Group II excitations from plantar foot muscles to human leg and thigh motoneurones.

Projections of group II afferents from intrinsic foot muscles to lower limb motoneurones were investigated in humans after electrical stimuli were applied to the tibial nerve (TN) at ankle level, using modulation of the quadriceps H reflex, on-going EMG of the quadriceps and peroneus brevis, and PSTHs of single quadriceps, biceps, semitendinosus, tibialis anterior, and peroneus brevis motor units. TN stimulation evoked late and high-threshold excitation in all leg and thigh muscles investigated. The mean latency of the late excitation was 13.5+/-0.4 ms longer than that of the heteronymous monosynaptic Ia excitation, and the more caudal the motor nucleus the longer the central delay of the late effect, suggesting mediation through interneurones located rostral to motoneurones. The electrical threshold and conduction velocity of the largest diameter fibres evoking the late excitation were estimated to be approximately 2 and 0.67 times, respectively, those of the fastest Ia afferents, i.e. consistent with a mediation by group II afferents. Stimulation of the skin areas innervated by TN did not evoke late excitations. Further support for mediation through group II afferents was provided by the findings that: 1. the latency of the TN-induced late and high-threshold excitation in Per brev units was more delayed by cooling the nerve than that of the excitation evoked by group I afferents, and 2. tizanidine intake (known to depress selectively transmission of group II effects) suppressed the TN-induced late and high-threshold excitation whereas the group I facilitation was not modified.

Perception of non-voluntary brief contractions in normal subjects and in a deafferented patient.

The accuracy of force perception by human subjects in the absence of voluntary motor command was evaluated by exploring how they perceived isometric twitches of wrist extensor muscles produced by external stimulation. Twelve normal subjects and a well-known patient lacking large-diameter afferent fibres (GL) performed estimation, production and reproduction tasks. Magnetic stimulation of the radial nerve and, in normal subjects, transcranial magnetic stimulation (TMS) of the motor cortex were used to produce weak brief non-voluntary twitches. In estimation tasks, the subjects had to ascribe verbal marks on a 1-5 scale to the forces of stimulation-induced twitches. Loose covariations of marks and forces were observed, while directions of force variations between successive twitches were relatively well detected. GL did less well than normal subjects in detecting directions of force variations. In production tasks, subjects had to produce twitches matching verbal command marks in a 1-5 range, with or without visual feedback. Performances of normal subjects and GL resembled those of estimation tasks and were not improved by visual feedback. In reproduction tasks, subjects had to duplicate stimulation-induced test twitches: first without visual feedback, second with and third again without. Large errors were observed but all subjects did better with visual feedback. In the third step, improvement with respect to the first one was significantly more marked with TMS than with peripheral stimulation. GL improved her performance in the third step, possibly because she could use information provided by group III and group IV afferents still present in her nerves. Altogether, for normal subjects (1) the performances in estimation tasks are consistent with the known behaviour of Golgi tendon organs as observed in animal experiments, and (2) results observed in reproduction tasks suggest that cortical stimulation might elicit, in addition to corticospinal activation of motoneurones, collateral discharges that could be stored as a memory of motor command.

Interruption of a relay of corticospinal excitation by a spinal lesion at C6-C7.

In a patient with a limited lesion of the spinal cord at the C6-C7 junction, ulnar and superficial radial-induced modulations of the motor evoked potentials (MEP) and of ongoing electromyographic (EMG) activity were observed in the biceps (above the lesion) but not in the triceps (below the lesion). This suggests an interruption of the axons of cervical propriospinal neurons. This relay transmits an indirect (disynaptic) component of corticospinal excitation to human upper limb motoneurons. Changes in it might be involved in compensatory mechanisms following central motor disorders.

Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans.

