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, 9 (3), e91754

Sustained Maximal Voluntary Contraction Produces Independent Changes in Human Motor Axons and the Muscle They Innervate


Sustained Maximal Voluntary Contraction Produces Independent Changes in Human Motor Axons and the Muscle They Innervate

David A Milder et al. PLoS One.


The repetitive discharges required to produce a sustained muscle contraction results in activity-dependent hyperpolarization of the motor axons and a reduction in the force-generating capacity of the muscle. We investigated the relationship between these changes in the adductor pollicis muscle and the motor axons of its ulnar nerve supply, and the reproducibility of these changes. Ten subjects performed a 1-min maximal voluntary contraction. Activity-dependent changes in axonal excitability were measured using threshold tracking with electrical stimulation at the wrist; changes in the muscle were assessed as evoked and voluntary electromyography (EMG) and isometric force. Separate components of axonal excitability and muscle properties were tested at 5 min intervals after the sustained contraction in 5 separate sessions. The current threshold required to produce the target muscle action potential increased immediately after the contraction by 14.8% (p<0.05), reflecting decreased axonal excitability secondary to hyperpolarization. This was not correlated with the decline in amplitude of muscle force or evoked EMG. A late reversal in threshold current after the initial recovery from hyperpolarization peaked at -5.9% at ∼35 min (p<0.05). This pattern was mirrored by other indices of axonal excitability revealing a previously unreported depolarization of motor axons in the late recovery period. Measures of axonal excitability were relatively stable at rest but less so after sustained activity. The coefficient of variation (CoV) for threshold current increase was higher after activity (CoV 0.54, p<0.05) whereas changes in voluntary (CoV 0.12) and evoked twitch (CoV 0.15) force were relatively stable. These results demonstrate that activity-dependent changes in motor axon excitability are unlikely to contribute to concomitant changes in the muscle after sustained activity in healthy people. The variability in axonal excitability after sustained activity suggests that care is needed when using these measures if the integrity of either the muscle or nerve may be compromised.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Schematic representation of the experimental setup and protocol.
The experimental setup is viewed from above. The experimental protocol (not shown to scale) consisted of a control period, a sustained 1-min adductor pollicis MVC, and the recovery period. The “nerve testing” rectangle represents the TRONDNF protocol. After the stimulus-response curve (src) one component of axonal excitability was measured every 5 min for 40 min through the recovery period in 4 experimental sessions with measures of muscle force in the 5th session.
Figure 2
Figure 2. Changes in components of axonal excitability after sustained activity.
Black symbols: control data; red symbols: data recorded after the 1 min sustained contraction; blue symbols: data recorded after the 40 min recovery period. A: stimulus-response curves with the CMAP normalised to Mmax. B: charge-duration curves. τ SD and rheobase were derived from the x-intercepts and gradients of the linear regressions, respectively. C: threshold electrotonus. D: current-threshold relationship. E: slope of the current-threshold relationship. F: recovery cycle. Four subjects were excluded from the data at an interstimulus interval of 2 ms only because the output of the stimulator was insufficient to produce the target potential. Data presented as mean ± 95% confidence intervals. TC: threshold current.
Figure 3
Figure 3. Recovery of axonal excitability after sustained activity.
Open symbols represent the data for each subject; pooled data are presented as mean (solid bars) and 95% confidence intervals. A: threshold current. B: resting IV slope. C: τ SD. D: rheobase. D: the duration of the superexcitable period. F: the duration of the refractory period (RP). *: p<0.05.
Figure 4
Figure 4. Changes in muscle properties with sustained activity.
Open symbols represent the mean for each subject across 5 experimental sessions; pooled data for 10 subjects are shown beside the individual data as mean (solid bars) and 95% confidence intervals. A: there was no change in the area of Mmax after the sustained contraction; B: there was a significant change in the resting twitch force immediately after the 1-min MVC compared to control values; C: the peak amplitude of the voluntary EMG was significantly larger at the start than at the end of the 1-min MVC; D: peak voluntary force was significantly smaller at the end of the 1-min MVC than at the start demonstrating an activity-dependent reduction in the force-generating capacity of the muscle (ie fatigue). ns: not significant; ***: p<0.001.
Figure 5
Figure 5. Relationship between the activity-dependent changes in muscle output and axonal excitability.
Symbols represent the mean for each subject across 5 experimental sessions. A: There was no relationship between the activity-dependent increases in threshold current and the decline in the amplitude (black symbols) or area (white symbols) of resting twitch force. B: Similarly, there was no relationship between increases in threshold current and the decline in voluntary force (black symbols) and voluntary EMG (white s). ns: not significant.

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Grant support

This work was supported by the National Health and Medical Research Council of Australia and the New South Wales Office of Science and Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.