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Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the postcue delay period, left MEPs were suppressed when the left hand had been cued for the forthcoming response, suggestive of a form of inhibition specifically directed at selected response representations. H-reflexes were also suppressed on these trials, indicating that the effects of this inhibition extend to spinal circuits. In addition, left MEPs were suppressed when the right hand was cued, but only when left hand movements were a possible response option before the onset of the cue. Notably, left hand H-reflexes were not modulated on these trials, consistent with a cortical locus of inhibition that lowers the activation of task-relevant, but nonselected responses. These results suggest the concurrent operation of two inhibitory mechanisms during response preparation: one decreases the activation of selected responses at the spinal level, helping to control when selected movements should be initiated by preventing their premature release; a second, upstream mechanism helps to determine what response to make during a competitive selection process.

The aim of the present study was to investigate the existence or otherwise of a functional recurrent inhibitory system (Renshaw cell system) in the motoneurons that innervate human masticatory muscles. In a previous study, L: -acetylcarnitine (L: -Ac), a substance known to potentiate recurrent inhibition in humans was found to alter, in a specific way, the discharge variability, and the synchronous activity of motor units depending on the presence or absence of recurrent inhibition in the corresponding motoneuron pool. Using a similar paradigm, we have recorded the tonic discharge activity of motor unit pairs from the masseter muscle during voluntary isometric contraction while subjects were undergoing continuous intravenous saline (SAL, NaCl 0.9%) perfusion. Following a brief baseline-recording period, the subjects were given a test injection of either L: -Ac or isotonic saline (SAL) in a double blind manner. The variability, synchronization, and coherence between the motor unit discharges were analysed during three successive periods: pre-injection, during injection, and post-injection, each lasting 2-3 min. Neither L: -Ac nor SAL injection induced a significant change in the inter-spike interval (ISI) or the coefficient of variation of the ISIs in the motor units tested. There were also no significant changes in the pattern of synchronous activity or in the coherence, which reflects the common frequency content of the unit discharges. Reminiscent of what had been observed previously with motoneurons without recurrent inhibition in the Abductor Digitorum Minimi muscle, the lack of effects of L: -Ac injection on the firing behaviour of masseter motoneurons may suggest that classical Renshaw cell inhibition is lacking in this motoneuron pool.

The systemic injection of L-Acetylcarnitine (L-Ac) induces a reversible increase in recurrent inhibition. In addition, L-Ac potentiation of recurrent inhibition has been found to increase the synchronous activity of single motor units, as detected by traditional linear analysis in the time domain. This result has been recently confirmed using a nonlinear method based on the analysis of embedded determinism (%DET) extracted from the surface EMG. The present study aimed at testing the general applicability of RQA methodology, as a viable tool for assessing motor unit synchronization, by extending the analysis of surface EMG, as revealed by changes in %DET induced by L-Ac, to many upper and lower limb muscles and to muscles that are not easily studied by needle electrodes, such as the orbicularis oculi. Subjects performed brief periods of tonic contractions, alternated to periods of rests to avoid muscle fatigue. Pharmacological enhancement of recurrent inhibition was obtained by a short-lasting intravenous injection of L-Ac. Control experiments were performed replacing L-Ac injection with saline injection. The average %DET showed a significant increase during L-Ac injection in the deltoid, biceps brachii, extensor carpi radialis, while no effect was observed in the opponens pollicis and abductor digiti minimi for the upper limb muscles. Similarly, the average %DET showed a significant increase during L-Ac injection in the quadriceps, soleus, and tibialis anterior, while no effect was observed in the abductor hallucis for the lower limb muscles. RQA of orbicularis oculi muscle activity showed no increase in %DET during L-Ac injection in analogy to what found in the intrinsic muscles of the hand and foot, known to be devoid of recurrent inhibition. The presence or absence of drug-induced increase in motor unit synchronization agrees with the known distribution of recurrent inhibition in the various motor nuclei. The overall significance of these findings is the potential application of RQA methodology as a reliable and independent tool for generally assessing motor unit synchronization from surface EMG under strictly controlled experimental condition.

