(a)
(b) (c)
Fig. 2.13. Reduction of post-activation depression in spastic patients. (a) The mean value (± SEM) of the soleus H reflex (expressed as a percentage of its control value) plotted against the time after the onset of passive dorsiflexion of the foot (illustrated by the dotted line at the bottom of the panel, 10◦in 600 ms, too slow and too small to evoke any EMG activity) in 30 healthy subjects (●) and 17 spastic patients with multiple sclerosis or spinal cord injury (❍). (b), (c) The mean value (+ SEM) of the FCR (b ) and soleus (c ) H reflex elicited every 2 s, and expressed as a percentage of its value when elicited every 8 s, is compared in 16 normal subjects () and on the affected () and unaffected (dashed columns) of hemiplegic patients (n = 16 in (b), and 10 in (c)). Modified from Hultborn & Nielsen (1998) (a ), and Aymard et al. (2000) ((b ), (c )), with permission.
efficacy of the Ia-motoneurone synapse develop following the changes in activity of motoneurones and Ia fibres resulting from the impairment of the motor command. (i) The fact that spastic-ity progresses during weeks or months after the causal lesion (whether a spinal lesion or stroke) fits this hypothesis, because such adaptive changes develop over time. (ii) In this respect, a longitu-dinal study of one patient with spinal cord injury found that the reduction of post-activation depres-sion developed with the transition from flaccid to spastic paralysis, even though reduced post-activation depression preceded clinically observ-able spasticity (Schindler-Ivens & Shield, 2000).
(iii) Contrary to several other electrophysiological changes explored (see Chapter12, pp.577–9), post-activation depression is unchanged on the unaf-fected side of patients with hemiplegia (Fig.2.12(b ), (c ), dashed columns). (iv) The synaptic efficacy of primary afferents can be up- or down-regulated by disuse or use of synapses, respectively (Gallago et al., 1979).
R´esum´e 101
so far experiments have focused on the role of the long-latency stretch reflex rather than the spinal reflex pathway.
Heteronymous monosynaptic Ia connections In the cat and the baboon hindlimb these connec-tions link motoneurones of muscles acting syner-gistically at the same joint but, in the human lower limb, these connections are more widespread and transjoint connections are almost the rule. The more widespread distribution of Ia connections found in the human lower limb could have evolved to pro-vide the more elaborate reflex assistance required for bipedal stance and gait, in which the equilibrium is less stable than in quadrupeds. In the upper limb, there is also a different organisation, with absence of the proximal-to-distal projections used in feline locomotion, but with strong projections from intrin-sic hand muscles to muscles acting at the wrist and elbow, projections which serve to stabilise the limb for manipulatory tasks.
Changes in monosynaptic Ia excitation in patients
Reflex attenuation
A decrease in the amplitude (and an increase in the latency) of the H reflex ocurs in various radicu-lopathies, plexus and nerve lesions, and in polyneu-ropathies, and will occur when there is loss of con-ducting afferents and/or dispersion of the afferent volley.
Spasticity
In spasticity the Hmax/Mmax ratio is increased in soleus, but is largely unchanged in FCR. Post-activation depression following previous Post-activation of Ia fibres is reduced in spastic patients. This reduc-tion could be a consequence of altered use due to motor impairment, and may be an important spinal mechanism underlying spasticity.
R´esum´e
Importance of studies of Ia connections
Several reasons account for the continuing interest in studies of monosynaptic Ia excitation of motoneu-rones.
(i) One objective of the study of reflexes is to trace the effects of a given input. The monosynaptic exci-tation of Ia afferents occurs without an interneurone, and therefore constitutes the simplest example of reflex function.
(ii) It is a challenging problem to understand how different feedback systems have adapted to evolu-tionary demands for changed patterns of movement, and here again investigations of the distribution of monosynaptic Ia connections provides the easiest way to approach evolutionary changes.
(iii) They are technically the easiest to study because Ia effects are the first to appear in motoneu-rones after peripheral stimulation and do so with the lowest threshold.
(iv) -innervation modulates the sensitivity of spindle endings and the resulting Ia discharges, and it is likely that this modulation helps maintain move-ment (see Chapter3).
(v) Reduction of post-activation depression at the Ia-motoneurone synapse could be one of the main spinal mechanisms underlying spasticity.
As discussed below, there is little doubt that the monosynaptic Ia pathway contributes to the spinal stretch reflex, but whether it is the sole input driving the reflex discharge is debatable. With this caveat, the following focuses on the Ia contribution.
Background from animal experiments
Ia afferents originate from the primary endings of muscle spindles, and are sensitive to muscle stretch and high-frequency vibration. They have excitatory monosynaptic projections to homony-mous motoneurones, and this constitutes the exci-tatory pathway underlying the tendon jerk and the
short-latency spinal stretch reflex. Projections are stronger on motoneurones innervating slow-twitch units than on those of fast-twitch units. Heterony-mous projections are weaker than homonyHeterony-mous projections, and exist to motoneurones of close syn-ergists operating at the same joint. Transjoint con-nections are more developed in the forelimb than in the hindlimb of the cat.
Methodology
Homonymous monosynaptic Ia excitation Evidence for a two-neurone arc in the human soleus
Stimulation of the posterior tibial nerve produces a synchronised response in the soleus muscle, and this has become known as the Hoffmann reflex or H reflex. Recordings of the action potentials from both dorsal and ventral roots intrathecally have demon-strated that the first motoneurones discharging in the soleus H reflex may do so at a latency consistent with a monosynaptic pathway. Besides the mono-synaptic latency, several arguments indicate that the pathway is fed by Ia afferents: low electrical thresh-old, similar excitation elicited by a tap on the Achilles tendon, facilitation by a homonymous volley to the inferior branch of the soleus nerve, and simulta-neous blockade by ischaemia of the homonymous facilitation and of the Achilles tendon jerk.
Routine diagnostic studies
In routine studies there is a number of advantages of studying the H reflex during voluntary contrac-tion, because it is then possible to record the reflex in virtually all accessible limb muscles, to reduce the latency variability, to increase the stimulus rate, and to direct the reflex response to the active motoneu-rone pool.
PSTH method
Stimulation of the parent nerve evokes an early peak in PSTHs with the characteristics of homonymous
monosynaptic Ia excitation in all limb muscles tested (same latency as the H reflex after allowance for the trigger delay of the unit, low threshold, elicitation by tendon taps).
Critique
By analogy with the soleus H reflex, the H reflex and the early peak in the PSTHs of single units in other muscles are probably evoked by Ia afferents with a monosynaptic linkage. However, so far, unequivo-cal evidence for a ‘two-neurone-arc’ in humans has been presented only for the soleus H reflex.
Heteronymous monosynaptic Ia excitation Heteronymous facilitation of the H reflex
H reflex studies do not allow reliable assessment of the central delay of the resulting facilitation.
PSTHs of single motor units
The principle is to compare the latencies of the early facilitation evoked in the same unit by stimulation of homonymous and heteronymous nerves. The dif-ference between the two latencies must reflect the differences in the afferent conduction times and in the central (synaptic) delay of the Ia effects of the homonymous and heteronymous volleys. If, like homonymous excitation, heteronymous excitation is mediated through a monosynaptic pathway, the difference in latencies between heteronymous and homonymous peaks should be explained by the dif-ference in afferent conduction times. Afferent con-duction times for the Ia homonymous and heterony-mous volleys can be estimated from the distance from stimulation sites to the arrival of the afferent volleys at the spinal cord, as measured on the skin, and the conduction velocity in Ia afferents. The valid-ity of the calculation depends on the reliabilvalid-ity of these estimates.
Bidirectional connections
To eliminate uncertainties in estimates of peripheral conduction times, studies have been performed on
R´esum´e 103
Ia connections linking a pair of motor units in two different muscles (e.g. soleus and peroneus brevis).
In this case, the homonymous volley for one member of the pair is the heteronymous volley for the other, and vice versa. The absolute value of the difference in afferent conduction times is the same for the two members of the pair. Such studies provide cogent evidence for heteronymous monosynaptic connec-tions, independent of estimates of peripheral affer-ent conduction times.
Facilitation of the on-going EMG
Some heteronymous monosynaptic Ia connections described in PSTH experiments are sufficiently strong to be demonstrable in averages of unrectified on-going voluntary EMG activity.
Ia afferent origin
Besides the monosynaptic connection, several fea-tures argue that the heteronymous pathway is fed by Ia afferents: low electrical threshold, similar excita-tion elicited by a tendon tap, increase in the thresh-old of the excitation by long-lasting vibration applied to the tendon of the ‘conditioning’ muscle, a man-oeuvre that raises the threshold of Ia afferents, and inability of cutaneous stimulation to reproduce the early peak of excitation.
The difference between the stimulus intensity required for the full recruitment of Ia afferents in cat and human experiments (2× Ia threshold and 8× Ia threshold, respectively) is due to the fact that, in human experiments, the afferents are stimulated through surface electrodes at a distance from the nerve. This factor is important because:
(i) the ‘true monosynaptic latency’ can only be disclosed at intensities much greater than 1× MT;
and (ii) if some Ia afferents are only activated by such strong stimuli, the potential Ia reflex contri-bution may have been underestimated in previous human studies performed with stimulus intensities
≤1 × MT.
Organisation and pattern of connections
Homonymous monosynaptic Ia excitation In virtually all limb muscles, stimulation of the par-ent nerve can elicit an H reflex and a peak of mono-synaptic Ia excitation in PSTHs of single motor units during voluntary contractions. At rest, H reflexes can be recorded from the soleus, quadriceps and FCR in healthy subjects. The ease with which the H reflex can be elicited at rest and the size of the peak of excitation elicited by stimulation subthresh-old for the compound H reflex are closely related. The efficacy of the monosynaptic Ia input in activating motoneurones depends on its preferential distribu-tion to early recruited (small) motoneurones in most muscles (Henneman’s size principle), and inhibitory mechanisms limiting the efficacy of the Ia volley (e.g.
presynaptic inhibition of Ia terminals; contamina-tion of monosynaptic EPSPs by oligosynaptic IPSPs).
Heteronymous monosynaptic Ia excitation Lower limb
In the human lower limb, in striking contrast with data for the cat hindlimb, connections between some close synergists operating at the same joint (e.g. the different heads of triceps surae) are weak or absent.
This pattern is consistent with weaker connec-tions in the baboon than the cat. Conversely, trans-joint connections are rare in the cat and baboon hindlimb, but are almost the rule in the human lower limb. These transjoint connections can be strong, e.g. gastrocnemius medialis to biceps femoris. They often link a muscle or group of muscles to a pair of antagonistic muscles operating at another joint, e.g. quadriceps onto all tested muscles acting at the ankle.
Upper limb
The upper limb lacks the proximal-to-distal trans-joint connections used in feline locomotion, while distal-to-proximal connections, in particular from
intrinsic hand muscles, are stronger and more widespread than in the cat.
Maturation of Ia connections during development
It has been reported that, in the normal newborn baby, a tendon tap may elicit short-latency heterony-mous excitatory responses in antagonistic muscle pairs in the upper and lower limbs (e.g. biceps and tri-ceps brachii) at monosynaptic latencies. However, it would be prudent to retain reservations about these conclusions (see p.86). This ‘reciprocal excitation’
disappears during the first years of life.
Motor tasks and physiological implications
Muscle stretch elicits a reflex response from the corresponding motoneurone pool, and this has at least two separate components: the classical short-latency spinal reflex (M1), the short-latency of which is compatible with monosynaptic Ia excitation, and a medium-latency component (M2) of more complex origin.
The short-latency spinal stretch reflex during natural motor tasks
The spinal stretch reflex utilises the simplest reflex pathway and interacts with pre-programmed and other reflex mechanisms to compensate for distur-bances during natural motor tasks. There is con-siderable literature about the contribution of the short-latency stretch reflex of triceps surae to various natural movements, but few data for other muscles.
Running, hopping and landing
During the stance phase of running and hopping and after the impact of landing, the short-latency spinal stretch reflex of the triceps surae is superimposed on pre-programmed activity and contributes to the muscle contraction responsible for the pushing off of
the foot. There is probably also a concomitant short-latency stretch response in the quadriceps.
Walking
The spinal stretch reflex can produce a mechani-cally effective contraction and provides a pathway through which rapid automatic load compensation to an unexpected disturbance can be generated.
Short-latency stretch reflexes in triceps surae, trig-gered by unexpected ankle joint displacement, con-tribute significant stabilisation of the supporting limb during walking. Heteronymous Ia connections between ankle muscles that are not synergistic in flexion–extension movements probably contribute further to the stability of the ankle.
Perturbations of upright stance
Perturbations of the upright stance in subjects stand-ing on a rotatstand-ing platform produce an early spinal stretch reflex response (M1), which is prominent in soleus. After loss of large-diameter muscle spindle afferents, M1 is absent but posture is quite stable, suggesting that M1 is not essential for equilibrium control during quiet stance.
Spinal and transcortical stretch reflexes The medium-latency (M2) response to stretch fol-lowing the early spinal (M1) response has a different origin in various muscles: in the flexor pollicis longus (and intrinsic muscles of the hand) the long latency is due to a transcortical pathway fed by Ia afferents, whereas in foot and leg muscles the stretch response is mediated through a spinal pathway fed by slowly conducting group II afferents. Both transcortical and spinal group II pathways could contribute to the M2 response in proximal upper limb muscles, such as the biceps brachii.
Heteronymous monosynaptic Ia excitation There are little experimental data on the functional role of heteronymous Ia connections. However, the
R´esum´e 105
different organisation of these connections in the cat and baboon hindlimb and the human lower limb suggests that the connections are functionally important, having adapted to provide the particular reflex assistance required in each species.
Weak connections between ankle extensors The weakness of the connections between ankle extensors in human subjects may be related to the role of triceps surae in walking: it resists and brakes the passive ankle dorsiflexion produced by extrinsic forces (kinetic force and gravity), but must be over-come by these forces if the body is to be brought forward. It would then be undesirable to have exces-sive activity from the triceps surae stretch reflex, and weak Ia connections between the different heads of the muscle would help ensure this.
Transjoint connections
Widespread transjoint connections in the lower limb have probably evolved to provide the more elabor-ate reflex assistance required in bipedal stance and gait, in which equilibrium is much less stable than in quadrupedal stance and gait. Some of these connec-tions are weak, but their strength has been under-estimated in experimental studies and, in any case, this would not prevent them from modulating the excitability of motoneurones that are already depo-larised. During the stance phase of running, hop-ping and landing, all extensors undergo a lengthen-ing contraction that evokes a strong Ia discharge, and it is probable that the extensive Ia connections link-ing muscles across joints modulate the role played by the different muscles in load compensation.
Projections onto antagonists operating at another joint
These projections are desirable functionally because of the versatile synergisms required to accomplish the various tasks of the human lower limb (e.g.
co-contraction of quadriceps and gastrocnemius-soleus in running and hopping, but of quadriceps
and tibialis anterior when leaning backward). On the other hand, diffuse Ia connections could become functionally inconvenient, because the activation of Ia afferents from a contracting muscle might result in the automatic unwanted activation of muscles linked by Ia synergism. Suppression of unwanted heterony-mous Ia discharges can be achieved through focused corticospinal control of presynaptic inhibition of Ia terminals and of recurrent inhibition. The need for this control suggests that the heteronymous Ia discharge does play a functional role, because it must be suppressed in tasks for which it is not required.
Upper limb
The diffuse distribution of the Ia projections from intrinsic hand muscles and the finding that they are stronger on muscles operating at the wrist than on long flexors and extensors of the fingers suggest that these projections might be used to stabilise the wrist to provide a firm support to hand muscles during manipulatory movements.
Studies in patients and clinical implications
In practice, assessing Ia connectivity involves meas-urements of the H reflex. There are a number of advantages of doing so during voluntary contrac-tions (see above). Modulation of the on-going EMG by a heteronymous volley may allow access to a motoneurone pool by afferent inputs that do not tra-verse the same nerve or nerve root as homonymous afferents.
Peripheral neuropathies, mononeuropathies and nerve lesions
These may be accompanied by a decrease in the amplitude and an increase in the latency of the H reflex. Reflex depression usually results from an afferent abnormality and will occur when there is either a loss of conducting afferents or dispersion of
the afferent volley. Tests of reflex function provide a tool to distinguish between isolated peripheral nerve lesions and lesions involving roots or plexus.
Spasticity
The ratio Hmax/Mmax is, on average, increased in soleus but not, or hardly so, in FCR in hemiplegics.
