Intramuscular Pressure of Human Tibialis Anterior Muscle Detects Age-related Changes in Muscle Performance

Abstract

Intramuscular pressure (IMP) reflects forces produced by a muscle. Age is one of the determinants of skeletal muscle performance. The present study aimed to test whether IMP mirrors known age-related muscular changes. We simultaneously measured the tibialis anterior (TA) IMP, compound muscle action potential (CMAP), and ankle torque in thirteen older adults (60–80 years old) in vivo by applying different stimulation intensities and frequencies. We found significant positive correlations between the stimulation intensity and IMP and CMAP. Increasing stimulation frequency caused ankle torque and IMP to increase. The electromechanical delay (EMD) (36 ms) was longer than the onset of IMP (IMPD) (29 ms). Compared to the previously published data collected from young adults (21–40 years old) in identical conditions, the TA CMAP and IMP of older adults at maximum intensity of stimulation were 23.8% and 39.6% lower, respectively. For different stimulation frequencies, CMAP, IMP, as well as ankle torque of older adults were 20.5%, 24.2%, and 13.2% lower, respectively. Surprisingly, the EMD did not exhibit any difference between young and older adults and the IMPD was consistent with the EMD. Data supporting the hypotheses suggest that IMP measurement is an indicator of muscle performance in older adults.

INTRODUCTION

The ability to measure muscle strength, the force a muscle can produce, in an objective, reliable, reproducible, and clinically meaningful way is important for the clinician as well as clinical and basic scientists. In clinical practice and research, manual muscle testing is used even though it is recognized to be subjective, depend on the skill of the examiner as well as the cooperation of the subject, and without specific instructions to the examiner lacks intra- and inter- examiner reproducibility (Dyck et al., 2010). Further, manual muscle testing is known to be less sensitive when compared to quantitative strength testing in assessing muscle weakness (Beasley, 1961, Shahgholi et al., 2012). Measurement of strength using an isokinetic dynamometer may be sufficient for quantifying joint function (Kannus, 1994), but calculating the force generated by individual muscles based on joint torque is indirect and requires many assumptions. Most of these assumptions are based on anthropometric information and do not necessarily correlate with individual muscle function (Ates et al., 2013, Yucesoy et al., 2010, Yucesoy et al., 2017). It is possible to measure muscle force directly by attaching a force transducer to the muscle tendon. However, this is an invasive procedure (Ates et al., 2016, 2018c, Froberg et al., 2009), and is only feasible in muscles with superficial tendons. There is need for a sensitive, reliable, and less invasive approach to measure individual muscle performance. Such a technique would complement other approaches presently used to evaluate muscle function like electromyography and has the potential for contributing additional information to muscle function in normal conditions as well as in neuromuscular disease.

Intramuscular pressure (IMP) is the hydrostatic pressure of a muscle’s interstitial fluid. Animal studies have demonstrated that IMP reflects muscle passive and active forces (Aratow et al., 1993, Davis et al., 2003). Recently, we have shown that in vivo IMP of the human tibialis anterior (TA) muscle in young adults correlates with its mechanical and electrical events (Ates et al., 2018b, Ates et al., 2019). These studies support the concept that IMP measurement provides robust means for assessment of the mechanical properties of individual muscles and a better understanding of their changes related to aging. However, it has not been determined if this relationship is true for older adults.

The goal of the present study was to assess the role of IMP in assessing the mechanical properties of muscles in older adults. We hypothesized that in older adults, (i) IMP can detect aging related mechanical changes occurring in the tibialis anterior (TA) and follow the electrical response of the muscle, (ii) the onset delay of IMP (IMPD) will be shorter than the EMD, and (iii) IMP can reflect increasing muscle activity, proportional to the compound muscle action potential (CMAP) with increasing strength of nerve stimulation and (iv) the IMP is proportional to the force generated by a muscle with increasing stimulation frequency. To test these hypotheses, the TA IMP, compound muscle action potential (CMAP), and ankle torque were simultaneously measured in vivo in older adults under varying electrical stimulation parameters.

