Neuromodulatory Contribution to Muscle Force Production after Short-Term Unloading and Active Recovery.

PURPOSE: Prior evidence has shown that neural factors contribute to the loss of muscle force after skeletal-muscle disuse. However, little is known about the specific neural mechanisms altered by disuse. Persistent inward current (PIC) is an intrinsic property of motoneurons responsible for prolonging and amplifying the synaptic input, proportionally to the level of neuromodulation, thus influencing motoneuron discharge rate and force production. Here, we hypothesized that short-term unilateral lower-limb suspension (ULLS) would reduce the neuromodulatory input associated with PICs, contributing to the reduction of force generation capacity. Additionally, we tested whether physical exercise would restore the force generation capacity by re-establishing the initial level of neuromodulatory input. METHODS: In 12 young adults, we assessed maximal voluntary contraction (MVC) pre- and post- 10 days of ULLS and following 21 days of active recovery (AR) based on resistance exercise. PIC was estimated from high-density surface electromyograms of the vastus lateralis muscle as the delta frequency (∆F) of paired motor units calculated during isometric ramped contractions. RESULTS: The values of ∆F were reduced after 10 days of ULLS (-33%, p < 0.001), but were fully re-established after the AR (+29.4%, p < 0.001). The changes in estimated PIC values were correlated (r = 0.63, p = 0.004) with the reduction in MVC after ULLS (-29%, p = 0.002) and its recovery after the AR (+28.5%, p = 0.003). CONCLUSIONS: Our findings suggest that PIC estimates are reduced by muscle disuse and may contribute to the loss of force production and its recovery with exercise. Overall, this is the first study demonstrating that, in addition to peripheral neuromuscular changes, central neuromodulation is a major contributor to the loss of force generation capacity after disuse, and can be recovered after resistance exercise.

Are all hamstring injuries equal? A retrospective analysis of time to return to full training following BAMIC type 'c' and T-junction injuries in professional men's rugby union.

We aimed to determine whether the anatomical location (intramuscular tendon or T-Junction) of hamstring muscle injuries in professional men's rugby union associates with a prolonged time to return to full training and a higher rate of re-injury/subsequent injury. We reviewed the medical records of an Irish professional rugby union club to identify hamstring muscle injuries incurred across five seasons. Clinicians and players were not blinded to MRI results at the time of rehabilitation. A blinded musculoskeletal radiologist re-classified all included injuries (n = 91) according to the British Athletics Muscle Injury Classification framework. Players who sustained an injury with intramuscular tendon involvement required a longer time to return to full training compared to players who sustained an injury without intramuscular tendon involvement (78 days vs. 24 days). Players who sustained a biceps femoris injury with T-junction involvement did not require a longer time to return to full training compared to players who sustained a biceps femoris injury without T-junction involvement (29 days vs. 27 days). Injuries with either intramuscular tendon or T-junction involvement were not associated with an increased rate of re-injury/subsequent injury to the same limb (intramuscular tendon involvement - odds ratio = 0.96, T-junction involvement - odds ratio = 1.03). When a hamstring muscle injury involves the intramuscular tendon, the injured player and stakeholders should be made aware that a longer time to return to full training is likely required. T-junction involvement does not alter the expected clinical course of biceps femoris injuries.

Tutorial: Analysis of central and peripheral motor unit properties from decomposed High-Density surface EMG signals with openhdemg.

High-Density surface Electromyography (HD-sEMG) is the most established technique for the non-invasive analysis of single motor unit (MU) activity in humans. It provides the possibility to study the central properties (e.g., discharge rate) of large populations of MUs by analysis of their firing pattern. Additionally, by spike-triggered averaging, peripheral properties such as MUs conduction velocity can be estimated over adjacent regions of the muscles and single MUs can be tracked across different recording sessions. In this tutorial, we guide the reader through the investigation of MUs properties from decomposed HD-sEMG recordings by providing both the theoretical knowledge and practical tools necessary to perform the analyses. The practical application of this tutorial is based on openhdemg, a free and open-source community-based framework for the automated analysis of MUs properties built on Python 3 and composed of different modules for HD-sEMG data handling, visualisation, editing, and analysis. openhdemg is interfaceable with most of the available recording software, equipment or decomposition techniques, and all the built-in functions are easily adaptable to different experimental needs. The framework also includes a graphical user interface which enables users with limited coding skills to perform a robust and reliable analysis of MUs properties without coding.

Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery.

PURPOSE: This study aimed to non-invasively test the hypothesis that (a) short-term lower limb unloading would induce changes in the neural control of force production (based on motor units (MUs) properties) in the vastus lateralis muscle and (b) possible changes are reversed by active recovery (AR). METHODS: Ten young males underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of AR. During ULLS, participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position (15°-20°) and with the contralateral foot raised by an elevated shoe. The AR was based on resistance exercise (leg press and leg extension) and executed at 70% of each participant's 1 repetition maximum, 3 times/week. Maximal voluntary isometric contraction (MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline, after ULLS, and after AR. MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%, 25%, and 50% of the current MVC, and individual MUs were tracked across the 3 data collection points. RESULTS: We identified 1428 unique MUs, and 270 of them (18.9%) were accurately tracked. After ULLS, MVC decreased by 29.77%, MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities (with changes between the 2 variables strongly correlated), while discharge rate was reduced at 10% and 25% but not at 50% MVC. Impaired MVC and MUs properties fully recovered to baseline levels after AR. Similar changes were observed in the pool of total as well as tracked MUs. CONCLUSION: Our novel results demonstrate, non-invasively, that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs, suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold. However, after 21 days of AR, the impaired MUs properties were fully restored to baseline levels, highlighting the plasticity of the components involved in neural control.

Grip strength positively correlates with blood pressure in individuals with abnormal adiposity.

Although strong positive correlations exist between grip strength and cardiovascular health, the association between grip strength and blood pressure (BP) is less clear. In this regard, a more precise relationship between grip strength and BP may be revealed by considering adiposity. We examined the association between grip strength and BP in 9424 individuals aged 18-92 years, while controlling for or stratifying by body mass index (BMI) or body fat (BF)%. Grip strength, BP and BF% were determined using dynamometry, sphygmomanometry and dual-energy x-ray absorptiometry. Overall, those with elevated BP had greater grip strength than those with normal BP (39.17 kg vs 38.38 kg, p < 0.001); however, following stratification this was only observed in overweight or obese individuals (42.08 kg vs 41.10 kg, p = 0.003 and 41.34 kg vs 40.03 kg, p = 0.033), and those within the highest BF% tertile (37.95 kg vs 36.52 kg, p < 0.001). Overall, higher grip strength was associated with an increased odds for elevated BP (OR = 1.014, 95% CI = 1.004-1.024, p = 0.004); however, after stratification the increased odds was only observed in overweight or obese individuals (OR = 1.025, 95% CI = 1.010-1.039, p < 0.001 and OR = 1.018, 95% CI = 1.004-1.031, p = 0.010), and those within the highest BF% tertile (OR = 1.036, 95% CI = 1.022-1.051, p < 0.001). Individuals with low grip strength and high BF% had lower odds for elevated BP (OR = 0.514, 95% CI = 0.341-0.775, p = 0.002), whereas those with low grip strength and low BF% had higher odds for elevated BP (OR = 2.162, 95% CI = 1.026-4.555, p = 0.043). Our findings show that higher grip strength is related to higher BP in overweight or obese individuals, or those with a high BF%. Having a BMI < 25 kg/m2 or lower BF% may neutralise this association.

Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition.

Diabetes mellitus represents a group of physiological dysfunctions characterized by hyperglycaemia resulting directly from insulin resistance (in the case of type 2 diabetes mellitus-T2DM), inadequate insulin secretion/production, or excessive glucagon secretion (in type 1 diabetes mellitus-T1DM) [...].

Handgrip strength asymmetry as a new biomarker for sarcopenia and individual sarcopenia signatures.