Post-activation depression at the Ia-motoneurone synapse
Background from animal experiments
It has long been known that the size of the mono-synaptic reflex decreases when it is repeatedly elicited. This results from a decrease in transmit-ter release due the repetitive activation of the Ia-motoneurone synapse. The results from a variety of preparations indicate the presence of an early facili-tation of relatively short duration superimposed on a depression of much longer duration. Post-activation depression helps to maintain the synaptic efficacy of the Ia-motoneurone synapse at a relatively low level during voluntary movements.
Methodology Passive stretch
Passive stretch of the tested muscle depresses the H reflex, a phenomenon confined to the Ia pathway activated by the passive stretch. There is experimen-tal evidence that this depression is not due to pre-synaptic inhibition of Ia terminals with primary afferent depolarisation or to post-synaptic inhibition of the motoneurones.
Increasing the stimulus rate
This produces a reflex depression that is prominent at relatively high stimulus rates (>0.3 Hz), lessens when the stimulus rate is decreased, and disappears at stimulus rates below 0.1 Hz. During a voluntary contraction of the test muscle, the reflex
depres-sion is markedly attenuated, probably because the enhanced Ia firing during voluntary contraction causes a background level of post-activation depres-sion, which can be increased further by only a small amount.
Post-activation depression in spastic patients Whether measured as the depression induced by passive stretch of the test muscle or by high stimu-lus rate, post-activation depression is significantly decreased in spastic patients due to spinal cord injury and multiple sclerosis, and on the affected side of patients with hemiplegia. This reduction is probably a consequence of the disuse due to motor impairment, and may be an important spinal mech-anism underlying spasticity.
REFERENCES
Ashby, P. & Labelle, K. (1977). Effects of extensor and flexor group I afferent volleys on the excitability of individual soleus motoneurones in man. Journal of Neurology, Neurosurgery and Psychiatry, 40, 910–19.
Ashby, P. & Zilm, D. (1982). Characteristics of postsynaptic potentials produced in single human motoneurones by homonymous group I volleys. Experimental Brain Research, 47, 41–8.
Ashby, P., Hilton-Brown, P. & St˚alberg, E. (1986). Afferent projec-tions to human tibialis anterior motor units active at various levels of muscle contraction. Acta Physiologica Scandinav-ica, 127, 523–32.
Awiszus, F. & Feistner, H. (1993). The relationship between esti-mates of Ia-EPSP amplitude and conduction velocity in human soleus motoneurons. Experimental Brain Research, 95, 365–70.
Aymard, C., Katz, R., Lafitte, C. et al. (2000). Presynaptic inhibi-tion and homosynaptic depression: a comparison between lower and upper limbs in normal subjects and patients with hemiplegia. Brain, 123, 1688–702.
Baldissera, F., Hultborn, H. & Illert, M. (1981). Integration in spinal neuronal systems. In Handbook of Physiology, sec-tion I, The Nervous System, vol. II, Motor Control, ed. V. B.
Brooks, pp. 508–95. Bethesda, USA: American Physiological Society.
References 107
Bayoumi, A. & Ashby, P. (1989). Projections of group Ia affer-ents to motoneurons of thigh muscles in man. Experimental Brain Research, 76, 223–8.
Beevor, C. E. (1904). The Croonian Lectures on Muscular Move-ments and their Representation in the Central Nervous Sys-tem. London: Adlard.
Berger, W., Dietz, V. & Quintern, J. (1984). Corrective reactions to stumbling in man: neuronal coordination of bilateral leg muscle activity during gait. Journal of Physiology (London), 405, 1–37.
Bergmans, J., Delwaide, P. J. & Gadea-Ciria, M. (1978). Short-latency effects of low-threshold muscular afferent fibers on different motoneuronal pools of the lower limb in man.
Experimental Neurology, 60, 380–5.
Birnbaum, A. & Ashby, P. (1982). Postsynaptic potentials in indi-vidual soleus motoneurons in man produced by Achilles tendon taps and electrical stimulation of tibial nerve. Elec-troencephalography and Clinical Neurophysiology, 54, 469–
71.
Bouaziz, Z., Bouaziz, M. & Hugon, M. (1975). Modulation of soleus electromyogram by electrical stimulation of medial gastrocnemius nerve in man. Electromyography, 15, 31–42.