METHODS

Participants

Thirteen healthy adults between 60–80 years old (eight females, five males; mean (SD) = 66.6 (3.6) years old with 29.5 (5.9) kg/m² body mass index) participated. Exclusion criteria were (i) current use of blood thinners or medications that affect muscle strength, (ii) history of nervous system disorders or musculoskeletal diseases, and (iii) history of musculoskeletal injuries or surgeries on the right lower limb. This study was performed in accordance with the Declaration of Helsinki and Mayo Clinic Institutional Review Board approval. All participants provided written informed consent.

Experimental Procedures

The participant was positioned supine with the foot secured to a custom torque measurement system (Fig. 1). The fibular nerve was identified at the level of the fibular head and confirmed with percutaneous nerve electrical stimulation. A fine-wire electrode was inserted near the nerve (cathode) and a disposable surface electrode (anode) was placed two centimeters rostral to the cathode along the nerve course. This setup allowed for nerve stimulation at low currents and prevented movement of the stimulation electrodes. All stimulation was performed using a Nicolet Viking EDX (Natus Neurology, Madison, WI).

Fig 1.

Left Experimental setup: The right foot of the participant strapped into a custom torque measurement system. The center of the torque cell was aligned with the ankle axis using a laser pointer whose light was in line with the lateral malleolus. A wooden wedge with an angle of 20° was placed underneath the foot in order to promote the optimal line of action of the tibialis anterior (TA) muscle. Black circles on the TA show the locations of the anode and cathode of the CMAP surface recording electrodes. The arrow on the left side shows the entry of the catheter. The tip of the sensor is below the black circled electrode inside the muscle. The arrow below shows the entry of the fine-wire and the surface electrode needed for fibular nerve stimulation. Note that data collected from surface EMG electrodes and fine-wire EMG electrodes that are visible in the picture were not used in this study. Right Examples of compound muscle action potential (CMAP) (upper panel) generated by fibular nerve stimulation up to obtaining max CMAP and corresponding IMP response (lower panel).

Surface Electrodes for CMAP recordings

Standard disposable electrodes (Natus Neurology, Madison, WI) with a recording surface of 15 mm diameter were used to record CMAPs. The active electrode was placed over the TA motor end plate, one-third of the distance between the patella and the bi-malleolar line. The reference electrode was placed over the TA tendon at the bi-malleolar line (Aquilonius et al., 1984). The ground electrode was placed between the active electrode and the stimulating cathode (Fig. 1). The CMAPs were recorded at a 4.8 KHz sampling frequency and were filtered with the Nicolet Viking EDX using a band pass filter of 2 Hz – 1.5 KHz.

Ankle Torque Measurements

A torque cell with a maximal output of 565 Nm (Model 2110–5K; Honeywell International Inc., Morris Plains, NJ, USA. Non-linearity: ± 0.1% of rated output. Hysteresis: ± 0.1% of rated output. Repeatability: ± 0.05% of rated output) was attached to an aluminum plate designed to rigidly hold the ankle (Fig 1). Test-retest reliability of the torque measurement was excellent with an intraclass correlation coefficient of 0.88 and 0.96 for plantarflexion and dorsiflexion maximum voluntary contraction. The torque cell was connected to a strain gauge amplifier (SGA/A, Mantracourt Electronics Ltd. Exeter, UK) and calibrated with known weights prior to the experiments.

The ankle was immobilized at 20° plantarflexion. The torque cell axis was positioned coincident with the ankle axis by using a laser light aligned with the lateral malleolus. A wooden wedge with an angle of 20° was placed underneath the foot to achieve a slightly inverted ankle position and assure an optimal TA muscle line of action (Fig. 1). The TA assists in foot inversion, so this ankle position ensured that the TA muscle line of action was perpendicular to the torque measurement system axis and, thereby, optimized its contribution to the measured joint torque (Kendall et al., 1993).

IMP Measurements

A 22-gauge IV catheter (Introcan Safety, B. Braun, Medical Inc., Bethlehem, PA) was inserted into the TA. The catheter was placed parallel to its muscle fibers and was positioned using ultrasound guidance (ACUSON Freestyle, Siemens Medical Solutions USA, Inc., Mountain View, CA) between the deep surface of the crural fascia and the central tendon (Fig. 1). The tip of the needle was inserted approximately two centimeters proximal to the motor end plate region. The catheter stylet was removed and a fiber optic pressure sensor (FOP-M260, FISO Technologies, Inc., Quebec, Canada) was inserted. The sensor tip was positioned one centimeter beyond the catheter lumen tip. The fiber optic sensor was attached to a signal conditioning system (FPI-LS-10 Module on EVO-SD-5 Evolution Chassis, FISO Technologies, Inc., Quebec, Canada) configured for a 3 KHz sampling frequency.

Data Collection Protocol

Participants initially performed maximal voluntary contraction (MVC) in dorsiflexion direction three times.

I. Stimulation Intensity:

The fibular nerve was stimulated with a constant electrical current by using the Nicolet Viking EDX. Using a stimulus duration of 0.05ms, the current was increased to obtain a maximal CMAP amplitude. A supramaximal stimulation was then applied by increasing the current an additional 10% to ensure the CMAP response was maximal. After the maximal CMAP was obtained and recorded twice, the current was reduced to obtain a minimal amplitude CMAP, i.e. the lowest level a CMAP could be recorded. Next, the current was increased until the subsequent smallest reproducible CMAP response could be observed. This process was repeated in a stepwise fashion for seven levels, each time minimally increasing the current. At each stimulation level the TA IMP and CMAP were recorded simultaneously.

II. Stimulation Frequency:

Supramaximal stimulation of the fibular nerve was performed at 2 Hz, 5 Hz, 10 Hz, and 20 Hz for 2 seconds. Each trial was repeated twice.

For each trial; the ankle torque, TA IMP, and the trigger signal for each stimulation, which was exported from the Nicolet Viking EDX, were acquired simultaneously at 3 KHz using a 16-bit analog to digital converter (NI USB-6225, National Instruments, Austin, TX, USA) and customized software (LabVIEW National Instruments Corporation, Austin, TX, USA). To prevent muscle fatigue, there was a minimum of 30 seconds rest between electrical stimulation.

Data Processing and Analyses

Data processing was performed using custom MATLAB software (The MathWorks, Natick, MA). The quiescent IMP (IMP value at rest) and torque values for each trial were calculated from the mean values of these parameters prior to activation, i.e., in its passive state. Raw IMP and torque data were adjusted for the quiescent values for each trial. Raw IMP and torque signals were filtered with a 50 Hz 4^th-order low-pass Butterworth filter.

I. Stimulation Intensity:

The peak value of the CMAPs (Daube and Rubin, 2009) and the peak IMP responses at different stimulation intensity levels were calculated for each trial as the difference between baseline and the peak values.

II. Stimulation Frequency:

The peak IMP responses, ankle torque and CMAP values at different stimulation frequencies were calculated for each trial.

III. Onset Delay:

The CMAPs onset was obtained from the Nicolet Viking EDX recorded signal and referred to as the CMAP delay. The ankle torque and IMP onsets were identified using a custom MATLAB (The MathWorks, Natick, MA) algorithm. The quiescent value (initial 25ms) and the mean and standard deviation of this resting state value were calculated using raw data. Signal onset was defined as the time when the signal was three standard deviations greater than the average quiescent value (Di Fabio, 1987). Onsets were confirmed visually for each tracing within each trial. The delay between stimulation and the onsets of ankle torque and IMP are referred to as EMD and IMPD, respectively.

Statistical Analyses

Distribution normality was tested using the Shapiro-Wilk test to determine if a parametric or nonparametric test should be used. Statistical significance was set at p < 0.05. Spearman’s rank correlation coefficient was used to analyze the association between the IMP and the CMAP for different stimulation levels. Friedman test was used to detect (1) the differences in (i) CMAP and (ii) IMP response at different levels of stimulation and (2) the differences in (iii) ankle torque, (iv) CMAP, and (v) IMP response for different stimulation frequencies. If significant differences were found, pairwise comparisons were performed using Nemenyi post-hoc tests without any corrections to locate further differences. A Kruskal Wallis test was used to detect differences between IMPD, EMD and CMAP onset delay. Wilcoxon pair tests were performed to locate further differences.

RESULTS

TA IMP at passive state (the resting IMP) median (interquartile range (IQR)) was 757.8 (10.5) mmHg. Peak IMP during MVC at tested position was 96.76 (77.21) mmHg. Dorsiflexion MVC torque was measured as 26.19 (6.43) Nm.

Stimulation Intensity Levels

For each participant, the peak IMP was significantly correlated with the CMAP amplitude (ρ average (SD) = 0.98 (0.05), P = 0.001). With increasing stimulation intensity, the CMAP responses increased (P < 0.001) (Fig. 2). Median (IQR) values of CMAP for the L1, L2, L3, L4, L5, L6, L7, and the maximal levels were 0.20 (0.15), 0.40 (0.20), 0.65 (0.25), 0.80 (0.38), 1.10 (0.43), 1.30 (0.35), 1.60 (0.28), and 6.50 (1.43) mV, respectively.

Fig 2.

Box and whisker plot of compound muscle action potential (CMAP) at different stimulation intensity levels collected from TA muscles of older adults. The stimulation level that generates maximum CMAP (max) and level 1 (L1) refer to the maximum and minimum intensity applied, respectively. The CMAP changed significantly with the increasing stimulation amplitude (P < 0.001).

Similarly, increasing the stimulation intensity resulted in a significant increase in the IMP (P < 0.001) (Fig. 3). Median (IQR) values of IMP for the L1, L2, L3, L4, L5, L6, L7, and the maximal levels were 1.35 (0.65), 2.00 (2.17), 2.44 (2.30), 3.33 (3.29), 3.90 (3.26), 4.86 (3.87), 5.27 (7.81), and 15.22 (16.79) mmHg, respectively. Table 1 shows the results of pairwise comparisons between each level for CMAP as well as IMP.

Fig 3.

Box and whisker plot of intramuscular pressure (IMP) at different stimulation intensity levels collected from TA muscles of older adults. The stimulation level that generates maximum CMAP (max) and level 1 (L1) refer to the maximum and minimum intensity applied, respectively. The IMP changed significantly with the increasing stimulation amplitude (P < 0.001).

Table 1.

P values obtained from pairwise comparisons of stimulation intensity levels^*

	CMAP							IMP
	max	L1	L2	L3	L4	L5	L6	max	L1	L2	L3	L4	L5	L6
L1	0.000							0.000
L2	0.000	0.961						0.000	0,997
L3	0.000	0.452	0.979					0.000	0.784	0.990
L4	0.000	0.026	0.376	0.933				0.000	0.122	0.478	0.944
L5	0.023	0.001	0.034	0.352	0.974			0.042	0.002	0.020	0.209	0.895
L6	0.376	0.000	0.000	0.020	0.401	0.953		0.209	0.000	0.002	0.042	0.531	0.999
L7	0.961	0.000	0.000	0.000	0.030	0.352	0.961	0.922	0.000	0.000	0.000	0.034	0.584	0.922

^*Grey-shaded cells show significant difference.

Stimulation Frequency

Increasing stimulation frequency did not change the CMAP amplitudes recorded from the TA (P = 0.902) while it increased ankle torque (P < 0.001) and IMP (P < 0.001) (Fig. 4). Compared to the torque at 2 Hz stimulation, the ankle torque was higher at 10 Hz by 37.0% (14.4%), and 20 Hz by 58.9% (11.4%) stimulation (Table 2). The ankle torque was also higher at 20 Hz stimulation compared to 5 Hz by 53.3% (11.8%). IMP showed similar characteristics to torque in response to change in stimulation frequency. Compared to the IMP at 2 Hz stimulation, the peak IMP was higher at 10 Hz by 55.0% (22.4%), and 20 Hz stimulation by 70.2% (17.7%). The IMP was also higher at 20 Hz stimulation compared to the IMP measured at 5 Hz stimulation by 61.8% (17.6%) (Table 2).

Fig 4.

Box and whisker plot of the ankle torque (upper panel), the intramuscular pressure (Relative IMP) (middle panel), and the CMAP (lower panel) values collected from TA muscles of older adults at different stimulation frequencies. The TA CMAP did not change (P = 0.902) whereas the ankle torque (P < 0.001) and the IMP (P < 0.001) increased significantly with the increasing stimulation frequency.

Table 2.

P values obtained from pairwise comparisons of stimulation frequencies^*

	Force			IMP
	2Hz	5Hz	10Hz	2Hz	5Hz	10Hz
5Hz	0.295			0.339
10Hz	0.000	0.124		0.001	0.145
20Hz	0.000	0.000	0.170	0.000	0.000	0.197

^*Grey-shaded cells show significant difference.

Onset Delay

The CMAP delay, EMD and IMPD were found to be significantly different (P < 0.001) (Fig. 5). The ankle torque EMD (median (IQR) = 35.8 (11.4) ms) was later than the IMPD (28.8 (5.1) ms) (P = 0.018) as well as the CMAP delay (3.6 (0.6) ms) (P < 0.001).

Fig 5.

Box and whisker plot of the onset delay of the ankle torque (EMD), the intramuscular pressure (IMPD) and CMAP of tibialis anterior (TA).

DISCUSSION

This study revealed that IMP represents the TA mechanical behavior and reflects its electrical activity in healthy older adults. Importantly, IMP parallels the nerve-stimulated increases in muscle force. Further, the IMP onset delay is earlier than the EMD in older adults, indicating that IMP measurements identify the local muscle mechanical response. These results show that IMP is a minimally invasive in vivo method that can evaluate muscle force production capacity in older adults. Therefore, it can be used to detect muscular changes due to aging. The ability to quantify skeletal muscle electromechanical coupling opens a new avenue to investigating neuromuscular diseases.

Muscular Changes due to Aging and IMP

Comparing the present data collected from the older adults with the recently published data collected from young adults (Ates et al., 2019), we found that the CMAP (P < 0.001) as well as IMP (P < 0.001) responses of TA collected from older adults at different stimulation intensities were significantly different from those of young adults (21–40 years old). The average TA CMAP and IMP responses of older adults at the maximum level of stimulation were 23.8% and 39.6% lower than those of the young adults, respectively. Comparison of young and older adults in terms of their muscle responses to the stimulation frequencies were consistent as well: The ankle torque (P < 0.001), CMAP amplitude (P < 0.001), and IMP (P < 0.001) responses of TA collected from older adults at different stimulation frequencies were significantly different from young adults (A two-factor ANOVA with repeated measures on one factor (stimulation) applied). On average, the CMAP amplitude, IMP, and the ankle torque of older adults were 20.5%, 24.2%, and 13.2% lower than those of young adults, respectively.

