Modality-Independent Effect of Gravity in Shaping the Internal Representation of 3D Space for Visual and Haptic Object Perception.

Visual and haptic perceptions of 3D shape are plagued by distortions, which are influenced by nonvisual factors, such as gravitational vestibular signals. Whether gravity acts directly on the visual or haptic systems or at a higher, modality-independent level of information processing remains unknown. To test these hypotheses, we examined visual and haptic 3D shape perception by asking male and female human subjects to perform a "squaring" task in upright and supine postures and in microgravity. Subjects adjusted one edge of a 3D object to match the length of another in each of the three canonical reference planes, and we recorded the matching errors to obtain a characterization of the perceived 3D shape. The results show opposing, body-centered patterns of errors for visual and haptic modalities, whose amplitudes are negatively correlated, suggesting that they arise in distinct, modality-specific representations that are nevertheless linked at some level. On the other hand, weightlessness significantly modulated both visual and haptic perceptual distortions in the same way, indicating a common, modality-independent origin for gravity's effects. Overall, our findings show a link between modality-specific visual and haptic perceptual distortions and demonstrate a role of gravity-related signals on a modality-independent internal representation of the body and peripersonal 3D space used to interpret incoming sensory inputs.

Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells.

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.

How Tilting the Head Interferes With Eye-Hand Coordination: The Role of Gravity in Visuo-Proprioceptive, Cross-Modal Sensory Transformations.

To correctly position the hand with respect to the spatial location and orientation of an object to be reached/grasped, visual information about the target and proprioceptive information from the hand must be compared. Since visual and proprioceptive sensory modalities are inherently encoded in a retinal and musculo-skeletal reference frame, respectively, this comparison requires cross-modal sensory transformations. Previous studies have shown that lateral tilts of the head interfere with the visuo-proprioceptive transformations. It is unclear, however, whether this phenomenon is related to the neck flexion or to the head-gravity misalignment. To answer to this question, we performed three virtual reality experiments in which we compared a grasping-like movement with lateral neck flexions executed in an upright seated position and while lying supine. In the main experiment, the task requires cross-modal transformations, because the target information is visually acquired, and the hand is sensed through proprioception only. In the other two control experiments, the task is unimodal, because both target and hand are sensed through one, and the same, sensory channel (vision and proprioception, respectively), and, hence, cross-modal processing is unnecessary. The results show that lateral neck flexions have considerably different effects in the seated and supine posture, but only for the cross-modal task. More precisely, the subjects' response variability and the importance associated to the visual encoding of the information significantly increased when supine. We show that these findings are consistent with the idea that head-gravity misalignment interferes with the visuo-proprioceptive cross-modal processing. Indeed, the principle of statistical optimality in multisensory integration predicts the observed results if the noise associated to the visuo-proprioceptive transformations is assumed to be affected by gravitational signals, and not by neck proprioceptive signals per se. This finding is also consistent with the observation of otolithic projections in the posterior parietal cortex, which is involved in the visuo-proprioceptive processing. Altogether these findings represent a clear evidence of the theorized central role of gravity in spatial perception. More precisely, otolithic signals would contribute to reciprocally align the reference frames in which the available sensory information can be encoded.

Conservation of locomotion-induced oculomotor activity through evolution in mammals.

