Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.

Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post-RE (∼200%, P = 0.018) and returned to pre-exercise levels by 6 h post-RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post-RE (8.6 ± 6.3-fold vs. 2.1 ± 0.7-fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post-RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease-associated muscle atrophy affect these outcomes is needed. HIGHLIGHTS: What is the central question of this study? How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation. What is the main finding and its importance? This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.

Resistance training-induced changes in muscle proteolysis and extracellular matrix remodeling biomarkers in the untrained and trained states.

PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period. RESULTS: There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged. CONCLUSION: Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.

Effects of Resistance Training Overload Progression Protocols on Strength and Muscle Mass.

The aim of this study was to compare the effects of progressive overload in resistance training on muscle strength and cross-sectional area (CSA) by specifically comparing the impact of increasing load (LOADprog) versus an increase in repetitions (REPSprog). We used a within-subject experimental design in which 39 previously untrained young persons (20 men and 19 women) had their legs randomized to LOADprog and REPSprog. Outcomes were assessed before and after 10 weeks of training. Muscle strength was assessed using the one repetition maximum (1RM) test on the leg extension exercise, and the CSA of the vastus lateralis was assessed by ultrasonography. Both protocols increased 1RM values from pre (LOADprog: 52.90±16.32 kg; REPSprog: 51.67±15.84 kg) to post (LOADprog: 69.05±18.55 kg, REPSprog: 66.82±17.95 kg), with no difference between them (P+>+0.05). Similarly, both protocols also increased in CSA values from pre (LOADprog: 21.34±4.71 cm²; REPSprog: 21.08±4.62 cm²) to post (LOADprog: 23.53±5.41 cm², REPSprog: 23.39±5.19 cm²), with no difference between them (P+>+0.05). In conclusion, our findings indicate that the progression of overload through load or repetitions can be used to promote gains in strength and muscle hypertrophy in young men and women in the early stages of training.

Time Course of Proteolysis Biomarker Responses to Resistance, High-Intensity Interval, and Concurrent Exercise Bouts.

ABSTRACT: Godwin, JS, Telles, GD, Vechin, FC, Conceição, MS, Ugrinowitsch, C, Roberts, MD, and Libardi, CA. Time course of proteolysis biomarker responses to resistance, high-intensity interval, and concurrent exercise bouts. J Strength Cond Res 37(12): 2326-2332, 2023-Concurrent exercise (CE) combines resistance exercise (RE) and high-intensity interval exercise (HIIE) in the same training routine, eliciting hypertrophy, strength, and cardiovascular benefits over time. Some studies suggest that CE training may hamper muscle hypertrophy and strength adaptations compared with RE training alone. However, the underlying mechanisms related to protein breakdown are not well understood. The purpose of this study was to examine how a bout of RE, HIIE, or CE affected ubiquitin-proteasome and calpain activity and the expression of a few associated genes, markers of skeletal muscle proteolysis. Nine untrained male subjects completed 1 bout of RE (4 sets of 8-12 reps), HIIE (12 × 1 minute sprints at V̇ o2 peak minimum velocity), and CE (RE followed by HIIE), in a crossover design, separated by 1-week washout periods. Muscle biopsies were obtained from the vastus lateralis before (Pre), immediately post, 4 hours (4 hours), and 8 hours (8 hours) after exercise. FBXO32 mRNA expression increased immediately after exercise (main time effect; p < 0.05), and RE and CE presented significant overall values compared with HIIE ( p < 0.05). There was a marginal time effect for calpain-2 mRNA expression ( p < 0.05), with no differences between time points ( p > 0.05). No significant changes occurred in TRIM63/MuRF-1 and FOXO3 mRNA expression, or 20S proteasome or calpain activities ( p > 0.05). In conclusion, our findings suggest that 1 bout of CE does not promote greater changes in markers of skeletal muscle proteolysis compared with 1 bout of RE or HIIE.

Risk of falls using the Biodex Balance System in non-faller patients with Parkinson Disease.

