The hormonal profile in women using combined monophasic oral contraceptive pills varies across the pill cycle: a temporal analysis of serum endogenous and exogenous hormones using liquid chromatography with tandem mass spectroscopy.

Oral contraceptive pills, of all types, are used by approximately 151 million women worldwide; however, a clear understanding of the concentrations of endogenous and exogenous hormones across a 28-day combination monophasic oral contraceptive pill pack is not well described. In our study of 14 female participants taking various combination monophasic oral contraceptive pills, we found significant fluctuations in endogenous and exogenous hormone levels throughout the pill cycle. Our analysis revealed significantly greater levels of ethinyl estradiol on the 20th and 21st days of active pill ingestion, compared with days 1-2 (active) and days 27-28 (inactive pill ingestion). Conversely, estradiol concentrations decreased during active pill consumption, while progestin and progesterone levels remained stable. During the 7 days of inactive pill ingestion, estradiol levels rose sharply and were significantly higher at days 27-28 compared with the mid and late active phase time points, while ethinyl estradiol declined and progestin did not change. These findings challenge the previous assumption that endogenous and exogenous hormones are stable throughout the 28-day pill cycle.NEW & NOTEWORTHY The results from this study have wide-ranging implications for research and treatment in women's health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.

Myoelectric interface for neurorehabilitation conditioning to reduce abnormal leg co-activation after stroke: a pilot study.

BACKGROUND: The ability to walk is an important factor in quality of life after stroke. Co-activation of hip adductors and knee extensors has been shown to correlate with gait impairment. We have shown previously that training with a myoelectric interface for neurorehabilitation (MINT) can reduce abnormal muscle co-activation in the arms of stroke survivors. METHODS: Here, we extend MINT conditioning to stroke survivors with leg impairment. The aim of this pilot study was to assess the safety and feasibility of using MINT to reduce abnormal co-activation between hip adductors and knee extensors and assess any effects on gait. Nine stroke survivors with moderate to severe gait impairment received 6 h of MINT conditioning over six sessions, either in the laboratory or at home. RESULTS: MINT participants completed a mean of 159 repetitions per session without any adverse events. Further, participants learned to isolate their muscles effectively, resulting in a mean reduction of co-activation of 70% compared to baseline. Moreover, gait speed increased by a mean of 0.15 m/s, more than the minimum clinically important difference. Knee flexion angle increased substantially, and hip circumduction decreased. CONCLUSION: MINT conditioning is safe, feasible at home, and enables reduction of co-activation in the leg. Further investigation of MINT's potential to improve leg movement and function after stroke is warranted. Abnormal co-activation of hip adductors and knee extensors may contribute to impaired gait after stroke. Trial registration This study was registered at ClinicalTrials.gov (NCT03401762, Registered 15 January 2018, https://clinicaltrials.gov/study/NCT03401762?tab=history&a=4 ).

Identifying spinal tracts transmitting distant effects of trans-spinal magnetic stimulation.

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.NEW & NOTEWORTHY This study explored the capability of trans-spinal magnetic stimulation (TSMS) over the thoracic spine to modulate distal reflex circuits, H-reflexes involving sacral-level motoneurons, in young adults. TSMS induced two inhibition phases of H-reflex across interstimulus intervals (ISIs): a relatively long-lasting period at 2- to 9-ms ISIs, and a short phase at 11- to 12-ms ISIs. An estimated probability model constructed from tract-specific conduction velocities allowed the identification of potential spinal tracts contributing to the changes in motoneuron excitability.

Can Increased Locomotor Task Difficulty Differentiate Knee Muscle Forces After Anterior Cruciate Ligament Reconstruction?

