Objective. Non-invasive electromyographic techniques can detect action potentials from muscle units with high spatial dimensionality. These technologies allow the decoding of large samples of motor ...units by using high-density grids of electrodes that are placed on the skin overlying contracting muscles and therefore provide a non-invasive representation of the human spinal cord output. Approach. From a sample of >1200 decoded motor neurons, we show that motor neuron activity can be identified in humans in the full muscle recruitment range with high accuracy. Main results. After showing the validity of decomposition with novel test parameters, we demonstrate that the same motor neurons can be tracked over a period of one-month, which allows for the longitudinal analysis of individual human neural cells. Significance. These results show the potential of an accurate and reliable assessment of large populations of motor neurons in physiological investigations. We discuss the potential of this non-invasive neural interfacing technology for the study of the neural determinants of movement and man-machine interfacing.
ABSTRACT
The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) recently reported evidence for the presence of a common stochastic signal across their array of pulsars. The ...origin of this signal is still unclear. One possibility is that it is due to a stochastic gravitational-wave background (SGWB) in the ∼1–10 nHz frequency region. Taking the NANOGrav observational result at face value, we show that this signal would be fully consistent with an SGWB produced by an unresolved population of in-spiralling massive black hole binaries (MBHBs) predicted by current theoretical models. Considering an astrophysically agnostic model, the MBHB merger rate is loosely constrained. Including additional constraints from galaxy pairing fraction and MBH–bulge scaling relations, we find that the MBHB merger rate is ${1.2\times 10^{-5}}{\rm -}{4.5\times 10^{-4}}\, \mathrm{Mpc}^{-3}\, \mathrm{Gyr}^{-1}$ , the MBHB merger time-scale is $\le 2.7\, \mathrm{Gyr}$, and the norm of the MBH−Mbulge relation is $\ge 1.2\times 10^{8}\, {\rm M}_\odot$ (all quoted at 90 per cent credible intervals). Regardless of the astrophysical details of MBHB assembly, the NANOGrav result would imply that a sufficiently large population of massive black holes pair up, form binaries and merge within a Hubble time.
Recent work demonstrated that it is possible to identify motor unit discharge times from high-density surface EMG (HDEMG) decomposition. Since then, the number of studies that use HDEMG decomposition ...for motor unit investigations has increased considerably. Although HDEMG decomposition is a semi-automatic process, the analysis and interpretation of the motor unit pulse trains requires a thorough inspection of the output of the decomposition result. Here, we report guidelines to perform an accurate extraction of motor unit discharge times and interpretation of the signals. This tutorial includes a discussion of the differences between the extraction of global EMG signal features versus the identification of motor unit activity for physiological investigations followed by a comprehensive guide on how to acquire, inspect, and decompose HDEMG signals, and robust extraction of motor unit discharge characteristics.
Key points
Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi‐muscle EMG recordings.
We quantified the ...strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un‐matched forces in different directions.
We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control.
The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire.
Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi‐muscle EMG recordings. Here we quantify the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles in humans during voluntary contractions. To remove confounds associated with previous studies, we used a task that required the two hand muscles to exert matched or un‐matched forces in different directions. Despite the force production task consisting of uncommon digit force coordination patterns, we found that synaptic input to motor neurons is shared across all frequency bands, reflecting cortical and spinal inputs associated with force control. The coherence between discharge timings of the two pools of motor neurons was significant at the delta (0–5 Hz), alpha (5–15 Hz) and beta (15–35 Hz) bands (P < 0.05). These results suggest that correlated input to motor neurons of two hand muscles can occur even during tasks not belonging to a common behavioural repertoire and despite lack of common innervation. Moreover, we show that the extraction of activity from motor neurons during voluntary force control removes cross‐talk associated with global EMG recordings, thus allowing direct in vivo interrogation of spinal motor neuron activity.
Key points
Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi‐muscle EMG recordings.
We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un‐matched forces in different directions.
We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control.
The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire.