PURPOSE: Biodex Balance System (BBS) is a low-cost platform used to assess balance in different populations. However, no study has used this tool to evaluate the risk of falls related to balance changes in non-faller individuals with Parkinson Disease (PD). OBJECTIVE: The aim of this study was to determine the changes in the balance in non-faller individuals with mild to moderate PD compared to healthy elders. METHODS: Forty-six PD patients at stages 2 and 3 were assessed in the 'on' state (fully medicated) as well as 31 age-matched healthy controls. They were submitted to the fall risk protocol of BBS and performed three 20-s trials and a 60-s rest interval between the trials. RESULTS: Non-faller PD patients had an increased instability when compared to the healthy controls in the anteroposterior (controls: 1.54 ± 1.00 vs. PD patients: 2.91 ± 0.93) and mediolateral directions (controls: 1.21 ± 0.57 vs. PD patients: 1.42 ± 0.46), resulting in a great overall instability in the PD patients (controls: 1.28 ± 0.61 vs. PD patients: 4.09 ± 1.22). A significant correlation between overall instability and UPDRS-III (motor symptoms) in individuals with PD was observed. CONCLUSION: BBS was able to identify the risk of falls in non-fallers, showing that PD patients have a greater risk of falls in unstable conditions than age-matched healthy elders, mainly due to the large sway in the anteroposterior direction. Furthermore, the severity of motor symptoms was related to overall instability which can increase the risk of falls in PD patients.

Resistance training variable manipulations are less relevant than intrinsic biology in affecting muscle fiber hypertrophy.

We aimed to investigate whether muscle fiber cross-sectional area (fCSA) and associated molecular processes could be differently affected at the group and individual level by manipulating resistance training (RT) variables. Twenty resistance-trained subjects had each leg randomly allocated to either a standard RT (RT-CON: without specific variables manipulations) or a variable RT (RT-VAR: manipulation of load, volume, muscle action, and rest interval at each RT session). Muscle fCSA, satellite cell (SC) pool, myonuclei content, and gene expression were assessed before and after training (chronic effect). Gene expression was assessed 24 h after the last training session (acute effect). RT-CON and RT-VAR increased fCSA and myonuclei domain in type I and II fibers after training (p < 0.05). SC and myonuclei content did not change for both conditions (p > 0.05). Pax-7, MyoD, MMP-2 and COL3A1 (chronic) and MGF, Pax-7, and MMP-9 (acute) increased similar for RT-CON and RT-VAR (p < 0.05). The increase in acute MyoG expression was significantly higher for the RT-VAR than RT-CON (p < 0.05). We found significant correlation between RT-CON and RT-VAR for the fCSA changes (r = 0.89). fCSA changes were also correlated to satellite cells (r = 0.42) and myonuclei (r = 0.50) changes. Heatmap analyses showed coupled changes in fCSA, SC, and myonuclei responses at the individual level, regardless of the RT protocol. The high between and low within-subject variability regardless of RT protocol suggests that the intrinsic biological factors seem to be more important to explain the magnitude of fCSA gains in resistance-trained subjects.

Individual Muscle Adaptations in different Resistance Training Systems in Well-Trained Men.

