Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

fNIRS is capable of distinguishing laterality of lower body contractions.

The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. However, the spatial resolution of fNIRS is lower than that of other imaging modalities. It is unclear whether fNIRS has sufficient spatial resolution to differentiate nearby areas of the cortex, such as the leg areas of the motor cortex. Therefore, the purpose of this study was to determine fNIRS' ability to discern laterality of lower body contractions. Activity in the primary motor cortex was recorded in forty participants (mean = 23.4 years, SD = 4.5, female = 23, male = 17) while performing unilateral lower body contractions. Contractions were performed at 30% of maximal force against a handheld dynamometer. These contractions included knee extension, knee flexion, dorsiflexion, and plantar flexion of the left and right legs. fNIRS signals were recorded and stored for offline processing and analysis. Channels of fNIRS data were grouped into regions of interest, with five tolerance conditions ranging from strict to lenient. Four of five tolerance conditions resulted in significant differences in cortical activation between hemispheres. During right leg contractions, the left hemisphere was more active than the right hemisphere. Similarly, during left leg contractions, the right hemisphere was more active than the left hemisphere. These results suggest that fNIRS has sufficient spatial resolution to distinguish laterality of lower body contractions. This makes fNIRS an attractive technology in research and clinical applications in which laterality of brain activity is required during lower body activity.

Sex-Specific Reliability of Lower-Limb Corticospinal Excitability and Silent Periods.

ABSTRACT: Pagan, JI, Harmon, KK, Girts, RM, MacLennan, RJ, Beausejour, JP, Hernandez-Sarabia, JA, Coker, NA, Carr, JC, Ye, X, DeFreitas, JM, and Stock, MS. Sex-specific reliability of lower-limb corticospinal excitability and silent periods. J Strength Cond Res 37(9): 1882-1887, 2023-Transcranial magnetic stimulation (TMS) is a research tool that has potential to provide new insights into strength training-induced adaptations. However, using TMS to study the lower limbs is challenging, and sex-specific reliability has yet to be reported. We examined the reliability of corticospinal excitability and silent periods for the rectus femoris, vastus lateralis, and biceps femoris in both sexes. Thirteen males and 14 females reported to the laboratory twice. During both trials, a double cone coil was used to deliver 20 pulses to the rectus femoris hotspot with a stimulator output of 130% of active motor threshold. Motor-evoked potential peak-to-peak amplitude, which reflects corticospinal excitability, and silent period duration were quantified. Our results offer 4 novel findings. First, corticospinal excitability and silent period demonstrated higher reliability for the females. Second, regardless of sex and muscle, the silent period was more reliable than corticospinal excitability. Third, reliability was highest for our target muscle (rectus femoris), with lower reliability for the vastus lateralis and biceps femoris, suggesting that these methods cannot be used to study coactivation. Fourth, active motor threshold showed less variability than corticospinal excitability and silent period but increased at trial 2 in females. Many of the intraclass correlation coefficients were excellent (≥0.90), although we attribute this finding to variability between subjects. Reliability of lower-limb TMS measures may be sex, muscle, and variable dependent. Our findings suggest that both males and females should be included in lower-limb TMS research, although combining data between sexes should be approached cautiously.

Effects of Strength and Conditioning on Maximal Isometric Strength, Motor Unit Behavior, and Concentric Isokinetic Peak Torque in Middle-School Boys'.

ABSTRACT: MacLennan, RJ, Mota, JA, Thompson, BJ, and Stock, MS. Effects of strength and conditioning on maximal isometric strength, motor unit behavior, and concentric isokinetic peak torque in middle-school boys. J Strength Cond Res 36(5): 1318-1326, 2022-It has long been theorized that improvements in muscle strength in young athletes are mediated by motor unit adaptations. The ability to decompose surface electromyographic signals obtained during isometric contractions now allow for such research questions to be answered. We examined changes in isometric and concentric isokinetic strength, as well as vastus lateralis motor unit behavior, after 16 weeks of strength training and conditioning in middle-school aged boys. Nine boys (mean ± SD age = 12 ± 1 years) participated in training. Five boys (age = 13 ± 1 years) served as control subjects. The training subjects performed 90 minutes of high-intensity, multi-joint exercise twice per week. Assessments of unilateral maximal voluntary isometric contraction (MVIC) force of the knee extensors, concentric peak torque at velocities of 60, 180, and 300°·s-1, and vastus lateralis motor unit data during 50 and 80% MVIC tests were performed. Strength training and conditioning did not improve MVIC force. Greater training-induced strength increases were observed at faster isokinetic velocities, with a large effect size at 300°·s-1 (d = 0.813). The slopes and y-intercepts of the mean firing rate vs. recruitment threshold relationship and the action potential amplitude vs. recruitment threshold relationship were unaffected by training. Sixteen weeks of middle-school strength and conditioning did not enhance maximal isometric strength or vastus lateralis motor unit control, but improvements were observed during rapid isokinetic muscle actions. Given the lack of training (multi-joint) vs. testing (single-joint) specificity, we propose that motor unit adaptations in youth are task specific.

Motor unit action potential amplitude during low torque fatiguing contractions versus high torque non-fatiguing contractions: a multilevel analysis.

PURPOSE: The ability to maintain an absolute, submaximal torque level during fatiguing contractions is controlled, in part, by the recruitment of larger motor units. These motor units are commonly identified based on greater action potential peak-to-peak amplitude values. It is unclear, however, if motor unit action potential (MUAP) amplitude values during low torque, fatiguing contractions reach similar levels as those observed during non-fatigued, high torque contractions. To establish a clearer understanding of motor unit control during fatigue, we compared MUAP amplitude during 50 and 80% maximum voluntary contraction (MVC) torque contractions and at the beginning, middle, and end of a 30% MVC fatigue protocol. METHODS: Eleven untrained men (mean age = 24 years) performed isometric contractions at 50 and 80% MVC, followed by repeated contractions at 30% MVC. Surface electromyographic (EMG) signals were detected from the vastus lateralis and decomposed to quantify the peak-to-peak amplitude of individual MUAPs. A two-level multilevel model was estimated, allowing examination of simultaneous measures of MUAP amplitude within participants and controlling for the dependence between measures within participants. RESULTS: Results from the multilevel analyses suggested that there were not statistically significant differences in MUAP amplitude between 80% MVC and end fatigue. Separate repeated-measures analyses of variance indicated that there were not statistically significant mean differences in greatest MUAP or surface EMG amplitude between 80% MVC and end fatigue. CONCLUSIONS: MUAP and surface EMG amplitude values during a 30% MVC fatiguing protocol appear to be comparable to those observed during a non-fatigued 80% MVC condition.

No acute effects of placebo or open-label placebo treatments on strength, voluntary activation, and neuromuscular fatigue.

PURPOSE: Recent evidence suggests that deception may not be necessary for placebos to improve clinical outcomes. We tested the hypothesis that placebo and open-label placebo (OLP) treatments would acutely improve strength and voluntary activation, as well as minimize neuromuscular fatigue, in untrained participants. METHODS: Twenty-one males (n = 11) and females (n = 10) visited the laboratory on three occasions (placebo, OLP, control) to receive each treatment in a randomized, counter-balanced manner. Trials involved a pretest, a 15-min intervention, and posttests. For the placebo trial, participants were informed that they would be ingesting a capsule that would improve their performance and make them feel more energetic. For the OLP intervention, participants were told that the capsules would have no effects. In "Experiment #1", knee extensor maximal voluntary contraction (MVC) peak torque and percent voluntary activation were evaluated. In "Experiment #2", participants performed 20 consecutive MVCs while surface electromyographic signals were detected from the vastus lateralis. Subjective assessments of energy and perceived exertion were examined. RESULTS: The interventions had no effect on strength or voluntary activation, but energy levels increased following treatments (p = 0.016, η2 = 0.257). Neither treatment influenced neuromuscular fatigue. Though some variables showed moderate-to-large effect sizes, these results were consistent for individuals with lower voluntary activation. CONCLUSION: Placebo and OLP treatments had minimal influence on strength, voluntary activation, and fatigue resistance. As these findings differ from recent reports, we speculate that placebos and OLPs are more likely to enhance muscle function in patient populations seeking medical care.

Clinical Trial Site Perspectives and Practices on Study Participant Diversity and Inclusion.

Clinical trial participant populations fail to adequately represent target populations that drugs are intended to serve. Improving racial and ethnic diversity of clinical trial participants is essential for generalizable, quality clinical research results and ensuring social and medical equity. Site-level clinical research professionals (CRPs) have unique insights on diversity improvement strategies for clinical trial enrollment. A survey was distributed to current CRPs working at clinical research sites in the United States to describe current practices and perceptions of the impact these practices have on participant diversity. Subsequently, descriptive quantitative analysis and inductive content analysis were performed. For the practices surveyed, there are discrepancies between frequency of use and perceived impact on diversity enrollment. Common current practices include phone-based or telemedicine study visits, electronic/digital data collection, and participant compensation. However, we report travel reimbursement and services, translated documents and translator services, and adequate participant compensation as most impactful on diverse enrollment. A multistakeholder approach is necessary to enhance diversity and inclusion (D&I) of study participants. Besides large-scale solutions such as countering community distrust, actionable steps are needed by sponsors and study sites to improve D&I of trial participants. Study leadership at the sponsor, contract research organization (CRO), and site-level should create diversity plans prior to study start, and CRO and sponsor budgets should consider D&I strategies during study planning. Planning should incorporate strategies to improve D&I including adequate participant compensation, translated documents and translator services, and travel reimbursements.

The impact of skeletal muscle disuse on distinct echo intensity bands: A retrospective analysis.

Echo intensity (EI) is a novel tool for assessing muscle quality. EI has traditionally been reported as the mean of the pixel histogram, with 0 and 255 arbitrary units (A.U.) representing excellent and poor muscle quality, respectively. Recent work conducted in youth and younger and older adults suggested that analyzing specific EI bands, rather than the mean, may provide unique insights into the effectiveness of exercise and rehabilitation interventions. As our previous work showed deterioration of muscle quality after knee joint immobilization, we sought to investigate whether the increase in EI following disuse was limited to specific EI bands. Thirteen females (age = 21 yrs) underwent two weeks of left knee immobilization and ambulated via crutches. B-mode ultrasonography was utilized to obtain images of the immobilized vastus lateralis. The percentage of the total number of pixels within bands of 0-50, 51-100, 101-150, 151-200, and 201-255 A.U. was examined before and after immobilization. We also sought to determine if further subdividing the histogram into 25 A.U. bands (i.e., 0-25, 26-50, etc.) would be a more sensitive methodological approach. Immobilization resulted in a decrease in the percentage of pixels within the 0-50 A.U. band (-3.11 ± 3.98%), but an increase in the 101-150 A.U. (2.94 ± 2.64%) and 151-200 A.U. (0.93 ± 1.42%) bands. Analyses of variance on the change scores indicated that these differences were large and significant (%EI0-50 vs. %EI101-150: p < .001, d = 1.243); %EI0-50 vs. %EI151-200: p = .043, d = 0.831). The effect size for the %EI51-100 versus %EI101-150 comparison was medium/large (d = 0.762), but not statistically significant (p = .085). Further analysis of the 25 A.U. bands indicated that the percentage of pixels within the 25-50 A.U. band decreased (-2.97 ± 3.64%), whereas the 101-125 (1.62 ± 1.47%) and 126-150 A.U. (1.18 ± 1.07%) bands increased. Comparison of the 50 A.U. and 25 A.U. band methods found that 25 A.U. bands offer little additional insight. Though studies are needed to ascertain the factors that may influence specific bands, changes in EI during muscle disuse are not homogeneous across the pixel histogram. We encourage investigators to think critically about the robustness of data obtained from EI histograms, rather than simply reporting the EImean value, in muscle quality research.

The time course of neuromuscular impairment during short-term disuse in young women.

