Subaryani Dambawati H. Soedirdjo

A bstract: Dynamic endocrine transitions govern female physiology, yet several reproductive hormones remain incompletely characterized across the natural menstrual cycle. Relaxin, a peptide hormone classically associated with pregnancy, has recognized vascular, extracellular matrix, and anti-fibrotic actions, but its physiology in nonpregnant women remains poorly defined. We performed dense longitudinal endocrine profiling across 80 natural menstrual cycles from 34 healthy women, complemented by oral contraceptive users, to define circulating relaxin-2 dynamics relative to ovarian steroids. Using generalized additive modeling of cycle-normalized trajectories, we identified relaxin as a highly phase-locked late-luteal hormone with a sharp, reproducible peak distinct from estradiol and progesterone. Progesterone rose earlier after ovulation and peaked at cycle day 23.9, whereas relaxin peaked significantly later at day 28.0, revealing an approximately 4-day temporal offset. Relaxin showed lower inter-cycle variability and narrower temporal dispersion than progesterone, indicating unexpectedly precise endocrine timing. Detectable relaxin persisted into early menses, suggesting continued luteal peptide release across the menstrual boundary. In combined oral contraceptive users, endogenous cyclicity was attenuated and circulating relaxin was effectively absent despite exogenous progestin exposure, implicating ovulation-dependent corpus luteum biology rather than steroid exposure alone as the primary determinant of relaxin secretion. These findings identify relaxin as a reproducible component of normal cyclic endocrine physiology rather than a hormone restricted to pregnancy. The discrete late-luteal relaxin window establishes a previously under-resolved temporal feature of the menstrual cycle and provides a framework for investigating its reproductive, vascular, and connective-tissue significance.

Tracking individual motor units (MUs) across multiple testing visits is critical for understanding neuromuscular adaptations and disease progression. However, existing methods fail to account reliably for spatiotemporal variations in motor unit action potentials (MUAPs) and lack validation for longitudinal tracking. Here, we present a robust computational framework for continuous MU tracking that integrates automatic estimation of electrode grid displacements and compensation for MUAP shape variations. Our algorithm demonstrated superior tracking accuracy, capturing 63% and 75% of MUs in the tibialis anterior and medial gastrocnemius, respectively, substantially outperforming state-of-the-art methods. By applying this approach to investigate estradiol-driven neuromuscular plasticity as a model system, we reveal previously undetectable modulations in recruitment thresholds and firing rates, linking hormonal fluctuations to motor unit behavior. Beyond advancing fundamental neuromuscular research, our approach holds promise for enhancing biomarker sensitivity in clinical trials, particularly in conditions such as amyotrophic lateral sclerosis, where reliable MU tracking is paramount. These findings establish a new standard for non-invasive motor unit tracking, unlocking opportunities for longitudinal neurophysiological assessment and evaluation of therapeutics.

Objective. Non-invasive spinal stimulation has the potential to modulate spinal excitability. This study explored the modulatory capacity of sub-motor grid-based transcutaneous spinal cord stimulation (tSCS) applied to the lumbar spinal cord in neurologically intact participants. Our objective was to examine the effect of grid spinal stimulation on polysynaptic reflex pathways involving motoneurons and interneurons likely activated by Aβ/δ fiber-mediated cutaneous afferents. Approach. Stimulation was delivered using two grid electrode montages, generating a net electric field in transverse or diagonal directions. We administered tSCS with the center of the grid aligned with the T10–T11 spinous process. Participants were seated for the 20 min stimulation duration. At 30 min after the cessation of spinal stimulation, we examined neuromodulatory effects on spinal circuit excitability in the tibialis anterior muscle by employing the classical flexion reflex paradigms. Additionally, we evaluated spinal motoneuron excitability using the H-reflex paradigm in the soleus muscle to explore the differential effects of tSCS on the polysynaptic versus monosynaptic reflex pathway and to test the spatial extent of the grid stimulation. Main results. Our findings indicated significant neuromodulatory effects on the flexion reflex, resulting in a net inhibitory effect, regardless of the grid electrode montages. Our data further indicated that the flexion reflex duration was significantly shortened only by the diagonal montage. Significance. Our results suggest that grid-based tSCS may specifically modulate spinal activities associated with polysynaptic flexion reflex pathways, with the potential for grid-specific targeted neuromodulation.

Estimating the state of tract-specific inputs to spinal motoneurons is critical to understanding movement deficits induced by neurological injury and potential pathways to recovery but remains challenging in humans. In this study, we explored the capability of trans-spinal magnetic stimulation (TSMS) to modulate distal reflex circuits in young adults. TSMS was applied over the thoracic spine to condition soleus H-reflexes involving sacral-level motoneurons. Three TSMS intensities below the motor threshold were applied at interstimulus intervals (ISIs) between 2 and 20 ms relative to peripheral nerve stimulation (PNS). Although low-intensity TSMS yielded no changes in H-reflexes across ISIs, the two higher stimulus intensities yielded two phases of H-reflex inhibition: a relatively long-lasting period at 2- to 9-ms ISIs, and a short phase at 11- to 12-ms ISIs. H-reflex inhibition at 2-ms ISI was uniquely dependent on TSMS intensity. To identify the candidate neural pathways contributing to H-reflex suppression, we constructed a tract-specific conduction time estimation model. Based upon our model, H-reflex inhibition at 11- to 12-ms ISIs is likely a manifestation of orthodromic transmission along the lateral reticulospinal tract. In contrast, the inhibition at 2-ms ISI likely reflects orthodromic transmission along sensory fibers with activation reaching the brain, before descending along motor tracts. Multiple pathways may contribute to H-reflex modulation between 4- and 9-ms ISIs, orthodromic transmission along sensorimotor tracts, and antidromic transmission of multiple motor tracts. Our findings suggest that noninvasive TSMS can influence motoneuron excitability at distal segments and that the contribution of specific tracts to motoneuron excitability may be distinguishable based on conduction velocities.

Electromyogram (EMG) recordings are often corrupted by power line interference (PLI) even though the skin is prepared and well-designed instruments are used. This study focuses on the analysis of some of the recent and classical existing digital signal processing approaches have been used to attenuate, if not eliminate, the power line interference from EMG signals. A comparison of the signal to interference ratio (SIR) of the output signals is presented, for four methods: classical notch filter, spectral interpolation, adaptive noise canceller with phase locked loop (ANC-PLL) and adaptive filter, applied to simulated multichannel monopolar EMG signals with different SIR. The effect of each method on the shape of the EMG signals is also analyzed. The results show that ANC-PLL method gives the best output SIR and lowest shape distortion compared to the other methods. Classical notch filtering is the simplest method but some information might be lost as it removes both the interference and the EMG signals. Thus, it is obvious that notch filter has the lowest performance and it introduces distortion into the resulting signals.