Evidence for a Supraspinal Contribution to the Human Crossed Reflex Response During Human Walking

International audienceIn humans, an ipsilateral tibial nerve (iTN) stimulation elicits short-latency-crossed-responses (SLCR) comprised of two bursts in the contralateral gastrocnemius lateralis (cGL) muscle. The average onset latency has been reported to be 57–69 ms with a duration of 30.4 ± 6.6 ms. The aim of this study was to elucidate if a transcortical pathway contributes to the SLCR. In Experiment 1 (n = 9), single pulse supra-threshold transcranial magnetic stimulation (supraTMS) was applied alone or in combination with iTN stimulation (85% of the maximum M-wave) while participants walked on a treadmill (delay between the SLCR and the motor evoked potentials (MEP) varied between −30 and 200 ms). In Experiment 2 (n = 6), single pulse sub-threshold TMS (subTMS) was performed and the interstimulus interval (ISI) varied between 0–30 ms. In Experiment 3, somatosensory evoked potentials (SEPs) were recorded during the iTN stimulation to quantify the latency of the resulting afferent volley at the cortical level. SLCRs and MEPs in cGL occurred at 63 ± 6 ms and 29 ± 2 ms, respectively. The mean SEP latency was 30 ± 3 ms. Thus, a transcortical pathway could contribute no earlier than 62–69 ms (SEP+MEP+central-processing-delay) after iTN stimulation. Combined iTN stimulation and supraTMS resulted in a significant MEP extra-facilitation when supraTMS was timed so that the MEP would coincide with the late component of the SLCR, while subTMS significantly depressed this component. This is the first study that demonstrates the existence of a strong cortical control on spinal pathways mediating the SLCR. This likely serves to enhance flexibility, ensuring that the appropriate output is produced in accord with the functional demand

Absence of hyperexcitability of spinal motoneurons in patients with amyotrophic lateral sclerosis

International audienceExperimental models have primarily revealed spinal motoneuron hypoexcitability in amyotrophic lateral sclerosis (ALS), which is contentious considering the role of glutamate-induced excitotoxicity in neurodegeneration and clinical features rather supporting hyperexcitability. This phenomenon was evaluated in human patients by investigating changes in motor unit firing during contraction and relaxation. Twenty-two ALS patients with subtle motor deficits and 28 controls performed tonic contractions of extensor carpi radialis, triceps brachialis, tibialis anterior and quadriceps, aiming to isolate a low-threshold unit (U1) on the electromyogram (EMG). Subsequently, they performed a stronger contraction or tendon vibration was delivered, to recruit higher threshold unit (U2) for 10 s before they relaxed progressively. EMG and motor unit potential analyses suggest altered neuromuscular function in all muscles, including those with normal strength (Medical Research Council score at 5). During the preconditioning tonic phase, U1 discharge frequency did not differ significantly between groups. During recruitment, the increase in U1 frequency (∆F-R) was comparable between groups both during contraction and tendon vibration. During derecruitment, the decrease in U1 frequency (∆F-D) was reduced in ALS regardless of the recruitment mode, particularly for ∆F-R <8 Hz in the upper limbs, consistent with the muscle weakness profile of the group. ∆F-D was associated with functional disability and its reduction was more pronounced in patients with more rapid disease progression rate. This in vivo study has demonstrated reduced motoneuron capacity for self-sustained discharge, and further supports that motoneurons are normo- to hypoexcitable in ALS patients, similar to observations in experimental models

Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations

Exploring different movement sonification strategies for rehabilitation in clinical settings

International audienceWe describe an interactive system that allows for sonifying arm movements. The aim is to support stroke patients going through rehabilitation by providing them with augmented auditory feedback that reacts to their movements. The system is based on IMU sensors (Inertial Measurements Unit) attached to each arm. The movement data are streamed in real-time to a laptop computer that generates various sounds or musical interactions using a program we developed. We tested different types of auditory feedback, each of them using a specific strategy for the sound-movement mapping. The first type of movement-sound mappings is based on direct relationships between the reaching distance and either the pitch of a continuous tone, or the tempo of a regular beat pattern. The second type of mapping is music-oriented: the user movement allows for controlling the tempo of musical pieces. The third type of mapping associates the hand position to specific environmental sounds. We report here on the technical system along with preliminary results in a clinical setting with both post-stroke patients and healthy users. CCS CONCEPTS • Human-centered computing → Sound-based input / output; Auditory feedback; Gestural input; Usability testing; Interaction devices

Transient increase in recurrent inhibition in amyotrophic lateral sclerosis as a putative protection from neurodegeneration

International audienceAim: Adaptive mechanisms in spinal circuits are likely involved in homeostatic responses to maintain motor output in amyotrophic lateral sclerosis. Given the role of Renshaw cells in regulating the motoneuron input/output gain, we investigated the modulation of heteronymous recurrent inhibition.Methods: Electrical stimulations were used to activate recurrent collaterals resulting in the Hoffmann reflex depression. Inhibitions from soleus motor axons to quadriceps motoneurons, and vice versa, were tested in 38 patients and matched group of 42 controls.Results: Compared to controls, the mean depression of quadriceps reflex was larger in patients while that of soleus was smaller suggesting that heteronymous recurrent inhibition was enhanced in quadriceps but reduced in soleus. The modulation of recurrent inhibition was linked to the size of maximal direct motor response and lower limb dysfunctions suggesting a significant relationship with the integrity of the target motoneuron pool and functional abilities. No significant link was found between the integrity of motor axons activating Renshaw cells and the level of inhibition. Enhanced inhibition was particularly observed in patients within the first year after symptom onset and with slow progression of lower limb dysfunctions. Normal or reduced inhibitions were mainly observed in patients with motor weakness first in lower limbs and greater dysfunctions in lower limbs.Conclusion: We provide the first evidence for enhanced recurrent inhibition and speculate that Renshaw cells might have transient protective role on motoneuron by counteracting hyperexcitability at early stages. Several mechanisms likely participate including cortical influence on Renshaw cell and reinnervation by slow motoneurons

