Clinical trials for implantable neural prostheses: understanding the ethical and technical requirements.

Neuroprosthetics research has entered a stage in which animal models and proof-of-concept studies are translated into clinical applications, often combining implants with artificial intelligence techniques. This new phase raises the question of how clinical trials should be designed to scientifically and ethically address the unique features of neural prostheses. Neural prostheses are complex cyberbiological devices able to acquire and process data; hence, their assessment is not reducible to only third-party safety and efficacy evaluations as in pharmacological research.

Wearable non-invasive neuroprosthesis for targeted sensory restoration in neuropathy.

Peripheral neuropathy (PN), the most common complication of diabetes, leads to sensory loss and associated health issues as pain and increased fall risk. However, present treatments do not counteract sensory loss, but only partially manage its consequences. Electrical neural stimulation holds promise to restore sensations, but its efficacy and benefits in PN damaged nerves are yet unknown.

Closing the sensory feedback loop is necessary for effective neurorehabilitation.

Recent advances in neurotechnology enable somatosensory feedback restoration in disabled individuals. This Perspective discusses how closing the sensory feedback loop with brain implants and nerve electrodes for stimulation may improve rehabilitation and assistive systems for patients.

Unraveling the physiological and psychosocial signatures of pain by machine learning.

Background: Pain is a complex subjective experience, strongly impacting health and quality of life. Despite many attempts to find effective solutions, present treatments are generic, often unsuccessful, and present significant side effects. Designing individualized therapies requires understanding of multidimensional pain experience, considering physical and emotional aspects.

Unconscious multisensory integration: behavioral and neural evidence from subliminal stimuli.

Introduction: The prevailing theories of consciousness consider the integration of different sensory stimuli as a key component for this phenomenon to rise on the brain level. Despite many theories and models have been proposed for multisensory integration between supraliminal stimuli (e.g.

Towards enhanced functionality of vagus neuroprostheses through in silico optimized stimulation.

Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model.

Bionic blink improves real-time eye closure in unilateral facial paralysis.

Facial paralysis is the inability to move facial muscles thereby impairing the ability to blink and make facial expressions. Depending on the localization of the nerve malfunction it is subcategorised into central or peripheral and is usually unilateral. This leads to health deficits stemming from corneal dryness and social ostracization.

Biomimetic computer-to-brain communication enhancing naturalistic touch sensations via peripheral nerve stimulation.

Artificial communication with the brain through peripheral nerve stimulation shows promising results in individuals with sensorimotor deficits. However, these efforts lack an intuitive and natural sensory experience. In this study, we design and test a biomimetic neurostimulation framework inspired by nature, capable of "writing" physiologically plausible information back into the peripheral nervous system.

Neural population dynamics reveals disruption of spinal circuits' responses to proprioceptive input during electrical stimulation of sensory afferents.

While neurostimulation technologies are rapidly approaching clinical applications for sensorimotor disorders, the impact of electrical stimulation on network dynamics is still unknown. Given the high degree of shared processing in neural structures, it is critical to understand if neurostimulation affects functions that are related to, but not targeted by, the intervention. Here, we approach this question by studying the effects of electrical stimulation of cutaneous afferents on unrelated processing of proprioceptive inputs.

Sensory-Motor Neurostimulation to Enhance Exosuit Performance.

Exosuits typically provide limited mechanical support and rely on a user's residual functional ability. However, people with neurological impairments often suffer from both motor and sensory deficits that limit the assistance an exosuit can provide. To overcome these limitations, we developed the REINFORCE system, that complements the mechanical assistance provided by an exosuit, the Myosuit, with (1) functional electrical stimulation to enhance the activities of leg muscles, and (2) transcutaneous electrical nerve stimulation to restore somatosensory information.

Automated calibration of somatosensory stimulation using reinforcement learning.

Background: The identification of the electrical stimulation parameters for neuromodulation is a subject-specific and time-consuming procedure that presently mostly relies on the expertise of the user (e.g., clinician, experimenter, bioengineer).

Brain-Computer Interface to Deliver Individualized Multisensory Intervention for Neuropathic Pain.