Changes in knee mechanics following anterior cruciate ligament (ACL) reconstruction are known to be magnified during more difficult locomotor tasks, such as when descending stairs. However, it is unclear if increased task difficulty could distinguish differences in forces generated by the muscles surrounding the knee. This study examined how knee muscle forces differ between individuals with ACL reconstruction with different graft types (hamstring tendon and patellar tendon autograft) and "healthy" controls when performing tasks with increasing difficulty. Dynamic simulations were used to identify knee muscle forces in 15 participants when walking overground and descending stairs. The analysis was restricted to the stance phase (foot contact through toe-off), yielding 162 separate simulations of locomotion in increasing difficulty: overground walking, step-to-floor stair descent, and step-to-step stair descent. Results indicated that knee muscle forces were significantly reduced after ACL reconstruction, and stair descent tasks better discriminated changes in the quadriceps and gastrocnemii muscle forces in the reconstructed knees. Changes in quadriceps forces after a patellar tendon graft and changes in gastrocnemii forces after a hamstring tendon graft were only revealed during stair descent. These results emphasize the importance of incorporating sufficiently difficult tasks to detect residual deficits in muscle forces after ACL reconstruction.

The Effect of Implanted Functional Electrical Stimulation on Gait Performance in Stroke Survivors: A Systematic Review.

The emerging literature suggests that implantable functional electrical stimulation may improve gait performance in stroke survivors. However, there is no review providing the possible therapeutic effects of implanted functional electrical stimulation on gait performance in stroke survivors. We performed a web-based, systematic paper search using PubMed, the Cochrane Library, and EMBASE. We limited the search results to human subjects and papers published in peer-reviewed journals in English. We did not restrict demographic or clinical characteristics. We included 10 papers in the current systematic review. Across all included studies, we found preliminary evidence of the potential therapeutic effects of functional electrical stimulation on walking endurance, walking speed, ankle mobility, and push-off force in stroke survivors. However, due to the heterogeneity between the included studies, small sample size, and lack of randomized controlled trials, more studies are critically needed to confirm whether implanted functional electrical stimulation can improve gait performance in stroke survivors.

Assessing the spatial distribution of cervical spinal cord activity during tactile stimulation of the upper extremity in humans with functional magnetic resonance imaging.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n â€‹= â€‹24, age â€‹= â€‹36.8 â€‹± â€‹11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

Evidence of impaired neuromuscular responses in the support leg to a destabilizing swing phase perturbation in hemiparetic gait.

The neuromuscular mechanisms that underlie post-stroke impairment in reactive balance control during gait are not fully understood. Previous research has described altered muscle activations in the paretic leg in response to postural perturbations from static positions. Additionally, attenuation of interlimb reflexes after stroke has been reported. Our goal was to characterize post-stroke changes to neuromuscular responses in the stance leg following a swing phase perturbation during gait. We hypothesized that, following a trip, altered timing, sequence, and magnitudes of perturbation-induced activations would emerge in the paretic and nonparetic support legs of stroke survivors compared to healthy control subjects. The swing foot was interrupted, while subjects walked on a treadmill. In healthy subjects, a sequence of perturbation-induced activations emerged in the contralateral stance leg with mean onset latencies of 87-147 ms. The earliest latencies occurred in the hamstrings and hip abductor and adductors. The hamstrings, the adductor magnus, and the gastrocnemius dominated the relative balance of perturbation-induced activations. The sequence and balance of activations were largely preserved after stroke. However, onset latencies were significantly delayed across most muscles in both paretic and nonparetic stance legs. The shortest latencies observed suggest the involvement of interlimb reflexes with supraspinal pathways. The preservation of the sequence and balance of activations may point to a centrally programmed postural response that is preserved after stroke, while post-stroke delays may suggest longer transmission times for interlimb reflexes.

17ß-Estradiol Effects in Skeletal Muscle: A 31P MR Spectroscopic Imaging (MRSI) Study of Young Females during Early Follicular (EF) and Peri-Ovulation (PO) Phases.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17ß-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17ß-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17ß-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17ß-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17ß-estradiol suggests that 17ß-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

Oral Contraception Use and Musculotendinous Injury in Young Female Patients: A Database Study.