Using a within-subject design we compared the individual responses between drop-set (DS) vs. traditional resistance training (TRAD) (n=16) and crescent pyramid (CP) vs. TRAD (n=15). Muscle cross-sectional area (CSA), leg press and leg extension 1 repetition maximum (1-RM) were assessed pre and post training. At group level, CSA increased from pre to post (DS: 7.8% vs. TRAD: 7.5%, P=0.02; CP: 7.5% vs. TRAD: 7.8%, P=0.02). All protocols increased the 1-RM from pre to post for leg press (DS: 24.9% vs. TRAD: 26.8%, P < 0.0001; CP: 27.3% vs. TRAD:2 6.3%, P < 0.0001) and leg extension (DS: 17.1% vs. TRAD: 17.3%, P < 0.0001; CP: 17.0% vs. TRAD: 16.6%, P < 0.0001). Individual analysis for CSA demonstrated no differences between protocols in 15 subjects. For leg press 1-RM, 5 subjects responded more to TRAD, 2 to DS and 9 similarly between protocols. In TRAD vs. CP, 4 subjects responded more to CP, 1 to TRAD and 10 similarly between protocols. For leg extension 1-RM 2 subjects responded more to DS, 3 to TRAD and 11 similarly between protocols. Additionally, 2 subjects responded more to CP, 2 to TRAD and 11 similarly between protocols. In conclusion, all protocols induced similar individual responses for CSA. For 1-RM, some subjects experience greater gains for the protocol performed with higher loads, such as CP.

Session Rating of Perceived Exertion as an Efficient Tool for Individualized Resistance Training Progression.

ABSTRACT: Gomes, RL, Lixandrão, ME, Ugrinowitsch, C, Moreira, A, Tricoli, V, and Roschel, H. Session rating of perceived exertion as an efficient tool for individualized resistance training progression. J Strength Cond Res 36(4): 971-976, 2022-The present study aimed to investigate the effects of an individualized resistance training (RT) progression model based on the session rating of perceived exertion (RPE) on gains in muscle mass and strength when compared with a conventional predetermined progression method (PP). Twenty previously trained young male subjects were randomly allocated to 1 of the 2 groups: RPE (n = 10) or PP (n = 10). Muscle cross-sectional area (CSA) and maximum dynamic strength were assessed at baseline and after 6 weeks. The RPE-based progression model resulted in a lower number of high-intensity sessions compared with the PP-based model. Despite this, both groups showed significant and similar increases in CSA (p < 0.0001; RPE = 6.55 ± 5.27% and PP = 9.65 ± 3.63%) and strength (p < 0.0001; RPE = 9.68 ± 4.57% and PP = 9.28 ± 4.01%) after the intervention period. No significant between-group difference was observed for total training volume (RPE = 45,366.00 ± 10,190.00 kg and PP = 47,779.00 ± 5,685.00 kg; p = 0.52). Our results showed that an RT progression model based on session-to-session physiological response assessments resulted in fewer high-intensity training sessions while allowing for similar gains in muscle strength and mass. Thus, trainees are encouraged to adopt session RPE as a potential tool to control workload progression throughout a training period and allowing the optimization of training stimulus on an individual basis.

Progressive Resistance Training Volume: Effects on Muscle Thickness, Mass, and Strength Adaptations in Resistance-Trained Individuals.

