Daniel Cattaert

Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.

We showed recently that a novel prosthesis control, based on natural arm movement reconstructed from an Artificial Neural Network (ANN) that receives movement goal and stump motion as inputs, enables close-to-natural reaching control in Virtual Reality (VR). Here, we applied and tested this control in the physical world using first-person teleoperation of Reachy2, an open-source humanoid robot made by Pollen Robotics that ranked 2nd at ANA Avatar XPRIZE. Direct teleoperation reproducing all arm joints of able-bodied participants (n=14) elicited a 100% success rate for grasping objects at various locations, with best possible usability scores and small workload scores. High success rates (>92%) were also obtained when all distal joints from the elbow onward were operated with the novel prosthesis control, using a movement goal identified through gaze-guided computer vision. While usability and workload scores were slightly degraded when able-bodied participants used the prosthesis control as compared to direct teleoperation, both were scored similarly well by a sample from our target population (n=8 participants with transhumeral limb loss). This platform and control schemes offer broad perspectives for prosthesis control, but also for teleoperation robotics and human-robot interactions.

During rapid voluntary elbow movement on horizontal plane, a stereotyped triphasic pattern is typically observed in the electromyograms (EMGs) of antagonistic muscles acting at this joint. To explain the origin of such triphasic commands, two types of theories have been proposed. Peripheral theories consider that triphasic commands result from sensorimotor spinal networks, either through a combination of reflexes or through a spinal central pattern generator. Central theories consider that the triphasic command is elaborated in the brain. Although both theories were partially supported by physiological data, there is still no consensus about how exactly triphasic commands are elaborated. Moreover, capacities of simple spinal sensorimotor circuits to elaborate triphasic commands on their own have not been tested yet. In order to test this, we modelled arm musculoskeletal system operating in the absence of gravity, muscle activation dynamics, proprioceptive spindle and Golgi afferent activities and spinal sensorimotor circuits. Step commands were designed to modify the activity of spinal neurons and the strength of their synapses, either to prepare (SET) the network before movement onset, or to launch the movement (GO). Since these step commands do not contain any dynamics, changes in muscle activities responsible for arm movement rest entirely upon interactions between the spinal network and the musculoskeletal system. Critically, we selected step commands using a Goal Exploration Process inspired from baby babbling during development. In this task, the Goal Exploration Process proved very efficient at discovering step commands that enabled spinal circuits to handle a broad spectrum of functional behaviors, displayed in a behavioral space characterized by movement amplitude and maximal speed. All over the behavioral space, specific SET and GO commands elicited natural triphasic commands, thereby substantiating the inherent capacity of the spinal network in generating them.

Traditional myoelectric controls of trans-humeral prostheses fail to provide intuitive coordination of the necessary degrees of freedom. We previously showed that by using artificial neural network predictions to reconstruct distal joints, based on the shoulder posture and movement goals (i.e., position and orientation of the targeted object), participants were able to position and orient an avatar hand to grasp objects with natural arm performances. However, this control involved rapid and unintended prosthesis movements at each modification of the movement goal, impractical for real-life scenarios. Here, we eliminate this abrupt change using novel methods based on an angular trajectory, determined from the speed of stump movement and the gap between the current and the ‘goal’ distal configurations. These new controls are tested offline and online (i.e., involving participants-in-the-loop) and compared to performances obtained with a natural control. Despite a slight increase in movement time, the new controls allowed twelve valid participants and six participants with trans-humeral limb loss to reach objects at various positions and orientations without prior training. Furthermore, no usability or workload degradation was perceived by participants with upper limb disabilities. The good performances achieved highlight the potential acceptability and effectiveness of those controls for our target population.

Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1^G93A ALS mouse model at a late pre‐symptomatic stage (10–12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild‐type (WT) and decreased excitability in SOD1^G93A animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst‐induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2–P1) from the deeper layers. In SOD1^G93A mice, stress did not affect N1 but suppressed the N2–P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1^G93A mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress‐induced activity changes in M1 may therefore influence ALS outcomes. image Key points: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions. Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1^G93A ALS mouse model) vs. physiological (wild‐type) conditions. The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress‐induced motor cortex changes because it may be of importance when evaluating ALS outcomes.

Amyotrophic lateral sclerosis (ALS) is a fatal adult‐onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1^G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (R_in) E17.5 MNs from the SOD1^G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild‐type (WT) MNs with low R_in was inhibited by incoming dGPSPs, whereas low R_in SOD1^G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD‐like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri‐somatic inhibitory terminals in SOD1^G93A MNs compared to WT littermates. Putative fast ALS‐vulnerable MNs with low R_in are therefore lacking functional inhibition at the near‐term prenatal stage. image Key points: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low R_in lack functional inhibition at the near‐term stage.

During rapid voluntary limb movement about a single joint, a stereotyped triphasic pattern is typically observed in the electromyograms (EMGs) of antagonistic muscles acting at this joint. To explain the origin of such triphasic commands, two types of theories have been proposed. Peripheral theories consider that triphasic commands result from sensorimotor spinal networks, either through a combination of reflexes or through a spinal central pattern generator. Central theories consider that the triphasic command is elaborated in the brain. Although both theories were partially supported by physiological data, there is still no consensus about how exactly triphasic commands are elaborated. Moreover, capacities of simple spinal sensorimotor circuits to elaborate triphasic commands on their own have not been tested yet. In order to test this, we modelled arm musculoskeletal system, muscle activation dynamics, proprioceptive spindle and Golgi afferent activities and spinal sensorimotor circuits. Step commands were designed to modify the activity of spinal neurons and the strength of their synapses, either to prepare (SET) the network before movement onset, or to launch the movement (GO). Since these step commands do not contain any dynamics, changes in muscle activities responsible for arm movement rest entirely upon interactions between the spinal network and the musculo-skeletal system. Critically, we selected step commands using a Goal Exploration Process inspired from baby babbling during development. In this task, the Goal Exploration Process proved very efficient at discovering step commands that enabled spinal circuits to handle a broad spectrum of functional behaviors, displayed in a behavioral space characterized by movement amplitude and maximal speed. All over the behavioral space, specific SET and GO commands elicited natural triphasic commands, thereby substantiating the inherent capacity of the spinal network in generating them. Key points Summary: Spinal sensorimotor circuits, despite extensive physiological analyses, remain poorly understood in the context of voluntary movement. This study models the capabilities of these spinal networks, alongside musculoskeletal dynamics, to achieve single-joint arm flexion following minimum jerk principles. Preparatory (SET) and launch (GO) step commands modulate spinal network states, including neuron activity and synaptic strength. Notably, arm movement results from sensorimotor interactions within spinal circuits, even with basic step commands that have no dynamics. A Goal Exploration Process (GEP), inspired by developmental baby babbling through trial and error, was used to refine step commands. The spinal networks, when in appropriate states, were shown to spontaneously generate triphasic commands across a broad range of valid movement amplitudes and speeds. These findings highlight the intrinsic capacity of spinal sensorimotor circuits to manage complex movement dynamics, offering novel testable insights as to their possible functional role in voluntary motor control.

Impressive progress is being made in bionic limbs design and control. Yet, controlling the numerous joints of a prosthetic arm necessary to place the hand at a correct position and orientation to grasp objects remains challenging. Here, we designed an intuitive, movement-based prosthesis control that leverages natural arm coordination to predict distal joints missing in people with transhumeral limb loss based on proximal residual limb motion and knowledge of the movement goal. This control was validated on 29 participants, including seven with above-elbow limb loss, who picked and placed bottles in a wide range of locations in virtual reality, with median success rates over 99% and movement times identical to those of natural movements. This control also enabled 15 participants, including three with limb differences, to reach and grasp real objects with a robotic arm operated according to the same principle. Remarkably, this was achieved without any prior training, indicating that this control is intuitive and instantaneously usable. It could be used for phantom limb pain management in virtual reality, or to augment the reaching capabilities of invasive neural interfaces usually more focused on hand and grasp control.

Impressive progress is being made in bionic limbs design and control. Yet, controlling the numerous joints of a prosthetic arm necessary to place the hand at a correct position and orientation to grasp objects remains challenging. Here, we designed an intuitive, movement-based prosthesis control that leverages natural arm coordination to predict distal joints missing in people with transhumeral limb loss based on proximal residual limb motion and knowledge of the movement goal. This control was validated on 29 participants, including seven with above-elbow limb loss, who picked and placed bottles in a wide range of locations in virtual reality, with median success rates over 99% and movement times identical to those of natural movements. This control also enabled 15 participants, including three with limb differences, to reach and grasp real objects with a robotic arm operated according to the same principle. Remarkably, this was achieved without any prior training, indicating that this control is intuitive and instantaneously usable. It could be used for phantom limb pain management in virtual reality, or to augment the reaching capabilities of invasive neural interfaces usually more focused on hand and grasp control.

Impressive progress is being made in bionic limbs design and control. Yet, controlling the numerous joints of a prosthetic arm necessary to place the hand at a correct position and orientation to grasp objects remains challenging. Here, we designed an intuitive, movement-based prosthesis control that leverages natural arm coordination to predict distal joints missing to people with transhumeral limb loss based on proximal residual limb motion and knowledge of the movement goal. This control was validated on 29 participants, including 7 with above-elbow limb loss, who picked and placed bottles in a wide range of locations in virtual reality, with median success rates over 99% and movement times identical to those of natural movements. This control also enabled 15 participants, including 3 with limb difference, to reach and grasp real objects with a robotic arm operated according to the same principle. Remarkably, this was achieved without any prior training, indicating that this control is intuitive and instantaneously usable. It could be used for phantom limb pain management in virtual reality, or to augment reaching capabilities of invasive neural interfaces usually more focused on hand and grasp control.