PURPOSE: The purpose of this study is to characterize the effect of sex and the influence of oral contraception usage on musculotendinous injury (MTI). Current literature suggests a disparity in the incidence of MTI between males and females. This may be attributed to inherent biological differences between the sexes, such as in the sex hormonal milieu. There is a lack of information associating sex hormone milieu and MTI. METHODS: We searched the PearlDiver database (a for-fee healthcare database) for males, females taking oral contraceptives (OC), and eumenorrheic females not taking any form of hormonal contraceptives (non-OC) 18-39 yr old. The three populations were matched by age and body mass index. We queried the database for lower-extremity skeletal MTI diagnoses in these groups. RESULTS: Each group contained 42,267 patients with orthopedic injuries. There were a total of 1476 (3.49%) skeletal MTI in the male group, 1078 (2.55%) in non-OC females, and 231 (0.55%) in OC females. Both the non-OC and the OC groups had a significantly smaller proportion of MTI than males ( P < 0.0001), and therefore these groups were less likely (adjusted odds ratios, 0.72 and 0.15, respectively) to experience MTI when controlled for potential covariates. CONCLUSIONS: In this study, we show that females are less likely to develop MTI to total injuries, when compared with males, with OC using females being least likely followed by non-OC females. These results are consistent with other epidemiological studies; however, overall results in the literature are variable. This study adds to the emerging body of literature on sex hormone-influenced musculoskeletal injury but, more specifically, MTI, which have not been rigorously investigated.

Cervical spinal cord morphometrics in degenerative cervical myelopathy: quantification using semi-automated normalized technique and correlation with neurological dysfunctions.

BACKGROUND CONTEXT: Degenerative cervical myelopathy (DCM) is characterized by spinal cord atrophy. Accurate estimation of spinal cord atrophy is key to the understanding of neurological diseases, including DCM. However, its clinical application is hampered by difficulties in its precise and consistent estimation due to significant variability in spinal cord morphometry along the cervical spine, both within and between individuals. PURPOSE: To characterize morphometrics of the compressed spinal cord in DCM patients. We employed our semiautomated analysis framework that incorporates the Spinal Cord Toolbox (SCT) and a normalization approach to effectively address the challenges posed by cord compression in these patients. Additionally, we examined the clinical relevance of these morphometric measures to enhance our understanding of DCM pathophysiology. STUDY DESIGN: Prospective study. PATIENT SAMPLE: This study investigated 36 DCM patients and 31 healthy controls (HCs). OUTCOME MEASURES: Clinical scores including 9-hole peg test for hand dexterity, hand grip strength, balance, gait speed, modified Japanese Orthopaedic Association (mJOA) score, and imaging-based spinal cord morphometrics. METHOD: Using the generic spine acquisition protocol and our semiautomated analysis pipeline, spinal cord morphometrics, including cross-sectional area (CSA), anterior-posterior (AP) and transverse (RL) diameters, eccentricity, and solidity, were estimated from sagittal T2w magnetic resonance imaging (MRI) images using the Spinal Cord Toolbox (SCT). Normalized metrics were extracted from the C1 to C7 vertebral levels and compared between DCM patients and HC. Morphometric data at regions of maximum spinal cord compression (MSCC) were correlated with the clinical scores. A subset of participants underwent follow-up scans at 6 months to monitor longitudinal changes in spinal cord atrophy. RESULTS: Spinal cord morphometric data were normalized against the healthy population morphometry (PAM50 database) and extracted for all participants. DCM patients showed a notable reduction in CSA, AP, and RL diameter across all vertebral levels compared to HC. MSCC metrics correlated significantly with clinical scores like dexterity, grip strength, and mJOA scores. Longitudinal analysis indicated a decrease in CSA and worsening clinical scores in DCM patients. CONCLUSION: Our processing pipeline offers a reliable method for assessing spinal cord compression in DCM patients. Normalized spinal cord morphometrics, particularly the CSA could have potential for monitoring DCM disease severity and progression, guiding treatment decisions. Furthermore, to our knowledge our study is the first to apply the generic spinal cord acquisition protocol, ensuring consistent imaging across different MRI scanners and settings. Coupled with our semiautomated analysis pipeline, this protocol is key for the detailed morphometric characterization of compressed spinal cords in patients with DCM, a disease that is both complex and heterogenous. This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) (K23:NS091430) and (R01: NS129852-01A1).

