ECSS Paris 2023: IS-PN08
Male and female hormonal environments are distinctly different throughout the adult lifespan, which may influence age-related changes within the neuromuscular system. Oestrogen and progesterone are the predominant female sex hormones and are able to cross the blood-brain barrier potentially influencing crucial central nervous system (CNS) functions including and MU firing properties. Throughout most of adulthood females experience a cyclical pattern of sex hormone fluctuations through the menstrual cycle. Oestrogen elicits excitatory effects via potentiation of glutamatergic receptors (Ansdell et al., 2019; Smith and Woolley, 2004) while progesterone increases activity of GABA, causing inhibitory effects (Ansdell et al., 2019; Smith et al., 1989). Cellular research utilising animal models has demonstrated the neuroprotective properties of oestrogen (Guo et al., 2020; Cardona-Rossinyol et al 2013). Similarly, testosterone, the predominant male sex hormone, has an anabolic impact on skeletal muscle and is associated with electrophysiological characteristics in older males. Later on in life females experience a dramatic change in the levels of Oestrogen and Progesterone through the menopausal transition beyond which the hormones remain much lower. Through this period females experience an array of often debilitating symptoms that are vasomotor related, further highlighting the importance of female sex hormones for functionality of the neuromuscular system. Furthermore, hormonal profiles of females may be further altered through the life course via pregnancy, hormonal contraceptives and hormonal replacement therapy. Thus, every female has a unique hormonal profile, further impacting their neuromuscular system in an individual manner. Females also typically live longer than males, but spend a greater proportion of their life in poor health (Public Health England., 2018) with higher frailty index scores. This distinction between the sexes is known as the health-survival paradox. Understanding and combating the health paradox between biological sexes, and the contributing role of menopause, is a public health priority, and it is imperative that future research seeks to address the disproportionate detrimental effects in older females. This presentation will seek to address some of the possible contributions of sex hormones in neuromuscular function and ultimately the mechanisms that may therefore contribute to neuromuscular deconditioning in age, that seems to be sex specific. We will showcase recent data that combines assessment of the central and peripheral nervous system that provides some initial explanation, ultimately leading to a framework for future research targeting the development of sex specific neurorehabilitation interventions.
Read CV Jessica PiaseckiECSS Paris 2023: IS-PN08
Neuromuscular electrical stimulation (NMES) is an exercise modality consisting of the application of intermittent tetanic stimulation over a muscle group to trigger visible muscle contractions. NMES is widely used as a (re)training strategy in both athletes and clinical populations; however, its effectiveness can be limited by factors such as restricted motor unit recruitment and discomfort during stimulation, particularly in frail individuals. These limitations highlight the need for optimized stimulation protocols to maximize NMES-induced adaptations (Blazevich et al., 2021). The development of wide-pulse, high-frequency (WPHF) NMES—characterized by 1 ms pulses delivered at 100 Hz—may help overcome these challenges. WPHF NMES can increase torque output by promoting reflexive motor unit recruitment at relatively low stimulation intensities, thereby reducing antidromic collision. In some individuals, this reflexive recruitment leads to the phenomenon of ‘extra torque,’ a progressive increase in torque during tetanic stimulation delivered at a constant stimulation intensity (Wegrzyk et al., 2015). Over recent years, our laboratory has investigated the mechanisms underlying acute and chronic responses to WPHF NMES (e.g., Neyroud et al., 2016 & 2019; Popesco et al., 2024a,b). We have explored interventions such as caffeine ingestion, spatially distributed sequential stimulation, and sensory stimulation combined with WPHF NMES (unpublished data) to enhance evoked torque. These studies focused on centrally mediated responses to WPHF NMES, including sustained electromyographic activity after stimulation and motor unit activation patterns. Beyond its application as a potential (re)training tool, WPHF NMES offers a unique opportunity to probe conditions associated with altered motoneuron excitability (e.g., stroke, muscle cramps) and holds promise for mitigating skeletal muscle weakness, thereby improving quality of life in frail populations. This presentation will integrate mechanistic insights with practical applications, providing researchers and clinicians with novel perspectives on the adaptability of the neuromuscular system to NMES.
Read CV Nicolas PlaceECSS Paris 2023: IS-PN08
Effective motor commands are comprised of excitatory, inhibitory, and neuromodulatory components, and disruptions in descending inputs caused by neural injuries such as spinal cord injury (SCI) affect all three of these components. Due to the heterogeneous nature of SCIs, there is also substantial functional heterogeneity within the SCI population, yet we know very little about the underlying mechanisms. Since motor units (MUs) are the fundamental building blocks for neuromuscular force transduction, their firing behavior may reveal important physiological insights about this heterogeneity. Over the past three years, we have assessed MU firing patterns in individuals with SCI during triangular isometric contractions in several limb muscles, including the biceps brachii, triceps brachii, vastus lateralis, vastus medialis, tibialis anterior, and soleus. We then compared these firing patterns to age-matched, non-injured (NI) participants. We have quantified several firing rate metrics to glean insights about synaptic inputs to motoneurons, and their biophysical properties. General findings indicate that firing rates are substantially lower in people with SCI (particularly in flexor muscles), but estimates of motoneuron excitability are greater in people with SCI. Although our results indicate substantial intermuscular and inter-individual heterogeneity in MU firing patterns after SCI, which may contribute to the observed heterogeneity in functional recovery, there are significant relationships between firing patterns and function. Preliminary results suggest that motoneuron excitability is lowest in SCI participants with low-function and highest in the SCI participants with high-function. This suggests that intrinsic motoneuron excitability may be of critical importance, since it is impaired in low-functioning, but enhanced in high-functioning, SCI participants, and that enhanced motoneuron excitability may augment function in some people with incomplete SCI in the presence of disrupted motor commands. These findings have directly informed therapeutic strategies to enhance function in people living with chronic incomplete SCI. One such intervention is acute intermittent hypoxia, which is known to facilitate motoneuron excitability. Recent experiments from our group have now shown that breathing 30-60s of low-oxygen air interspersed with 60s of normoxic air improves function of people with SCI, which is accompanied by increased MU firing rates and estimates of motoneuron excitability.
Read CV Gregory PearceyECSS Paris 2023: IS-PN08