Skeletal muscle disuse results in rapid functional declines. Previous studies have typically been at least 1 week in duration and focused on the responsiveness of men. Herein, we report the timeline of initial impairments in strength, voluntary activation (VA), and motor unit control during 2 weeks of knee joint immobilization. Thirteen women (mean age =21 years) underwent 2 weeks of left knee joint immobilization via ambulation on crutches and use of a brace. Participants visited the laboratory for testing on seven occasions (two familiarization visits, pretest, 48 and 72 h, 1 and 2 weeks). Knee extensor isometric and concentric isokinetic strength at two velocities (180 and 360 degrees⋅s-1 ), VA, and submaximal vastus lateralis motor unit activity were evaluated. Moderate-to-large decreases in isometric and concentric strength at 180 degrees⋅s-1 and VA were observed within 48 hours. Isometric strength continued to decline beyond 72 h, whereas other variables plateaued. The B-term of the motor unit mean firing rate versus action potential amplitude relationship demonstrated a moderate increase 1 week into immobilization, suggesting that greater firing rates were necessary to maintain pretest torque levels. Concentric strength at a velocity of 360 degrees s-1 was not affected. Decreases in knee extensor strength occur within a matter of days after immobilization, although the time course and magnitude vary among assessment methods. These changes are mediated by the nervous system's capacity to activate skeletal muscle. Clinically appropriate interventions which target nervous system plasticity should be implemented early to minimize the rapid functional impairments associated with disuse.

Declines in skeletal muscle quality vs. size following two weeks of knee joint immobilization.

BACKGROUND: Disuse of a muscle group, which occurs during bedrest, spaceflight, and limb immobilization, results in atrophy. It is unclear, however, if the magnitude of decline in skeletal muscle quality is similar to that for muscle size. The purpose of this study was to examine the effects of two weeks of knee joint immobilization on vastus lateralis and rectus femoris echo intensity and cross-sectional area. METHODS: Thirteen females (mean ± SD age = 21 ± 2 years) underwent two weeks of left knee joint immobilization via ambulating on crutches and use of a brace. B-mode ultrasonography was utilized to obtain transverse plane images of the immobilized and control vastus lateralis and rectus femoris at pretest and following immobilization. Effect size statistics and two-way repeated measures analyses of variance were used to interpret the data. RESULTS: No meaningful changes were demonstrated for the control limb and the rectus femoris of the immobilized limb. Analyses showed a large increase in vastus lateralis echo intensity (i.e., decreased muscle quality) for the immobilized limb (p = .006, Cohen's d = .918). For vastus lateralis cross-sectional area, no time × limb interaction was observed (p = .103), but the effect size was moderate (d = .570). There was a significant association between the increase in vastus lateralis echo intensity and the decrease in cross-sectional area (r =  - .649, p = .016). CONCLUSION: In female participants, two weeks of knee joint immobilization resulted in greater deterioration of muscle quality than muscle size. Echo intensity appears to be an attractive clinical tool for monitoring muscle quality during disuse.

Is the motor unit mean firing rate versus recruitment threshold relationship linear?

Advances in surface electromyographic (EMG) signal decomposition allow researchers to analyze data for 20-50 motor units per contraction. To simplify interpretation, some investigators rely on group mean analysis of the mean firing rate versus recruitment threshold relationship, but it is unclear if this association is linear. OBJECTIVE: To determine whether this relationship is strongest when analyzed via linear, quadratic, or cubic regression. APPROACH: Twenty-one men (mean ± SD age = 24 ± 4 years) and 16 women (21 ± 2 years) performed isometric contractions of the knee extensors at 50% of maximal force while bipolar surface EMG signals were recorded from the vastus lateralis. A decomposition algorithm was used to calculate the mean firing rate and recruitment threshold of each motor unit at accuracy levels ranging from 90.0%-93.0%. Polynominal regression was used to determine if each relationship was best fit with a linear, quadratic, or cubic model. We examined individual contractions and grouped data. MAIN RESULTS: Overall, 80% of the relationships were best fit with a linear model. Quadratic and cubic relationships were more appropriate for 16% and 2% of the contractions, respectively. Selecting varying accuracy levels within a range of 90.0%-93.0% had little influence on whether a given dataset was best fit with a linear, quadratic, or cubic model. Grouping of data provided different relationships than otherwise found on a contraction-by-contraction basis. SIGNIFICANCE: The mean firing rate versus recruitment threshold relationship is typically best fit with a linear model. These relationships should be examined on an individual contraction basis.