. We propose that this approach could equip upper-limb neuroprostheses with direct access to texture features acquired during active exploration of natural objects.

Non-invasive, Brain-controlled Functional Electrical Stimulation for Locomotion Rehabilitation in Individuals with Paraplegia.

Spinal cord injury (SCI) impairs the flow of sensory and motor signals between the brain and the areas of the body located below the lesion level. Here, we describe a neurorehabilitation setup combining several approaches that were shown to have a positive effect in patients with SCI: gait training by means of non-invasive, surface functional electrical stimulation (sFES) of the lower-limbs, proprioceptive and tactile feedback, balance control through overground walking and cue-based decoding of cortical motor commands using a brain-machine interface (BMI). The central component of this new approach was the development of a novel muscle stimulation paradigm for step generation using 16 sFES channels taking all sub-phases of physiological gait into account. We also developed a new BMI protocol to identify left and right leg motor imagery that was used to trigger an sFES-generated step movement. Our system was tested and validated with two patients with chronic paraplegia. These patients were able to walk safely with 65-70% body weight support, accumulating a total of 4,580 steps with this setup. We observed cardiovascular improvements and less dependency on walking assistance, but also partial neurological recovery in both patients, with substantial rates of motor improvement for one of them.