Thomas Klotz

Magnetomyography (MMG) holds great potential as a contactless alternative to electromyography (EMG). However, the spatiotemporal dynamics of the myomagnetic field in vivo remain largely unknown, limiting signal interpretability and hence the use of MMG. Here, the myomagnetic field of the abductor digiti minimi muscle is measured in vivo at 69‐by‐2 effective positions by scanning a grid of six triaxial optically pumped magnetometers (OPMs) along the muscle, while reproducible muscle contractions are evoked electrically. In this way, the compound muscle action field (CMAF) is measured with high density (1 mm sampling steps) and its evolution is referenced to the underlying anatomy based on 3D scans and magnetic resonance images. A model is used to simulate the expected signals. It suggests that the clinically relevant innervation zone (IZ) manifests as a zero‐crossing of the azimuthal CMAF component. Based on this, contactless IZ localization is demonstrated in three subjects by projecting the zero‐crossing onto the skin. The estimated IZ localizations deviate by 1.7 mm to 4.1 mm from estimates with simultaneously recorded 64‐channel surface EMG. With the first millimeter‐scale spatiotemporal mapping of magnetic muscle activity in vivo, this study paves the way for the use of MMG in biomedical applications.

Electromyography (EMG) is fundamental to clinical assessment, rehabilitation, neuromuscular research, and human-machine interfaces. Despite decades of use, no widely adopted standard exists for organizing and sharing EMG data, limiting reusability and large-scale data aggregation. We present EMG-BIDS, an extension to the Brain Imaging Data Structure (BIDS) that standardizes the organization of EMG recordings. EMG-BIDS addresses challenges unique to EMG, including diverse electrode types (surface or intramuscular, single channel to high-density arrays), heterogeneous electrode placements across anatomical locations, montages (e.g., monopolar or bipolar sensor designs), and the critical need for transparent documentation of sensor positioning. The specification introduces hierarchical coordinate systems that link local electrode grids to anatomical landmarks, enabling precise and reproducible placement documentation. EMG-BIDS is now part of BIDS as of version 1.11.0, supported by existing tools, including MNE-BIDS and EEGLAB. We demonstrate the specification through public datasets, including high-density surface EMG recordings. EMG-BIDS provides the foundation for FAIR (Findable, Accessible, Interoperable, Reusable) EMG data sharing, enabling meta-analyses, multi-site studies, and machine learning applications that require standardized, well-documented datasets.

Objective: Investigation of the feasibility and characteristics of contactless motor unit number estimation (MUNE) using optically pumped magnetometer–based magnetomyography (OPM-MMG) as compared to surface electromyography (EMG). Methods: Simultaneous electrically evoked OPM-MMG and EMG signals of the abductor digiti minimi muscle (ADM) were measured in three healthy participants. To characterize MUNE across both modalities and account for within-subject physiological variability, 20 repetitions of electrical stimulation of the ulnar nerve at randomized intensities ranging from 5 to 30 mA in 0.1 mA increments were performed, resulting in a total of 5,020 evoked responses per subject. We quantitatively compared of MUNE and evoked EMG/MMG signal characteristics, including signal-to-noise ratio (SNR) and motor unit response amplitudes. SNR was equalized between measurement modalities to estimate the effect of SNR on MUNE. Results: MMG-derived MUNE (mMUNE) could be assessed contactlessly. mMUNE estimates were on average 40% lower than EMG-derived MUNE (eMUNE), ranging from 30–65 for mMUNE versus 69–101 for eMUNE. Equalizing the EMG SNR (29–31 dB) to match the MMG SNR (18–27 dB) yielded comparable eMUNE and mMUNE estimates. Peak-to-peak amplitudes of the supramaximal compound motor unit fields ranged from 34–73 pT and single motor unit fields ranged from 0.7–1.4 pT. Significance: These findings demonstrate that OPM-MMG enables contactless motor unit number estimation.

Zusammenfassung: Die hochdichte oberflächliche Elektromyografie (HDsEMG) ermöglicht durch ihre hohe räumliche und zeitliche Auflösung in Kombination mit geeigneten Signaltrennmethoden die nicht-invasive, gleichzeitige Erfassung ganzer Populationen motorischer Einheiten (MU). Damit erweitert sie das diagnostische Spektrum des klassischen Nadel-EMGs, das sich durch die präzise Analyse einiger weniger MUs auszeichnet. Besonders bei Erkrankungen mit Veränderungen auf Populationsebene der MU, wie Amyotropher Lateralsklerose, hereditären Neuropathien, diabetischer Polyneuropathie oder Spastizität, bietet HDsEMG neue Einblicke in die Organisation und Dynamik der motorischen Kontrolle bei Willküraktivität. Somit eröffnet HDsEMG klinisch relevante Möglichkeiten für Verlaufsuntersuchungen und die Therapieüberwachung. Für die breite Implementierung sind jedoch standardisierte Workflows, validierte Kennwerte und geschultes Fachpersonal erforderlich.