Unilateral hand movements are accompanied by a transient decrease in corticospinal (CS) excitability of muscles in the opposite hand. However, the rules that govern this phenomenon are not completely understood. We measured the amplitude of motor evoked potentials (MEP) in the left first dorsal interosseus (FDI) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex in order to assess CS excitability changes that preceded eight possible combinations of unilateral and bilateral index finger movements with different right hand positions. Left FDI MEP amplitude (MEP(Left FDI)) increased when this muscle acted as an agonist and tended to decrease when it was an antagonist. Additionally, MEP(Left FDI) decreased substantially before right index finger abduction (a movement mediated by the right FDI) when both hands were lying flat (a movement mirroring left index finger abduction) but not when the right hand was turned at 90 degrees or flat with the palm up. Therefore, CS excitability of the resting FDI was differentially modulated depending on the direction of the opposite index finger movement, regardless of muscles engaged in the task. These results indicate that inhibitory interactions preceding unilateral finger movements are determined by movement kinematics possibly to counteract the default production of mirror motions.

Objective: To test the hypothesis that 'metabolites released during fatiguing muscle contractions excite group III-IV muscle nociceptive afferents, inhibiting homonymous motoneurones via Renshaw cells,' by recording changes in recurrent inhibition of soleus motoneurones when high-threshold, small-diameter afferents (group III-IV fibres) from the same muscle were tonically activated., Methods: Experiments were performed in 7 healthy subjects at rest and during weak isometric voluntary contraction of the soleus muscle. Muscle nociceptive afferents were activated by local standardized injection of levo-ascorbic acid. Renshaw cells were orthodromically activated by a conditioning H reflex and the resulting recurrent inhibition of the soleus motoneurones was assessed by a subsequent test H reflex. An additional H reflex of the same size as the test reflex was used to assess motoneurone excitability., Results: At rest, muscle nociceptive stimulation produced transient facilitation of both test H and reference H reflexes. Under weak voluntary contraction, muscle nociceptive stimulation produced long-lasting extra-inhibition and extra-facilitation of the test reflex and reference reflex respectively, the time course of which closely resembled that of the subjective muscle pain curve., Conclusions: Discharge of putative group III-IV muscle afferents facilitated homonymous recurrent inhibition. The filtering property of recurrent inhibition may contribute to limit motoneurone activity during muscle pain and/or adapt motoneurone firing rate to the modified contractile properties of motor units as muscle fatigue developed.

Changes in the excitability of the soleus H-reflex are were studied after oral administration of L-acetylcarnitine, a cholinomimetic substance, in eight healthy control subjects and 23 spastic patients presenting with slowly progressive paraparesis (n = 10), a cord lesion (n = 9) and a cerebral lesion (n = 4). Changes in the amount of recurrent inhibition of soleus motor neurons at rest were also estimated in order to assess the level of activity of Renshaw cells before and after L-acetylcarnitine administration. Recurrent inhibition elicited by a conditioning reflex discharge (H1) was assessed by a subsequent test reflex (H'). Four patients lacked an H' reflex. In approximately 50% of the remaining patients, recurrent inhibition was normal, while in the other half there was evidence of reduced or absent inhibitory activity at rest. Pooling the data relative to the effect of L-acetylcarnitine on the H-reflex in relation to the strength of recurrent inhibition disclosed that the ratio of peak-to-peak amplitude values of the maximum H reflex to maximum M wave responses (Hmax:Mmax) was reduced in all the cases in which the recurrent inhibition at rest was normal, while such a reduction was never observed in the patients in whom recurrent inhibition was found to be decreased at rest. In the former cases, the size of the H' reflex evoked by the same conditioning H1 discharge was further depressed after L-acetylcarnitine, pointing to a potentiating effect of the drug on Renshaw cells; in the latter cases no such effect was seen. A significant decrease in the mean Hmax:Mmax ratio after L-acetylcarnitine intake was also seen in the healthy control subjects. Possible changes in the amount of presynaptic inhibition on Ia terminals on soleus motor neurons after L-acetylcarnitine were ruled out. It is proposed that the differential effect of the drug on the H-reflex excitability is directly related to the level of Renshaw cell activity, a reduction of which probably follows a lesion interrupting reticulo-spinal pathways with tonic facilitatory influences on Renshaw cells. These findings support the hypothesis that Renshaw cell excitability is set via cortico-reticulo-spinal systems.

Interneurones mediating disynaptic inhibition from extensor to flexor carpi radialis muscles were characterized by pharmacological stimulation of Renshaw cells. It is, indeed, known that only Ia interneurones are blocked by recurrent inhibition. Renshaw cell potentiation, induced by intravenous administration of 2 g levo-acetylcarnitine, blocked Ia reciprocal inhibition from triceps to biceps muscles but not disynaptic inhibition from extensor to flexor carpi radialis muscles. It is concluded that the interneurones mediating this latter inhibition are not Ia interneurones. This kind of inhibition could be an example of a Ia non-reciprocal inhibitory pathway.