BACKGROUND: Although handgrip strength (HGS) asymmetry has clinical screening utility, its relevance to sarcopenia is unknown. This study examined the relationship between HGS asymmetry and sarcopenia signatures, and explored the relevance of circulating neural/neuromuscular markers. METHODS: 9403 individuals aged 18-92 years participated in this study. Maximal HGS and skeletal muscle index (SMI) were determined using hand dynamometry and DXA. Sarcopenia was diagnosed upon the presence of low HGS and low SMI, according to cohort-specific thresholds. Plasma biomarkers were measured by ELISA in a sub-group of 269 participants aged 50-83 years. Asymmetry was determined as the highest recorded HGS divided by the highest recorded HGS of the opposite hand. Individuals with a ratio > 1.10 were classified as having asymmetrical HGS. RESULTS: Subjects with asymmetrical HGS had significantly lower SMI (7.67 kg/m2 vs 7.71 kg/m2, p = 0.004) and lower HGS (37.82 kg vs 38.91 kg, p < 0.001) than those with symmetrical HGS. In those aged ≥ 50 years asymmetrical HGS was associated with 2.67 higher odds for sarcopenia [95% confidence interval: (CI) = 1.557-4.561, p < 0.001], 1.83 higher odds for low HGS only (CI 1.427-2.342, p < 0.001), and 1.79 higher odds for low SMI only (CI 1.257-2.554, p = 0.001). HGS asymmetry demonstrated acceptable diagnostic accuracy for sarcopenia (AUC = 0.727, CI 0.658-0.796, p < 0.001). Plasma neural cell adhesion molecule concentrations were 19.6% higher in individuals with asymmetrical HGS (185.40 ng/mL vs 155.00 ng/mL, p < 0.001) than those with symmetrical HGS. DISCUSSION: Our findings demonstrate the utility of HGS asymmetry as a screening tool that may complement existing strategies seeking to combat sarcopenia. Biomarker analyses suggest that heightened denervation may be an important aetiological factor underpinning HGS asymmetry.

Intramuscular Tendon Injuries of the Hamstring Muscles: A More Severe Variant? A Narrative Review.

Hamstring strain injuries (HSI) are one of the most common sport-related injuries. They have a high injury burden and a high recurrence rate. The development of novel muscle injury grading systems has provided new insights into the possible impact of injury location on the time to return to play (TTRTP) and re-injury following HSI. In particular, injuries to the intramuscular tendon (IMT) may be present in up to 41% of all HSI and have been described as a 'serious thigh muscle strain'. Re-injury rates as high as 60% have been described in elite track and field athletes, as well as prolonged TTRTP. A systematic search was carried out using appropriate keywords to identify articles reporting on HSI involving the IMT in athletes. The primary aim was to determine whether IMT injuries warrant being classified as a distinct clinical entity with different expected outcomes to other hamstring muscle injuries. This narrative review summarises the existing evidence on: (1) the anatomy of the IMT and its response to injury; (2) the role of MRI and novel grading scales in IMT injury management (3) clinical assessment of IMT injuries, (4) TTRTP and re-injury rates across sports following IMT, (5) conservative rehabilitation and the role of specific 'IMT-oriented' strategies, and (6) indications for and approaches to surgery. The review found that important clinical outcomes such as re-injury rates and TTRTP vary across populations, cohorts and sports which suggest that outcomes are specific to the sporting context. Bespoke rehabilitation, tailored to IMT injury, has been shown to significantly reduce re-injuries in elite track and field athletes, without compromising TTRTP. Continued prospective studies across other sports and cohorts, are warranted to further establish relevant clinical findings, indications for surgical intervention and outcomes across other sporting cohorts.

Influence of body composition and cardiorespiratory fitness on plasma HSP72, norepinephrine, insulin, and glucose responses to an acute aerobic exercise bout performed in the fed state.

Being overweight is already considered a metabolic risk factor, which can be overcome by increasing cardiorespiratory fitness (CRF). Acute exercise is known to induce changes in plasma hormones and heat shock proteins release. However, there is a lack of studies investigating the impact of body composition and CRF on these variables following acute aerobic exercise. To assess the influence of body composition and cardiorespiratory fitness on plasma heat shock protein 72 kDa (HSP72), norepinephrine (NE), insulin, and glucose responses to an acute aerobic exercise bout in the fed state. Twenty-four healthy male adults were recruited and allocated into three groups: overweight sedentary (n = 8), normal weight sedentary (n = 8), and normal weight active (n = 8). The volunteers performed an acute moderate exercise session on a treadmill at 70% of VO2 peak. Blood samples were drawn at baseline, immediately post-exercise, and at 1-h post-exercise. The exercise session did not induce changes in HSP72 nor NE but changes in glucose and insulin were affected by body mass index. Also, subjects with elevated CRF maintain reduced NE through exercise. At baseline, the overweight sedentary group showed elevated NE, insulin, and glucose; these last two impacting the HOMA-IR index. Thirty minutes of aerobic exercise at 70% VO2 peak, in the fed state, did not change the levels of plasma NE and HSP72. Elevated body composition seems to impact metabolic profile and increase sympathetic activity. Conversely, subjects with increased cardiorespiratory fitness seem to have attenuated sympathetic activity.