These findings demonstrate that IMP reflects age-related mechanical changes in the TA. Age is one of the determinants of skeletal muscle force output (Doherty, 2003). With advancing age, structural and functional changes occur within muscle including a reduction in fiber size, fiber type alterations (Lexell, 1995, Lexell et al., 1988, Sato et al., 1984), loss in muscle mass (Faulkner et al., 1995, Lexell, 1995, Lexell et al., 1988), and decrease in force production and strength (Alnaqeeb et al., 1984, Klein et al., 2001, Psatha et al., 2017, Vandervoort and McComas, 1986). A major indication of muscle weakness is a decrease in muscle’s ability to generate joint torque (Barber et al., 2013, Bemben et al., 1991). As anticipated, the older adults generated lower ankle torques. Consistently lower TA IMP values support the fact that the IMP can serve as an in-vivo measure of muscle function. Age related strength reduction occurs more rapidly and earlier than muscle atrophy (Delmonico et al., 2009, Mitchell et al., 2012). This directed our attention to the role of the existing muscle fibers’ ability to generate force (Goodpaster et al., 2006). Many studies report that the neurophysiological alterations due to aging such as neuromuscular junction impairments, as well as reduced and more variable synaptic input precede the apparent loss in physical capacity, the major decrease in strength, and the observed loss in muscle mass (Hepple and Rice, 2016, Hunter et al., 2016, Jang et al., 2010, Seidler et al., 2010). However, it is not straightforward to detect such morphological and functional processes leading to altered motor neuron activity, motor unit remodeling, and eventual motor unit loss early (Ansved and Larsson, 1990, Kanda and Hashizume, 1989). The fact that IMP can detect such changes offers a tool which can, therefore, be used to objectively quantify early muscle pathological changes. The CMAP represents the summated muscle action potentials of the activated muscle fibers and provides a physiological assessment of neuromuscular junction and muscle fiber function. The CMAP amplitude often correlates with the severity of neurological impairments in muscular disorders (Chan et al., 1998, Komyathy et al., 2013, Lewelt et al., 2010, Nozoe et al., 2020, Rajabally et al., 2012) and improves with training (Molin and Punga, 2016). In the present study, the CMAP showed age-related changes in muscle activity. Observing a CMAP amplitude reduction in older adults is consistent with previous studies in animals (Sheth et al., 2018, Wu et al., 2017) and human (Lauretani et al., 2006, Vandervoort and McComas, 1986). The significantly reduced TA IMP in older adults parallels the CMAP (Fig. 3). This indicates that IMP might be capable of reflecting changes in skeletal muscle recruitment. More importantly, the CMAP amplitude does not change with the applied stimulation frequency (Fig. 4), while the IMP, a mechanical measure of muscle force, increased with the increasing frequency.

The present work was motivated by clinical needs wherein muscular function is assessed during electrical stimulation. Almost all clinical EMG laboratories use similar measurement tools and apply various stimulation characteristics for diagnosis of muscular diseases. However, it should be noted that the recruitment order of MUs is accepted to be different during electrical stimulation compared to voluntary contraction where small MUs are recruited first based on the Henneman “size principle” (Henneman et al., 1965). In contrast, during electrical stimulation, MU recruitment has been shown to become nonselective, spatially fixed, and temporally synchronous (for review, see Bickel et al., 2011). With stimulation, there is a reverse selection recruitment wherein the larger fibers are recruited first, reversing the size-progression principle. Notably, reverse recruitment theory has been shown to be true for the TA (Feiereisen et al., 1997), which is the muscle we studied. Consequently, when implementing IMP use in the clinic for identifying muscular changes, the targeted muscle recruitment strategy should be considered. The TA muscle was chosen in the present study not only because it is practical to reach, stimulate, and test but also because it provides most of the ankle torque due to its position and orientation (for detail discussion see Ates et al., 2018b). Hence, it is also feasible to study during voluntary contraction and relate its force production to ankle joint function. The present study focused on electrical stimulation and provided only MVC values for the TA. More detailed IMP experiments should be performed during voluntary activity of the TA in older adults. Plantar flexor muscles are functionally more important in aging. It is also expected that the behavior of IMP is muscle specific depending on fascicle orientation and it is recommended that other muscles should be tested.

Passive Muscle Characteristics

A limitation of EMG is that it only reflects the electrical aspects of activated muscle. In contrast, IMP reflects both active and passive muscle tension. The resting IMP value of the TA measured from older adults (757.8 (10.5) mmHg) is not significantly different (Wilcoxon Test, P = 0.289) than the TA IMP values of young adults at rest (762.3 mmHg (14.1 mmHg) (Ates et al., 2019). Previous studies have shown that aging skeletal muscle exhibits an increase in stiffness attributed to collagen accumulation in the extra cellular matrix. Similarly, studies on the human rectus femoris and biceps brachii muscles (Agyapong-Badu et al., 2016) as well as sternocleidomasteoid and upper trapezius muscles (Kocur et al., 2019) supported these findings in animals. The fact that IMP magnitude did not differ between young and older adults could indicate that TA muscle passive stiffness does not change dramatically with age. Although, the IMP measurements were obtained at an ankle joint position with a moderate TA length whereas passive stiffness significantly increases at a comparatively longer muscle lengths (Ates et al., 2018a). To test if the pressure difference alters, IMP should be collected at different lengths under passive conditions. Furthermore, in vivo ankle joint stiffness is also critical for mobility during aging (Menz, 2015) or to determine the course of neuromuscular diseases (Ates et al., 2020). Activated muscle tension dominates over passive tension and, hence, often defines gait deformities (Kaya et al., 2019), while passive muscle characteristics still play a major role in determining force transmission (Maas, 2019). Therefore, there is a need for future studies to investigate the the relationship between IMP and muscle stiffness.

Neither EMD nor IMPD Change with Age

EMD is a measure of the excitation-contraction coupling pathway and mechanical properties of musculotendinous tissues (Norman and Komi, 1979). Compared to the EMD measured from young adults (Ates et al., 2019), we observe that the EMD presently calculated for older adults is not significantly different (P = 0.329) (Wilcoxon test). EMD is dependent on several factors including the muscle and joint studied as well as the measurement and calculation methods (Yavuz et al., 2010), indicating the need for similar measurement conditions when comparing two groups. This study ensured identical conditions for both young and older adults. An earlier work (Libardi et al., 2015) showing that the knee extensor muscle EMD did not change with age during maximal voluntary contraction supports the present finding. In contrast, other studies have reported a longer EMD for the triceps surae muscle group (Yavuz et al., 2010) and gluteus medius of women (but not men) (Kim et al., 2011) with advancing age. This limited number of studies and their conflicting or inconclusive results highlight the need for further investigations.

Compared to the IMPD measured from young adults (Ates et al., 2019), we also found that IMPD for older adults was not significantly different from younger adults (P = 0.085) (Wilcoxon test). We measured the IMP in the muscle mid-belly, and, therefore, the IMPD did not reflect the contributions of the distal muscle and the tendon. Differences between EMD and IMPD might reflect the mechanical contribution of the musculotendinous structures. However, no significant difference in the measured EMD and IMPD leads to the supposition that the tendon stiffness of these older adults is comparable to young adults. Reduced tendon stiffness is typically a sign for aging (Burgess et al., 2009) and causes an increase in EMD (Kim et al., 2011). IMPD occurred earlier than EMD, which might indicate that the observed weaknesses due to aging is related to electrophysiological factors rather than material properties. Our results, however, do not suggest any major changes in the excitation-contraction coupling due to aging. One explanation for this might be the fact that the older adults, who participated in our study, were self-declared to be physically active. This is in contrast to the generally expected fact that older people live a more sedentary lifestyle, which is one of the determinants of age-related muscular changes (DiPietro, 2001). Although the study cohort generated less force and had a lower CMAP compared to young adults, they might not have yet exhibited any major losses of electrophysiological properties, which would cause a significant latency in force production.