Reducing robotic guidance during robot-assisted gait training improves gait function: a case report on a stroke survivor.

OBJECTIVE: To test the feasibility of patient-cooperative robotic gait training for improving locomotor function of a chronic stroke survivor with severe lower-extremity motor impairments. DESIGN: Single-subject crossover design. SETTING: Performed in a controlled laboratory setting. PARTICIPANT: A 62-year-old man with right temporal lobe ischemic stroke was recruited for this study. The baseline lower-extremity Fugl-Meyer score of the subject was 10 on a scale of 34, which represented severe impairment in the paretic leg. However, the subject had a good ambulation level (community walker with the aid of a stick cane and ankle-foot orthosis) and showed no signs of sensory or cognitive impairments. INTERVENTIONS: The subject underwent 12 sessions (3 times per week for 4wk) of conventional robotic training with the Lokomat, where the robot provided full assistance to leg movements while walking, followed by 12 sessions (3 times per week for 4wk) of patient-cooperative robotic control training, where the robot provided minimal guidance to leg movements during walking. MAIN OUTCOME MEASURES: Clinical outcomes were evaluated before the start of the intervention, immediately after 4 weeks of conventional robotic training, and immediately after 4 weeks of cooperative control robotic training. These included: (1) self-selected and fast walking speed, (2) 6-minute walk test, (3) Timed Up & Go test, and (4) lower-extremity Fugl-Meyer score. RESULTS: Results showed that clinical outcomes changed minimally after full guidance robotic training, but improved considerably after 4 weeks of reduced guidance robotic training. CONCLUSIONS: The findings from this case study suggest that cooperative control robotic training is superior to conventional robotic training and is a feasible option to restoring locomotor function in ambulatory stroke survivors with severe motor impairments. A larger trial is needed to verify the efficacy of this advanced robotic control strategy in facilitating gait recovery after stroke.

Effect of Surgical Design Variations on the Knee Contact Behavior during Anterior Cruciate Ligament Reconstruction.

In this study, we aimed to develop an in-silico synthesis of the effect of critical surgical design parameters on articular contact behavior for a bone-patellar-tendon-bone anterior cruciate ligament reconstruction (ACL-R) surgery. A previously developed finite element model of the knee joint consisting of all relevant soft tissues was employed. The knee model was further updated with additional features to develop the parametric FE model of the biomechanical experiments that depicted the ACL-R surgery. The parametricity was created involving femoral tunnel architecture (orientations and locations) and graft fixation characteristics (pretension and angle of fixation). A global sensitivity analysis based on variance decomposition was used to investigate the contribution of the surgical parameters to the uncertainty in response to the ACL-R joint. Our examinations indicated that the total contact force was primarily influenced by either combined or individual action of the graft pretension and fixation angle, with a modest contribution of the graft insertion sites. The joint contact center and area were affected mainly by the angle of fixation and the tunnel placements. Graft pretension played the dominant role in the maximum contact pressure variability, an observation that has been well-documented in the literature. Interestingly, the joint contact behavior was almost insensitive to the tunnel's coronal and sagittal orientations. Our data provide an evaluation of how the surgical parameters affect the knee joint's contact behavior after ACL-R and may provide additional information to better explain the occurrence of osteoarthritis as an aftermath of such surgery.

Surrogate modeling of articular cartilage degradation to understand the synergistic role of MMP-1 and MMP-9: a case study.

A characteristic feature of arthritic diseases is cartilage extracellular matrix (ECM) degradation, often orchestrated by the overexpression of matrix metalloproteinases (MMPs) and other proteases. The interplay between fibril level degradation and the tissue-level aggregate response to biomechanical loading was explored in this work by a computational multiscale cartilaginous model. We considered the relative abundance of collagenases (MMP-1) and gelatinases (MMP-9) in surrogate models, where the diffusion (spatial distribution) of these enzymes and the subsequent, co-localized fibrillar damage were spatially randomized with Latin Hypercube Sampling. The computational model was constructed by incorporating the results from prior molecular dynamics simulations (tensile test) of microfibril degradation into a hyper-elastoplastic fibril-reinforced cartilage model. Including MMPs-mediated collagen fibril-level degradation in computational models may help understand the ECM pathomechanics at the tissue level. The mechanics of cartilage tissue and fibril show variations in mechanical integrity depending on the different combinations of MMPs-1 and 9 with a concentration ratio of 1:1, 3:1, and 1:3 in simulated indentation tests. The fibril yield (local failure) was initiated at 20.2 ± 3.0 (%) and at 23.0 ± 2.8 (%) of bulk strain for col 1:gel 3 and col 3: gel 1, respectively. The reduction in failure stress (global response) was 39.8% for col 1:gel 3, 37.5% for col 1:gel 1, and 36.7% for col 3:gel 1 compared with the failure stress of the degradation free tissue. These findings indicate that cartilage's global and local mechanisms of failure largely depend on the relative abundance of the two key enzymes-collagenase (MMP-1) and gelatinase (MMP-9) and the spatial characteristics of diffusion across the layers of the cartilage ECM.

Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading.

OBJECTIVE: Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints. DESIGN: Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-ß, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP). RESULTS: Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1ß, TNF-α, IL-10, and TGF-ß from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint. CONCLUSION: Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.

Sex hormone mediated change on flexion reflex.

It has been shown that estrogen and progesterone receptors are expressed in the spinal cord; therefore, fluctuation in their concentrations may affect the spinal network and modulate the control of movement. Herein, we assessed the neuro-modulatory effect of sex hormones on the polysynaptic spinal network by using a flexion reflex network as a model system. Twenty-four healthy eumenorrheic women (age 21-37 years) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were acquired at the time of testing. The flexion reflex of the tibialis anterior was elicited by sending an innocuous electrical stimulus directly to the posterior tibial nerve or plantar cutaneous afferent. Analyses were performed for each menstrual cycle phase: the follicular phase and the luteal phase. Increases in estradiol or progesterone concentrations were not associated with reflex duration or root mean squared (RMS) amplitude in either the follicular or luteal phases. In the luteal phase, an increase in the estradiol concentration was associated with a longer latency of the reflex (b = 0.23, p = 0.038). The estradiol × progesterone interaction was found towards significance (b = -0.017, p = 0.081). These results highlight the potential synergistic effect of estradiol and progesterone and may provide indirect confirmatory evidence of the observed modulatory effect.

Sex hormone-mediated change on muscle activation deactivation dynamics in young eumenorrheic women.

The goal of the study was to characterize muscle activation/deactivation dynamics across the menstrual cycle in healthy young women. Twenty-two healthy eumenorrheic women (age: 27.0 ± 4.4 years; mean ± SD) were tested every other day for one menstrual cycle. Serum estradiol and progesterone were quantified at the time of testing. Peak torque (PT), time to peak torque (TPT), and half relaxation time (HRT) of soleus muscle twitch were measured. Muscle twitch was elicited by delivering 1 ms width electrical pulses to the tibial nerve at an intensity that generated a maximum motor response (S-100) and at supramaximal intensity (S-120; 1.2 × S-100). The analyses were performed for each menstrual cycle phase: 1) the follicular phase to analyze the effect of estradiol while the progesterone concentrations remained at low concentrations; 2) the luteal phase to analyze the effect of progesterone with background estradiol concentrations. In the follicular phase, there was no association of estradiol for PT, TPT, and HRT. In the luteal phase, while estradiol had no association on PT, TPT, and HRT, progesterone expressed a significant association with HRT reduction but no association on PT or TPT. Also, there was a significant estradiol and progesterone interaction for HRT. However, the regression parameters are nearly zero, suggesting that the change in HRT may not have an impact on muscle performance across the menstrual cycle but implications on other women's health conditions with elevated sex hormone concentrations, such as pregnancy, may prove critical.