To unravel the complexity of the neuropathic pain experience, researchers have tried to identify reliable pain signatures (biomarkers) using electroencephalography (EEG) and skin conductance (SC). Nevertheless, their use as a clinical aid to design personalized therapies remains scarce and patients are prescribed with common and inefficient painkillers. To address this need, novel non-pharmacological interventions, such as transcutaneous electrical nerve stimulation (TENS) to activate peripheral pain relief via neuromodulation and virtual reality (VR) to modulate patients' attention, have emerged.

Design of an adaptable intrafascicular electrode (AIR) for selective nerve stimulation by model-based optimization.

Peripheral nerve stimulation is being investigated as a therapeutic tool in several clinical scenarios. However, the adopted devices have restricted ability to obtain desired outcomes with tolerable off-target effects. Recent promising solutions are not yet employed in clinical practice due to complex required surgeries, lack of long-term stability, and implant invasiveness.

Multiparametric non-linear TENS modulation to integrate intuitive sensory feedback.

. Transcutaneous electrical nerve stimulation (TENS) has been recently introduced in neurorehabilitation and neuroprosthetics as a promising, non-invasive sensory feedback restoration alternative to implantable neurostimulation. Yet, the adopted stimulation paradigms are typically based on single-parameter modulations (e.

Recalibration of neuromodulation parameters in neural implants with adaptive Bayesian optimization.

. Neuromodulation technology holds promise for treating conditions where physiological mechanisms of neural activity have been affected. To make treatments efficient and devices highly effective, neurostimulation protocols must be personalized.

Symbiotic electroneural and musculoskeletal framework to encode proprioception via neurostimulation: ProprioStim.

Peripheral nerve stimulation in amputees achieved the restoration of touch, but not proprioception, which is critical in locomotion. A plausible reason is the lack of means to artificially replicate the complex activity of proprioceptors. To uncover this, we coupled neuromuscular models from ten subjects and nerve histologies from two implanted amputees to develop ProprioStim: a framework to encode proprioception by electrical evoking neural activity in close agreement with natural proprioceptive activity.

Reshaping the full body illusion through visuo-electro-tactile sensations.

The physical boundaries of our body do not define what we perceive as self. This malleable representation arises from the neural integration of sensory information coming from the environment. Manipulating the visual and haptic cues produces changes in body perception, inducing the Full Body Illusion (FBI), a vastly used approach to exploring humans' perception.

Modeling foot sole cutaneous afferents: FootSim.

While walking and maintaining balance, humans rely on cutaneous feedback from the foot sole. Electrophysiological recordings reveal how this tactile feedback is represented in neural afferent populations, but obtaining them is difficult and limited to stationary conditions. We developed the FootSim model, a realistic replication of mechanoreceptor activation in the lower limb.

Multifaceted understanding of human nerve implants to design optimized electrodes for bioelectronics.

Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the over-time stability of implants and the related nerve reactions are unclear.

Cognitive benefits of using non-invasive compared to implantable neural feedback.

A non-optimal prosthesis integration into an amputee's body schema suggests some important functional and health consequences after lower limb amputation. These include low perception of a prosthesis as a part of the body, experiencing it as heavier than the natural limb, and cognitively exhausting use for users. Invasive approaches, exploiting the surgical implantation of electrodes in residual nerves, improved prosthesis integration by restoring natural and somatotopic sensory feedback in transfemoral amputees.

Optimally-calibrated non-invasive feedback improves amputees' metabolic consumption, balance and walking confidence.

Lower-limb amputees suffer from a variety of health problems, including higher metabolic consumption and low mobility. These conditions are linked to the lack of a natural sensory feedback (SF) from their prosthetic device, which forces them to adopt compensatory walking strategies that increase fatigue. Recently, both invasive (i.

Multisensory stimulation decreases phantom limb distortions and is optimally integrated.

The multisensory integration of signals from different senses is crucial to develop an unambiguous percept of the environment and our body. Losing a limb causes drastic changes in the body, sometimes causing pain and distorted phantom limb perception. Despite the debate over why these phenomena arise, some researchers suggested that they might be linked to an impairment of multisensory signals inflow and integration.

Corrigendum: A Psychometric Platform to Collect Somatosensory Sensations for Neuroprosthetic Use.

[This corrects the article DOI: 10.3389/fmedt.2021.