This study has some limitations. There is evidence for physiological differences in regional pressure, which may be a factor in IMP measurement. Previous studies have found that IMP increases with depth, increases near stiffer structures such as tendon and bone, and may be related to fiber curvature (Ameredes and Provenzano, 1997, Nakhostine et al., 1993, Sejersted et al., 1984). Thus, IMP represents a relatively local phenomenon. This pressure distribution, while physiologically relevant, creates a technical challenge in quantifying muscle tension. This challenge has been met by strategic sensor placement in a region with low pressure gradients. Pressure is generated by the interaction between changes in tissue volume and fluid influx to efflux ratio. Therefore, regional IMP may be affected by regional volumetric strain. Pertinently, muscle tissue strain demonstrates regional differences during passive tension and activation of skeletal muscle (Finni et al., 2003, Heidlauf and Rohrle, 2014, Pappas et al., 2002, Rohrle et al., 2019, Yaman et al., 2013). Accordingly, the region with a uniform volumetric strain was identified (Jensen et al., 2016) and the sensor was inserted in this region to maximize measurement repeatability.

CONCLUSIONS

This study has demonstrated that IMP reflects age-related mechanical changes and electrical events in human muscle. We show that IMP can capture the TA’s force production in older adults. Compared to the results from young adults, the IMP response as well as the CMAP and the ankle torque were consistently lower for older adults. IMP has the advantage of assessing passive mechanical properties. Interestingly, there was no significant change in the quiescent IMP, hence stiffness, of the TA due to aging. The potential of IMP in understanding passive mechanical characteristics needs to be further investigated at different joint positions. Finally, IMP captures the mechanical response of skeletal muscles to activation earlier than the mechanical output measured by torque generation for both young and older adults. Collectively, these findings suggest that IMP can be used clinically for early diagnosis of neuromuscular conditions and tracking disease changes over time.

Biography

Filiz Ates PhD is the head of the experimental biomechanics group at the Institute of Statics and Dynamics of Aerospace Structures (ISD) within the faculty of Aerospace Engineering at the University of Stuttgart. She received her Ph.D. degree in 2013 from the Institute of Biomedical Engineering of Bogazici University in Istanbul. She worked as a post-doctoral researcher at the laboratory “Motricite, Interactions, Performance”, Faculty of Sports Sciences, University of Nantes, France (2014) and later at the Faculty of Sports Sciences, Waseda University, Japan (2015). From 2016 to 2018, she worked at the Motion Analysis Laboratory at Mayo Clinic, Rochester, MN, USA, as a senior research fellow and as an assistant professor. Her research interests include soft tissue mechanics, sports biomechanics, neuromechanics of human movement, musculoskeletal biomechanics, orthopaedics biomechanics. She particularly focused on the behavior of skeletal muscles, mechanical interactions of skeletal muscles, myofascial force transmission, assessment of the effects and implications of orthopedic surgery and management of rehabilitation techniques in neuromuscular diseases.

William J. Litchy, M.D. is a Board-Certified Neurologist, Clinical Neurophysiologist, and Consultant in the Department of Neurology at the Mayo Clinic in Rochester, MN. He has over 40 years of experience in clinical electromyography as well as in the application of electromyographic techniques to basic research. His research interests revolve around development of tools for quantifying function of nerve and muscle to assess changes with neuromuscular disease and to measure the effects of interventions on these disorders.

Krista Coleman Wood, PhD, PT is a Physical Therapist in the Motion Analysis Laboratory at Mayo Clinic, Rochester, MN. She received her PhD in Biomechanics from the University of Minnesota. She has been Clinical and Research Physical Therapist since 1980. Her research interest is in the quantitative diagnosis of individuals with movement impairments.

Kenton R. Kaufman, PhD, PT is the W. Hall Wendel Jr Musculoskeletal Research Professor, Professor of Biomedical Engineering, Director of the Motion Analysis Laboratory, and Consultant in the Departments of Orthopedic Surgery, Physiology and Biomedical Engineering at Mayo Clinic. He is a registered professional engineer. He received the Ph.D. degree in Biomechanical Engineering from North Dakota State University in 1988. Dr. Kaufman’s primary area of expertise is musculoskeletal and rehabilitation science. He has focused on the development and application of experimental and analytical techniques for the analysis of human musculoskeletal function. He is a Past-President of the American Society of Biomechanics and the Gait and Clinical Movement Analysis Society.