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  • Journal article
    Hug F, Avrillon S, Sarcher A, Del Vecchio A, Farina Det al., 2023,

    Correlation networks of spinal motor neurons that innervate lower limb muscles during a multi-joint isometric task

    , The Journal of Physiology, Vol: 601, Pages: 3201-3219, ISSN: 0022-3751

    Movements are reportedly controlled through the combination of synergies that generate specific motor outputs by imposing an activation pattern on a group of muscles. To date, the smallest unit of analysis of these synergies has been the muscle through the measurement of its activation. However, the muscle is not the lowest neural level of movement control. In this human study (n = 10), we used a purely data-driven method grounded on graph theory to extract networks of motor neurons based on their correlated activity during an isometric multi-joint task. Specifically, high-density surface electromyography recordings from six lower limb muscles were decomposed into motor neurons spiking activity. We analyzed these activities by identifying their common low-frequency components, from which networks of correlated activity to the motor neurons were derived and interpreted as networks of common synaptic inputs. The vast majority of the identified motor neurons shared common inputs with other motor neuron(s). In addition, groups of motor neurons were partly decoupled from their innervated muscle, such that motor neurons innervating the same muscle did not necessarily receive common inputs. Conversely, some motor neurons from different muscles – including distant muscles – received common inputs. Our study supports the theory that movements are produced through the control of small numbers of groups of motor neurons via common inputs and that there is a partial mismatch between these groups of motor neurons and muscle anatomy. We provide a new neural framework for a deeper understanding of the structure of common inputs to motor neurons.Abstract figure legend Ten participants performed an isometric multi-joint task, which consisted in producing force on an instrumented pedal. Adhesive grids of 64 electrodes were placed over six lower limb muscles (gastrocnemius medialis [GM] and lateralis [GL], vastus lateralis [VL] and medialis [VM], biceps femoris [BF], semit

  • Journal article
    Ibanez Pereda J, Zicher B, Brown KE, Rocchi L, Casolo A, Del Vecchio A, Spampinato DA, Vollette C-A, Rothwell JC, Baker SN, Farina Det al., 2023,

    Standard intensities of transcranial alternating current stimulation over the motor cortex do not entrain corticospinal inputs to motor neurons

    , The Journal of Physiology, Vol: 601, Pages: 3187-3199, ISSN: 0022-3751

    Transcranial alternating current stimulation (TACS) is commonly used to synchronise a cortical area and its outputs to the stimulus waveform, but evidence for this based on brain recordings in humans is challenging. The corticospinal tract transmits beta oscillations (~21Hz) from motor cortex to tonically contracted limb muscles linearly. Therefore, muscle activity may be used to measure the level of beta entrainment in the corticospinal tract due to TACS over motor cortex. Here, we assessed if TACS is able to modulate the neural inputs to muscles, which would provide indirect evidence for TACS-driven neural entrainment. In the first part of this study, we ran simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results suggest that MNs are highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N=10) in which TACS (at 1mA) was delivered over the motor cortex at 21Hz (beta stimulation), or at 7Hz or 40Hz (control conditions) while the abductor digiti minimi or the tibialis anterior muscle were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the activity of pools of motor units innervating the muscles. By analysing motor unit pool activity, we observed that none of the TACS conditions could consistently alter the spectral contents of the common neural inputs received by the muscles. These results suggest that 1mA-TACS over motor cortex given at beta frequencies does not entrain corticospinal activity.

  • Journal article
    Hug F, Avrillon S, Sarcher A, Del Vecchio A, Farina D, Hug F, Avrillon S, Sarcher A, Del Vecchio A, Farina Det al., 2023,

    Correlation networks of spinal motor neurons that innervate lower limb muscles during a multi-joint isometric task

    , JOURNAL OF PHYSIOLOGY-LONDON, Vol: 601, Pages: 3201-3219, ISSN: 0022-3751
  • Journal article
    Farina D, Vujaklija I, Branemark R, Bull AMJ, Dietl H, Graimann B, Hargrove LJ, Hoffmann K-P, Huang HH, Ingvarsson T, Janusson HB, Kristjansson K, Kuiken T, Micera S, Stieglitz T, Sturma A, Tyler D, Weir RFF, Aszmann OCet al., 2023,

    Toward higher-performance bionic limbs for wider clinical use

    , Nature Biomedical Engineering, Vol: 7, Pages: 473-485, ISSN: 2157-846X

    Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs.

  • Journal article
    Vujaklija I, IEEE Member, Ki Jung M, Hasenoehrl T, Roche AD, Sturma A, Muceli S, Senior IEEE Member, Crevenna R, Aszmann OC, Farina D, IEEE Fellowet al., 2023,

    Biomechanical analysis of body movements of myoelectric prosthesis users during standardized clinical tests

    , IEEE Transactions on Biomedical Engineering, Vol: 70, Pages: 789-799, ISSN: 0018-9294

    Objective: The objective clinical evaluation of user's capabilities to handle their prosthesis is done using various tests which primarily focus on the task completion speed and do not explicitly account for the potential presence of compensatory motions. Given that the excessive body compensation is a common indicator of inadequate prosthesis control, tests which include subjective observations on the quality of performed motions have been introduced. However, these metrics are then influenced by the examiner's opinions, skills, and training making them harder to standardize across patient pools and compare across different prosthetic technologies. Here we aim to objectively quantify the severity of body compensations present in myoelectric prosthetic hand users and evaluate the extent to which traditional objective clinical scores are still able to capture them. Methods: We have instructed 9 below-elbow prosthesis users and 9 able-bodied participants to complete three established objective clinical tests: Box-and-Blocks-Test, Clothespin-Relocation-Test, and Southampton-Hand-Assessment-Procedure. During all tests, upper-body kinematics has been recorded. Results: While the analysis showed that there are some correlations between the achieved clinical scores and the individual body segment travel distances and average speeds, there were only weak correlations between the clinical scores and the observed ranges of motion. At the same time, the compensations were observed in all prosthesis users and, for the most part, they were substantial across the tests. Conclusion: The sole reliance on the currently available objective clinical assessment methods seems inadequate as the compensatory movements are prominent in prosthesis users and yet not sufficiently accounted for.

  • Journal article
    Nowak M, Vujaklija I, Sturma A, Castellini C, Farina Det al., 2023,

    Simultaneous and proportional real-time myocontrol of up to three degrees of freedom of the wrist and hand

    , IEEE Transactions on Biomedical Engineering, Vol: 70, Pages: 459-469, ISSN: 0018-9294

    Achieving robust, intuitive, simultaneous and proportional control over multiple degrees of freedom (DOFs) is an outstanding challenge in the development of myoelectric prosthetic systems. Since the priority inmyoelectric prosthesis solutions is robustness and stability, their number of functions is usually limited. Objective: Here, we introduce a system for intuitive concurrent hand and wrist control, based on a robust feature-extraction protocol and machine-learning. Methods: Using the meanabsolute value of high-density EMG, we train a ridge-regressor (RR) on only the sustained portions of the single-DOF contractions and leverage the regressor’s inherent ability to provide simultaneous multi-DOF estimates. In this way, we robustly capture the amplitude information of the inputs while harnessing the power of the RR to extrapolate otherwise noisy and often overfitted estimations of dynamic portions of movements. Results: The real-time evaluation of the system on 13 able-bodied participants and an amputee shows that almost all single-DOF tasks could be reached (96% success rate), while at the same time users were able to complete most of the two-DOF (62%) and even some of the very challenging three-DOF tasks (37%). To further investigate the translational potential of the approach, we reduced the original 192-channel setup to a 16-channel configuration and the observed performance did not deteriorate. Notably, the amputee performed similarly well to the other participants, according to all considered metrics. Conclusion: This is the first real-time operated myocontrol system that consistently provides intuitive simultaneous and proportional control over 3-DOFs of wrist and hand, relying on only surface EMG signals from the orearm. Significance: Focusing on reduced complexity, a real-time test and the inclusion of an amputee in the study demonstrate the translational potential of the control system for future applications in prosthetic control.

  • Journal article
    Tereshenko V, Maierhofer U, Dotzauer DC, Laengle G, Schmoll M, Festin C, Luft M, Carrero Rojas G, Politikou O, Hruby LA, Klein HJ, Eisenhardt SU, Farina D, Blumer R, Bergmeister KD, Aszmann OCet al., 2023,

    Newly identified axon types of the facial nerve unveil supplemental neural pathways in the innervation of the face.

    , J Adv Res, Vol: 44, Pages: 135-147

    INTRODUCTION: Neuromuscular control of the facial expressions is provided exclusively via the facial nerve. Facial muscles are amongst the most finely tuned effectors in the human motor system, which coordinate facial expressions. In lower vertebrates, the extracranial facial nerve is a mixed nerve, while in mammals it is believed to be a pure motor nerve. However, this established notion does not agree with several clinical signs in health and disease. OBJECTIVES: To elucidate the facial nerve contribution to the facial muscles by investigating axonal composition of the human facial nerve. To reveal new innervation pathways of other axon types of the motor facial nerve. METHODS: Different axon types were distinguished using specific molecular markers (NF, ChAT, CGRP and TH). To elucidate the functional role of axon types of the facial nerve, we used selective elimination of other neuronal support from the trigeminal nerve. We used retrograde neuronal tracing, three-dimensional imaging of the facial muscles, and high-fidelity neurophysiological tests in animal model. RESULTS: The human facial nerve revealed a mixed population of only 85% motor axons. Rodent samples revealed a fiber composition of motor, afferents and, surprisingly, sympathetic axons. We confirmed the axon types by tracing the originating neurons in the CNS. The sympathetic fibers of the facial nerve terminated in facial muscles suggesting autonomic innervation. The afferent fibers originated in the facial skin, confirming the afferent signal conduction via the facial nerve. CONCLUSION: These findings reveal new innervation pathways via the facial nerve, support the sympathetic etiology of hemifacial spasm and elucidate clinical phenomena in facial nerve regeneration.

  • Journal article
    Shirzadi M, Marateb HRR, McGill KCC, Muceli S, Mananas MAA, Farina Det al., 2023,

    An Accurate and Real-Time Method for Resolving Superimposed Action Potentials in MultiUnit Recordings

    , IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 70, Pages: 378-389, ISSN: 0018-9294
  • Journal article
    Jiang X, Liu X, Fan J, Ye X, Dai C, Clancy EA, Farina D, Chen Wet al., 2022,

    Optimization of HD-sEMG-Based Cross-Day Hand Gesture Classification by Optimal Feature Extraction and Data Augmentation

    , IEEE TRANSACTIONS ON HUMAN-MACHINE SYSTEMS, Vol: 52, Pages: 1281-1291, ISSN: 2168-2291
  • Journal article
    Koutsoftidis S, Barsakcioglu DY, Petkos K, Farina D, Drakakis Eet al., 2022,

    Myolink: A 128-Channel, 18 nV/√Hz, Embedded Recording System, Optimized for High-Density Surface Electromyogram Acquisition

    , IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 69, Pages: 3389-3396, ISSN: 0018-9294
  • Journal article
    Caillet A, Phillips ATM, Farina D, Modenese Let al., 2022,

    Mathematical relationships between spinal motoneuron properties

    , eLife, Vol: 11, ISSN: 2050-084X

    Our understanding of the behaviour of spinal alpha-motoneurons (MNs) in mammals partly relies on our knowledge of the relationships between MN membrane properties, such as MN size, resistance, rheobase, capacitance, time constant, axonal conduction velocity and afterhyperpolarization period. We reprocessed the data from 40 experimental studies in adult cat, rat and mouse MN preparations, to empirically derive a set of quantitative mathematical relationships between these MN electrophysiological and anatomical properties. This validated mathematical framework, which supports past findings that the MN membrane properties are all related to each other and clarifies the nature of their associations, is besides consistent with the Henneman’s size principle and Rall’s cable theory. The derived mathematical relationships provide a convenient tool for neuroscientists and experimenters to complete experimental datasets, to explore relationships between pairs of MN properties never concurrently observed in previous experiments, or to investigate inter-mammalian-species variations in MN membrane properties. Using this mathematical framework, modelers can build profiles of inter-consistent MN-specific properties to scale pools of MN models, with consequences on the accuracy and the interpretability of the simulations.

  • Journal article
    Lubel E, Sgambato BG, Barsakcioglu DY, Ibanez J, Tang M-X, Farina Det al., 2022,

    Kinematics of individual muscle units in natural contractions measured <i>in vivo</i> using ultrafast ultrasound

    , JOURNAL OF NEURAL ENGINEERING, Vol: 19, ISSN: 1741-2560
  • Journal article
    Del Vecchio A, Jones RHA, Schofield IS, Kinfe TM, Ibáñez J, Farina D, Baker SNet al., 2022,

    Interfacing motor units in non-human primates identifies a principal neural component for force control constrained by the size principle

    , The Journal of Neuroscience, Vol: 42, Pages: 7383-7399, ISSN: 0270-6474

    Motor units convert the last neural code of movement into muscle forces. The classic view of motor unit control is that the central nervous system sends common synaptic inputs to motoneuron pools and that motoneurons respond in an orderly fashion dictated by the size principle. This view however is in contrast with the large number of dimensions observed in motor cortex which may allow individual and flexible control of motor units. Evidence for flexible control of motor units may be obtained by tracking motor units longitudinally during tasks with some level of behavioural variability. Here we identified and tracked populations of motor units in the brachioradialis muscle of two macaque monkeys during ten sessions spanning over one month with a broad range of rate of force development (1.8 - 38.6 N∙m∙s-1). We found a very stable recruitment order and discharge characteristics of the motor units over sessions and contraction trials. The small deviations from orderly recruitment were fully predicted by the motor unit recruitment intervals, so that small shifts in recruitment thresholds happened only during contractions at high rate of force development. Moreover, we also found that one component explained more than ~50% of the motor unit discharge rate variance, and that the remaining components represented a time-shifted version of the first. In conclusion, our results show that motoneurons recruitment is determined by the interplay of the size principle and common input and that this recruitment scheme is not violated over time nor by the speed of the contractions.

  • Journal article
    de Oliveira DS, Casolo A, Balshaw TG, Maeo S, Lanza MB, Martin NRW, Maffulli N, Kinfe TM, Eskofier BM, Folland JP, Farina D, Del Vecchio Aet al., 2022,

    Neural decoding from surface high-density EMG signals: influence of anatomy and synchronization on the number of identified motor units

    , JOURNAL OF NEURAL ENGINEERING, Vol: 19, ISSN: 1741-2560
  • Journal article
    Yeung D, Guerra IM, Barner-Rasmussen I, Siponen E, Farina D, Vujaklija Iet al., 2022,

    Co-Adaptive Control of Bionic Limbs via Unsupervised Adaptation of Muscle Synergies

    , IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 69, Pages: 2581-2592, ISSN: 0018-9294
  • Journal article
    Yao L, Jiang N, Mrachacz-Kersting N, Zhu X, Farina D, Wang Yet al., 2022,

    Reducing the calibration time in somatosensory BCI by using tactile ERD

    , IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol: 30, ISSN: 1534-4320

    Objective: We propose a tactile-induced-oscillation approach to reduce the calibration time in somatosensory brain-computer interfaces (BCI). Methods: Based on the similarity between tactile induced event-related desynchronization (ERD) and imagined sensation induced ERD activation, we extensively evaluated BCI performance when using a conventional and a novel calibration strategy. In the conventional calibration, the tactile imagined data was used, while in the sensory calibration model sensory stimulation data was used. Subjects were required to sense the tactile stimulus when real tactile was applied to the left or right wrist and were required to perform imagined sensation tasks in the somatosensory BCI paradigm. Results: The sensory calibration led to a significantly better performance than the conventional calibration when tested on the same imagined sensation dataset (F(1,19)=10.89, P=0.0038), with an average 5.1% improvement in accuracy. Moreover, the sensory calibration was 39.3% faster in reaching a performance level of above 70% accuracy. Conclusion: The proposed approach of using tactile ERD from the sensory cortex provides an effective way of reducing the calibration time in a somatosensory BCI system. Significance: The tactile stimulation would be specifically useful before BCI usage, avoiding excessive fatigue when the mental task is difficult to perform. The tactile ERD approach may find BCI applications for patients or users with preserved afferent pathways.

  • Journal article
    Bracklein M, Barsakcioglu DY, Ibanez J, Eden J, Burdet E, Mehring C, Farina Det al., 2022,

    The control and training of single motor units in isometric tasks are constrained by a common input signal

    , ELIFE, Vol: 11, ISSN: 2050-084X
  • Journal article
    Gstoettner C, Festin C, Prahm C, Bergmeister KD, Salminger S, Sturma A, Hofer C, Russold MF, Howard CL, McDonnall D, Farina D, Aszmann OCet al., 2022,

    Feasibility of a Wireless Implantable Multi-electrode System for High-bandwidth Prosthetic Interfacing: Animal and Cadaver Study.

    , Clin Orthop Relat Res, Vol: 480, Pages: 1191-1204

    BACKGROUND: Currently used prosthetic solutions in upper extremity amputation have limited functionality, owing to low information transfer rates of neuromuscular interfacing. Although surgical innovations have expanded the functional potential of the residual limb, available interfaces are inefficacious in translating this potential into improved prosthetic control. There is currently no implantable solution for functional interfacing in extremity amputation which offers long-term stability, high information transfer rates, and is applicable for all levels of limb loss. In this study, we presented a novel neuromuscular implant, the the Myoelectric Implantable Recording Array (MIRA). To our knowledge, it is the first fully implantable system for prosthetic interfacing with a large channel count, comprising 32 intramuscular electrodes. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the MIRA in terms of biocompatibility, functionality, and feasibility of implantation to lay the foundations for clinical application. This was achieved through small- and large-animal studies as well as test surgeries in a human cadaver. METHODS: We evaluated the biocompatibility of the system's intramuscular electromyography (EMG) leads in a rabbit model. Ten leads as well as 10 pieces of a biologically inert control material were implanted into the paravertebral muscles of four animals. After a 3-month implantation, tissue samples were taken and histopathological assessment performed. The probes were scored according to a protocol for the assessment of the foreign body response, with primary endpoints being inflammation score, tissue response score, and capsule thickness in µm. In a second study, chronic functionality of the full system was evaluated in large animals. The MIRA was implanted into the shoulder region of six dogs and three sheep, with intramuscular leads distributed across agonist and antagonist muscles of shoulder flexion. During the observation perio

  • Journal article
    Gallina A, Disselhorst-Klug C, Farina D, Merletti R, Besomi M, Holobar A, Enoka RM, Hug F, Falla D, Søgaard K, McGill K, Clancy EA, Carson RG, van Dieën JH, Gandevia S, Lowery M, Besier T, Kiernan MC, Rothwell JC, Tucker K, Hodges PWet al., 2022,

    Consensus for experimental design in electromyography (CEDE) project: High-density surface electromyography matrix.

    , J Electromyogr Kinesiol, Vol: 64

    High-density surface electromyography (HDsEMG) can be used to measure the spatial distribution of electrical muscle activity over the skin. As this distribution is associated with the generation and propagation of muscle fiber action potentials, HDsEMG is processed to extract information on regional muscle activation, muscle fiber characteristics and behaviour of individual motor units. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, summarizes recommendations on the use of HDsEMG in experimental studies. For each application, recommendations are included regarding electrode montage, electrode type and configuration, electrode location and orientation, data analysis, and interpretation. Cautions and reporting standards are also included. The steps of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers when collecting, reporting, and interpreting HDsEMG data. It is hoped that this document will be used to generate new empirical evidence to improve how HDsEMG is used in research and in clinical applications.

  • Journal article
    Niazi IK, Navid MS, Rashid U, Amjad I, Olsen S, Haavik H, Alder G, Kumari N, Signal N, Taylor D, Farina D, Jochumsen Met al., 2022,

    Associative cued asynchronous BCI induces cortical plasticity in stroke patients.

    , Ann Clin Transl Neurol, Vol: 9, Pages: 722-733

    OBJECTIVE: We propose a novel cue-based asynchronous brain-computer interface(BCI) for neuromodulation via the pairing of endogenous motor cortical activity with the activation of somatosensory pathways. METHODS: The proposed BCI detects the intention to move from single-trial EEG signals in real time, but, contrary to classic asynchronous-BCI systems, the detection occurs only during time intervals when the patient is cued to move. This cue-based asynchronous-BCI was compared with two traditional BCI modes (asynchronous-BCI and offline synchronous-BCI) and a control intervention in chronic stroke patients. The patients performed ankle dorsiflexion movements of the paretic limb in each intervention while their brain signals were recorded. BCI interventions decoded the movement attempt and activated afferent pathways via electrical stimulation. Corticomotor excitability was assessed using motor-evoked potentials in the tibialis-anterior muscle induced by transcranial magnetic stimulation before, immediately after, and 30 min after the intervention. RESULTS: The proposed cue-based asynchronous-BCI had significantly fewer false positives/min and false positives/true positives (%) as compared to the previously developed asynchronous-BCI. Linear-mixed-models showed that motor-evoked potential amplitudes increased following all BCI modes immediately after the intervention compared to the control condition (p <0.05). The proposed cue-based asynchronous-BCI resulted in the largest relative increase in peak-to-peak motor-evoked potential amplitudes(141% ± 33%) among all interventions and sustained it for 30 min(111% ± 33%). INTERPRETATION: These findings prove the high performance of a newly proposed cue-based asynchronous-BCI intervention. In this paradigm, individuals receive precise instructions (cue) to promote engagement, while the timing of brain activity is accurately detected to establish a precise ass

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