Corticospinal control from M1 and PMv areas on inhibitory cervical propriospinal neurons in humans

International audienceInhibitory propriospinal neurons with diffuse projections onto upper limb motoneurons have been revealed in humans using peripheral nerve stimulation. This system is supposed to mediate descending inhibition to motoneu-rons, to prevent unwilling muscle activity. However, the corticospinal control onto inhibitory propriospinal neurons has never been investigated so far in humans. We addressed the question whether inhibitory cervical propriospinal neurons receive corticospinal inputs from primary motor (M1) and ventral premotor areas (PMv) using spatial facilitation method. We have stimulated M1 or PMv using transcranial magnetic stimulation (TMS) and/or median nerve whose afferents are known to activate inhibitory propriospinal neurons. Potential input convergence was evaluated by studying the change in monosy-naptic reflexes produced in wrist extensor electromyogram (EMG) after isolated and combined stimuli in 17 healthy subjects. Then, to determine whether PMv controlled propriospinal neurons directly or through PMv-M1 interaction, we tested the connectivity between PMv and propriospinal neu-rons after a functional disruption of M1 produced by paired continuous theta burst stimulation (cTBS). TMS over M1 or PMv produced reflex inhibition significantly stronger on combined stimulations, compared to the algebraic sum of effects induced by isolated stimuli. The extra-inhibition induced by PMv stimulation remained even after cTBS which depressed M1 excitability. The extra-inhibition suggests the existence of input convergence between peripheral afferents and corticospinal inputs onto inhibitory propriospinal neurons. Our results support the existence of direct descending influence from M1 and PMv onto inhibitory propriospinal neurons in humans, possibly though direct corticospinal or via reticulospinal inputs

Effects of Hand Configuration on the Grasping, Holding, and Placement of an Instrumented Object in Patients With Hemiparesis

International audienceObjective: Limitations with manual dexterity are an important problem for patients suffering from hemiparesis post stroke. Sensorimotor deficits, compensatory strategies and the use of alternative grasping configurations may influence the efficiency of prehensile motor behavior. The aim of the present study is to examine how different grasp configurations affect patient ability to regulate both grip forces and object orientation when lifting, holding and placing an object.Methods: Twelve stroke patients with mild to moderate hemiparesis were recruited. Each was required to lift, hold and replace an instrumented object. Four different grasp configurations were tested on both the hemiparetic and less affected arms. Load cells from each of the 6 faces of the instrumented object and an integrated inertial measurement unit were used to extract data regarding the timing of unloading/loading phases, regulation of grip forces, and object orientation throughout the task.Results: Grip forces were greatest when using a palmar-digital grasp and lowest when using a top grasp. The time delay between peak acceleration and maximum grip force was also greatest for palmar-digital grasp and lowest for the top grasp. Use of the hemiparetic arm was associated with increased duration of the unloading phase and greater difficulty with maintaining the vertical orientation of the object at the transitions to object lifting and object placement. The occurrence of touch and push errors at the onset of grasp varied according to both grasp configuration and use of the hemiparetic arm.Conclusion: Stroke patients exhibit impairments in the scale and temporal precision of grip force adjustments and reduced ability to maintain object orientation with various grasp configurations using the hemiparetic arm. Nonetheless, the timing and magnitude of grip force adjustments may be facilitated using a top grasp configuration. Conversely, whole hand prehension strategies compound difficulties with grip force scaling and inhibit the synchrony of grasp onset and object release

Corticospinal control from M1 and PMv areas on inhibitory cervical propriospinal neurons in humans

International audienceInhibitory propriospinal neurons with diffuse projections onto upper limb motoneurons have been revealed in humans using peripheral nerve stimulation. This system is supposed to mediate descending inhibition to motoneu-rons, to prevent unwilling muscle activity. However, the corticospinal control onto inhibitory propriospinal neurons has never been investigated so far in humans. We addressed the question whether inhibitory cervical propriospinal neurons receive corticospinal inputs from primary motor (M1) and ventral premotor areas (PMv) using spatial facilitation method. We have stimulated M1 or PMv using transcranial magnetic stimulation (TMS) and/or median nerve whose afferents are known to activate inhibitory propriospinal neurons. Potential input convergence was evaluated by studying the change in monosy-naptic reflexes produced in wrist extensor electromyogram (EMG) after isolated and combined stimuli in 17 healthy subjects. Then, to determine whether PMv controlled propriospinal neurons directly or through PMv-M1 interaction, we tested the connectivity between PMv and propriospinal neu-rons after a functional disruption of M1 produced by paired continuous theta burst stimulation (cTBS). TMS over M1 or PMv produced reflex inhibition significantly stronger on combined stimulations, compared to the algebraic sum of effects induced by isolated stimuli. The extra-inhibition induced by PMv stimulation remained even after cTBS which depressed M1 excitability. The extra-inhibition suggests the existence of input convergence between peripheral afferents and corticospinal inputs onto inhibitory propriospinal neurons. Our results support the existence of direct descending influence from M1 and PMv onto inhibitory propriospinal neurons in humans, possibly though direct corticospinal or via reticulospinal inputs