To investigate the mechanisms governing energy and redox balance in skeletal muscle, we developed a computational model describing the coupled biochemical reaction network of glycolysis and mitochondrial oxidative phosphorylation (OxPhos) in fast‐twitch oxidative glycolytic (FOG) muscle fibres. The model was identified against dynamic in vivo recordings of phosphocreatine (PCr), inorganic phosphate (Pi) and pH in rodent hindlimb muscle and verified against independent data from in vivo experiments and muscle biopsies. Step response testing reveals that mass action kinetics in combination with feedback control are sufficient to accomplish myoplasmic ATP homeostasis over a 100‐fold range of ATP turnover rates. This vital emergent property of the metabolic model is associated with intermediary metabolite dynamics typical of a second‐order underdamped system, which has been previously reported for the glycolytic pathway. Lactate dehydrogenase (LDH) knockout simulations suggest that the contribution of the LDH reaction to redox balance is more fundamental to muscle function than its role in counteracting myoplasmic acidification across the physiological range of ATP demands in this myofibre phenotype. Furthermore, LDH knockout simulations confirm that mitochondrial uptake of myoplasmic NADH and H ⁺ in and by itself is sufficient to maintain redox balance and proton balance over ATP turnover rates in the range of mitochondrial ATP synthesis. We conclude that aerobic lactate production in working muscles is a by‐product of the metabolic flexibility of FOG myofibres afforded by expression of high levels of LDH and OxPhos enzymes to support continual myoplasmic redox balance and ATP synthesis under conditions of high‐intensity mechanical work. image Key points: Feedback regulation suffices to accomplish myoplasmic ATP homeostasis over a 100‐fold range of ATP turnover. Second‐order underdamped behaviour is predicted to arise as a generic trait of the ATP metabolic network in mammalian cells. Aerobic lactate is a by‐product of the metabolic and functional flexibility. LDH's role in maintaining redox balance is more important than its role in counteracting cellular acidification.

Motor unit (MU) activity during electrically or mechanically evoked reflexes is used to examine the relationship between neural inputs and MU properties. However, variations in single-MU reflex amplitudes are not fully understood and limit their reliability in determining the input-output relation of motor neurons (MNs). Using experiments and computer simulations, we investigated (i) whether MN discharge statistics and muscle activation explain the variability of reflex amplitude estimates and (ii) whether these variations are reflected differently across distinct reflex amplitude estimation methods. We analyzed MU spike trains extracted from isometric contractions of the tibialis anterior muscle at 10 % and 20 % MVC (maximum voluntary contraction). Estimating reflex amplitudes based on the peristimulus frequencygram (PSF) at 10 % MVC, the linear regression between discharge rate (DR) and reflex amplitude was always positive, with p < 0.05 in 3 out of 6 subjects; however, the linear correlation was inconsistent at 20 % MVC. We thereby observed that inter-subject variability was associated with the coefficient of variation of the interspike intervals. Furthermore, the linear correlation between DR and peristimulus time histogram (PSTH) based reflex amplitudes was inconsistent for both contraction forces. To obtain further insights into the influence of MN properties, we simulated reflexes in a heterogeneous MN population using electrical circuit models and varied MN inputs. The simulations indicate that, besides mean input current and membrane noise, MN properties also contribute to the variability of reflex amplitude estimates. The MN heterogeneity is well captured by PSF-based reflex estimates but not by PSTH-based ones. These results show that variations in amplitude estimates of individual MU reflexes are due to complex interactions between intrinsic and extrinsic factors. As PSF-based reflex amplitude estimates reflect the MN size distribution, tracking PSF-based reflex amplitudes at fixed MVC levels across individual subjects could serve as a marker for investigating spinal adaptations under (patho)physiological conditions. Author summary: Motor neurons are specialized nerve cells that control human movement. Each motor neuron activates a specific set of muscle fibers, and the functional unit consisting of a motor neuron and muscle fibers is called a motor unit. We can observe the activity of motor neurons in humans by decomposing the electrical activity of muscles (the electromyogram) into contributions from individual motor units. Reflex responses of motor units are often used to study the input-output relation of motor neurons in humans. We used a combination of experiments and computer simulations to study the factors that influence the reflex amplitude of motor units during an excitatory reflex. We found that the reflex amplitude is non-linearly influenced by a number of intrinsic and extrinsic factors, e. g., motor neuron size, but also the muscle force. Additionally, we found that these factors have different effects on the results of the two common methods used to calculate the reflex amplitude. These results provide guidance on choosing a suitable evaluation method and on interpreting reflex experiments.