Imaging Approaches to Investigate Pathophysiological Mechanisms of Brain Disease in Zebrafish.

Zebrafish has become an essential model organism in modern biomedical research. Owing to its distinctive features and high grade of genomic homology with humans, it is increasingly employed to model diverse neurological disorders, both through genetic and pharmacological intervention. The use of this vertebrate model has recently enhanced research efforts, both in the optical technology and in the bioengineering fields, aiming at developing novel tools for high spatiotemporal resolution imaging. Indeed, the ever-increasing use of imaging methods, often combined with fluorescent reporters or tags, enable a unique chance for translational neuroscience research at different levels, ranging from behavior (whole-organism) to functional aspects (whole-brain) and down to structural features (cellular and subcellular). In this work, we present a review of the imaging approaches employed to investigate pathophysiological mechanisms underlying functional, structural, and behavioral alterations of human neurological diseases modeled in zebrafish.

Upregulation of Sarcolemmal Hemichannels and Inflammatory Transcripts with Neuromuscular Junction Instability during Lower Limb Unloading in Humans.

Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels' upregulation, neuromuscular junction and axonal damage, neurotrophins' receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.

The architectural characteristics of the hamstring muscles do not differ between male and female elite-level rugby union players.

Purpose: To determine whether differences exist in the architectural characteristics of the hamstring muscles of elite-level male and female rugby union players. Methods: Forty elite-level rugby union players (male n = 20, female n = 20) participated in this cross-sectional study. A sonographer acquired static ultrasound images using a 92 mm linear transducer to quantify (via a semi-automated tracing software tool) the architectural characteristics (muscle length, fascicle length, pennation angle, and muscle thickness) of the biceps femoris long head and semimembranosus muscles of participants' left limb. Muscle length and muscle thickness of the biceps femoris short head and semitendinosus muscles of participants' left limb were also quantified. Bonferroni adjusted independent samples t-tests were performed to evaluate whether differences exist in the architectural characteristics of the hamstring muscles of elite-level male and female rugby union players. Results: There were no significant differences in fascicle length or pennation angle of the hamstring muscles of elite-level male and female rugby union players. Some significant differences in muscle thickness (biceps femoris short head, and semimembranosus) and muscle length (biceps femoris short head, biceps femoris long head, semitendinosus, and semimembranosus) were observed; in all cases the male players had thicker and longer muscles. Conclusion: At a group level, hamstring muscle fascicle length and pennation angle are unlikely to be a sex-specific intrinsic risk factor for Hamstring strain injuries.

Genes encoding agrin (AGRN) and neurotrypsin (PRSS12) are associated with muscle mass, strength and plasma C-terminal agrin fragment concentration.

Although physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes. For replication, we combined genotype from whole genome sequencing with phenotypic data from 6715 GenoFit participants aged 18-83 years. Dual energy X-ray absorptiometry assessed whole body lean mass (WBLM) and appendicular lean mass (ALM), hand dynamometry determined grip strength and ELISA measured plasma CAF in a subgroup (n = 260). Follow-up analyses included eQTL analyses, carrier analyses, single-variant and gene-burden tests. rs2710873 (AGRN) and rs71608359 (PRSS12) associate with muscle mass and strength phenotypes, respectively, in the UKBB (p = 8.9 × 10-6 and p = 8.4 × 10-6) and GenoFit cohort (p = 0.019 and p = 0.014). rs2710873 and rs71608359 are eQTLs for AGRN and PRSS12, respectively, in ≥ three tissues. Compared to non-carriers, carriers of rs2710873 had 4.0% higher WBLM and ALM (both p < 0.001), and 9.5% lower CAF concentrations (p < 0.001), while carriers of rs71608359 had 2.3% lower grip strength (p = 0.034). AGRN and PRSS12 are associated with muscle strength and mass in single-variant analyses, while PRSS12 has further associations with muscle strength in gene-burden tests. Our findings provide novel evidence of the relevance of AGRN and PRSS12 to sarcopenia phenotypes and support existing physiological data illustrating the importance of the NMJ in maintaining muscle health during ageing.

Large-scale all-optical dissection of motor cortex connectivity shows a segregated organization of mouse forelimb representations.