ABSTRACT: Aube, D, Wadhi, T, Rauch, J, Anand, A, Barakat, C, Pearson, J, Bradshaw, J, Zazzo, S, Ugrinowitsch, C, and De Souza, EO. Progressive resistance training volume: effects on muscle thickness, mass, and strength adaptations in resistance-trained individuals. J Strength Cond Res 36(3): 600-607, 2022-This study investigated the effects of 12-SET, 18-SET, and 24-SET lower-body weekly sets on muscle strength and mass accretion. Thirty-five resistance-trained individuals (one repetition maximum [1RM] squat: body mass ratio [1RM: BM] = 2.09) were randomly divided into 12-SET: n = 13, 18-SET: n = 12, and 24-SET: n = 10. Subjects underwent an 8-week resistance-training (RT) program consisting of 2 weekly sessions. Muscle strength (1RM), repetitions to failure (RTF) at 70% of 1RM, anterior thigh muscle thickness (MT), at the medial MT (MMT) and distal MT (DMT) points, as well as the sum of both sites (ΣMT), along with region of interest for fat-free mass (ROI-FFM) were measured at baseline and post-testing. For the 1RM, there was a main time effect (p ≤ 0.0001). However, there was a strong trend toward significance (p = 0.052) for group-by-time interaction, suggesting that 18-SET increased 1RM back squat to a greater extent compared with 24-SET (24-SET: 9.5 kg, 5.4%; 18-SET: 25.5 kg, 16.2%; 12-SET: 18.3 kg, 11.3%). For RTF, only a main time-effect (p ≤ 0.0003) was observed (24-SET: 5.7 reps, 33.1%; 18-SET: 2.4 reps, 14.5%; 12-SET: 5.0 reps, 34.8%). For the MMT, DMT, ΣMT, and ROI-FFM, there was only main time-effect (p ≤ 0.0001) (MMT: 24-SET: 0.15 cm, 2.7%; 18-SET: 0.32 cm, 5.7%; 12-SET: 0.38 cm, 6.4%-DMT: 24-SET: 0.39 cm, 13.1%; 18-SET: 0.28 cm, 8.9%; 12-SET: 0.34 cm, 9.7%-ΣMT: 24-SET: 0.54 cm, 6.1%; 18-SET: 0.60 cm, 6.7%; 12-SET: 0.72 cm, 7.7%, and ROI-FFM: 24-SET: 0.70 kg, 2.6%; 18-SET: 1.09 kg, 4.2%; 12-SET: 1.20 kg, 4.6%, respectively). Although all of the groups increased maximum strength, our results suggest that the middle dose range may optimize the gains in back squat 1RM. Our findings also support that differences in weekly set number did not impact in MT and ROI-FFM adaptations in subjects who can squat more than twice their body mass.

Muscle Hypertrophy Response Is Affected by Previous Resistance Training Volume in Trained Individuals.

ABSTRACT: Scarpelli, MC, Nóbrega, SR, Santanielo, N, Alvarez, IF, Otoboni, GB, Ugrinowitsch, C, and Libardi, CA. Muscle hypertrophy response is affected by previous resistance training volume in trained individuals. J Strength Cond Res 36(4): 1153-1157, 2022-The purpose of this study was to compare gains in muscle mass of trained individuals after a resistance training (RT) protocol with standardized (i.e., nonindividualized) volume (N-IND), with an RT protocol using individualized volume (IND). In a within-subject approach, 16 subjects had one leg randomly assigned to N-IND (22 sets·wk-1, based on the number of weekly sets prescribed in studies) and IND (1.2 × sets·wk-1 recorded in training logs) protocols. Muscle cross-sectional area (CSA) was assessed by ultrasound imaging at baseline (Pre) and after 8 weeks (Post) of RT, and the significance level was set at p < 0.05. Changes in the vastus lateralis CSA (difference from Pre to Post) were significantly higher for the IND protocol (p = 0.042; mean difference: 1.08 cm2; confidence interval [CI]: 0.04-2.11). The inferential analysis was confirmed by the CI of the effect size (0.75; CI: 0.03-1.47). Also, the IND protocol had a higher proportion of individuals with greater muscle hypertrophy than the typical error of the measurement (chi-square, p = 0.0035; estimated difference = 0.5, CI: 0.212-0.787). In conclusion, individualizing the weekly training volume of research protocols provides greater gains in muscle CSA than prescribing a group standard RT volume.

Does Varying Repetition Tempo in a Single-Joint Lower Body Exercise Augment Muscle Size and Strength in Resistance-Trained Men?

ABSTRACT: Pearson, J, Wadhi, T, Barakat, C, Aube, D, Schoenfeld, BJ, Andersen, JC, Barroso, R, Ugrinowitsch, C, and De Souza, EO. Does varying repetition tempo in a single-joint lower body exercise augment muscle size and strength in resistance-trained men? J Strength Cond Res 36(8): 2162-2168, 2022-This study compared the effects of FAST and SLOW eccentric repetition tempo in a single exercise volume-matched intervention on muscle thickness (MT) and strength in resistance-trained men. Using a within-subject design, 13 subjects had each leg randomly assigned to SLOW (1-0-3) or FAST (1-0-1) repetition tempo. Subjects underwent an 8-week strength-training (ST) intervention performed twice weekly. Unilateral leg-extension one repetition-maximum (1RM) and anterior thigh MT at the proximal (MTP) and distal (MTD) portions were assessed via ultrasound imaging at baseline and after 8 weeks of RT. Rating of perceived exertion (RPE) assessments of the training sessions (i.e., 16 per leg) were averaged for further analysis. Both legs similarly increased MTP (estimated differences: FAST: 0.24 cm, 3.6%; SLOW: 0.20 cm, 3.1%). However, for MTD, analysis of covariance analysis showed a leg effect ( p = 0.02) in which absolute pre-to-post change was greater in FAST compared with SLOW (estimated differences: FAST 0.23 cm, 5.5%; SLOW: 0.13 cm, 2.2%). For 1RM, both legs similarly increased maximum strength (estimated differences: FAST: 9.1 kg, 17.0%; SLOW: 10.4 kg, 22.1%, p ≤ 0.0001). The SLOW group had a higher RPE than FAST (8.59 vs. 7.98, p = 0.002). Despite differences in RPE, our results indicate that both repetition tempos produced similar muscular adaptations. However, they also suggest that the FAST tempo may provide a small hypertrophic advantage at the distal quadriceps. From a practical standpoint, strength and conditioning professionals may implement a FAST tempo at least in one single-joint exercise during an 8-week training period to enhance regional hypertrophic adaptations in trained individuals.

Effects of Blood Flow Restriction Combined With Resistance Training or Neuromuscular Electrostimulation on Muscle Cross-Sectional Area.

CONTEXT: Low-load resistance training (LL) and neuromuscular electrostimulation (NES), both combined with blood flow restriction (BFR), emerge as effective strategies to maintain or increase muscle mass. It is well established that LL-BFR promotes similar increases in muscle cross-sectional area (CSA) and lower rating of perceived exertion (RPE) and pain compared with traditional resistance training protocols. On the other hand, only 2 studies with conflicting results have investigated the effects of NES-BFR on CSA, RPE, and pain. In addition, no study directly compared LL-BFR and NES-BFR. OBJECTIVE: The aim of the study was to compare the effects of LL-BFR and NES-BFR on vastus lateralis CSA, RPE, and pain. Individual response for muscle hypertrophy was also compared between protocols. DESIGN: Intrasubject longitudinal study. SETTING: University research laboratory. INTERVENTION: Fifteen healthy young males (age = 23 [5] y; weight = 77.6 [11.3] kg; height = 1.76 [0.08] m). MAIN OUTCOME MEASURES: Vastus lateralis CSA was measured through ultrasound at baseline (pre) and after 20 training sessions (post). The RPE and pain responses were obtained through modified 10-point scales, handled during all training sessions. RESULTS: Both protocols demonstrated significant increases in muscle CSA (P < .0001). However, the LL-BFR demonstrated significantly greater CSA changes compared with NES-BFR (LL-BFR = 11.2%, NES-BFR = 4.6%; P < .0001). Comparing individual increases in CSA, 12 subjects (85.7% of the sample) presented greater muscle hypertrophy for LL-BFR than for the NES-BFR protocol. In addition, LL-BFR produced significantly lower RPE and pain responses (P < .0001). CONCLUSIONS: The LL-BFR produced significantly greater increases in CSA with significant less RPE and pain than NES-BFR. In addition, LL-BFR resulted in greater individual muscle hypertrophy responses for most subjects compared with NES-BFR.

The Adapted Resistance Training with Instability Randomized Controlled Trial for Gait Automaticity.

BACKGROUND: Deficits in the cerebellar locomotor region (CLR) have been associated with loss of gait automaticity in individuals with freezing of gait in Parkinson's disease (freezers); however, exercise interventions that restore gait automaticity in freezers are lacking. We evaluated the effects of the adapted resistance training with instability ([ARTI] complex exercises) compared with traditional motor rehabilitation (without complex exercises) on gait automaticity and attentional set-shifting. We also verified associations between gait automaticity change and CLR activation change previously published. METHODS: Freezers were randomized either to the experimental group (ARTI, n = 17) or to the active control group (traditional motor rehabilitation, n = 15). Both training groups performed exercises 3 times a week for 12 weeks. Gait automaticity (dual-task and dual-task cost [DTC] on gait speed and stride length), single-task gait speed and stride length, attentional set-shifting (time between Trail Making Test parts B and A), and CLR activation during a functional magnetic resonance imaging protocol of simulated step initiation task were evaluated before and after interventions. RESULTS: Both training groups improved gait parameters in single task (P < 0.05), but ARTI was more effective than traditional motor rehabilitation in improving DTC on gait speed, DTC on stride length, dual-task stride length, and CLR activation (P < 0.05). Changes in CLR activation were associated with changes in DTC on stride length (r = 0.68, P = 0.002) following ARTI. Only ARTI improved attentional set-shifting at posttraining (P < 0.05). CONCLUSIONS: ARTI restores gait automaticity and improves attentional set-shifting in freezers attributed to the usage of exercises with high motor complexity. © 2020 International Parkinson and Movement Disorder Society.

Blood Flow Restriction Does Not Promote Additional Effects on Muscle Adaptations When Combined With High-Load Resistance Training Regardless of Blood Flow Restriction Protocol.

ABSTRACT: Teixeira, EL, Ugrinowitsch, C, de Salles Painelli, V, Silva-Batista, C, Aihara, AY, Cardoso, FN, Roschel, H, and Tricoli, V. Blood flow restriction does not promote additional effects on muscle adaptations when combined with high-load resistance training regardless of blood flow restriction protocol. J Strength Cond Res 35(5): 1194-1200, 2021-The aim of this study was to investigate, during high-load resistance training (HL-RT), the effect of blood flow restriction (BFR) applied during rest intervals (BFR-I) and muscle contractions (BFR-C) compared with HL-RT alone (no BFR), on maximum voluntary isometric contraction (MVIC), maximum dynamic strength (one repetition maximum [1RM]), quadriceps cross-sectional area (QCSA), blood lactate concentration ([La]), and root mean square of the surface electromyography (RMS-EMG) responses. Forty-nine healthy and untrained men (25 ± 6.2 years, 178.1 ± 5.3 cm and 78.8 ± 11.6 kg) trained twice per week, for 8 weeks. One leg of each subject performed HL-RT without BFR (HL-RT), whereas the contralateral leg was randomly allocated to 1 of 2 unilateral knee extension protocols: BFR-I or BFR-C (for all protocols, 3 × 8 repetitions, 70% 1RM). Maximum voluntary isometric contraction, 1RM, QCSA, and acute changes in [La] and RMS-EMG were assessed before and after training. The measurement of [La] and RMS-EMG was performed during the control sessions with the same relative load obtained after the 1RM test, before and after training. Similar increases in MVIC, 1RM, and QCSA were demonstrated among all conditions, with no significant difference between them. [La] increased for all protocols in pre-training and post-training, but it was higher for BFR-I compared with the remaining protocols. Increases in RMS-EMG occurred for all protocols in pre-training and post-training, with no significant difference between them. In conclusion, despite of a greater metabolic stress, BFR inclusion to HL-RT during rest intervals or muscle contraction did not promote any additive effect on muscle strength and hypertrophy.

Loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait.

