Determining the extent of neural activation during maximal effort.

PURPOSE: The purpose of this study was to compare the extent of neural activation assessed by the central activation ratio (CAR) versus activation estimated from T2 magnetic resonance imaging (MRI) and neuromuscular electrical stimulation (NMES). METHODS: Seven college-age individuals volunteered for this study. CAR was determined by manually superimposing a train of NMES (50 Hz, 450-mus biphasic pulses) for 1 s during a maximal voluntary effort. The MRI-NMES method assessed activation by stimulating the knee extensors for 3 min in a 2 s on, 2 s off cycle. T2 MR images were taken at rest and after NMES was administered. Theoretical maximal torque (TMT) of the knee extensors was calculated based on the MRI-NMES activation data. The TMT was then divided by the maximal voluntary isometric contraction (MVIC) of each subject to determine the extent of neural activation during a MVIC. RESULTS: The results for CAR reveal the percent activation (mean +/- SD) of the quadriceps femoris during a MVIC was 92 +/- 7% for the right thigh and 96 +/- 4% for the left thigh. The MRI-NMES method estimated that MVIC could be achieved if 75 +/- 14% of the knee extensors on the right thigh and 74 +/- 14% on the left thigh were activated. These results are similar to findings that showed MVIC could be achieved by stimulating 71% of the knee extensors. CONCLUSIONS: We conclude that CAR overestimates the extent of neural activation during an MVIC because the 3D shape of the thigh is altered. This will change electric current flow to the axonal motor neuron branches and limit the artificially evoked torque, thereby resulting in an overestimation of CAR.

Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia.

Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia.

Effects of chronic overload on muscle hypertrophy and mTOR signaling in young adult and aged rats.

We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6-month old) and aged (O; 30-month old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two thirds of the gastrocnemius muscle or sham surgery (CON). Although plantaris (PLA) muscle hypertrophy was attenuated by aging, mTOR phosphorylation was 44% and 35% greater in Y SA and O SA compared with CON (p = .038). Ribosomal protein S6 phosphorylation was 114% and 24% higher in Y SA and O SA compared with CON (p = .009). Eukaryotic initiation factor 2Bepsilon phosphorylation was 33% and 9% higher in Y SA and O SA compared with CON (p = .04). Translational signaling in young adult and aged plantaris muscle is equally responsive to chronic overload.

Effects of neuromuscular electrical stimulation parameters on specific tension.

This study examined the effects of altering surface neuromuscular electrical stimulation (SNMES) parameters on the specific tension of the quadriceps femoris muscle. Seven able-bodied subjects had magnetic resonance images taken of both thighs prior to and immediately after four SNMES protocols to determine the activated muscle cross-sectional area (CSA). The four protocols were: (1) research (RES, 100 Hz, 450 micros, and amplitude set to evoke 75% of maximal voluntary isometric torque, MVIT); (2) pulse duration (PD, 100 Hz, 150 micros, same current as in RES); (3) frequency (FREQ, 25 Hz, 450 micros, and same current as in RES); (4) amplitude (AMP, 100 Hz, 450 mus, and current set to evoke the average of the initial torques of PD and FREQ, 45 +/- 9% of MVIT). Reducing the amplitude of the current from 75 to 45% of MVIT did not alter specific tension, 25 +/- 8 N/cm2, suggesting that the amplitude probably affects torque and the area of activated muscle proportionally. Shortening the pulse duration from 450 to 150 micros caused specific tension to drop from 25 +/- 6 to 20 +/- 6 N/cm2 (P < 0.05), indicating that pulse duration increased torque and the activated CSA disproportionally. Alternatively, reducing the frequency from 100 to 25 Hz decreased specific tension from 25 +/- 6 to 17 +/- 4 N/cm2 (P < 0.05), suggesting that the frequency increased torque without affecting the activated CSA. Clinicians who administer SNMES should be aware of the magnitude of adaptations to a given amplitude, pulse duration, and frequency.