1. Group I projections from intrinsic plantar muscles to motoneurones (MNs) of human leg and thigh muscles were investigated. Changes in firing probability of single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous sensation. 2. Homonymous facilitation, attributable to monosynaptic Ia excitation, was found in all the sampled units. Early heteronymous excitation elicited by TN stimulation was found in many MUs. Later effects (3-5 ms central delay) were bigger and more frequently observed: excitation in most TA and Per brev MUs, and inhibition in most Sol, GM and Bi MUs and in many ST and VL MUs. The low threshold (approximately 0.5-0.6 x motor threshold) and the inability of a pure cutaneous stimulation to reproduce these effects (except the late excitation in TA MUs) indicate that they were due to stimulation of group I muscle afferents. 3. The early excitation was accepted to be monosynaptic when its central delay differed from that of the homonymous Ia excitation by less than 0.5 ms. Such a significant TN-induced monosynaptic Ia excitation was found in MUs belonging to all leg and thigh motor nuclei tested. Although its mean strength was relatively weak, it is argued that these monosynaptic connections might affect already depolarized MNs. 4. The late excitation found in TA and Per brev MUs is argued to be mediated through interneurones located rostral to MNs. 5. The late suppression, found in most Sol, GM and Bi MUs, and in many ST and VL MUs, was the dominant effect. It was accompanied by an inhibition of the Sol and quadriceps H reflexes at rest, and therefore reflects an inhibition directed to MNs. Its long latency is argued to reflect transmission by interneurones located rostral to MNs (the inhibitory counterpart of non-monosynaptic excitation). 6. The functional implications of these connections are discussed with respect to the requirements of the stance phase of human walking and running.

Corticospinal excitation of presumed cervical propriospinal neurones and its reversal to inhibition in humans.

1. This study addresses whether in human subjects indirect corticospinal excitation of upper limb motoneurones (MNs) relayed through presumed cervical propriospinal neurones (PNs) is paralleled by corticospinal activation of inhibitory projections to these premotoneurones. 2. The responses to transcranial magnetic stimulation (TMS), whether assessed as the compound motor-evoked potential (MEP) or the peak of corticospinal excitation elicited in the post-stimulus time histograms (PSTHs) of single motor units, were conditioned by weak volleys to musculo-cutaneous, ulnar and superficial radial nerves. 3. Afferent volleys, which hardly modified the H reflex, significantly facilitated the corticospinal response produced by weak TMS. In PSTHs, the central delay of the peripheral facilitation of the peak of corticospinal excitation in MNs located at either end of the cervical enlargement was longer the more caudal the MN pool, suggesting an interaction in premotoneurones located rostral to the tested MNs. 4. Small increases in the strength of TMS (approximately 2--5 % of the maximal stimulator output) caused the facilitation to disappear and then to be reversed to inhibition. The facilitatory and inhibitory effects had the same latencies and spared the initial 0.5--1 ms of the corticospinal excitatory response. Both effects were more readily demonstrable when there was a co-contraction of the target muscle and the muscle innervated by nerve used for the conditioning stimulus. 5. The above features suggest that the inhibition resulted from disfacilitation due to suppression of corticospinal excitation passing through the presumed premotoneuronal relay. The reversal of the facilitation to inhibition by stronger corticospinal volleys is consistent with a well-developed system of 'feedback inhibitory interneurones' activated by corticospinal and afferent inputs inhibiting the presumed propriospinal excitatory premotoneurones. 6. It is argued that these findings might explain why simply stimulating the pyramidal tract or the motor cortex would fail to demonstrate this indirect corticospinal projection in the macaque monkey and in humans.

Distribution of non-monosynaptic excitation to early and late recruited units in human forearm muscles.

The distribution of monosynaptic and nonmonosynaptic excitation was investigated within flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone (MN) pools. FCR H reflexes of different size were conditioned by various conditioning stimuli eliciting different effects: (1) musculocutaneous-induced non-monosynaptic excitation of FCR MNs at the onset of biceps contraction, (2) heteronymous monosynaptic Ia facilitation, (3) reciprocal Ia inhibition, and (4) presynaptic inhibition of Ia terminals. Musculocutaneous-induced non-monosynaptic excitation increased continuously with the size of the unconditioned reflex. In contrast, heteronymous monosynaptic Ia excitation first increased and then decreased, with increases in the unconditioned reflex size, reciprocal inhibition and presynaptic inhibition showing an approximately similar tendency. This suggests that the non-monosynaptic excitation is distributed more evenly to early and late recruited MNs than monosynaptic Ia excitation, reciprocal inhibition and presynaptic inhibition. A different pattern of homonymous radial-induced monosynaptic and non-monosynaptic excitation was also found for individual ECR MNs investigated with the poststimulus time histogram (PSTH) method. Whereas the monosynaptic Ia excitation tended to be most marked in lower threshold MUs, the nonmonosynaptic excitation was evenly distributed to lower and higher threshold MUs. We propose that the even distribution of the non-monosynaptic excitation in the motoneuronal pool may be of significance when it is necessary to activate a wide range of MNs more or less simultaneously.