Objective. Identifying the spiking activity of alpha motor neurons (MNs) non-invasively is possible by decomposing signals from active muscles, e.g. obtained with surface electromyography (EMG) or ultrasound. The theoretical background of MN identification using these techniques is convolutive blind source separation (cBSS), in which different algorithms have been developed and validated. However, the existence and identifiability of inverse solutions and the corresponding estimation errors are not fully understood. In addition, the guidelines for selecting appropriate hyper-parameters are often built on empirical observations, limiting the translation to clinical applications and other modalities. Approach. We revisited the cBSS model for EMG-based MN identification, augmented it with new theoretical insights and derived a framework that can predict the existence of solutions for spike train estimates. This framework allows the quantification of source estimation errors due to the imperfect inversion of the motor unit action potentials (MUAPs), physiological and non-physiological noise, and the ill-conditioning of the inverse problem. To bridge the gap between theory and practice, we used computer simulations. Main results. (1) Increasing the similarity of MUAPs or the correlation between spike trains increases the bias for detecting MN spike trains linked with high amplitude MUAPs. (2) The optimal objective function depends on the expected spike amplitude, spike amplitude statistics and the amplitude of background spikes. (3) There is some wiggle room for MN detection given non-stationary MUAPs, (4) There is no connection between MUAP duration and extension factor, in contrast to previous guidelines. (5) Source quality metrics like the silhouette score (SIL) or the pulse-to-noise ratio (PNR) are highly correlated with a source’s objective function output. (6) Considering established source quality measures, SIL is superior to PNR. Significance. We expect these findings will guide cBSS algorithm developments tailored for MN identification and translation to clinical applications.

In order to investigate the mechanisms governing energy and redox balance in skeletal muscle, we developed a computational model describing the coupled biochemical reaction network of glycolysis and mitochondrial oxidative phosphorylation (OxPhos) in fast-twitch oxidative glycolytic (FOG) muscle fibers. The model was identified against dynamic in vivo recordings of Phosphocreatine (PCr), inorganic Phosphate (Pi), and pH in rodent hindlimb muscle and verified against independent data from in vivo experiments and muscle biopsies. Step response testing revealed that mass action kinetics in combination with feedback control were sufficient to accomplish myoplasmic ATP homeostasis over a 100-fold range of ATP turnover rates. This vital emergent property of the metabolic model was associated with dynamic behaviour of intermediary metabolite concentrations similar to a second-order underdamped system that remains to be verified. The simulations additionally predicted that the lactate dehydrogenase (LDH) reaction makes substantial contributions to redox balance across the physiological range of ATP demands in this myofiber phenotype, while its role in slowing cellular acidification is minimal. Yet, LDH knock-out simulations revealed that oxidative recycling of myoplasmic NADH in and by itself sufficed to maintain redox balance over ATP turnover rates in the range of mitochondrial ATP synthesis. We conclude that aerobic lactate production in working muscles is a byproduct of the metabolic flexibility of FOG myofibers afforded by expression of high levels of LDH and OxPhos enzymes to support continual myoplasmic redox balance and ATP synthesis under conditions of high-intensity mechanical work. In the future, the presented simulation framework may be used to further enhance the understanding of how experimental observations in muscle emerge from the integrative behaviour of the metabolic network for carbohydrate metabolism in FOG myofibers.

Objective. Muscle fiber conduction velocity (MFCV) describes the speed at which electrical activity propagates along muscle fibers and is typically assessed using invasive or surface electromyography. Because electrical currents generate magnetic fields, propagation velocity can potentially also be measured magnetically using magnetomyography (MMG), offering the advantage of a contactless approach. Approach. To test this hypothesis, we recorded MMG signals from the right biceps brachii muscle of 24 healthy subjects (12 male, 12 female) using a linear array of seven optically pumped magnetometers (OPMs). Subjects maintained muscle force for 30 s at 20%, 40%, and 60% of their maximum voluntary contraction. Main results. In 20 subjects, propagation of MMG signals was observable. Change in polarity and signal cancellation enabled localization of the innervation zone. We estimated the MFCV for each condition by cross-correlating double-differentiated MMG signals. To validate our results, we examined whether MFCV estimations increased with higher force levels, a well-documented characteristic of the neuromuscular system. The median MFCV significantly increased with force (p = 0.007), with median values of 3.2 m s ⁻¹ at 20%, 3.8 m s ⁻¹ at 40%, and 4.4 m s ⁻¹ at 60% across all 20 subjects. Significance. Our results establish the first measurements of magnetic MFCV in MMG using OPMs. These findings pave the way for further developments and application of quantum sensors for contactless clinical neurophysiology.

Postinhibitory excitation is a transient overshoot of a neuron’s baseline firing rate following an inhibitory stimulus and can be observed in vivo in human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model, we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron’s firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the postinhibitory excitation’s strength correlates with the inhibitory stimulus’s amplitude and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50% of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition.