There are more subtle issues based on suggestions that the reflex gain can change and new findings that the intrinsic properties of motor neurons can be modulated dramatically (12,22). Finally, reflexes change markedly, depending on the type of movement. Figure 4 shows that the H-reflex, measured at a given M-wave and level of voluntary contraction, is very different between standing and walking. We refer to this difference in reflexes between standing and walking with the same level of EMG as a "task-dependent reflex modulation." Reflexes are presumably modulated between different tasks such as standing and walking because of the different functional requirements of the two tasks. We will first consider the requirements in standing before discussing walking and running.
WHAT DO EXCITATORY REFLEXES CONTRIBUTE TO FUNCTIONAL TASKS?
Traditionally, the rationale for the high reflex gain during standing was thought to be straightforward because the body can be considered as an inverted pendulum. The calf muscles typically show some activity to maintain the body at a position that is close to equilibrium, although an unstable one, because movement either forward or backward will tend to cause the body to fall. This precarious state might be stabilized, if reflexes restore the body to near the equilibrium position whenever the body sways a small distance. In this view, swaying forward stretches the calf muscles, and the stretch reflex restores the original position, if sufficiently strong to overcome the effects of gravity. Recently, the situation has become more complex. Patients who lack large sensory fibers such as the group Ia can balance to some degree using vision and other senses (22). In principle, balance could be maintained even without vision, if the stiffness of the ankle joint was sufficiently great. Then, body sway might produce a sufficient spring force to restore the body to the upright position. However, recent measurements show that the stiffness is between 10 and 35% below the value needed to stabilize the body (3).
Alternatively, reflexes from segmental receptors could effectively stabilize the ankle joints, but recent measurements of muscle length using a new ultrasound technique suggest another mechanism (14). Paradoxically, the calf muscles are shorter (not longer) when the ankle angle is smaller (the body is tilted forward, which stretches the calf muscles). In other words, the muscles are actively contracting and stretching the tendon. Furthermore, the muscle activity does not have the behavior expected of a simple reflex mechanism (i.e., responding continuously with a short delay to length and velocity changes). Rather, the EMG shows frequent, ballistic bursts of activity (approximately 2.6 times per second). These are referred to as ballistic bias impulses (13) and move the center of mass small distances (30-300 μm). Several of these bias impulses combine on average to correct sway movements, which occur at a lower peak frequency (<1 Hz). The nervous system responds to changes in the center of mass velocity but with a time delay of approximately 370 ms rather than tens of milliseconds, as expected for a reflex response.
Although the details are unknown, the data are consistent with the view that the nervous system functions not as a continuous controller of body position but as an intermittent control system that gathers information for more than several hundred milliseconds from all sensory systems. Then, probably, based on comparison with internal models of the body's orientation, a corrective, ballistic impulse is generated with the estimated, appropriate amplitude and direction. Loram et al. (13) give the following analogy: "Imagine trying to maintain a heavy ball as still as possible on a hillside. The ball is controlled by striking it with a bat at a relatively fixed rate. The motion of the ball will be caused by the blows themselves". "The batter has to judge the size of each blow. We suggest that in essence it is this never ending, trial and error process which has to be carried out in human standing". What is the role of reflexes, if any, in this process? As well as contributing to the general sensory information guiding this process, reflexes from muscle receptors may contribute to stabilize the body, if external or internal perturbations occur that are large and fast enough to disrupt the intermittent process described previously (22).
The situation is quite different during walking which generates large, purposeful movements. The calf muscles, such as soleus, are weakly active in the beginning of the stance phase; however, here, a reflex will be inappropriate for pro pulsion. The body is moving forward over the stance leg, and the movement stretches the calf muscles. A stretch reflex will impede this forward movement. The H-reflexes are small during this phase (Fig. 4) but still present. Perhaps, they help to stabilize the limb during the single-support phase of walking (10,22). Exactly how remains uncertain in the light of the changing views of balance mechanisms described previously.
Stein and Capaday (25) also described a phase dependence of the H-reflexes. Once the body has passed beyond the center of pressure of the leg (midstance), H-reflexes increase to near the values for standing. This makes functional sense because the reflex response will now have a vector that propels the body up and forward and hence aids the forward progression. In contrast, the calf muscles are again stretched during the swing phase. Any reflex response will now extend the ankle, and the foot may drag on the ground. During the swing phase, the reflex is largely suppressed in able-bodied individuals but not in some people with spasticity (22).