The monosynaptic reflex: a tool to investigate motor control in humans. Interest and limits.

The principle of the monosynaptic reflex used as a tool to explore the excitability of the motoneurones (MNs) is explained and the general methodology of the H reflex is described. The different drawbacks inherent in the technique are then considered: mechanisms other than the monosynaptic la excitation of MNs contributing to the H reflex size (limitation of the H reflex size by disynaptic IPSPs, presynaptic inhibition of la terminals, post-activation depression); non-linearity and changes in the 'recruitment gain' in the MN pool; and poor time resolution of the method. Despite these drawbacks, it is emphasized that the H reflex is the only available technique enabling one to investigate changes in transmission in spinal pathways during motor tasks.

Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans.

Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level. Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents. Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s-1). A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side. It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat, might be used to provide a support to the hand during manipulatory movements.

Posture-related changes in heteronymous recurrent inhibition from quadriceps to ankle muscles in humans.

The possibility was investigated that changes in heteronymous recurrent inhibition (RI) from quadriceps (Q) to soleus (Sol) and tibialis anterior (TA) motoneurons (MNs) occur during postural tasks requiring cocontraction of Q with one of these muscles. Stimulation of the femoral nerve (FN), which elicited a Q H-reflex discharge, was used to activate Renshaw cells. The resulting inhibition of TA and Sol MNs was assessed using three test responses: (1) the rectified and averaged ongoing electromyogram (EMG) activity in TA or Sol; (2) the motor-evoked potential (MEP) elicited by cortical stimulation in these muscles; and (3) the Sol H reflex. The characteristics of the depression (appearance and increase with the conditioning reflex discharge, short central delay and long duration) are consistent with a Renshaw origin. In addition, results obtained in control experiments (no change in the EMG suppression after an ischaemic blockade of group-I afferents from the leg, time course of the FN-induced depression of the MEP similar to that of the ongoing EMG) made a significant contribution from other pathways activated by FN stimulation unlikely. Posture-related heteronymous RI from Q was compared in different postural tasks at matched levels of background EMG activity: voluntary co-contraction of Q and of the relevant ankle muscle while sitting (control situation), postural co-contraction of Q and TA (while leaning backwards during stance), or contraction of Sol with (preparation for hopping) and without (standing on tip of toes and leaning forwards during stance) associated contraction of the Q. During stance, heteronymous RI from Q was reduced to TA (but not to Sol) while leaning backwards and to Sol in preparation for hopping, but not in the other situations. Thus, RI from Q to TA or Sol was specifically decreased when a co-contraction of the Q and of the relevant muscle operating at the ankle was required to maintain bipedal stance. It is argued that this control of Renshaw cells is descending in origin and contributes to selection of the appropriate synergism in various postural tasks.

The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents.

1. Heteronymous group II effects were investigated in the human lower limb. Changes in firing probability of single motor units in quadriceps (Q), biceps (Bi), semitendinosus (ST), gastrocnemius medialis (GM) and tibialis anterior (TA) were studied after electrical stimuli between 1 and 3 times motor threshold (MT) applied to common peroneal (CP), superficial (SP) and deep (DP) peroneal, Bi and GM nerves in those nerve-muscle combinations without recurrent inhibition. 2. Stimulation of the CP and Bi nerves evoked in almost all of the explored Q motor units a biphasic excitation with a low-threshold early peak, attributable to non-monosynaptic group I excitation, and a higher threshold late peak. When the CP nerve was cooled (or the stimulation applied to a distal branch, DP), the increase in latency was greater for the late than for the early peak, indicating that the late excitation is due to stimulation of afferents with a slower conduction velocity than group I fibres, presumably in the group II range. In ST motor units the group II excitation elicited by stimulation of the GM and SP nerves was particularly large and frequent, and the non-monosynaptic group I excitation was often replaced by an inhibition. 3. A late group II-induced excitation from CP to Q motoneurones and from GM and SP to ST motoneurones was also observed when using the H reflex as a test. 4. The electrical threshold and conduction velocity of the largest diameter fibres evoking the group II excitation were estimated to be 2.1 and 0.65 times those of the fastest Ia afferents, respectively. In the combinations tested in the present investigation the group II input seemed to be primarily of muscle origin. 5. The potent heteronymous group II excitation of motoneurones of both flexors and extensors of the knee contrasted with the absence of a group II effect from DP to GM and from GM to TA. In none of the combinations explored was there any evidence for group II inhibition of motoneurones. The possible contribution to postural reactions of the potent group II excitation of thigh motoneurones is discussed.