KEY POINTS: Individuals with freezing of gait (FoG) due to Parkinson's disease (PD) have small and long anticipatory postural adjustments (APAs) associated with delayed step initiation. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs due to supraspinal dysfunction. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, it may be deficient in freezers during APAs. We show that freezers presented PSI in quiet stance (control task), but they presented loss of PSI (i.e. higher ratio of the conditioned H-reflex relative to the test H-reflex) during APAs before step initiation (functional task), whereas non-freezers and healthy control individuals presented PSI in both the tasks. The loss of PSI in freezers was associated with both small APA amplitudes and FoG severity. We hypothesize that loss of PSI during APAs for step initiation in freezers may be due to FoG. ABSTRACT: Freezing of gait (FoG) in Parkinson's disease involves deficient anticipatory postural adjustments (APAs), resulting in a cessation of step initiation due to supraspinal dysfunction. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, here we hypothesized a loss of PSI in freezers during APA for step initiation, which would be associated with FoG severity. Seventy individuals [27 freezers, 22 non-freezers, and 21 age-matched healthy controls (HC)] performed a 'GO'-commanded step initiation task on a force platform under three conditions: (1) without electrical stimulation, (2) test Hoffman reflex (H-reflex) and (3) conditioned H-reflex. They also performed a control task (quiet stance). In the step initiation task, the H-reflexes were evoked on the soleus muscle when the amplitude of the APA exceeded 10-20% of the mean baseline mediolateral force. PSI was quantified by the ratio of the conditioned H-reflex relative to the test H-reflex in both the tasks. Objective assessment of FoG severity (FoG-ratio) was performed. Freezers presented lower PSI levels during quiet stance than non-freezers and HC (P < 0.05). During step initiation, freezers presented loss of PSI and lower APA amplitudes than non-freezers and HC (P < 0.05). Significant correlations were only found for freezers between loss of PSI and FoG-ratio (r = 0.59, P = 0.0005) and loss of PSI and APA amplitude (r = -0.35, P < 0.036). Our findings suggest that loss of PSI for step initiation in freezers may be due to FoG.

A Randomized, Controlled Trial of Exercise for Parkinsonian Individuals With Freezing of Gait.

BACKGROUND: Exercises with motor complexity induce neuroplasticity in individuals with Parkinson's disease (PD), but its effects on freezing of gait are unknown. The objective of this study was to verify if adapted resistance training with instability - exercises with motor complexity will be more effective than traditional motor rehabilitation - exercises without motor complexity in improving freezing-of-gait severity, outcomes linked to freezing of gait, and brain function. METHODS: Freezers were randomized either to the adapted resistance training with instability group (n = 17) or to the active control group (traditional motor rehabilitation, n = 15). Both training groups performed exercises 3 times a week for 12 weeks. The primary outcome was the New Freezing of Gait Questionnaire. Secondary outcomes were freezing of gait ratio (turning task), cognitive inhibition (Stroop-III test), motor signs (Unified Parkinson's Disease Rating Scale part-III [UPDRS-III]), quality of life (PD Questionnaire 39), anticipatory postural adjustment (leg-lifting task) and brain activation during a functional magnetic resonance imaging protocol of simulated anticipatory postural adjustment task. Outcomes were evaluated before and after interventions. RESULTS: Only adapted resistance training with instability improved all the outcomes (P < 0.05). Adapted resistance training with instability was more effective than traditional motor rehabilitation (in improving freezing-of-gait ratio, motor signs, quality of life, anticipatory postural adjustment amplitude, and brain activation; P < 0.05). Our results are clinically relevant because improvement in the New Freezing of Gait Questionnaire (-4.4 points) and UPDRS-III (-7.4 points) scores exceeded the minimally detectable change (traditional motor rehabilitation group data) and the moderate clinically important difference suggested for PD, respectively. The changes in mesencephalic locomotor region activation and in anticipatory postural adjustment amplitude explained the changes in New Freezing of Gait Questionnaire scores and in freezing-of-gait ratio following adapted resistance training with instability, respectively. CONCLUSIONS: Adapted resistance training with instability is able to cause significant clinical improvement and brain plasticity in freezers. © 2020 International Parkinson and Movement Disorder Society.

Auto-Regulated Exercise Selection Training Regimen Produces Small Increases in Lean Body Mass and Maximal Strength Adaptations in Strength-trained Individuals.