Myoelectric interface for neurorehabilitation conditioning to reduce abnormal leg co-activation after stroke: a pilot study.

Background: The ability to walk is an important factor in quality of life after stroke. Co-activation of hip adductors and knee extensors has been shown to correlate with gait impairment. We have shown previously that training with a myoelectric interface for neurorehabilitation (MINT) can reduce abnormal muscle co-activation in the arms of stroke survivors. Methods: Here, we extend MINT conditioning to stroke survivors with leg impairment. The aim of this pilot study was to assess the safety and feasibility of using MINT to reduce abnormal co-activation between hip adductors and knee extensors and assess any effects on gait. Nine stroke survivors with moderate to severe gait impairment received six hours of MINT conditioning over six sessions, either in the laboratory or at home. Results: MINT participants completed a mean of 159 repetitions per session without any adverse events. Further, participants learned to isolate their muscles effectively, resulting in a mean reduction of co-activation of 70% compared to baseline. Moreover, gait speed increased by a mean of 0.15 m/s, more than the minimum clinically important difference. Knee flexion angle increased substantially, and hip circumduction decreased. Conclusion: MINT conditioning is safe, feasible at home, and enables reduction of co-activation in the leg. Further investigation of MINT's potential to improve leg movement and function after stroke is warranted. Abnormal co-activation of hip adductors and knee extensors may contribute to impaired gait after stroke. Trial registration: This study was registered at ClinicalTrials.gov (NCT03401762, Registered 15 January 2018, https://clinicaltrials.gov/study/NCT03401762?tab=history&a=4).

Effect of Non-invasive Spinal Stimulation on Self-sustained Firing Motoneuron Model: In-Silico Study Using Human Body Model.

Transcutaneous spinal electrical stimulation (tSCS) is a non-invasive neuromodulation approach using a low intensity direct current. Recent developments in the technique have opened the possibility that tSCS can help restore motor function after spinal cord injury (SCI). However, the exact mechanism of action tSCS has on the spinal circuits is still unknown. Due to the complexity of experimental synthesis in a human model to delineate the mechanisms, models that link the stimulation paradigm and circuit behaviors are advantageous. Thus, this study aims to simulate the underlying changes in motor circuit firing rates in response to external stimuli induced by tSCS. Serial stimulations combining a high-fidelity finite element model with the human torso and spinal cord with a lumped motor neuron model is constructed. The parameters for both components of the model were derived from previous studies. We focused our analysis on a lumped motor neuron model that describes sustained firing behavior of the motor neuron driven primarily by persistent inward current (PIC), a signature behavior of the motor neuron after SCI. Modulation of the PIC behaviors was achieved by stimulating voltage-dependent calcium and sodium channels in the dendrite using a tSCS-induced electric field (E-field) expressed at different a spatial locations of the motor neuron in the gray matter. The PIC behaviors of spinal motor neurons in the left ventral horn were suppressed, while for the most part invariant in the right ventral horn. These initial simulations will provide a steppingstone for future examinations that incorporate additional neuronal models of inhibitory and excitatory interneurons to access the circuit-level effect of spinal stimulation.

Isolating Neurologic Deficits in Cervical Spondylotic Myelopathy: A Case-Controlled Study, Using the NIH Toolbox Motor Battery.

