Limb loss leads to severe sensorimotor deficits and requires the use of a prosthetic device, especially in lower-limb amputees. While direct recording from residual nerves offers a biomimetic route for an effective prosthetic control, the low amplitude and noisy nature of these neural signals together with the challenge of establishing a reliable nerve interfacing, have hindered its adoption. Intraneural multichannel electrodes could potentially establish an effective interface with the nerve fibers, enabling access to motor signals even from muscles lost after the amputation. In this study, we report the direct neural recordings of two transfemoral amputees using transversal intrafascicular multichannel electrodes (TIME) implanted in the tibial nerves. We observed multiunit activity associated with volitional phantom movements of the knee, ankle and toes flexion and extension, with joint- and direction-specific neural modulation in both participants. The motor signals were distributed across all the electrodes, showing both single-joint and multi-joint selectivity, as well as direction selectivity for limb flexion and extension. After characterizing the neural evoked activity, we developed a Spiking Neural Network (SNN)-based decoder that outperform conventional motor decoders in predicting attempted phantom leg movements. Decoding accuracy improved further by including a broader signal bandwidth that captured both intraneural (ENG) and inter-muscular (imEMG) activity. Finally, comparing motor maps (recording) with sensory maps (stimulation) revealed a minimal overlap, suggesting early segregation of motor and sensory fibers within the tibial nerve before the knee bifurcation. Our findings demonstrate the feasibility to record motor signal and decode lower-limb movements directly from the nerves in amputees using intraneural interfaces. This paves the way for bidirectional, neurally-controlled prosthetic limbs combining natural control with somatosensory feedback through a single implanted interface.

G.V. holds shares of MYNERVA AG, a start-up company dealing with the potential commercialization of non-invasive stimulating wearable for treating neuropathic pain. G.V. serves as a consultant for NeuroOne Medical Technologies Corporation (USA). The other authors do not have anything to disclose.

NCT03350061

This project has received funding from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program (FeelAgain grant agreement no. 759998).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval was obtained from the institutional ethics committees of the Clinical Center of Serbia (original IRB), Belgrade, Serbia (ClinicalTrials.gov identifier NCT03350061).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.