Brock, L. G., Eccles, J. C. & Rall, W. (1951). Experimental investi-gations on the afferent fibres in muscle nerves. Proceedings of the Royal Society B, 138, 453–75.
Buller, N. P., Garnett, R. & Stephens, J. A. (1980). The reflex responses of single motor unit in human hand muscles fol-lowing afferent stimulation. Journal of Physiology (London), 303, 337–49.
Burke, D., Hagbarth, K.-E., L¨ofstedt, L. & Wallin, B. G. (1976). The responses of human muscle spindle endings to vibration of non-contracting muscles. Journal of Physiology (London), 261, 673–93.
Burke, D., Gandevia, S. C. & McKeon, B. (1983). The afferent vol-leys responsible for spinal proprioceptive reflexes in man.
Journal of Physiology (London), 339, 535–52.
(1984). Monosynaptic and oligosynaptic contributions to human ankle jerk and H-reflex. Journal of Neurophysiology, 52, 435–48.
Burke, D., Adams, R. W. & Skuse, N. F. (1989). The effect of volun-tary contraction on the H reflex of various muscles. Brain, 112, 417–33.
Burke, R. E. (1981). Motor units: anatomy, physiology and func-tional organization. In Handbook of Physiology, section I, The Nervous System, vol. II, Motor Control, Part 1, ed. V. B.
Brooks, pp. 345–422. Bethesda, MD: American Physiologi-cal Society.
Bussel, B., Katz, R., Pierrot-Deseilligny, E., Bergego, C. & Hayat, A. (1980). Vestibular and proprioceptive influences on the
postural reactions to a sudden body displacement in man.
In Spinal and Supraspinal Mechanisms of Voluntary Motor Control and Locomotion, ed. J.E. Desmedt, vol. 8, pp. 310–
22. Basel: Karger.
Capaday, C. (2002). The special nature of human walk-ing and its neural control. Trends in Neurosciences, 25, 370–6.
Cavallari, P. & Katz, R. (1989). Pattern of projections of group I afferents from forearm muscles to motoneurones supply-ing biceps and triceps muscles in man. Experimental Brain Research, 78, 465–78.
Cavallari, P., Katz, R. & P´enicaud, A. (1992). Pattern of projec-tions of group I afferents from elbow muscles to motoneu-rones supplying wrist muscles in man. Experimental Brain Research, 91, 311–19.
Chalmers, G. R. & Bawa, P. (1997). Synaptic connections from large afferents of wrist flexor and extensor muscles to syner-gistic motoneurones in man. Experimental Brain Research, 116, 351–8.
Christensen, L. A. D., Andersen, J. B., Sinkjaer, T. & Nielsen, J. (2001). Transcranial magnetic stimulation and stretch reflexes in the tibialis anterior muscle during human walk-ing. Journal of Physiology (London), 531, 545–57.
Clough, J. F. M., Kernell, D. & Phillips, C. G. (1968). The distribu-tion of monosynaptic excitadistribu-tion from the pyramidal tract and from primary spindle afferents to motoneurones of the baboon’s hand and forearm. Journal of Physiology (London), 198, 145–66.
Cody, F. W. J., MacDermott, P. B., Matthews, P. B. C. & Richardson, H. C. (1986). Observations on the genesis of the stretch reflex in Parkinson’s disease. Brain, 109, 229–49.
Coppin, C. M. C., Jack, J. J. B. & MacLennan, C. R. (1970). A method for the selective electrical stimulation of tendon organ afferent fibres from the cat soleus muscle. Journal of Physiology (London), 210, 18–20P.
Cr´eange, A., Faist, M., Katz, R. & P´enicaud, A. (1992). Distri-bution of heteronymous Ia facilitation and recurrent inhi-bition in the human deltoid motor nucleus. Experimental Brain Research, 90, 620–4.
Crone, C. & Nielsen, J. (1989). Methodological implications of the post-activation depression of the soleus H-reflex in man.
Experimental Brain Research, 78, 28–32.
Curtis, D. R. & Eccles, J. C. (1960). Synaptic action during and after repetitive stimulation. Journal of Physiology (London), 150, 374–98.
Diener, H. C., Dichgans, J., Bootz, F. & Bacher, M. (1984a). Early stabilization of human posture after a sudden disturbance:
influence of rate and amplitude of displacement. Experi-mental Brain Research, 56, 126–34.