To be sure of the functional significance, stretches and electrical stimuli should be applied. A device was developed by Andersen and Sinkjær (1) at the University of Aalborg, Denmark that can rapidly perturb the ankle in either the flexion or extension direction. Figure 5A shows results using this device to produce gradual movements, referred to as enhancements and reductions (17). Note that the muscle is still being stretched by the forward movement of the body over the stance limb, although at a slightly faster or slower rate than would normally occur during walking. Figure 5 also shows clear changes in the soleus EMG that are proportional to velocity. The responses to stretches (enhancements) were affected by vibration and anesthetic that was selective for group Ia fibers, whereas the responses to reductions were not, suggesting a role for other muscle receptors in the reductions. Exactly which receptors are involved remains controversial, but the slow stretches certainly allow time for involving many receptors and pathways beyond the typical monosynaptic response. Nonetheless, slow perturbations can modulate the soleus EMG by up to ±40% (Fig. 5C), suggesting that reflex responses to stretch produce a substantial fraction of the normal EMG. This result does not disprove the existence of neural circuits that produce the basic walking pattern (central pattern generators). However, even if the basic pattern is produced centrally, reflexes can adapt it considerably to the environmental conditions (17). This result confirms earlier studies but uses more natural perturbations.
Stein and Capaday (25) originally studied running (Fig. 4B) and found that H-reflexes were reduced for a given level of EMG in this task as compared with walking. Simonsen and Dyhre-Poulsen (24) extended the range of speeds (up to 15 km·h−1) and made some improvements to the methodology, as described earlier. They found that the peak H-reflex actually increased from walking to high-speed running, although not in proportion to the increase in EMG. After analyzing the data in reduced gravity and eliminating points where there was little EMG, Ferris et al. (6) concluded that the main difference between walking and running was in the y-intercept (i.e., the value of the H-reflex in the absence of background EMG). Their conclusion differed from that shown in Figure 4B, where the slope of the relationship between the H-reflex and background EMG changed but not the intercept. This conclusion is rather strange because their results agreed with those shown in Figure 4B, when they included EMG data near zero, which would presumably help them estimate the y-intercept. Nonetheless, all studies agree that, for a given level of EMG, the H-reflex is highest during standing, intermediate in walking, and lowest during running.
Much less data are available for muscles other than soleus. The EMG pattern in quadriceps muscles differs from that in soleus. The activity is maximal during the transition from swing to stance and the early part of stance. The knee flexors are mainly coactive with the extensors. Although the knee flexes somewhat during early stance, the active contraction of the quadriceps muscles and the increased stiffness from the coactivation of flexors and extensors must prevent the knee from collapsing under the weight of the body. During the early stance phase of walking, the quadriceps H-reflex is actually larger than during standing, with matched M-waves and EMG levels, but decreases later in the stance phase and during the swing phase (22, p.547). The Aalborg device can also be used to perturb the knee joint (1). Responses were observed in all of the quadriceps muscles studied and the knee flexors. One striking result was the task dependence of the reflexes in the quadriceps muscles. The responses all increased with increased EMG activity during standing but decreased or did not change with increasing EMG activity during walking. This task dependence is probably caused by the differences in presynaptic inhibition, as will be discussed later. Mrachacz-Kersting et al. (20) explain the functional significance of the task dependence as follows: "the strongest reflex amplitudes were observed during the later part of the stance phase, at which time the background activity had already diminished. At this time the center of gravity moves over the foot in preparation for the following swing phase. A flexion of the knee joint would cause the center of gravity to shift to a position in front of the foot, making it difficult to maintain balance. In contrast, during standing the center of gravity is directly above the feet and not moving in relation to them." In conclusion, recent evidence indicates that strong excitatory reflexes control movements in both ankle and knee joint during walking.
Muscle spindles also have pathways that inhibit antagonist motor neurons (Fig. 6). These pathways are probably involved in the reciprocal organization of many of our movements. Thus, when flexor muscles are activated, the corresponding extensors are generally inhibited, and vice versa. This reciprocal organization applies to cutaneous and other pathways (e.g., the flexor reflex) and to descending voluntary control of some but not all movements (22). For example, we can coactivate antagonist muscle groups to stiffen the limb in one position. The reciprocal inhibitory pathway is strongly but not exclusively activated by group Ia fibers. The shortest latency pathway involves a single interneuron, as shown in Figure 6A, and is therefore referred to as disynaptic inhibition.
Short-Latency Reciprocal Inhibition
One method to study short-latency inhibition involves measuring the depression of ongoing voluntary activity (Fig. 6C). In the example shown, the common peroneal (CP) nerve was stimulated at just above the M-wave threshold. A small M-wave and an H-reflex are seen in the tibialis anterior (TA) muscle that is innervated by the CP nerve (Fig. 6B). The antagonist (soleus) muscle was contracted voluntarily at approximately 15-20% of the maximum voluntary contraction (MVC). Little change is observed in the soleus muscle EMG until just after the H-reflex in TA (EMG was rectified and averaged; 15 stimuli at 2-3 s apart). Then, the voluntary activity decreases for approximately 10 ms (dotted line in Fig. 6B). This is caused by the reciprocal inhibition, and the duration of the inhibition is what would be expected for a brief synaptic current (27). A second method involves pairing a stimulus to the CP nerve, with one to the tibial nerve (Fig. 6D). The stimulus to the tibial nerve produces an M-wave and an H-reflex in the soleus muscle, as described previously (Fig. 1). If the CP nerve is stimulated a few milliseconds before the tibial nerve, impulses will have time to conduct to the spinal cord and excite the interneurons to inhibit the soleus motor neurons (Fig. 6A). Therefore, pairing the stimuli will reduce the H-reflex.
Which method is better to measure inhibitory reflexes during voluntary activity? We tested both methods on six subjects. Figure 7A shows the effect of three different intensities of stimulation (1, 1.25, and 1.5 × motor threshold) and three different levels of voluntary contraction (10, 20, and 30% MVC; not shown). For method 1, the percent inhibition was independent of the level of voluntary contraction and was significantly related to the stimulus intensity (P < 0.001). For method 2, we tested the three different levels of CP stimulus intensity, two levels of voluntary contraction (0 and 20% MVC), and two levels of tibial nerve stimulation, which gave approximately 0.5 Hmax and Hmax. Figure 7B shows the average results for the four conditions. Only the condition with 0.5 Hmax at rest showed a significant inhibition. The other conditions showed a small mean level of inhibition, but the variability between subjects (note the large SE bars) was such that the mean level was not significant. Thus, the results are sensitive to several factors (22, p.208). The measured inhibition also increases during dorsiflexion of the ankle and almost disappears during plantar flexion (23). These voluntary contractions modify the size of the H-reflex as well, so the effects interact with one another and make it extremely difficult to interpret, when alternating dorsiflexion and plantar flexion form part of the behavior, as in walking. The conditioned H-reflex method is traditionally measured at rest, and it can only be used in the few muscles that show an H-reflex at rest. It will also be affected by subthreshold changes (Fig. 3).
In summary, our results show that the inhibition of voluntary contraction (method 1) is independent of the level of contraction and varies directly with the level of stimulation. In contrast, the conditioned H-reflex (method 2) depends on the following: 1) the level of voluntary contraction, 2) the level of CP stimulation, 3) the level of the tibial nerve stimulation, and 4) the time interval between the CP and the tibial nerve stimulation. There is only a 3-ms window in which inhibition occurs (22), despite the fact that inhibitory postsynaptic potentials typically last much longer (5). Also, because of the small size of the effect, compared with that of method 1 (Fig. 7A), more stimuli must be used. In the experiments of Figure 7A, we estimated that approximately 70 stimuli (35 test and 35 conditioned) are required to obtain statistically reliable results, compared with 15 stimuli during voluntary inhibition. Despite the methodological concerns, there is now reasonable agreement that reciprocal inhibition is modulated between standing, walking, and running and decreases with age (10,11,22). However, the changes are not as dramatic as those shown by the H-reflexes.
Other Forms of Inhibition
There are several other forms of inhibition, for example, from Golgi tendon organs, although this inhibition can reverse to excitation during walking (18). There are also nonreciprocal forms of inhibition that act at one or more joints. In general, both the excitatory and inhibitory connections across joints seem to be much more widespread in humans than in cats, where they have been studied most extensively (5,22). This may be caused by the more complex requirements of bipedal walking, but widespread connections are also seen in the human upper limb. More importantly, reflex connections in cats have traditionally been studied under anesthesia, which will particularly depress multisynaptic connections.
Pierrot-Deseilligny and Burke (22) developed an ingenious method to study the recurrent inhibition mediated through Renshaw cells, pairing an H-reflex stimulus with one 10 ms later that generates a maximum M-wave. Voluntarily activating a muscle can increase or decrease the amount of Renshaw inhibition, which lasts for tens of milliseconds. This has been interpreted in terms of a variable gain control, but other explanations are possible (29). The inhibition from Renshaw cells is widely distributed, and the inhibition from soleus to the quadriceps muscles is reduced in those tasks (e.g., standing and late stance phase of walking) when the muscles are co-contracted.
Presynaptic inhibition can reduce transmission through many sensory pathways for 100 ms or more. It serves as a gain control on the first and second synaptic relays in these pathways and is responsible for much of the task dependence of H-reflexes (25). The inhibition can be measured as a decrease in an H-reflex produced by a brief vibration of an antagonist tendon or a stimulus to the antagonist nerve (22). Thus, modulation of the H-reflex can be studied on a millisecond time scale (reciprocal inhibition), a 10-ms time scale (recurrent inhibition), or a 100-ms time scale (presynaptic inhibition). Some of the same methodological concerns apply to presynaptic inhibition as to the previous types, plus additional ones (22). Because the response is so delayed, there is time for many pathways to be involved. As a result, changes in the H-reflex may differ from those in a tendon jerk or stretch reflex (19,22). Also, responses that are secondary to muscle contractions elicited by the stimulus can occur. Thus, changes in ongoing voluntary activity (our preferred method for reciprocal inhibition) are difficult to interpret. Again, we recommend a small level of voluntary activity while ensuring that the level is maintained until the delayed H-reflex occurs. The effects tend to be larger with presynaptic inhibition, and the timing is less critical, so the conditioned H-reflex technique can yield useful results.
Finally, we return to the three questions that were raised in the title of the article. First, how should reflexes be measured during movement? Clearly, electrical stimulation with EMG recording is the most convenient method. Stimulation should be applied, as far as possible, while the subjects are performing the movements of interest, and must be used with care. The nervous system is complex and adaptive, so it is all too easy to think that you are measuring one thing but are actually measuring something else. Although they also have limitations, specialized devices that perturb movements mechanically and new methods, such as ultrasound, to detect muscle movements have produced some major and recent advances. The simplest (monosynaptic and disynaptic) reflexes from large afferents are the easiest to measure, but clever methods have been developed to measure more complex pathways, as described here and, in more detail, in another reference (22). Second, what do reflexes contribute to various movements? The evidence is now quite convincing that excitatory reflexes contribute to a substantial fraction of the force generated during human walking and help to adapt it to the terrain. Inhibitory pathways modulate the activity appropriately for the requirements of different tasks and phases within the tasks. However, reflexes surprisingly do not seem to contribute much in quiet standing, although they will respond to larger perturbations that threaten balance. Third, why should they be measured? The answer is simply that there are important task- and phase-dependent changes in reflexes in different human movements. Understanding these adaptations is essential to understanding how we control movement, and only a very few basic movements have been studied to date with suitable methods.
The authors thank Drs. Dave Bennett, Charles Capaday, Dave Collins, Monica Gorassini, and Kelvin Jones for helpful comments on the manuscript. This work was supported by grants from the Canadian Institutes of Health Research and the Christopher Reeve Paralysis Foundation.
1. Andersen, J.B., and T. Sinkjær. An actuator system for investigating electrophysiological and biomechanical features around the human
ankle joint during gait. IEEE Trans. Rehabil. Eng.
2. Brooke, J.D., and E.P. Zehr. Limits to fast-conducting somatosensory feedback in movement
control. Exerc. Sport Sci. Rev.
3. Casadio, M., P.G. Morasso, and V. Sanguineti. Direct measurement of ankle stiffness during quiet standing: implications for control modelling and clinical application. Gait Posture
4. Duysens, J., F. Clarac, and H. Cruse. Load-regulating mechanisms in gait and posture: comparative aspects. Physiol. Rev.
5. Eccles, J.C. The Physiology of Synapses
, Berlin, Germany: Springer-Verlag, 1964.
6. Ferris, D.P., P. Aagaard, E.B. Simonsen, C.T. Farley, and P. Dyhre-Poulsen. Soleus H-reflex gain in humans walking and running under simulated reduced gravity. J. Physiol.
7. Hultborn, H., M. Illert, J. Nielsen, A. Paul, M. Ballegaard, and H.Wiese. On the mechanism of the post-activation depression of the H-reflex in human
subjects. Exp. Brain Res.
8. Inman, V.T., H.J. Ralston, J.B. Saunders, B. Feinstein, and E.W. Wright Jr. Relation of human
electromyogram to muscular tension. Electroencephalogr. Clin. Neurophysiol. Suppl.
9. Kido, A., N. Tanaka, and R.B. Stein. Spinal excitation
decrease as humans age. Can. J. Physiol. Pharmacol.
10. Kido, A., N. Tanaka, and R.B. Stein. Spinal reciprocal inhibition
locomotion. J. Appl. Physiol.
11. Lavoie, B.A., H. Devanne, and C. Capaday. Differential control of reciprocal inhibition
during walking versus
postural and voluntary motor tasks in humans. J. Neurophysiol.
12. Li, Y., M.A. Gorassini, and D.J. Bennett. Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats. J. Neurophysiol.
13. Loram, I.D., C.N. Maganaris, and M. Lakie. Human
postural sway results from frequent, ballistic bias impulses by soleus and gastrocnemius. J. Physiol.
14. Loram, I.D., C.N. Maganaris, and M. Lakie. The use of ultrasound to make non-invasive, in vivo measurement of continuous changes in human
muscle contractile length. J. Appl. Physiol.
15. Luscher, H., P.W. Ruenzel, and E. Henneman. Effects of impulse frequency, PTP, and temperature on responses elicited in large populations of motoneurons by impulses in single Ia-fibers. J. Neurophysiol.
16. Matthews, P.B.C. Review lecture: evolving views on the internal operation and functional role of the muscle spindle. J. Physiol.
17. Mazzaro, N., M.J. Grey, and T. Sinkjaer. Contribution of afferent feedback to the soleus muscle activity during human
locomotion. J. Neurophysiol.
18. McCrea, D.A., S.J. Shefchyk, M.J. Stephens, and K.G. Pearson. Disynaptic group I excitation
of synergist ankle extensor motoneurons during fictive locomotion in the cat. J. Physiol.
19. Morita, H., N. Petersen, N. Christensen, L.O. Sinkjaer, and T. Nielsen. Sensitivity of H-reflexes and stretch reflexes to presynaptic inhibition
in humans. J. Neurophysiol.
20. Mrachacz-Kersting, N., B.A. Lavoie, J.B. Andersen, and T. Sinkjaer. Characterisation of the quadriceps stretch reflex during the transition from swing to stance phase of human
walking. Exp. Brain Res.
21. Petersen, N., H. Morita, and J. Nielsen. Modulation of reciprocal inhibition
between ankle extensors and flexors during walking in man. J. Physiol.
22. Pierrot-Deseilligny, E., and D. Burke. The Circuitry of the Human Spinal Cord: Its Role in Motor Control and Movement Disorders
, New York, NY: Cambridge University Press, 2005.
23. Shindo, M., H. Harayama, K. Kondo, N. Yanagisawa, and R. Tanaka. Changes in reciprocal Ia inhibition
during voluntary contraction in man. Exp. Brain Res.
24. Simonsen, E.B., and P. Dyhre-Poulsen. Amplitude of the human
soleus H reflex during walking and running. J. Physiol.
25. Stein, R.B., and C. Capaday. The modulation of human
reflexes during functional motor tasks. Trends Neurosci.
26. Stein, R.B., and S.C. McGie. Reciprocal inhibition
and post-activation depression following electrical stimulation of human
nerves. Can. Physiol. Soc.
, Lake Louise, 2006.
27. Turker, K.S., and R.K. Powers. Black box revisited: a technique for estimating postsynaptic potentials in neurons. Trends Neurosci.
28. Vallbo, A.B., K.E. Hagbarth, H.E. Torebjork, and B.G. Wallin. Somatosensory, proprioceptive, and sympathetic activity in human
peripheral nerves. Physiol. Rev.
29. Windhorst, U. On the role of recurrent inhibitory feedback in motor control. Prog. Neurobiol.
30. Zehr, E.P., and R.B. Stein. Interaction of the Jendrássik maneuver with segmental presynaptic inhibition
. Exp. Brain Res.
Keywords:©2006 The American College of Sports Medicine
movement; human; excitation; inhibition; task dependence; phase dependence