In this research the importance of several choice attributes of beef for Piedmontese consumers was examined. The survey was conducted on a sample of consumers in sixteen meat stores in Piedmont, ...Northwest Italy. A choice experiment (Best-Worst scaling methodology) was used to identify consumer preferences and five clusters of purchaser. The responses were also analyzed on the basis of two variables, the frequency of meat consumption and the place of purchase. Piedmontese consumers considered “price” as the most important factor in meat purchasing, but “animal welfare” considerations played some part too.
Abstract
Vertical land movements (VLM) play a crucial role in affecting the sea level rise along the coasts. They need to be estimated and included in the analysis for more accurate Sea Level (SL) ...projections. Here we focus on the Mediterranean basin characterized by spatially variable rates of VLM that affect the future SL along the coasts. To estimate the VLM rates we used geodetic data from continuous global navigation satellite system stations with time series longer than 4.5 years in the 1996–2023 interval, belonging to Euro-Mediterranean networks and located within 5 km from the coast. Revised SL projections up to the year 2150 are provided at 265 points on a geographical grid and at the locations of 51 tide gauges of the Permanent Service for Mean Sea Level, by including the estimated VLM in the SL projections released by the Intergovernmental Panel on Climate Change (IPCC) in the AR6 Report. Results show that the IPCC projections underestimate future SL along the coasts of the Mediterranean Sea since the effects of tectonics and other local factors were not properly considered. Here we show that revised SL projections at 2100, when compared to the IPCC, show a maximum and minimum differences of 1094 ± 103 mm and −773 ± 106 mm, respectively, with an average value that exceeds by about 80 mm that of the IPCC in the reference Shared Socio-economic Pathways and different global warming levels. Finally, the projections indicate that about 19.000 km
2
of the considered Mediterranean coasts will be more exposed to risk of inundation for the next decades, leading to enhanced impacts on the environment, human activities and infrastructures, thus suggesting the need for concrete actions to support vulnerable populations to adapt to the expected SL rise and coastal hazards by the end of this century.
The adenosine A1 receptor (A1-AR) is a G-protein-coupled receptor that plays a vital role in cardiac, renal, and neuronal processes but remains poorly targeted by current drugs. We determined a 3.2 Å ...crystal structure of the A1-AR bound to the selective covalent antagonist, DU172, and identified striking differences to the previously solved adenosine A2A receptor (A2A-AR) structure. Mutational and computational analysis of A1-AR revealed a distinct conformation of the second extracellular loop and a wider extracellular cavity with a secondary binding pocket that can accommodate orthosteric and allosteric ligands. We propose that conformational differences in these regions, rather than amino-acid divergence, underlie drug selectivity between these adenosine receptor subtypes. Our findings provide a molecular basis for AR subtype selectivity with implications for understanding the mechanisms governing allosteric modulation of these receptors, allowing the design of more selective agents for the treatment of ischemia-reperfusion injury, renal pathologies, and neuropathic pain.
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•3.2 Å resolution antagonist-bound structure of the adenosine A1 receptor solved•Major differences found in extracellular loop regions relative to the A2A structure•Drug selectivity is predominantly determined by binding site shape, not composition•Unexpectedly wide A1 receptor cavity reveals insights into allosteric drug actions
The structure of the adenosine receptor A1 provides insights into the ways selectivity among adenosine receptor subtypes is achieved, opening avenues for design of subtype-specific drugs.