Renshaw cells, which mediate the recurrent inhibition of spinal a-motoneurones, are activated by acetylcholine, both through motoneurone collaterals and the reticulo-spinal system. Since it is known that L-acetylcarnitine (L-AC) has central cholinergic effects, we tested in ten normal subjects and three spastic patients the ability of L-AC to induce changes in excitability of the Renshaw cells. These were activated by a conditioning monosynaptic reflex of the soleus muscle, evoked by electrical stimulation of the tibial nerve, and the resulting recurrent inhibition of the motoneurones was assessed by a subsequent monosynaptic reflex (H'). Recurrent inhibition was tested prior to, during and after an intravenous administration of a solution containing 2000 mg of L-AC. L-AC administration proved to be able to induce in all subjects a decrease in the H'-reflex. This effect ensued approximately 30 min after onset of L-AC administration, reached the peak after 40 min and vanished in about one hour. The extent of the decrease in H' varied among subjects, being on the average 22% of the control values. A relationship was found between duration of L-AC administration and time for reaching the maximal effect. These results show that L-AC is able to decrease a-motoneurone excitability by increasing Renshaw cell activity, both in normal and spastic subjects.

Experiments involving the acute administration of a central cholinergic substance (L-acetylcarnitine) were performed on 6 healthy subjects to obtain additional evidence that the electrophysiological method developed by Bussel and Pierrot-Deseilligny in 1977 does actually assess recurrent inhibition in man. In all the subjects, the drug further decreased the amplitude of a test H reflex (H') following a conditioning H reflex (H1). The amount of this supplementary inhibition was found to be related to the size of H1 reflex. Experimental evidence is also presented that H' reflex supplementary depression is not contaminated by homonymous Ib effects. It is concluded that the method effectively tests the excitability of Renshaw cells in man.

The study was performed on a group of 17 patients with spastic paraparesis: 12 with hereditary spastic paraparesis, 3 with cord compression and 2 with complete spinal transection. 10 healthy volunteers acted as controls. Recurrent inhibition of the soleus alpha-motoneurones was estimated at rest and during voluntary contraction of triceps surae. At rest, there was evidence for a substantial decrease in the excitability of Renshaw cells in 9 out of the 12 patients with hereditary spastic paraparesis; this was also observed in the 2 patients with complete spinal transection, while the 3 patients with cord compression exhibited a normal Renshaw cell activity. In 3 out of 4 patients with hereditary spastic paraparesis, the changes in Renshaw cell excitability expected to occur during voluntary contraction were not found, whereas in one patient with hereditary spastic paraparesis and one with spastic paraparesis due to cord compression recurrent inhibition was normally influenced by the motor command. Our results indicate that recurrent inhibition is likely to be differently affected according to the type and/or localization of the lesion. It is also suggested that the central nervous system might control the excitability of Renshaw cells at rest and during voluntary contraction via partly separate pathways. The role of recurrent inhibition in spasticity is discussed.

Reciprocal inhibition from the anterior tibial muscle onto antagonist motoneurones of the soleus muscle was studied in normal man under control conditions and after low intensity stimulation of cutaneous afferent fibres from the sole and dorsal region of the ipsilateral and contralateral foot. Ipsilateral cutaneous stimulation increased the reciprocal inhibition to the soleus motoneurones, without qualitative differences between the effect from the sole and that from the dorsal region of the foot. Stimulation of cutaneous afferent fibres from the contralateral foot produced the reverse effect, i.e., depression of the Ia reciprocal inhibition from the tibialis anterior to the soleus motoneurones. No effects could be observed when cutaneous areas other than those of the foot were stimulated. The effects of cutaneous stimulation on the reciprocal inhibition became evident only when this inhibition approached its maximum and, thus, they most strongly influenced its recovery phase. Since cutaneous stimulation does not modify the test reflex when given alone, it is likely that there must be convergence on common premotoneuronal interneurones. Indirect evaluation of central delay suggests that the cutaneous afferent fibres from the foot have oligosynaptic spinal connections with interneurones belonging to the group I pathways to the antagonists. Our findings furnish additional evidence that short-latency inhibition of soleus motoneurones after a single conditioning stimulation of group I afferents from the tibialis anterior muscle constitutes a true example of disynaptic Ia reciprocal inhibition in man.