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

Objective. 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.g. pulse amplitude (PA), pulse-width (PW) or pulse frequency (PF)). They elicit artificial sensations characterized by a low intensity resolution (e.g. few perceived levels), low naturalness and intuitiveness, hindering the acceptance of this technology. To address these issues, we designed novel multiparametric stimulation paradigms, featuring the simultaneous modulation of multiple parameters, and implemented them in real-time tests of performance when exploited as artificial sensory inputs.Approach. We initially investigated the contribution of PW and PF variations to the perceived sensation magnitude through discrimination tests. Then, we designed three multiparametric stimulation paradigms comparing them with a standard PW linear modulation in terms of evoked sensation naturalness and intensity. The most performant paradigms were then implemented in real-time in a Virtual Reality-TENS platform to assess their ability to provide intuitive somatosensory feedback in a functional task.Main results. Our study highlighted a strong negative correlation between perceived naturalness and intensity: less intense sensations are usually deemed as more similar to natural touch. In addition, we observed that PF and PW changes have a different weight on the perceived sensation intensity. As a result, we adapted the activation charge rate (ACR) equation, proposed for implantable neurostimulation to predict the perceived intensity while co-modulating the PF and charge per pulse, to TENS (ACRT). ACRTallowed to design different multiparametric TENS paradigms with the same absolute perceived intensity. Although not reported as more natural, the multiparametric paradigm, based on sinusoidal PF modulation, resulted being more intuitive and subconsciously integrated than the standard linear one. This allowed subjects to achieve a faster and more accurate functional performance.Significance. Our findings suggest that TENS-based, multiparametric neurostimulation, despite not consciously perceived naturally, can provide integrated and more intuitive somatosensory information, as functionally proved. This could be exploited to design novel encoding strategies able to improve the performance of non-invasive sensory feedback technologies.

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. The model simulates neural spiking responses to arbitrary mechanical stimuli from the combined population of all four types of mechanoreceptors innervating the foot sole. It considers specific mechanics of the foot sole skin tissue, and model internal parameters are fitted using human microneurography recording dataset. FootSim can be exploited for neuroscientific insights, to understand the overall afferent activation in dynamic conditions, and for overcoming the limitation of currently available recording techniques. Furthermore, neuroengineers can use the model as a robust in silico tool for neuroprosthetic applications and for designing biomimetic stimulation patterns starting from the simulated afferent neural responses.

Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain.

Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1-4. The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg5,6. To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes7 in the remaining tibial nerve (ClinicalTrials.gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback.