Biology subjects

Ibanez, J.

Publications and source records attributed to Ibanez, J..

28 records · Page 2Linked to original sources

bioRxiv2022

Concurrent assessment of individual motoneuron discharges and muscle unit displacement velocity in humans by high-density EMG and ultrafast ultrasound

ObjectiveThe study of human neuromechanical control at the motor unit (MU) level has predominantly focussed on electrical activity and force generation, whilst the link between these, the muscle deformation, has not been widely studied. An important example of this is excitation-contraction coupling (E-C coupling) - the process by which electrical excitation is converted into contraction in the muscle fibres. Despite this being a clear marker for progression of certain diseases, it cannot be measured in vivo in natural contractions. To address this, we analyse the kinematics of muscle units in natural contractions. ApproachWe combine high density surface electromyography (HDsEMG) and ultrafast ultrasound (US) recordings of a mildly contracted muscle (tibialis anterior) to measure the deformation of the muscular tissue caused by individual MU twitches (decomposed from the HDsEMG). With a novel analysis on the US images we identified, with high spatio-temporal precision, the velocity maps associated with single muscle unit movements. From the individual MU profiles obtained from the velocity maps the region of movement, the duration of the mechanical twitch, the total and active contraction times, and the activation time (equivalent to E-C coupling) were computed. Main resultsThe E-C coupling was 3.8 {+/-} 3.0 ms (n = 390), providing the first measurement of this value in for single MUs in non-stimulated contractions. Furthermore, the experimental measures provided the first evidence of single muscle unit twisting during voluntary contractions and showed the presence of MUs with territories with multiple distinct split regions across the muscle region. SignificanceWe show that the combined use of HDsEMG and ultrafast US can allow for the study of kinematics of individual MU twitches, including measurement of the excitation-contraction coupling time under natural neural control conditions. These measurements and characterisations open new avenues for study of neuromechanics in healthy and pathological conditions.

bioengineering↗

bioRxiv2022

Transcranial alternating current stimulation does not modulate corticospinal activity in humans

Transcranial alternating current stimulation (TACS) is commonly used to synchronise the output of a cortical area to other parts of the nervous system, but evidence for this based on brain recordings in humans is challenging. The brain transmits beta oscillations (~21Hz) to tonically contracted limb muscles linearly and through the fastest corticospinal pathways. Therefore, muscle activity may be used as a proxy measure for 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 an indirect evidence for TACS-driven neural entrainment. In the first part of this study, we ran a series of simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results indicated that MNs should be 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 (ADM) or the tibialis anterior muscle (TA) were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the spiking activity of pools of motor units innervating the studied muscles. By analysing motor unit pool activity, we observed that none of the tested TACS conditions could consistently alter the spectral characteristics of the common neural inputs received by the muscles. These results suggest that 1mA-TACS over motor cortex given at frequencies in the beta band does not affect corticospinal beta entrainment. Highlights- TACS is commonly used to entrain the communication between brain regions - It is challenging to find direct evidence supporting TACS-driven neural entrainment - Simulations show that motor neurons are sensitive to corticospinal beta entrainment - Motor unit activity from human muscles does not support TACS-driven entrainment

neuroscience↗

bioRxiv2021

Interfacing Spinal Motor Units in Non-Human Primates Identifies a Principal Neural Component for Force Control Constrained by the Size Principle

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 the performance of 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 during high force isometric contractions with a broad range of rate of force development (1.8 - 38.6 N{middle dot}m{middle dot}s-1). During the same sessions we recorded intramuscular EMG signals from 16 arm muscles of both limbs and elicited the full recruitment through neural stimulation of the median and deep radial nerves. 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 observed between motor units with close recruitment thresholds, and only during 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 could be described as a time-shifted version of the first, as it could be predicted from the interplay between the size principle of recruitment and one common input. 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.

neuroscience↗

bioRxiv2021

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

Recent developments in neural interfaces enable the real-time and non-invasive tracking of motor neuron spiking activity. Such novel interfaces provide a promising basis for human motor augmentation by extracting potential high-dimensional control signals directly from the human nervous system. However, it is unclear how flexibly humans can control the activity of individual motor neurones to effectively increase the number of degrees-of-freedom available to coordinate multiple effectors simultaneously. Here, we provided human subjects (N=7) with real-time feedback on the discharge patterns of pairs of motor units (MUs) innervating a single muscle (tibialis anterior) and encouraged them to independently control the MUs by tracking targets in a 2D space. Subjects learned control strategies to achieve the target-tracking task for various combinations of MUs. These strategies rarely corresponded to a volitional control of independent input signals to individual MUs. Conversely, MU activation was consistent with a common input to the MU pair, while individual activation of the MUs in the pair was predominantly achieved by alterations in de-recruitment order that could be explained with history-dependent changes in motor neuron excitability. These results suggest that flexible MU control based on independent synaptic inputs to single MUs is not a simple to learn control strategy.

neuroscience↗

bioRxiv2021

Double nerve transfer to a single target muscle: experimental model in the upper extremity

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available for multiple nerve transfers to a common target muscle in the upper extremity. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers. For this purpose, we developed a forelimb model to enable tension-free transfer of one or two donor nerves in the upper extremity. Anatomic dissections were performed to design the double nerve transfer model (n=8). In 62 male Sprague-Dawley rats the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps long head was transected at the motor entry point and resected up to its original branch to prevent auto-reinnervation. In all animals, coaptation of both nerves to the motor entry point could be performed tension-free. Mean duration of the procedure was 49 {+/-} 13 min for the single nerve transfer and 78 {+/-} 20 min for the double nerve transfer. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

neuroscience↗

bioRxiv2021

Analysis of motor unit spike trains estimated from high-density surface electromyography is highly reliable across operators

There is a growing interest in decomposing high-density surface electromyography (HDsEMG) into motor unit spike trains to improve knowledge on the neural control of muscle contraction. However, the reliability of decomposition approaches is sometimes questioned, especially because they require manual editing of the outputs. We aimed to assess the inter-operator reliability of the identification of motor unit spike trains. Eight operators with varying experience in HDsEMG decomposition were provided with the same data extracted using the convolutive kernel compensation method. They were asked to manually edit them following established procedures. Data included signals from three lower leg muscles and different submaximal intensities. After manual analysis, 126 {+/-} 5 motor units were retained (range across operators: 119-134). A total of 3380 rate of agreement values were calculated (28 pairwise comparisons x 11 contractions/muscles x 4-28 motor units). The median rate of agreement value was 99.6%. Inter-operator reliability was excellent for both mean discharge rate and time at recruitment (intraclass correlation coefficient > 0.99). These results show that when provided with the same decomposed data and the same basic instructions, operators converge toward almost identical results. Our data have been made available so that they can be used for training new operators.

neuroscience↗

bioRxiv2020

Only the fastest corticospinal fibers contribute to beta corticomuscular coherence

A common way to study human corticospinal transmission is with transcranial magnetic stimulation. However, this is biased to activity in the fastest conducting axons. It is unclear whether conclusions obtained in this context are representative of volitional activity in mild-to-moderate contractions. A possible alternative to overcome this limitation is to study the corticospinal transmission of endogenously generated brain activity. Here we study the transmission speeds of cortical beta rhythms travelling to the muscles during steady contractions. To do this, we introduce new methods to improve delay estimates in the corticomuscular transmission of beta rhythms, and which we validate both in simulations and experimentally. Applying these approaches to experimental data from humans, we show that corticomuscular beta transmission delays are only 1-2ms longer than expected from the fastest corticospinal pathway. Simulations using realistic distributions of the conduction velocities for descending axons projecting to lower motoneurons suggest two scenarios that can explain these results: either a very small fraction of only the fastest corticospinal axons selectively transmit beta activity, or else the entire pool does. The implications that these two scenarios have for our understanding of corticomuscular interactions are discussed in the final part of this manuscript. SIGNIFICANCEWe present and validate an improved methodology to measure the delay in the transmission of cortical beta activity to tonically active muscles. The estimated corticomuscular beta transmission delays which this yields are remarkably similar to those expected from transmission in the fastest corticospinal axons. A simulation of beta transmission along a pool of corticospinal axons using a realistic distribution of fiber diameters suggests two possible mechanisms by which fast corticomuscular transmission is achieved: either a very small fraction of descending axons transmits beta activity to the muscles or, alternatively, the entire population does and natural cancellation of slow channels occurs due to the distribution of axon diameters in the corticospinal tract.

neuroscience↗

bioRxiv2020

Clonal propagation history shapes the intra-cultivar genetic diversity in Malbec grapevines

Grapevine (Vitis vinifera L.) cultivars are clonally propagated to preserve their varietal attributes. However, novel genetic variation still accumulates due to somatic mutations. Aiming to study the potential impact of clonal propagation history on grapevines intra-cultivar genetic diversity, we have focused on Malbec. This cultivar is appreciated for red wines elaboration, it was originated in Southwestern France and introduced into Argentina during the 1850s. Here, we generated whole-genome resequencing data for four Malbec clones with different historical backgrounds. A stringent variant calling procedure was established to identify reliable clonal polymorphisms, additionally corroborated by Sanger sequencing. This analysis retrieved 941 single nucleotide variants (SNVs), occurring among the analyzed clones. Based on a set of validated SNVs, a genotyping experiment was custom-designed to survey Malbec genetic diversity. We successfully genotyped 214 samples and identified 14 different clonal genotypes, that clustered into two genetically divergent groups. Group-Ar was driven by clones with a long history of clonal propagation in Argentina, while Group-Fr was driven by clones that have longer remained in Europe. Findings show the ability of such approaches for clonal genotypes identification in grapevines. In particular, we provide evidence on how human actions may have shaped Malbec extant genetic diversity pattern.

genomics↗

bioRxiv2020

Mapping of safe and early chemo-attenuated live Plasmodium falciparum immunization identifies immune signature of vaccine efficacy

Potent protection against malaria can be induced by attenuated live-immunization with Plasmodium falciparum (Pf) sporozoites (SPZ). However, a better understanding of the critical processes involved in the establishment of protective immunity is needed. We explored the safety and vaccine efficacy of early chemo-attenuation of PfSPZ under atovaquone-proguanil (AP). AP caused early arrest of P. berghei liver stages. Despite the absence of replication, robust protection in mice correlated with parasite-specific effector-memory CD8+ T-cell responses. In a phase I clinical trial a single dose of AP prevented Pf infections in the liver of adult, human subjects who received three doses of 5.12x104 or 1.5x105 PfSPZ by direct venous inoculation combined with oral AP. However, only 2 of 8 (25%) and 2 of 10 (20%), respectively, were protected against controlled human malaria infection (CHMI) 10 weeks after the last vaccine dose, despite levels of IgG antibodies to the Pf circumsporozoite protein (PfCSP) comparable to those achieved in fully protected volunteers after immunization with 5.12x104 PfSPZ with chloroquine chemoprophylaxis active only against subsequent blood stages. We identify lower IgG recognition of the secreted liver stage-specific antigens LISP2 and LSA1 and the multi-stage antigen MSP5 as immune signatures of inferior vaccine efficacy compared to PfSPZ with chloroquine chemoprophylaxis. In conclusion, we show that immune signatures of liver stage antigens, but neither an established rodent malaria model nor concentrations of antibodies against the major surface protein of sporozoites, permit prediction of vaccine efficacy. Thus, this study provides a clear rationale for the development of live sporozoite vaccination protocols that boost exposure to Pf liver stage antigens. Significance StatementOur research demonstrates that attenuation of liver infection of high doses of Plasmodium falciparum sporozoites by concomitant single-dose administration of atovaquone-proguanil is safe in humans. However, vaccine efficacy was modest when compared to an identical protocol using chloroquine that acts only on the subsequent blood infection. Immune signatures of secreted P. falciparum liver stage antigens, but neither an established rodent malaria model nor concentrations of sporozoite antibodies, permit prediction of vaccine efficacy.

immunology↗

bioRxiv2018

Excitability changes in the motor cortex in preparation for self-paced and cue-guided movements: a transcranial magnetic stimulation study

In a warned reaction time (RT) task, corticospinal excitability (CSE) decreases in task-related muscles at the time of the imperative signal (preparatory inhibition). Because RT tasks emphasise speed of response, it is impossible to distinguish whether preparatory inhibition reflects a mechanism preventing premature reactions, or whether it is an inherent part of movement preparation. We used transcranial magnetic stimulation (TMS) to study CSE changes preceding RT movements and movements that were either self-paced (SP) or performed at predictable times to coincide with an external event (PT). Results show that CSE changes over a similar temporal profile in all cases, suggesting that preparatory inhibition is a necessary state in planned movements allowing the transition between rest and movement. Additionally, TMS given shortly before the times to move speeded the onset of movements in both RT and SP contexts, suggesting that their initiation depends on a form of trigger that can be conditioned by external signals. On the contrary, PT movements do not show this effect, suggesting the use of a mechanistically different triggering strategy. This relative immunity of PT tasks to be biased by external events may reflect a mechanism that ensures priority of internal predictive signals to trigger movement onset.

neuroscience↗