Cortical control of spinal pathways mediating group II excitation to human thigh motoneurones.

1. The possibility was investigated that cortical excitation to human thigh motoneurones is relayed via lumbar premotoneurones. 2. Test responses were evoked by transcranial magnetic stimulation (TMS) in voluntarily contracting quadriceps (Q) and semitendinosus (ST) muscles: either a motor evoked potential (MEP) in surface recordings or a peak of cortical excitation in the post-stimulus time histogram (PSTH) of single motor units was used. These test responses were conditioned by stimuli to the common peroneal (CP) or gastrocnemius medialis (GM) nerves. 3. CP stimulation evoked a large biphasic facilitation of the Q MEP, with early, short-lasting, low-threshold (0.6-0.8 x motor threshold (MT)) and late, longer lasting and higher threshold (1.2-1.5 x MT) peaks separated by a period of depression. GM nerve stimulation evoked a similar early depression and late facilitation in the ST MEP. 4. CP-induced effects in the Q H reflex were different (smaller late facilitation not preceded by any depression), suggesting that CP and cortical volleys interact at a premotoneuronal level to modify the Q MEP. 5. Peaks of cortical excitation evoked by TMS in single motor unit PSTHs were modulated by the conditioning volley like the MEPs with, in Q motor units, early and late CP-induced facilitations separated by a depression, and in ST motor units a late GM-induced facilitation. Facilitations on combined stimulation (i) were greater than the sum of effects by separate stimuli and (ii) never affected the initial part of the cortical peak. 6. It is concluded that the features of the reported facilitatory interactions between cortical and peripheral volleys are consistent with interactions in a population of lumbar excitatory premotoneurones co-activated by group I and group II afferents. The potency of the effects suggests that a significant part of the cortical excitation to motoneurones of thigh muscles is relayed via these interneurones. 7. It is argued that the early depression in ST motoneurones and the separation of the two peaks of facilitation in Q motoneurones reflect a cortical facilitation of spinal inhibitory interneurones projecting on excitatory premotoneurones.

Handedness-related asymmetry in transmission in a system of human cervical premotoneurones.

The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles. Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.

Recurrent inhibition in humans.

Methods have been developed to investigate recurrent inhibition (RI) in humans. A conditioning reflex discharge is used to evoke in motoneurones (MNs) supplying homonymous and synergistic muscles, an inhibition the characteristics of which are consistent with RI: it appears and increases with the conditioning motor discharge, has a short latency and a long duration, and is enhanced by an agonist of acetylcholine. As in the cat, homonymous RI exists in all explored motor nuclei of the limbs except those of the digits and the pattern of distribution of heteronymous RI closely matches that of monosynaptic Ia excitation. However, striking inter-species differences exist concerning the distribution of heteronymous RI since it is much more widely extended in the human lower limb than in the cat hindlimb, whereas it is more restricted in the upper limb than in the cat forelimb. Changes in transmission in the recurrent pathway have been investigated during various voluntary or postural contractions involving different (homonymous, synergistic, antagonistic) muscles and it has been found that the activation of Renshaw cells (RCs) by the voluntary motor discharge via recurrent collaterals was powerfully controlled by descending tracts: for example, during homonymous contraction, RI evoked by a given conditioning reflex discharge is much smaller during strong than during weak contraction, which suggests that the descending control of RCs might contribute to the regulation of muscle force. The finding that RC inhibition is more marked during phasic than during tonic contraction of similar force of the homonymous muscle is discussed in relation with the projections of RCs to Ia interneurones mediating reciprocal inhibition. Only in patients with progressive paraparesis is there evidence for decreased RI at rest which may contribute to the exaggeration of the passively-induced stretch reflex underlying spasticity. However, despite the seemingly normal RI at rest in most patients, the control of RCs during voluntary movements is disturbed in these patients, which probably contributes to their motor disability.

Role of spinal premotoneurones in mediating corticospinal input to forearm motoneurones in man.

1. Evidence was sought to support the suggestion that corticospinal input can be relayed to motoneurones (MNs) via a population of interneurones (premotoneurones) in the cervical cord, and that this pathway operates in parallel with the direct monosynaptic pathway. 2. Single motor units were recorded in forearm muscles and post-stimulus time histograms (PSTHs) of their firing pattern were constructed during voluntary activation. Weak transcranial magnetic stimulation of the contralateral motor cortex was used to produce a small facilitation in the PSTH. We then examined how the size of this peak was affected by low threshold electrical stimulation of either the homonymous muscle nerve or the musculo-cutaneous nerve at various interstimulus intervals (ISIs). 3. Homonymous nerve stimulation had the following characteristics: (a) the cortical peak was facilitated when stimuli were timed so that both inputs arrived simultaneously at the MN; (b) the amount of facilitation was only slightly greater than the sum of the effects of each stimulus given alone; and (c) facilitation affected even the earliest bins of the cortically evoked peak. These three features are consistent with a monosynaptic input onto the MN from both sources. 4. Stimulation of the musculo-cutaneous nerve (which has no monosynaptic connections with forearm MNs) had no effect at similar timings. It (a) produced facilitation only at longer intervals corresponding to an extra central delay of 4-6 ms; (b) always gave a significantly larger facilitation than expected from the algebraic sum of the effects of each stimulus given alone; and (c) never affected the earliest bins of the cortical peak. These features are compatible with interaction of peripheral and cortical inputs at a population of premotoneurones. 5. These results confirm the suggestion that premotoneurones mediate part of the cortical command to MNs innervating forearm muscles. 6. Excitation is followed by an inhibition which may almost completely suppress the cortical peak. It is suggested that cortical and musculo-cutaneous volleys also converge onto inhibitory interneurones projecting to the premotoneuronal pool.

Cortical control of presynaptic inhibition of Ia afferents in humans.

The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus.

Overactivity of cervical premotor neurons in Parkinson's disease.

OBJECTIVES: Cortical command to upper limb motor neurons is transmitted, in humans, not only through the monosynaptic corticomotor neuronal pathway, but also through cervical premotor neurons. Whether activity in this non-monosynaptic corticospinal pathway is modified in Parkinson's disease was explored. METHODS: Ongoing EMG activity recorded in wrist extensors during tonic extension of the wrist is suppressed by a volley evoked by stimulating the superficial radial nerve. It has been shown that this cutaneous induced suppression is due to inhibition of transmission of the cortical command at a premotor neuronal level. By comparing the cutaneous induced EMG depression between 45 de novo parkinsonian patients and 23 age matched controls it has been possible to appreciate if and to what extent the "non-monosynaptic" part of the cortical command is modified in these patients. RESULTS: At the early stage of the illness the EMG depression, reflecting the "non-monosynaptic" part of the cortical command, was bilaterally increased despite very asymmetric clinical status. When the duration of the disease was more than 36 months, EMG depression returned to its control level. No correlation was found between the amount of the EMG depression and parkinsonian symptoms before and after levodopa treatment. CONCLUSION: Increase of the relative "non-monosynaptic" part of the cortical command could reflect a compensatory motor mechanism elaborated upstream from the motor cortex.

Further evidence for non-monosynaptic group I excitation of motoneurones in the human lower limb.