Background and Objectives: Patients with cervical spondylotic myelopathy (CSM) have motor impairments, including weakness, imbalance, and loss of dexterity. The reliable assessment of these symptoms is critical for treatment decisions. This study aimed to determine, for the first time, the use of the NIH Toolbox motor battery (NIHTBm) in the objective assessment of motor deficits in patients with CSM. Methods: Patients with symptoms and MRI evidence of CSM and age-matched healthy controls (HC), with no evidence of spinal disorder or surgery were included in this case-control study based on our inclusion and exclusion criteria. We performed motor tests, dexterity, gait speed, grip strength, and balance tests, using the NIHTBm in patients with CSM and HCs. Motor impairment rates were determined in patients with CSM based on the NIHTBm scores. We determined the association between NIHTBm scores and patient-reported outcome scores; patient-reported outcome measures (the modified Japanese Orthopedic Association [mJOA] and Nurick grade) to determine the association. One-way analysis of variance was used to analyze group differences and the Spearman rank correlation to determine the relationship between assessment scores. Results: We enrolled 24 patients with CSM with a mean age (SD) of 57.96 (10.61) years and 24 age-matched HCs with a mean age (SD) of 53.17 (6.04) years in this study. Overall, we observed a significant decrease in the motor function T-scores mean (SD): dexterity 31.54 (14.82) vs 51.54 (9.72), grip strength 32.00 (17.47) vs 56.79 (8.46), balance 27.58 (16.65) vs 40.21 (6.35), and gait speed 0.64 (0.18) vs 0.99 (0.17) m/s, in patients with CSM compared with that in HCs. The lower extremity dysfunction scores on the NIHTBm, balance (ρ = -0.67) and gait speed (ρ = -0.62), were associated with higher Nurick grades. We observed a similar but weaker association with the Nurick grades and NIHTBm tests: dexterity (ρ = -0.49) and grip strength (ρ = -0.31) scores. The total motor mJOA showed a positive but weak association with NIHTBm scores, gait speed (ρ = 0.38), balance (ρ = 0.49), grip strength (ρ = 0.41), and dexterity (ρ = 0.45). Discussion: Patients with CSM had significantly lower NIHTBm scores compared with HCs. The results from the NIHTBm are consistent with the clinical presentation of CSM showing patients have motor impairments in both upper and lower extremities. As a neurologic-specific scale, NIHTBm should be used in the evaluation and clinical management of patients with CSM.

Contributions of feed-forward and feedback strategies at the human ankle during control of unstable loads.

The nervous system can regulate the mechanical properties of the human ankle through feed-forward mechanisms such as co-contraction and rapid feedback mechanisms such as stretch reflexes. Though each of these strategies may contribute to joint stability, it is unclear how their relative contribution varies when ankle stability is threatened. We addressed this question by characterizing co-contraction and stretch reflexes during balance of an inverted pendulum simulated by a rotary motor configured as an admittance servo. The stability of this haptic environment was manipulated by varying the stiffness of a virtual spring supporting the pendulum. We hypothesized that co-contraction and stretch reflex amplitude would increase as the stability of the haptic load attached to the ankle was reduced. Electromyographic activity in soleus, medial and lateral gastrocnemius, and tibialis anterior was used to characterize co-contraction patterns and stretch reflex amplitude as subjects stabilized the haptic load. Our results revealed that co-contraction was heightened as stability was reduced, but that the resulting joint stiffness was not sufficient to fully counteract the imposed instability. Reflex amplitude, in comparison, was attenuated as load stability was reduced, contrary to results from upper limb studies using similar paradigms. Together these findings suggest that the nervous system utilizes feed-forward co-contraction rather than rapid involuntary feedback to increase ankle stability during simple balance tasks. Furthermore, since the stiffness generated through co-contraction was not sufficient to fully balance the haptic load, our results suggest an important role for slower, volitional feedback in the control of ankle stability during balancing tasks.