NeurOne: High-performance Motor Unit-Computer Interface for the Paralyzed

We have recently demonstrated that humans with motor-and-sensory complete cervical spinal cord injury (SCI) can modulate the activity of spared motor neurons that control the movements of paralyzed muscles. These motor neurons still receive highly functional cortical inputs that proportionally control flexion and extension movements of the paralyzed hand digits. In this study, we report a series of longitudinal experiments in which subjects with motor complete SCI received motor unit feedback from NeurOne. NeurOne is a software that realizes super-fast digitalization of motor neuron spiking activity (32 frames/s) and control of these neural ensembles through a physiological motor unit twitch model that enables intuitive brain-computer interactions closely matching the voluntary force modulation of healthy hand digits. We asked the subjects (n=3, 3-4 laboratory visits) to match a target displayed on a monitor through a cursor that was controlled by the modulation of the recruitment and rate coding of the spared motor units using a motor unit twitch model. The attempted movements of the paralyzed hands involved grasping and hand digit extension/flexion. The target cursor was scaled in a way that the subjects could increase or decrease feedback by either recruiting or derecruiting motor units, or by modulating the instantaneous discharge rate. The subjects learned to control the motor unit output with high levels of accuracy across different target intensities up to the maximal achievable discharge rate. Indeed, the high-performance motor output was surprisingly stable in a similar way as healthy subjects modulated the muscle force output recorded by a dynamometer. Therefore, NeurOne enables tetraplegic individuals an intuitive control of the paralyzed muscles through a digital neuromuscular system. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This study is not a clinical trial. ### Funding Statement This study was partly funded by d.hip (Digital Health Innovation Platform), a cooperation between Siemens Healthineers, Medical Valley, University Hospital Erlangen, and Friedrich-Alexander University Erlangen-Nuremberg, and the German Aerospace Center (DLR) as part of the MYOREHAB project. ### Author Declarations 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 Committee of Friedrich-Alexander-Universitaet Erlangen-Nuernberg gave ethical approval for experiment 1 in this work (approval no. 22-138-Bm). Ethical Committee of Imperial College London gave ethical approval for experiment 2 in this work (approval no. 18IC4685). Ethical Committee of University Rome 'Foro Italico' gave ethical approval for experiment 3 in this work (approval no. 44 680). 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. An executable of NeurOne can be found in the public repository of the Neuromuscular Physiology and Neural Interfacing Laboratory at the Friedrich-Alexander-Universitaet Erlangen-Nuernberg.