Non-monosynaptic group I and group II excitation of human lower limb motoneurones was investigated. Changes in the firing probability of individual voluntarily activated motor units belonging to various muscles (soleus, gastrocnemius medialis, tibialis anterior, peroneus brevis, quadriceps and biceps femoris) were investigated after stimulation of various nerves (posterior tibial, common peroneal and femoral nerves) with weak (0.4-0.6x motor threshold) electrical stimuli. In all investigated motor nuclei, stimulation of the "homonymous" nerve evoked a peak of increased firing probability with a latency that was 3-7 ms longer than the monosynaptic Ia latency. The more caudal the motor nucleus explored, the greater the central delay. This strongly suggests a transmission through neurones located above the lumbar enlargement. If one excepts the sural-induced excitation of peroneus brevis units, which seems to be mediated through a particular pathway, the main peripheral input to neurones mediating non-monosynaptic excitation evoked by these weak stimuli is group I in origin. The pattern of distribution of non-monosynaptic group I excitation was very diffuse, since stimulation of each nerve was able to evoke excitation in all investigated nuclei. In most cases, non-monosynaptic excitation evoked in a given motor unit by stimulation of one nerve was depressed on combined stimulation of two nerves, and evidence is presented that this lateral inhibition is exerted at a premotoneuronal level. By contrast, there was no evidence that increasing the afferent input in a given pathway evokes an "autogenetic" inhibition in this pathway. The negative correlation found between non-monosynaptic group I-induced and late group II-induced facilitation of the quadriceps H-reflex when using high stimulus intensities applied on the common peroneal nerve suggests that these two effects could be mediated through common interneurones.

Assessing changes in presynaptic inhibition of Ia afferents during movement in humans.

Different methods, based on different principles, have been proposed to estimate changes in presynaptic inhibition of Ia terminals (accompanied by primary afferent depolarization, (PAD)) during voluntary contraction in humans. (i) A discrepancy between the H-reflex amplitude, at an equal level of EMG activity, in two situations (e.g., walking and standing) may be taken as suggesting a different control of PAD interneurones in the two cases. (ii) A conditioning stimulation (vibration or electrical stimulation) is used to activate PAD interneurones and to evoke presynaptic inhibition of the afferent volley of the test reflex. The resulting long-lasting depression of the reflex depends on the excitability of PAD interneurones, but can be contaminated by long-lasting post-synaptic effects. (iii) The amount of reflex facilitation evoked by a purely monosynaptic Ia volley varies inversely with the on-going presynaptic inhibition of Ia afferents mediating the conditioning volley, and can be used to assess this on-going presynaptic inhibition. None of these methods can provide by itself unequivocal evidence for a change in presynaptic inhibition of Ia terminals, but reasonably reliable interpretations may be proposed when congruent results are obtained with different methods. Thus it has been shown that, during selective voluntary contraction, presynaptic inhibition is decreased on Ia afferents projecting on motoneurones of the contracting muscle and increased on Ia afferents projecting on motor nuclei not involved in the contraction.

Modulation, probably presynaptic in origin, of monosynaptic Ia excitation during human gait.

Modulation of presynaptic inhibition of Ia afferents projecting monosynaptically to soleus motoneurones was investigated during human gait. Changes in presynaptic inhibition of Ia afferents were deduced from alterations in the amount of heteronymous soleus H-reflex facilitation evoked by a constant femoral nerve stimulation. It has been shown that this facilitation is mediated through a monosynaptic Ia pathway and that during its first 0.5 ms it is still uncontaminated by any polysynaptic effect and can be used to assess ongoing presynaptic inhibition of Ia terminals to soleus motoneurones. During gait, heteronymous facilitation was reduced with respect to its control value (rest during sitting) and modulated during the step cycle: it reached its maximum at mid-stance and decreased to near zero by the end of stance. At the same time the H-reflex amplitude was to some extent similarly modulated. It is argued that this decrease in heteronymous Ia facilitation and in H-reflex amplitude reflects an increased, ongoing presynaptic inhibition of Ia terminals projecting onto soleus motoneurones, which could be from central and/or peripheral origin. D1 inhibition, i.e. the late and long-lasting inhibition of the soleus H-reflex evoked by a train of stimuli to the common peroneal nerve, was used as another method to assess presynaptic inhibition. This D1 inhibition was decreased during gait, and it is argued that this decrease might reflect an occlusion in presynaptic pathways or increased presynaptic inhibition of pathways mediating the conditioning volley.