Force is generated by muscle units according to the neural activation sent by motor neurons. The motor unit is therefore the interface between the neural coding of movement and the musculotendinous ...system. Here we propose a method to accurately measure the latency between an estimate of the neural drive to muscle and force. Furthermore, we systematically investigate this latency, which we refer to as the neuromechanical delay (NMD), as a function of the rate of force generation. In two experimental sessions, eight men performed isometric finger abduction and ankle dorsiflexion sinusoidal contractions at three frequencies and peak-to-peak amplitudes {0.5, 1, and 1.5 Hz; 1, 5, and 10 of maximal force %maximal voluntary contraction (MVC)}, with a mean force of 10% MVC. The discharge timings of motor units of the first dorsal interosseous (FDI) and tibialis anterior (TA) muscle were identified by high-density surface EMG decomposition. The neural drive was estimated as the cumulative discharge timings of the identified motor units. The neural drive predicted 80 ± 0.4% of the force fluctuations and consistently anticipated force by 194.6 ± 55 ms (average across conditions and muscles). The NMD decreased nonlinearly with the rate of force generation ( R
= 0.82 ± 0.07; exponential fitting) with a broad range of values (from 70 to 385 ms) and was 66 ± 0.01 ms shorter for the FDI than TA ( P < 0.001). In conclusion, we provided a method to estimate the delay between the neural control and force generation, and we showed that this delay is muscle-dependent and is modulated within a wide range by the central nervous system. NEW & NOTEWORTHY The motor unit is a neuromechanical interface that converts neural signals into mechanical force with a delay determined by neural and peripheral properties. Classically, this delay has been assessed from the muscle resting level or during electrically elicited contractions. In the present study, we introduce the neuromechanical delay as the latency between the neural drive to muscle and force during variable-force contractions, and we show that it is broadly modulated by the central nervous system.
Massive black holes are key components of the assembly and evolution of cosmic structures, and a number of surveys are currently on going or planned to probe the demographics of these objects and to ...gain insight into the relevant physical processes. Pulsar Timing Arrays (PTAs) currently provide the only means to observe gravitational radiation from massive black hole binary systems with masses ≳107 M⊙. The whole cosmic population produces a stochastic background that could be detectable with upcoming PTAs. Sources sufficiently close and/or massive generate gravitational radiation that significantly exceeds the level of the background and could be individually resolved. We consider a wide range of massive black hole binary assembly scenarios, investigate the distribution of the main physical parameters of the sources, such as masses and redshift, and explore the consequences for PTAs observations. Depending on the specific massive black hole population model, we estimate that on average at least one resolvable source produces timing residuals in the range ∼5–50 ns. PTAs, and in particular the future Square Kilometre Array, can plausibly detect these unique systems, although the events are likely to be rare. These observations would naturally complement on the high-mass end of the massive black hole distribution function future surveys carried out by the Laser Interferometer Space Antenna.
Massive black hole binary systems, with masses in the range ∼104–1010M⊙, are among the primary sources of gravitational waves in the frequency window ∼10−9–0.1 Hz. Pulsar Timing Arrays (PTAs) and the ...Laser Interferometer Space Antenna (LISA) are the observational means by which we will be able to observe gravitational radiation from these systems. We carry out a systematic study of the generation of the stochastic gravitational-wave background from the cosmic population of massive black hole binaries. We consider a wide variety of assembly scenarios and we estimate the range of signal strength in the frequency band accessible to PTAs. We show that regardless of the specific model of massive black hole binaries formation and evolution, the characteristic amplitude hc of the gravitational-wave stochastic background at 10−8 Hz varies by less than a factor of 2. However, taking into account the uncertainties surrounding the actual key model parameters, the amplitude lies in the interval hc(f= 10−8Hz) ≈ 5 × 10−16–8 × 10−15. The most optimistic predictions place the signal level at a factor of ≈3 below the current sensitivity of PTAs, but within the detection range of the complete Parkes PTA for a wide variety of models, and of the future Square-Kilometer Array PTA for all the models considered here. We also show that at frequencies ≳10−8 Hz, the frequency dependency of the generated background follows a power law significantly steeper than hc∝f−2/3, which has been considered so far; the value of the spectral index depends on the actual assembly scenario and provides therefore an additional opportunity to extract astrophysical information about the cosmic population of massive black holes. Finally, we show that LISA observations of individual resolvable massive black hole binaries are complementary and orthogonal to PTA observations of a stochastic background from the whole population in the Universe. In fact, the detection of gravitational radiation in both frequency windows will enable us to fully characterize the cosmic history of massive black holes.
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