Rauch, JT, Ugrinowitsch, C, Barakat, CI, Alvarez, MR, Brummert, DL, Aube, DW, Barsuhn, AS, Hayes, D, Tricoli, V, and De Souza, EO. Auto-regulated exercise selection training regimen produces small increases in lean body mass and maximal strength adaptations in highly trained individuals. J Strength Cond Res 34(4): 1133-1140, 2020-The purpose of this investigation was to compare the effects of auto-regulatory exercise selection (AES) vs. fixed exercise selection (FES) on muscular adaptations in strength-trained individuals. Seventeen men (mean ± SD; age = 24 ± 5.45 years; height = 180.3 ± 7.54 cm, lean body mass [LBM] = 66.44 ± 6.59 kg; squat and bench press 1 repetition maximum (1RM): body mass ratio 1.87, 1.38, respectively) were randomly assigned into either AES or FES. Both groups trained 3 times a week for 9 weeks. Auto-regulatory exercise selection self-selected the exercises for each session, whereas FES was required to perform exercises in a fixed order. Lean body mass was assessed via dual-energy X-ray absorptiometry and maximum strength via 1RM testing, pre-, and post-training intervention. Total volume load was significantly higher for AES than for FES (AES: 573,288 ± 67,505 kg; FES: 464,600 ± 95,595 kg, p = 0.0240). For LBM, there was a significant main time effect (p = 0.009). However, confidence interval analysis (95% CIdiff) suggested that only AES significantly increased LBM (AES: 2.47%, effect size [ES]: 0.35, 95% CIdiff [0.030-3.197 kg]; FES: 1.37%, ES: 0.21, 95% CIdiff [-0.500 to 2.475 kg]). There was a significant main time effect for maximum strength (p ≤ 0.0001). However, 95% CIdiff suggested that only AES significantly improved bench press 1RM (AES: 6.48%, ES: 0.50, 95% CIdiff [0.312-11.42 kg]; FES: 5.14%, ES: 0.43, 95% CIdiff [-0.311 to 11.42 kg]). However for back squat 1RM, similar responses were observed between groups (AES: 9.55%, ES: 0.76, 95% CIdiff [0.04-28.37 kg]; FES: 11.54%, ES: 0.80, 95% CIdiff [1.8-28.5 kg]). Our findings suggest that AES may provide a small advantage in LBM and upper body maximal strength in strength-trained individuals.

Individual Muscle Hypertrophy and Strength Responses to High vs. Low Resistance Training Frequencies.

Damas, F, Barcelos, C, Nóbrega, SR, Ugrinowitsch, C, Lixandrão, ME, Santos, LMEd, Conceição, MS, Vechin, FC, and Libardi, CA. Individual muscle hypertrophy and strength responses to high vs. low resistance training frequencies. J Strength Cond Res 33(4): 897-901, 2019-The aim of this short communication was to compare the individual muscle mass and strength gains with high (HF) vs. low (LF) resistance training (RT) frequencies using data from our previous study. We used a within-subject design in which 20 subjects had one leg randomly assigned to HF (5× per week) and the other to LF (2 or 3× per week). Muscle cross-sectional area and 1 repetition maximum were assessed at baseline and after 8 weeks of RT. HF showed a higher 8-week accumulated total training volume (TTV) (p < 0.0001) compared with LF. Muscle cross-sectional area and 1 repetition maximum values increased significantly and similarly for HF and LF protocols (p > 0.05). This short communication highlights that some individuals showed greater muscle mass and strength gains after HF (31.6 and 26.3% of individuals, respectively), other had greater gains with LF (36.8 and 15.8% of individuals, respectively), and even others showed similar responses between HF and LF, regardless of the consequent higher or lower TTV resulted from HF and LF, respectively. Importantly, individual manipulation of RT frequency can improve the intrasubject responsiveness to training, but the effect is limited to each individual's capacity to respond to RT. Finally, individual response to different frequencies and resulted TTV does not necessarily agree between muscle hypertrophy and strength gains.