Motor unit firing pattern, synchrony and coherence in a deafferented patient.

The firing of spinal motoneurons (MNs) is controlled continuously by inputs from muscle, joint and skin receptors. Besides altering MN synaptic drive, the removal of these inputs is liable to alter the synaptic noise and, thus, the variability of their tonic activity. Sensory afferents, which are a major source of common and/or synchronized inputs shared by several MNs, may also contribute to the coupling in the time and frequency domains (synchrony and coherence, respectively) observed when cross-correlation and coherence analyses are applied to the discharges of MN pairs. Surprisingly, no consistent changes in firing frequency, nor in synchrony and coherence were reported to affect the activity of 3 pairs of motor units (MUs) tested in a case of sensory polyradiculoneuropathy (SPRNP), leading to an irreversible loss of large diameter sensory afferents (Farmer et al., 1993). Such a limited sample, however, precludes a definite conclusion about the actual impact that a chronic loss of muscle and cutaneous afferents may have on the firing properties of human MUs. To address this issue, the firing pattern of 92 MU pairs was analyzed at low contraction force in a case of SPRNP leading similarly to a permanent loss of proprioceptive inputs. Compared with 8 control subjects, MNs in this patient tended to discharge with slightly shorter inter-spike intervals but with greater variability. Synchronous firing tended to occur more frequently with a tighter coupling in the patient. There was no consistent change in coherence in the 15-30 Hz frequency range attributed to the MN corticospinal drive, but a greater coherence was observed below 5 Hz and between 30 and 60 Hz in the patient. The possible origins of the greater irregularity in MN tonic discharges, the tighter coupling of the synchronous firing and the changes in coherence observed in the absence of proprioceptive inputs are discussed.

Progression of cortical and spinal dysfunctions over time in amyotrophic lateral sclerosis.

In view of the conflicting results about the links between lower and upper motor neuron (LMN, UMN) dysfunction in amyotrophic lateral sclerosis (ALS), we undertook this study to correlate their changes over time. Single motor units (MUs) were characterized by their macro-MU potentials, twitch amplitude, and excitatory responses to transcranial magnetic stimulation (TMS). Ten ALS patients were studied 2 to 4 times and their data were subdivided into epochs corresponding to mean disease duration of 12 (58 MUs), 20 (60 MUs), 32 (50 MUs), 43 (40 MUs), and 168 months (55 MUs). The MU size increased and the contractile effectiveness and the excitatory response rates decreased significantly with time. The contractile effectiveness of MUs producing normal excitatory responses decreased with time, whereas a gradual loss of excitatory responses was observed among MUs with normal electromechanical properties. Since no correlation was found between UMN and LMN dysfunction, we conclude that UMN and LMN probably degenerate independently in ALS.

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis.

Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state.

Recurrent inhibition of wrist extensor motoneurones: a single unit study on a deafferented patient.

In order to document the effects of recurrent inhibition on the firing times of human alpha-motoneurones during natural motor behaviour, a case study was performed on a deafferented patient. The fact that this subject had completely lost the large-diameter sensory afferents provided us with a unique opportunity of selectively stimulating the motor axons in the nerves. The tonic activity of single motor units (n = 21) was recorded in the extensor carpi radialis muscles while applying randomly timed antidromic electrical stimuli to the radial nerve. The peristimulus time histogram analysis showed the presence of biphasic inhibitory effects, including an early, short-lasting component followed by a longer-lasting component occurring 20-40 ms later. The interspike interval (ISI) during which the stimulation occurred was generally lengthened as compared to the previous ISIs. The stimulation was most effective when delivered early (20-30 ms) after a spike. It was also effective, although less so, when delivered at the end of the ISI (70-100 ms after a spike). The lengthening effect sometimes extended over one or two of the subsequent ISIs. The lengthening effect of the motor axon stimulation was followed by an excitatory-like effect, which took the form of a shortening that affected up to five ISIs after the stimulation. The biphasic inhibitory effects and the subsequent facilitatory effects are discussed in terms of the dual nature of the synaptic processes involved in the recurrent inhibitory network, the postactivation facilitation/depression processes and the mutual inhibition occurring between Renshaw cells.

Pharmacologically induced enhancement of recurrent inhibition in humans: effects on motoneurone discharge patterns.

The aim of the present study was to investigate the effects of spinal recurrent inhibition on human motoneurone discharge patterns. The tonic discharge activity of motor unit pairs was recorded in the extensor carpi radialis (ECR) and abductor digiti minimi (ADM) muscles during voluntary isometric contraction. While undergoing continuous intravenous saline (NaCl 0.9 %) perfusion, the subjects were given a short lasting injection of L-acetylcarnitine (L-Ac), which has been found to potentiate recurrent inhibition in humans. The variability, synchronization and coherence of the motor unit discharges were analysed during four successive test periods (lasting 2-3 min each). A significant decrease in the inter-spike interval (ISI) coefficient of variation was observed in the discharge patterns of the motor units tested in the ECR and not in the ADM, which were not accompanied by any consistent changes in the mean ISIs of the motor unit activity in either muscle. The L-Ac injection also led to a significant increase in the synchronization in half of the motor unit pairs tested in the ECR muscle (n = 29), whereas no consistent changes were observed with the ADM motor units (n = 25). However, coherence analysis failed to reveal any consistent differences in the incidence of significant values of coherence spectrum between the pre-injection and injection periods among the motor unit pairs tested with either saline or L-Ac injections, in either the ECR or ADM muscles. The contrasting effects on the variability and the synchronization of the motor unit discharges observed with ECR motoneurones known to undergo recurrent inhibition and with ADM motoneurones known to lack recurrent inhibition suggest that the drug may have specific effects which are mediated by an enhancement of the Renshaw cell activity. The decrease in the ISI variability is in line with the hypothesis that recurrent inhibition may contribute along with the post-spike after-hyperpolarization to limiting the influence of the synaptic noise on the firing times of steadily discharging motoneurones. The present data, which suggest that recurrent inhibition plays a synchronizing rather than a desynchronizing role, are in keeping with the fact that the Renshaw cells may provide an important source of common inhibitory inputs.

Presynaptic and disynaptic inhibition induced by group I muscle afferents.

The task related changes in the Gp I inputs were investigated in type-identified motor units in the wrist extensor muscles. During wrist extension, the monosynaptic inputs generated by applying radial nerve stimulation were distributed among the motoneurone pool in line with the size principle. Their effectiveness was enhanced in the same way during hand clenching and during wrist extension combined with stimulation of the palm and finger cutaneous receptors. The orderly distribution of the monosynaptic Gp I inputs was reversed by the presynaptic inhibition induced by stimulating the Gp I flexor afferents. The effects of the presynaptic inhibition were partially released by applying cutaneous stimulation. During wrist extension, the Gp I flexor afferents generated disynaptic excitatory inputs acting specifically on high-threshold motor units together with disynaptic inhibitory inputs distributed in line with the size principle among the wrist extensor motor nucleus. During hand lenching, their effectiveness was differentially modulated depending on the motor unit type.