Véronique Marchand-Pauvert

Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking

1 The involvement of the motor cortex during human walking was evaluated using transcranial magnetic stimulation (TMS) of the motor cortex at a variety of intensities. Recordings of EMG activity in tibialis anterior (TA) and soleus muscles during walking were rectified and averaged. 2 TMS of low intensity (below threshold for a motor‐evoked potential, MEP) produced a suppression of ongoing EMG activity during walking. The average latency for this suppression was 40.0 ± 1.0 ms. At slightly higher intensities of stimulation there was a facilitation of the EMG activity with an average latency of 29.5 ± 1.0 ms. As the intensity of the stimulation was increased the facilitation increased in size and eventually a MEP was clear in individual sweeps. 3 In three subjects TMS was replaced by electrical stimulation over the motor cortex. Just below MEP threshold there was a clear facilitation at short latency (≈28 ms). As the intensity of the electrical stimulation was reduced the size of the facilitation decreased until it eventually disappeared. We did not observe a suppression of the EMG activity similar to that produced by TMS in any of the subjects. 4 The present study demonstrates that motoneuronal activity during walking can be suppressed by activation of intracortical inhibitory circuits. This illustrates for the first time that activity in the motor cortex is directly involved in the control of the muscles during human walking.

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.

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 (≈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.

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 × motor threshold (MT)) and late, longer lasting and higher threshold (1·2‐1·5 × 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.

Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.

Objective To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. Results At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Conclusion Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

Mediation of late excitation from human hand muscles via parallel group II spinal and group I transcortical pathways

This study addresses the question of the origin of the long‐latency responses evoked in flexors in the forearm by afferents from human hand muscles. The effects of electrical stimuli to the ulnar nerve at wrist level were assessed in healthy subjects using post‐stimulus time histograms for flexor digitorum superficialis and flexor carpi radialis (FCR) single motor units (eight subjects) and the modulation of the ongoing rectified FCR EMG (19 subjects). Ulnar stimulation evoked four successive peaks of heteronymous excitation that were not produced by purely cutaneous stimuli: a monosynaptic Ia excitation, a second group I excitation attributable to a propriospinally mediated effect, and two late peaks. The first long‐latency excitation occurred 8–13 ms after monosynaptic latency and had a high‐threshold (1.2–1.5 × motor threshold). When the conditioning stimulation was applied at a more distal site and when the ulnar nerve was cooled, the latency of this late excitation increased more than the latency of monosynaptic Ia excitation. This late response was not evoked in the contralateral FCR of one patient with bilateral corticospinal projections to FCR motoneurones. Finally, oral tizanidine suppressed the long‐latency high‐threshold excitation but not the early low‐threshold group I responses. These results suggest that the late high‐threshold response is mediated through a spinal pathway fed by muscle spindle group II afferents. The second long‐latency excitation, less frequently observed (but probably underestimated), occurred 16–18 ms after monosynaptic latency, had a low threshold indicating a group I effect, and was not suppressed by tizanidine. It is suggested that this latest excitation involves a transcortical pathway.

Suppression of the H reflex in humans by disynaptic autogenetic inhibitory pathways activated by the test volley

The present studies were designed to increase an existing limitation on the size of the H reflex by accentuating an inhibitory effect of group I afferents in the test volley. They were precipitated by the observation that, during strong voluntary contractions of quadriceps (Q), the late deep peroneal (DP) facilitation of the Q H reflex was suppressed but the facilitation of the ongoing EMG was not. The effects of conditioning stimuli to DP, superficial peroneal (SP) and articular afferents on the excitation of Q motoneurones (MNs) produced by femoral nerve (FN) stimulation were assessed in 11 healthy human subjects using the H reflex of vastus intermedius or the peak of group I excitation in post‐stimulus time histograms (PSTHs) of single motor units (MUs) in vastus lateralis. The suppression of the late H reflex facilitation was observed during strong contractions after stimulation of DP and articular afferents, and at rest when DP and SP volleys were combined. In all single MUs tested, the FN‐induced peak of excitation was suppressed by DP stimulation during strong Q contractions and by a combination of conditioning volleys (SP with DP or articular) during weak contractions. By themselves these conditioning volleys did not inhibit the background MU discharge even when delivered together. The suppression did not involve the initial bins of the peak; it began 0.7 ms later than the probable onset of monosynaptic Ia facilitation. It is argued that the suppression is not due to presynaptic inhibition of Ia terminals or to recurrent inhibition, but probably reflects convergence between the conditioning volleys and group I afferents in the test FN volley onto interneurones of the disynaptic non‐reciprocal group I inhibition. It is concluded that the size of the H reflex is limited by disynaptic inhibition, and that changes in the excitability of this inhibitory pathway can produce prominent changes in the H reflex.

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

1 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. 2 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. 3 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). 4 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. 5 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.

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.

Reduction of common motoneuronal drive on the affected side during walking in hemiplegic stroke patients

OBJECTIVE The objective of this study was to use motor unit coupling in the time and frequency domains to obtain evidence of changes in motoneuronal drive during walking in subjects with stroke. METHODS Paired tibialis anterior (TA) EMG activity was sampled during the swing phase of treadmill walking in eight subjects with unilateral stroke. RESULTS On the unaffected side, short-term synchronization was evident from the presence of a narrow central peak in cumulant densities and from the presence of significant coherence between these signals in the 10-25 Hz band. Such indicators of short-term synchrony were either absent or very small on the affected side. Instead, pronounced 10 Hz coupling was observed. CONCLUSIONS It is suggested that reduced corticospinal drive to the spinal motoneurones is responsible for the reduced short-term synchrony and coherence in the 10-25 Hz frequency band on the affected side in hemiplegic patients during walking. SIGNIFICANCE This is of importance for understanding the mechanisms responsible for reduced gait ability and development of new strategies for gait restoration.