In rodent motor cortex, the rostral forelimb area (RFA) and the caudal forelimb area (CFA) are major actors in orchestrating the control of complex forelimb movements. However, their intrinsic connectivity and reciprocal functional organization are still unclear, limiting our understanding of how the brain coordinates and executes voluntary movements. Here, we causally probe cortical connectivity and activation patterns triggered by transcranial optogenetic stimulation of ethologically relevant complex movements exploiting a large-scale all-optical method in awake mice. Results show specific activation features for each movement class, providing evidence for a segregated functional organization of CFA and RFA. Importantly, we identify a second discrete lateral grasping representation area, namely the lateral forelimb area (LFA), with unique connectivity and activation patterns. Therefore, we propose the LFA as a distinct forelimb representation in the mouse somatotopic motor map.

Hamstring muscle architecture assessed sonographically using wide field of view: A reliability study.

PURPOSE: To assess the intra-rater reliability of static wide field of view ultrasound to quantify the architectural characteristics of the hamstring muscles. METHODS: Twenty amateur male athletes were recruited. Their left hamstring muscles were assessed using static wide field of view ultrasound on two separate occasions. Static ultrasound images were acquired by a single sonographer using a 92mm linear transducer. The architectural characteristics (muscle length, fascicle length, pennation angle and muscle thickness) from two distinct locations of the bicep femoris long head and semimembranosus were evaluated. Muscle length and thickness of the bicep femoris short head and semitendinosus muscle were also evaluated. Intraclass correlation coefficient analyses were performed to determine the intra-rater reliability of the performed measurements. RESULTS: Both muscle (intraclass correlation coefficient = 0.99; standard error of measurement = 4.3 to 6.6mm) and fascicle (intraclass correlation coefficient = 0.92 to 0.98; standard error measurement = 1.1 to 2.4mm) length were measured with excellent intra-rater reliability. Muscle thickness was measured with excellent reliability (intraclass correlation coefficient = 0.9 to 0.96; standard error of measurement = 0.91mm to 1.4mm) for all hamstring muscles except for the proximal segments of the bicep femoris short head (intraclass correlation coefficient = 0.85; standard error of measurement = 0.84mm) and semitendinosus (intraclass correlation coefficient = 0.88; standard error of measurement = 0.82mm), which were measured with good reliability. Pennation angle was measured with good reliability (intraclass correlation coefficient = 0.77 to 0.87; standard error of measurement = 1 to 1.6°). CONCLUSION: The architectural characteristics of the hamstring muscles of male amateur athletes can be reliably quantified using static wide field of view ultrasound.

Effects of short-term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile.

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes.

Multimodal Characterization of Seizures in Zebrafish Larvae.

Epilepsy accounts for a significant proportion of the world's disease burden. Indeed, many research efforts are produced both to investigate the basic mechanism ruling its genesis and to find more effective therapies. In this framework, the use of zebrafish larvae, owing to their peculiar features, offers a great opportunity. Here, we employ transgenic zebrafish larvae expressing GCaMP6s in all neurons to characterize functional alterations occurring during seizures induced by pentylenetetrazole. Using a custom two-photon light-sheet microscope, we perform fast volumetric functional imaging of the entire larval brain, investigating how different brain regions contribute to seizure onset and propagation. Moreover, employing a custom behavioral tracking system, we outline the progressive alteration of larval swim kinematics, resulting from different grades of seizures. Collectively, our results show that the epileptic larval brain undergoes transitions between diverse neuronal activity regimes. Moreover, we observe that different brain regions are progressively recruited into the generation of seizures of diverse severity. We demonstrate that midbrain regions exhibit highest susceptibility to the convulsant effects and that, during periods preceding abrupt hypersynchronous paroxysmal activity, they show a consistent increase in functional connectivity. These aspects, coupled with the hub-like role that these regions exert, represent important cues in their identification as epileptogenic hubs.

Fast whole-brain imaging of seizures in zebrafish larvae by two-photon light-sheet microscopy.

Light-sheet fluorescence microscopy (LSFM) enables real-time whole-brain functional imaging in zebrafish larvae. Conventional one-photon LSFM can however induce undesirable visual stimulation due to the use of visible excitation light. The use of two-photon (2P) excitation, employing near-infrared invisible light, provides unbiased investigation of neuronal circuit dynamics. However, due to the low efficiency of the 2P absorption process, the imaging speed of this technique is typically limited by the signal-to-noise-ratio. Here, we describe a 2P LSFM setup designed for non-invasive imaging that enables quintuplicating state-of-the-art volumetric acquisition rate of the larval zebrafish brain (5 Hz) while keeping low the laser intensity on the specimen. We applied our system to the study of pharmacologically-induced acute seizures, characterizing the spatial-temporal dynamics of pathological activity and describing for the first time the appearance of caudo-rostral ictal waves (CRIWs).

Plasma neurofilament light levels associate with muscle mass and strength in middle-aged and older adults: findings from GenoFit.

BACKGROUND: Efforts to enhance diagnostic measures for sarcopenia have led to an increased focus on the screening utility of blood-based biomarkers. In this regard, circulating neurofilament light chain (NfL) levels are a potent indicator of axonal damage and have been linked with several neurological disorders. However, despite the strong neurogenic contribution to skeletal muscle health, no studies have explored the relevance of NfL concentrations to sarcopenia. With that in mind, this study aimed to examine the association between plasma NfL concentration and sarcopenic domains. METHODS: Three hundred adults aged between 50 and 83 years participated to this study (male participants, n = 150; mean age: 64.2 ± 8.7 years and female participants, n = 150; mean age: 63.9 ± 8.3 years). Body composition was assessed using dual-energy X-ray absorptiometry, and a skeletal muscle index (SMI) was calculated. Muscle strength was assessed with hand dynamometry. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Plasma NfL concentration was determined using a highly sensitive, enzyme-linked immunosorbent assay. RESULTS: Neurofilament light chain levels were associated with grip strength and SMI (P = 0.005 and P = 0.045, respectively) and were significantly elevated in sarcopenic individuals, compared with non-sarcopenic participants (P < 0.001). Individuals with pre-sarcopenia (either low grip strength or low SMI) had significantly higher NfL levels, compared with healthy controls (P = 0.001 and P = 0.006, respectively). Male participants with either low grip strength or low SMI had significantly raised NfL levels (P = 0.006 and P = 0.002, respectively), while in female participants, NfL concentrations were significantly elevated only in those with low grip strength (P = 0.049). NfL concentration displayed acceptable diagnostic accuracy for sarcopenia (area under the curve = 0.726, P < 0.001). CONCLUSIONS: Our study clearly demonstrates the indicative pertinence of circulating NfL levels to sarcopenic domains, supporting its potential use as a biomarker of sarcopenia. More studies are needed, however, to further illuminate the diagnostic value of circulating NfL. Future research should explore whether NfL levels are more powerfully linked with muscle strength than mass and whether sex mediates the relevance of NfL concentrations to sarcopenic phenotypes.

Its not all about sprinting: mechanisms of acute hamstring strain injuries in professional male rugby union-a systematic visual video analysis.

OBJECTIVES: The mechanisms of hamstring strain injuries (HSIs) in professional Rugby Union are not well understood. The aim of this study was to describe the mechanisms of HSIs in male professional Rugby Union players using video analysis. METHODS: All time-loss acute HSIs identified via retrospective analysis of the Leinster Rugby injury surveillance database across the 2015/2016 to 2017/2018 seasons were considered as potentially eligible for inclusion. Three chartered physiotherapists (analysts) independently assessed all videos with a consensus meeting convened to describe the injury mechanisms. The determination of the injury mechanisms was based on an inductive process informed by a critical review of HSI mechanism literature (including kinematics, kinetics and muscle activity). One of the analysts also developed a qualitative description of each injury mechanism. RESULTS: Seventeen acute HSIs were included in this study. Twelve per cent of the injuries were sustained during training with the remainder sustained during match-play. One HSI occurred due to direct contact to the injured muscle. The remainder were classified as indirect contact (ie, contact to another body region) or non-contact. These HSIs were sustained during five distinct actions-'running' (47%), 'decelerating' (18%), 'kicking' (6%), during a 'tackle' (6%) and 'rucking' (18%). The most common biomechanical presentation of the injured limb was characterised by trunk flexion with concomitant active knee extension (76%). Fifty per cent of cases also involved ipsilateral trunk rotation. CONCLUSION: HSIs in this study of Rugby Union were sustained during a number of playing situations and not just during sprinting. We identified a number of injury mechanisms including: 'running', 'decelerating', 'kicking', 'tackle', 'rucking' and 'direct trauma'. Hamstring muscle lengthening, characterised by trunk flexion and relative knee extension, appears to be a fundamental characteristic of the mechanisms of acute HSIs in Rugby Union.