Publications

In this study, we present and provide validation data for a tool that predicts forced vital capacity (FVC) from speech acoustics collected remotely via a mobile app without the need for any additional equipment (e.g. a spirometer). We trained a machine learning model on a sample of healthy participants and participants with amyotrophic lateral sclerosis (ALS) to learn a mapping from speech acoustics to FVC and used this model to predict FVC values in a new sample from a different study of participants with ALS. We further evaluated the cross-sectional accuracy of the model and its sensitivity to within-subject change in FVC. We found that the predicted and observed FVC values in the test sample had a correlation coefficient of .80 and mean absolute error between .54 L and .58 L (18.5% to 19.5%). In addition, we found that the model was able to detect longitudinal decline in FVC in the test sample, although to a lesser extent than the observed FVC values measured using a spirometer, and was highly repeatable (ICC = 0.92-0.94), although to a lesser extent than the actual FVC (ICC = .97). These results suggest that sustained phonation may be a useful surrogate for VC in both research and clinical environments.

NEW FINDINGS: What is the central question of this study? Is the oestrous cycle affected during disuse atrophies and, if so, how are oestrous cycle changes related to musculoskeletal outcomes? What is the main finding and its importance? Rodent oestrous cycles were altered during disuse atrophy, which was correlated with musculoskeletal outcomes. However, the oestrous cycle did not appear to be changed by Lewis lung carcinoma, which resulted in no differences in muscle size in comparison to healthy control animals. These findings suggest a relationship between the oestrous cycle and muscle size during atrophic pathologies.

ABSTRACT: Recent efforts have focused on improving our understanding of female muscle physiology during exposure to muscle atrophic stimuli. A key feature of female rodent physiology is the oestrous cycle. However, it is not known how such stimuli interact with the oestrous cycle to influence muscle health. In this study, we investigated the impact of muscle atrophic stimuli on the oestrous cycle and how these alterations are correlated with musculoskeletal outcomes. A series of experiments were performed in female rodents, including hindlimb unloading (HU), HU followed by 24 h of reloading, HU combined with dexamethasone treatment, and Lewis lung carcinoma. The oestrous cycle phase was assessed throughout each intervention and correlated with musculoskeletal outcomes. Seven or 14 days of HU increased the duration in dioestrus or metoestrus (D/M; low hormones) and was negatively correlated with gastrocnemius mass. Time spent in D/M was also negatively correlated with changes in grip strength and bone density after HU, and with muscle recovery 24 h after the cessation of HU. The addition of dexamethasone strengthened these relationships between time in D/M and reduced musculoskeletal outcomes. However, in animals with Lewis lung carcinoma, oestrous cyclicity did not differ from that of control animals, and time spent in D/M was not correlated with either gastrocnemius mass or tumour burden. In vitro experiments suggested that enhanced protein synthesis induced by estrogen might protect against muscle atrophy. In conclusion, muscle atrophic insults are correlated with changes in the oestrous cycle, which are associated with deterioration in musculoskeletal outcomes. The magnitude of oestrous cycle alterations depends on the atrophic stimuli.

Ground-based animal models have been used extensively to understand the effects of microgravity on various physiological systems. Among them, hindlimb suspension (HLS), developed in 1979 in rats, remains the gold-standard and allows researchers to study the consequences of total unloading of the hind limbs while inducing a cephalic fluid shift. While this model has already brought valuable insights to space biology, few studies have directly compared functional decrements in the muscles of males and females during HLS. We exposed 28 adult Wistar rats (14 males and 14 females) to 14 days of HLS or normal loading (NL) to better assess how sex impacts disuse-induced muscle deconditioning. Females better maintained muscle function during HLS than males, as shown by a more moderate reduction in grip strength at 7 days (males: -37.5 ± 3.1%, females: -22.4 ± 6.5%, compared to baseline), that remains stable during the second week of unloading (males: -53.3 ± 5.7%, females: -22.4 ± 5.5%, compared to day 0) while the males exhibit a steady decrease over time (effect of sex × loading p = 0.0002, effect of sex × time × loading p = 0.0099). This was further supported by analyzing the force production in response to a tetanic stimulus. Further functional analyses using force production were also shown to correspond to sex differences in relative loss of muscle mass and CSA. Moreover, our functional data were supported by histomorphometric analyzes, and we highlighted differences in relative muscle loss and CSA. Specifically, female rats seem to experience a lesser muscle deconditioning during disuse than males thus emphasizing the need for more studies that will assess male and female animals concomitantly to develop tailored, effective countermeasures for all astronauts.

Electrical impedance myography (EIM) using surface techniques has shown promise as a means of diagnosing and tracking disorders affecting muscle and assessing treatment efficacy. However, the relationship between such surface-obtained impedance values and pure muscle impedance values has not been established. Here we studied three groups of diseased and wild-type (WT) animals, including a Duchenne muscular dystrophy model (the D2-mdx mouse), an amyotrophic lateral sclerosis (ALS) model (the SOD1 G93A mouse), and a model of fat-related atrophy (the db/db diabetic obese mouse), performing hind limb measurements using a standard surface array and ex vivo measurements on freshly excised gastrocnemius muscle. A total of 101 animals (23 D2-mdx, 43 ALS mice, 12 db/db mice, and corresponding 30 WT mice) were studied with EIM across a frequency range of 8 kHz to 1 MHz. For both D2-mdx and ALS models, moderate strength correlations (Spearman rho values generally ranging from 0.3-0.7, depending on the impedance parameter (i.e., resistance, reactance and phase) were obtained. In these groups of animals, there was an offset in frequency with impedance values obtained at higher surface frequencies correlating more strongly to impedance values obtained at lower ex vivo frequencies. For the db/db model, correlations were comparatively weaker and strongest at very high and very low frequencies. When combining impedance data from all three disease models together, moderate correlations persisted (with maximal Spearman rho values of 0.45). These data support that surface EIM data reflect ex vivo muscle tissue EIM values to a moderate degree across several different diseases, with the highest correlations occurring in the 10-200 kHz frequency range. Understanding these relationships will prove useful for future applications of the technique of EIM in the assessment of neuromuscular disorders.

Objective.Needle electromyography (EMG) is used to study the electrical behavior of myofiber properties in patients with neuromuscular disorders. However, due to the complexity of electrical potential spatial propagation in nonhomogeneous diseased muscle, a comprehensive understanding of volume conduction effects remains elusive. Here, we develop a framework to study the conduction effect of extracellular abnormalities and electrode positioning on extracellular local field potential (LFP) recordings.Methods.The framework describes the macroscopic conduction of electrical potential in an isotropic, nonhomogeneous (i.e. two tissue) model. Numerical and finite element model simulations are provided to study the conduction effect in prototypical monopolar EMG measurements.Results.LFPs recorded are influenced in amplitude, phase and duration by the electrode position in regards to the vicinity of tissue with different electrical properties.Conclusion.The framework reveals the influence of multiple mechanisms affecting LFPs including changes in the distance between the source-electrode and tissue electrical properties.Clinical significance.Our modeled predictions may lead to new ways for interpreting volume conduction effects on recorded EMG activity, for example in neuromuscular diseases that cause structural and compositional changes in muscle tissue. These change will manifest itself by changing the electric properties of the conductor media and will impact recorded potentials in the area of affected tissue.

Goal: Current instruments for bulbar assessment exhibit technical limitations that hinder the execution of clinical studies. The volume conduction properties (VCP) of the tongue reflect ionic content and myofiber integrity and they can serve as a new biomarker for evaluating neurological disorders with bulbar dysfunction. Methods: We designed a standalone bioimpedance measurement system that enables accurate, multi-frequency measurement of tongue anisotropic VCP including conductivity and relative permittivity. The system includes a tongue depressor with 16 non-invasive surface sensors for electrical contact with the tongue at directions 0[Formula: see text], 45[Formula: see text], 90[Formula: see text] and 150[Formula: see text]. The depressor is interfaced with the tongue electronic system with Bluetooth connectivity, and a smartphone application. De-identified patient data is sent by email. Results: We first determined the accuracy of the hardware performing phantom measurements mimicking a broad range of tongue values and determined the error to be [Formula: see text]1%. We then validated our new technology measuring a cohort of 7 healthy human subjects under Institutional Review Board approval. Conclusions: None of the subjects who participated suffered discomfort or gag reflexes. The novel technique presented for intra-oral assessment of tongue VCP provides standard, objective and quantitative data potentially sensitive to alterations in tongue internal structure and composition.