Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

Abstract

During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. Following a sustained contraction of the abductor digiti minimi muscle at 50 % maximal force maintained to exhaustion there was an immediate reduction of the TST response from > 95 % to about 60 %. This effect recovered to control levels within 1 min and implies that a decreased number of spinal MNs were excited. Additional TST experiments after maximal and submaximal efforts showed that the decrease in size of the TST response was related to duration and strength of exercise. Motor evoked potentials (MEPs) after conventional transcranial magnetic stimulation (TMS) and responses to peripheral nerve stimulation were recorded following the same fatigue protocol. The size of both the MEPs and the peripheral responses increased after the contraction and were in direct contrast to the decrease in size of the TST response. This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST response depression. Overall, the results suggest that the outflow from the motor cortex could become insufficient to drive all spinal MNs to discharge when the muscle is fatigued and that complex interactions between failure of activation and compensatory mechanisms to maintain motor unit activation occur during sustained voluntary activity. When inability to maintain force occurs during submaximal effort, failure of activation of motor units is predominant.

Figure 1. The principle of the triple stimulation technique is illustrated in this simulated example

On the left the motor tract is simplified to three spinal MNs, a-c. Horizontal lines depict the muscle fibres of the three motor units. Arrows represent action potentials; filled arrows represent action potentials that give rise to a recorded trace deflection from the ADM, while open arrows do not. TST test and control recordings are shown on the right. The sweep of the traces is delayed and starts at the time of the second stimulus (wrist). A1, TMS causes 2/3 MNs to discharge and two desynchronised action potentials descend in the axon of these neurones. MN (a) discharges twice so that a second action potential descends (*). A2, after a delay, usually around 17-19 ms (delay I: the minimal latency of the MEP minus the CMAP_wrist latency), a maximal electrical stimulus is applied to the wrist (W). Descending orthodromic potentials at wrist stimulation evoke the first deflection of the TST_test (CMAP_wrist) while the ascending antidromic potentials collide and cancel with descending activity from the brain stimulus. The second action potential (*) descending on MN (a) may not be cancelled and continues to descend. Surviving activity on axon (c) ascends toward Erb's point. A3, after a delay, usually around 9-11 ms (delay II: the CMAP_Erb latency minus the CMAP_wrist latency) a third maximal electrical stimulus is applied to Erb's point (E), and action potentials descend on axon (a) and (b) while a collision occurs in axon (c). The second discharge (*) in axon (a) arrives at the muscle and causes a small negative deflexion after the first deflexion of the TST_test. A4, as a result of Erb's point stimulation a synchronised response from the two axons that were initially excited by the cortical stimulus (but occluded by wrist stimulation) is recorded as a second main deflection of the TST_test. B left, the TST_control is recorded by replacing the cortical stimulus by a stimulus at Erb's point (sequence of stimuli: Erb (1)-wrist (2)-Erb (3)) with adjustments of the delays (delay I and II: the CMAP_Erb latency minus the CMAP_wrist latency). B right, the ratio (amplitude and area) of the TST_testversus the TST_control estimates the proportion of spinal MNs that are excited by TMS, which is 67 % in this example.

Figure 2. TST responses before and after exercise sustained to exhaustion

Typical TST recordings from one subject before and after exercise are shown. In each trace four recordings are superimposed (1 TST_control, 2 TST_test, 1 CMAP_wrist). The sweep of the traces is delayed and starts at the time of the second stimulus (wrist). The bold line in trace 2 indicates TST_control. Immediately after exercise at time 0 the TST response was markedly depressed reflecting that a large proportion of MNs were not excited when the muscle was fatigued. One minute after the contraction, the TST amplitude and area ratio were recovered to near 100 %. Note the changes in shape of the first negative deflection that stems from the second stimulation (wrist).

Figure 3. Depression of TST responses after 50% MVC sustained to exhaustion

Changes in TST ratios for amplitude and area after contractions at 50 % MVC sustained to exhaustion are shown (means ± S.E.M. for 17 subjects). The standard error of the means for the majority of values was below 1.6 and is thus invisible. Time 0 corresponds to 3-4 s after the end of exercise. Following the contraction TST ratios were markedly depressed, but recovered rapidly within 1 min and remained stable for 20 min.

Figure 4. Relationship between post-contraction depression in size of TST responses and duration of exercise

A, the post-contraction TST amplitude ratios (means ± S.E.M.) are shown after MVC (left) and 50 % MVC (right) for 5 s (□), 15 s (▵) and 30 s (•). After MVC (n = 6) the decrease in size of the TST response measured at time 0 became more pronounced the longer the contraction while after submaximal exercise (5 s contraction, n = 4; 15 s contraction, n = 9; 30 s contraction, n = 10) the TST response was significantly depressed only after 30 s of contraction. B, the relationship between the TST amplitude ratio (mean ± S.E.M.) measured at time 0 and duration of exercise is shown after MVC (left, n = 6) and after 50 % MVC (right, 5 s contraction, n = 4; 15 s contraction, n = 9; 30 s contraction, n = 10). C, the association between loss of force (mean ± S.E.M.) and duration of exercise at MVC is shown left (n = 6). In the same subjects the association between the TST amplitude ratio and loss of force (means ± S.E.M.) is illustrated right after MVC for 5 s (□), 15 s (▵) and 30 s (•). ▪ depicts the control values before exercise.

Figure 5. Changes in size of conventional MEP and CMAP_wrist after sustained 50 % MVC

A, values are expressed as a percentage of those obtained before contraction. Group data (means ± S.E.M., n = 11 for MEP area, n = 9 for CMAP_wrist area) are shown. Time 0 corresponds to 3-4 s after the end of exercise. MEPs and CMAPs_wrist increased in size and recovered in parallel after the contraction. B, the normalised MEP size (area and amplitude) in percentage of the size of CMAP_wrist is shown (mean ± S.E.M., n = 9). Values remained unchanged after exercise indicating that changes of MEP size paralleled changes in the periphery. The arrow indicates control values before exercise.

Figure 6. Changes in silent period duration following cortical stimulation

Group data (means ± S.E.M., n = 11) are shown. The grey area denotes 1 S.E.M.calculated on the absolute values of SP duration before exercise. Silent period lengthened after exercise at 50 % MVC but recovered within 30 s.