P. Marque

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.

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in healthy subjects and post-stroke patients

It has been shown on hand muscles in normal subjects that paired associative stimulation (PAS) combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) induces lasting changes in cortical motor excitability (Stefan etxa0al., Brain 123 (Pt3):572–584, 2000). Because the motor recovery of distal upper limb and particularly wrist extension in post-stroke patients is one of the major rehabilitation challenge, we investigate here the effect of one session of paired associative stimulation on the excitability of the corticospinal projection to extensor carpi radialis (ECR) muscle (motor evoked potential size) before and after PAS in 17 healthy subjects and in two patients 5xa0months after stroke. The time course, the topographical specificity, changes in rest motor threshold (RMT), short intracortical inhibition and intracortical facilitation (SICI and ICF), the respective role of cutaneous and muscular afferents and the effect of a prolonged peripheral stimulation alone were also studied in normal subjects. Using a protocol derived from that of Ridding etxa0al. J Physiol 537:623–631 (2001), PAS was able to induce lasting changes in the excitability of corticospinal projection to wrist muscles in healthy subjects and in the two post-stroke patients studied. Electrophysiological features of these plastic changes were similar to those previously observed in hand muscles: rapid evolution, 30–60xa0min duration, reversibility, relative topographical specificity and associative dependence suggesting an LTP-like mechanism. A contribution of cutaneous afferents in inducing PAS effects was also demonstrated. The decrease in ECR RMT after PAS observed in patients and in healthy subjects was an unexpected result because it has not been previously reported in the hand muscles of healthy subjects. However, it has been observed in dystonic patients (Quartarone etxa0al., Brain 126:2586–2596, 2003). This suggests that other mechanisms like changes in membrane excitability could be involved in ECR facilitation after PAS. Further studies performed on patients using daily repeated PAS protocols and showing a functional improvement in hand motor function will be necessary to confirm that this technique could be relevant in motor rehabilitation, at least for some selected patients.

Increase in group II excitation from ankle muscles to thigh motoneurones during human standing

In standing subjects, we investigated the excitation of quadriceps (Q) motoneurones by muscle afferents from tibialis anterior (TA) and the excitation of semitendinosus (ST) motoneurones by muscle afferents from gastrocnemius medialis (GM). Standing with a backward lean stretches the anterior muscle pair (TA and Q) and they must be cocontracted to maintain balance. Equally, forward lean stretches the posterior muscle pair (GM and ST) and they must be cocontracted. We used these conditions of enhanced lean to increase the influence of γ static motoneurones on muscle spindle afferents, which enhances the background input from these afferents to extrafusal motoneurones. The effects of the conditioning volleys on motoneurone excitability was estimated using the modulation of the on‐going rectified EMG and of the H reflex. Stimulation of afferents from TA in the deep peroneal nerve at 1.5–2 × MT (motor threshold) evoked early group I and late group II excitation of Q motoneurones. Stimulation of afferents in the GM nerve at 1.3–1.8 MT evoked only late group II excitation of ST motoneurones. The late excitation produced by the group II afferents was significantly greater when subjects were standing and leaning than when they voluntarily cocontracted the same muscle pairs at the same levels of activation. The early effect produced by the group I afferents was unchanged. We propose that this increase in excitation by group II afferents reflects a posture‐related withdrawal of a tonic inhibition that is exerted by descending noradrenergic control and is specific to the synaptic actions of group II afferents.

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 (∼0.5–0.6 × 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.

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 ~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, and2.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.

Transcranial magnetic stimulation in brain injury

OBJECTIVESnTranscranial magnetic stimulations (TMS) have been used for many years as a diagnostic tool to explore changes in cortical excitability, and more recently as a tool for therapeutic neuromodulation. We are interested in their applications following brain injury: stroke, traumatic and anoxic brain injury.nnnDATA SYNTHESISnFollowing brain injury, there is decreased cortical excitability and changes in interhemispheric interactions depending on the type, the severity, and the time-lapse between the injury and the treatment implemented. rTMS (repetitive TMS) is a therapeutic neuromodulation tool which restores the interhemispheric interactions following stroke by inhibiting the healthy cortex with frequencies ≤1Hz, or by exciting the lesioned cortex with frequencies between 3 and 50Hz. Results in motor recovery are promising and those in improving aphasia or visuospatial neglect are also encouraging. Finally, the use of TMS is mainly limited by the risk of seizure, and is therefore contraindicated for many patients.nnnCONCLUSIONnTMS is a useful non-invasive brain stimulation tool to diagnose the effects of brain injury, to study the mechanisms of recovery and a non-invasive neuromodulation promising tool to influence the post-lesional recovery.

Mécanismes cérébraux de la rééducation: apport de l’imagerie fonctionnelle

Durant les vingt dernieres annees, les outils d’imagerie fonctionnelle cerebrale se sont largement repandus, en particulier grâce a l’imagerie par resonance magnetique fonctionnelle (IRMf) qui est maintenant facilement accessible. De nombreuses etudes utilisent ces outils afi n d’explorer la plasticite cerebrale postlesionnelle ou le mecanisme d’action d’une prise en charge reeducative. Alors qu’il est techniquement possible de realiser un examen d’imagerie fonctionnelle cerebrale dans les suites d’un accident vasculaire cerebral (AVC), pourquoi cette pratique ne s’est-elle pas encore imposee en clinique courante pour etudier le potentiel de recuperation d’un patient ou choisir le protocole de reeducation le plus adapte ?