A virtual reality platform to evaluate the effects of supernumerary limbs' appearance.

Supernumerary robot limbs (SL) can expand the ability of users by increasing the number of degrees of freedom that they control. While several SLs have been designed and tested on human participants, the effect of the limb's appearance on the user's acceptance, embodiment and device usage is not yet understood. We developed a virtual reality platform with a three-arm avatar that enabled us to systematically investigate the effect of the supernumerary limb's appearance on their perception and motion control performance. A pilot study with 14 participants exhibited similar performance, workload and preference in human-like or robot-like appearance with a trend of preference for the robotic appearance.

Dissociating haptic feedback from physical assistance does not improve motor performance.

In robots for motor rehabilitation and sports training, haptic assistance typically provides both mechanical guidance and task-relevant information. With the natural human tendency to minimise metabolic cost, mechanical guidance may however prevent efficient short term learning and retention. In this work, we explore the effect of providing haptic feedback to the not active hand during a tracking task. We test four types of haptic feedback: task- or error-related information, no information and irrelevant information. The results show that feedback provided to the hand not carrying out the tracking task did not improve task performance. However, irrelevant information to the task worsened performance, and negatively influenced the participants' perception of helpfulness, assistance, likability and predictability.

Redundancy Resolution in Trimanual vs. Bimanual Tracking Tasks.

Supernumerary limbs promise to allow users to perform complex tasks that would otherwise require the actions of teams. However, how the user's capability for multimanual coordination compares to bimanual coordination, and how the motor system decides to configure its limb contributions given task redundancy is unclear. We conducted bimanual and trimanual (with the foot as a third-hand controller) virtual reality visuomotor tracking experiments to study how 32 healthy participants changed their limb coordination in response to uninstructed cursor mapping changes. This used a shared cursor mapped to the average limbs' position for different limb combinations. The results show that most participants correctly identified the different mappings during bimanual tracking, and accordingly minimized task-irrelevant motion. Instead during trimanual coordination, participants consistently moved all three limbs concurrently, showing weaker ipsilateral hand-foot coordination. These findings show how redundancy resolution and the resulting coordination patterns differ between similar bimanual and trimanual tasks. Further research is needed to consider the effect of learning on coordination behaviour.

The Impact of Stiffness in Bimanual Versus Dyadic Interactions Requiring Force Exchange.

During daily activities, humans routinely manipulate objects bimanually or with the help of a partner. This work explored how bimanual and dyadic coordination modes are impacted by the object's stiffness, which conditions inter-limb haptic communication. For this, we recruited 20 healthy participants who performed a virtual task inspired by object handling, where we looked at the initiation of force exchange and its continued maintenance while tracking. Our findings suggest that while individuals and dyads displayed different motor behaviours, which may stem from the dyad members' need to estimate their partner's actions, they exhibited similar tracking accuracy. For both coordination modes, increased stiffness resulted in better tracking accuracy and more correlated motions, but required a larger effort through increased average torque. These results suggest that stiffness may be a key consideration in applications such as rehabilitation, where bimanual or external physical assistance is often provided.

Object Recognition Using Mechanical Impact, Viscoelasticity, and Surface Friction During Interaction.

Current robotic haptic object recognition relies on statistical measures derived from movement dependent interaction signals such as force, vibration or position. Mechanical properties, which can be estimated from these signals, are intrinsic object properties that may yield a more robust object representation. Therefore, this paper proposes an object recognition framework using multiple representative mechanical properties: stiffness, viscosity and friction coefficient as well as the coefficient of restitution, which has been rarely used to recognise objects. These properties are estimated in real-time using a dual Kalman filter (without tangential force measurements) and then are used for object classification and clustering. The proposed framework was tested on a robot identifying 20 objects through haptic exploration. The results demonstrate the technique's effectiveness and efficiency, and that all four mechanical properties are required for the best recognition rate of 98.18 ± 0.424%. For object clustering, the use of these mechanical properties also results in superior performance when compared to methods based on statistical parameters.

How virtual and mechanical coupling impact bimanual tracking.

Bilateral training systems look to promote the paretic hand's use in individuals with hemiplegia. Although this is normally achieved using mechanical coupling (i.e., a physical connection between the hands), a virtual reality system relying on virtual coupling (i.e., through a shared virtual object) would be simpler to use and prevent slacking. However, it is not clear whether different coupling modes differently impact task performance and effort distribution between the hands. We explored how 18 healthy right-handed participants changed their motor behaviors in response to the uninstructed addition of mechanical coupling, and virtual coupling using a shared cursor mapped to the average hands' position. In a second experiment, we then studied the impact of connection stiffness on performance, perception, and effort imbalance. The results indicated that both coupling types can induce the hands to actively contribute to the task. However, the task asymmetry introduced by using a cursor mapped to either the left or right hand only modulated the hands' contribution when not mechanically coupled. The tracking performance was similar for all coupling types, independent of the connection stiffness, although the mechanical coupling was preferred and induced the hands to move with greater correlation. These findings suggest that virtual coupling can induce the hands to actively contribute to a task in healthy participants without hindering their performance. Further investigation on the coupling types' impact on the performance and hands' effort distribution in patients with hemiplegia could allow for the design of simpler training systems that promote the affected hand's use.NEW & NOTEWORTHY We showed that the uninstructed addition of a virtual and/or a mechanical coupling can induce both hands to actively contribute in a continuous redundant bimanual tracking task without impacting performance. In addition, we showed that the task asymmetry can only alter the effort distribution when the hands are not connected, independent of the connection stiffness. Our findings suggest that virtual coupling could be used in the development of simpler VR-based training devices.

Can Training Make Three Arms Better Than Two Heads for Trimanual Coordination?

Supernumerary effectors have been proposed to enable users to perform tasks alone that normally require assistance from a partner. While various supernumerary robotic limbs have been developed in the last decade, the capability of users to operate them effectively has not yet been proven. Here we tested whether users (i) can complete a task that requires simultaneous and fine control of three effectors, and (ii) can be trained to do so with similar or superior performance as through collaboration with a human partner. As in previous studies, initial augmented capability was less than that of working with a partner. However, one hour of dedicated solo trimanual training across three days significantly increased task performance, so that participants became able to perform trimanual control alone as well as or better than they could with a new partner. This shows the viability of augmentation systems for applications such as in robotic surgery or industrial assembly, which can be further validated on real tasks with physical systems.

Interaction with a reactive partner improves learning in contrast to passive guidance.

Many tasks such as physical rehabilitation, vehicle co-piloting or surgical training, rely on physical assistance from a partner. While this assistance may be provided by a robotic interface, how to implement the necessary haptic support to help improve performance without impeding learning is unclear. In this paper, we study the influence of haptic interaction on the performance and learning of a shared tracking task. We compare in a tracking task the interaction with a human partner, the trajectory guidance traditionally used in training robots, and a robot partner yielding human-like interaction. While trajectory guidance resulted in the best performance during training, it dramatically reduced error variability and hindered learning. In contrast, the reactive human and robot partners did not impede the adaptation and allowed the subjects to learn without modifying their movement patterns. Moreover, interaction with a human partner was the only condition that demonstrated an improvement in retention and transfer learning compared to a subject training alone. These results reveal distinctly different learning behaviour in training with a human compared to trajectory guidance, and similar learning between the robotic partner and human partner. Therefore, for movement assistance and learning, algorithms that react to the user's motion and change their behaviour accordingly are better suited.

Lateralization of Impedance Control in Dynamic Versus Static Bimanual Tasks.

In activities of daily living that require bimanual coordination, humans often assign a role to each hand. How do task requirements affect this role assignment? To address this question, we investigated how healthy right-handed participants bimanually manipulated a static or dynamic virtual object using wrist flexion/extension while receiving haptic feedback through the interacting object's torque. On selected trials, the object shook strongly to destabilize the bimanual grip. Our results show that participants reacted to the shaking by increasing their wrist co-contraction. Unlike in previous work, handedness was not the determining factor in choosing which wrist to co-contract to stabilize the object. However, each participant preferred to co-contract one hand over the other, a choice that was consistent for both the static and dynamic objects. While role allocation did not seem to be affected by task requirements, it may have resulted in different motor behaviours as indicated by the changes in the object torque. Further investigation is needed to elucidate the factors that determine the preference in stabilizing with either the dominant or non-dominant hand.

Human Performance of Three Hands in Unimanual, Bimanual and Trimanual Tasks.

Trimanual operation using a robotic supernumerary limb is a new and challenging mechanism for human operators that could enable a single user to perform tasks requiring more than two hands. Foot-controlled interfaces have previously proven able to be intuitively controlled, enabling simple tasks to be performed. However, the effect of going from unimanual to bimanual and then to trimanual tasks on subjects performance and coordination is not well understood. In this paper, unimanual, bimanual and trimanual teleoperation tasks were performed in a virtual reality scene to evaluate the impact of extending to trimanual actions. 15 participants were required to move their limbs together in a coordinated reaching activity. The results show that the addition of another hand resulted in an increase in operating time, where the time increased in going from unimanual to bimanual operation and then increased further when going from bimanual to trimanual. Moreover, the success rate for performing bimanual and trimanual tasks was strongly influenced by the subject's performance in ipsilateral hand-foot activities, where the ipsilateral combination had a lower success rate than contralateral limbs. The addition of a hand did not affect any two-hand coordination rate and even in some cases reduced coordination deviations. Clinical relevance - This work can contribute to build efficient training and learning framework on human multiple limbs motion control and coordination for both rehabilitation and augmentation.

The control and training of single motor units in isometric tasks are constrained by a common input signal.

Recent developments in neural interfaces enable the real-time and non-invasive tracking of motor neuron spiking activity. Such novel interfaces could provide a promising basis for human motor augmentation by extracting potentially high-dimensional control signals directly from the human nervous system. However, it is unclear how flexibly humans can control the activity of individual motor neurons to effectively increase the number of degrees of freedom available to coordinate multiple effectors simultaneously. Here, we provided human subjects (N = 7) with real-time feedback on the discharge patterns of pairs of motor units (MUs) innervating a single muscle (tibialis anterior) and encouraged them to independently control the MUs by tracking targets in a 2D space. Subjects learned control strategies to achieve the target-tracking task for various combinations of MUs. These strategies rarely corresponded to a volitional control of independent input signals to individual MUs during the onset of neural activity. Conversely, MU activation was consistent with a common input to the MU pair, while individual activation of the MUs in the pair was predominantly achieved by alterations in de-recruitment order that could be explained by history-dependent changes in motor neuron excitability. These results suggest that flexible MU recruitment based on independent synaptic inputs to single MUs is unlikely, although de-recruitment might reflect varying inputs or modulations in the neuron's intrinsic excitability.

Principles of human movement augmentation and the challenges in making it a reality.

Augmenting the body with artificial limbs controlled concurrently to one's natural limbs has long appeared in science fiction, but recent technological and neuroscientific advances have begun to make this possible. By allowing individuals to achieve otherwise impossible actions, movement augmentation could revolutionize medical and industrial applications and profoundly change the way humans interact with the environment. Here, we construct a movement augmentation taxonomy through what is augmented and how it is achieved. With this framework, we analyze augmentation that extends the number of degrees-of-freedom, discuss critical features of effective augmentation such as physiological control signals, sensory feedback and learning as well as application scenarios, and propose a vision for the field.

Perception and Performance of Electrical Stimulation for Proprioception.

Proprioception, yielding awareness of the body's position and motion in space, is typically lacking in prostheses and supernumerary limbs. Electrical stimulation is one technique that may provide these devices with proprioception. This paper first investigates how the modalities of electrotactile cues, such as frequency and intensity, are perceived. Using the results, we designed and compared several comfortable and perceptible feedback mappings for spatial cues. Two experiments were conducted using a 16-electrode bracelet worn above the elbow to provide electrical stimuli. We found that subjects could localize the stimulating electrode with a precision of ±1 electrode (110 mm) in all feedback conditions. Moreover, within the range of pulse intensities perceived as comfortable, the participants' performance was more sensitive to changes in frequency than in intensity. The highest performance was obtained for the condition which increased both intensity and frequency with radial distance. These results suggest that electrical stimulation can be used for artificial proprioceptive feedback, which can ensure a comfortable and intuitive interaction and provides high spatial accuracy.

An eye tracking based virtual reality system for use inside magnetic resonance imaging systems.

Patients undergoing Magnetic Resonance Imaging (MRI) often experience anxiety and sometimes distress prior to and during scanning. Here a full MRI compatible virtual reality (VR) system is described and tested with the aim of creating a radically different experience. Potential benefits could accrue from the strong sense of immersion that can be created with VR, which could create sense experiences designed to avoid the perception of being enclosed and could also provide new modes of diversion and interaction that could make even lengthy MRI examinations much less challenging. Most current VR systems rely on head mounted displays combined with head motion tracking to achieve and maintain a visceral sense of a tangible virtual world, but this technology and approach encourages physical motion, which would be unacceptable and could be physically incompatible for MRI. The proposed VR system uses gaze tracking to control and interact with a virtual world. MRI compatible cameras are used to allow real time eye tracking and robust gaze tracking is achieved through an adaptive calibration strategy in which each successive VR interaction initiated by the subject updates the gaze estimation model. A dedicated VR framework has been developed including a rich virtual world and gaze-controlled game content. To aid in achieving immersive experiences physical sensations, including noise, vibration and proprioception associated with patient table movements, have been made congruent with the presented virtual scene. A live video link allows subject-carer interaction, projecting a supportive presence into the virtual world.

Short Time Delay Does Not Hinder Haptic Communication Benefits.

Haptic communication, the exchange of force and tactile information during dancing or moving a table together, has been shown to benefit the performance of human partners. Similarly, it could also be used to improve the performance of robots working in contact with a human operator. As we move to more robot integrated workspaces, how common network features such as delay or jitter impact haptic communication need to be better understood. Here using a human-like interactive robotic controller, that has been found to be indistinguishable by humans to human interaction, we evaluate how subjects' performance and perception is altered by varying levels of transmission delay. We find that subjects are able to recognise haptic delay at very small levels within haptic interaction. However, while they are consciously aware of the delay they can only compensate for it up until a certain point, after which they perceive it as the addition of noise/impedance into the system.

For Motion Assistance Humans Prefer to Rely on a Robot Rather Than on an Unpredictable Human.

Objective: The last decades have seen a surge of robots for physical training and work assistance. How to best control these interfaces is unknown, although arguably the interaction should be similar to human movement assistance. Methods: We compare the behaviour and assessment of subjects tracking a moving target with assistance from (i) trajectory guidance (as typically used in robots for physical training), (ii) a human partner, and (iii) the reactive robot partner of Takagi et al. Results: Trajectory guidance was recognised as robotic, while the robot partner was felt as human-like. However, trajectory guidance was preferred to assistance from a human partner, which was recognised as less predictable. The robot partner also was felt to be more predictable and helpful than a human partner, and was preferred. Conclusions: While subjects like to rely on predictable interaction, such as in trajectory guidance, the control reactivity of the robot partner is essential for perceiving an interaction as human-like.

Discovery of AZD3147: a potent, selective dual inhibitor of mTORC1 and mTORC2.

High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC50-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.

SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors.

A novel series of 5-aminopyrimidinyl quinazolines has been developed from anilino-quinazoline 1, which was identified in a high throughput screen for Aurora A. Introduction of the pyrimidine ring and optimisation of the substituents both on this ring and at the C7 position of the quinazoline led to the discovery of compounds that are highly specific Aurora kinase inhibitors. Co-crystallisation of one of these inhibitors with a fragment of Aurora A shows the importance of the benzamido group in achieving selectivity.