Efference copies are neural replicas of motor outputs used to anticipate the sensory consequences of a self-generated motor action or to coordinate neural networks involved in distinct motor behaviors.1 An established example of this motor-to-motor coupling is the efference copy of the propulsive motor command, which supplements classical visuo-vestibular reflexes to ensure gaze stabilization during amphibian larval locomotion.2 Such feedforward replica of spinal pattern-generating circuits produces a spino-extraocular motor coupled activity that evokes eye movements, spatiotemporally coordinated to tail undulation independently of any sensory signal.3,4 Exploiting the developmental stages of the frog,1 studies in metamorphing Xenopus demonstrated the persistence of this spino-extraocular motor command in adults and its developmental adaptation to tetrapodal locomotion.5,6 Here, we demonstrate for the first time the existence of a comparable locomotor-to-ocular motor coupling in the mouse. In neonates, ex vivo nerve recordings of brainstem-spinal cord preparations reveal a spino-extraocular motor coupled activity similar to the one described in Xenopus. In adult mice, trans-synaptic rabies virus injections in lateral rectus eye muscle label cervical spinal cord neurons closely connected to abducens motor neurons. Finally, treadmill-elicited locomotion in decerebrated preparations7 evokes rhythmic eye movements in synchrony with the limb gait pattern. Overall, our data are evidence for the conservation of locomotor-induced eye movements in vertebrate lineages. Thus, in mammals as in amphibians, CPG-efference copy feedforward signals might interact with sensory feedback to ensure efficient gaze control during locomotion.

Multisensory Integration in Stroke Patients: A Theoretical Approach to Reinterpret Upper-Limb Proprioceptive Deficits and Visual Compensation.

For reaching and grasping, as well as for manipulating objects, optimal hand motor control arises from the integration of multiple sources of sensory information, such as proprioception and vision. For this reason, proprioceptive deficits often observed in stroke patients have a significant impact on the integrity of motor functions. The present targeted review attempts to reanalyze previous findings about proprioceptive upper-limb deficits in stroke patients, as well as their ability to compensate for these deficits using vision. Our theoretical approach is based on two concepts: first, the description of multi-sensory integration using statistical optimization models; second, on the insight that sensory information is not only encoded in the reference frame of origin (e.g., retinal and joint space for vision and proprioception, respectively), but also in higher-order sensory spaces. Combining these two concepts within a single framework appears to account for the heterogeneity of experimental findings reported in the literature. The present analysis suggests that functional upper limb post-stroke deficits could not only be due to an impairment of the proprioceptive system per se, but also due to deficiencies of cross-references processing; that is of the ability to encode proprioceptive information in a non-joint space. The distinction between purely proprioceptive or cross-reference-related deficits can account for two experimental observations: first, one and the same patient can perform differently depending on specific proprioceptive assessments; and a given behavioral assessment results in large variability across patients. The distinction between sensory and cross-reference deficits is also supported by a targeted literature review on the relation between cerebral structure and proprioceptive function. This theoretical framework has the potential to lead to a new stratification of patients with proprioceptive deficits, and may offer a novel approach to post-stroke rehabilitation.

Long term visuo-vestibular mismatch in freely behaving mice differentially affects gaze stabilizing reflexes.

The vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) work synergistically to stabilize gaze in response to head movements. We previously demonstrated that a 14-day visuo-vestibular mismatch (VVM) protocol applied in freely behaving mice decreased the VOR gain. Here, we show for the first time that the OKR gain is also reduced and report on the recovery dynamics of both VOR and OKR after the end of the VVM protocol. Using sinusoidally-modulated stimulations, the decreases in VOR and OKR were found to be frequency-selective with larger reductions for frequencies < 0.5 Hz. Constant-velocity OKR stimulation tests demonstrated that the persistent components of the OKR were not modified while the transient, initial responses were. To identify the signals driving VOR and OKR reductions, we compared the responses of mice exposed to a high-contrast and no-contrast VVM. Despite being more robust in the high-contrast conditions, reductions were largely comparable and recovered with a similar time course. An analysis that directly compared VOR and OKR responses revealed that, alterations in the VOR were of significantly larger amplitude with significantly slower dynamics of recovery. Our findings are evidence for a frequency-selective influence of visual signals in the tuning of gaze stabilizing reflexes in normal mice.

Stabilization of Gaze during Early Xenopus Development by Swimming-Related Utricular Signals.

Locomotor maturation requires concurrent gaze stabilization improvement for maintaining visual acuity [1, 2]. The capacity to stabilize gaze, in particular in small aquatic vertebrates where coordinated locomotor activity appears very early, is determined by assembly and functional maturation of inner ear structures and associated sensory-motor circuitries [3-7]. Whereas utriculo-ocular reflexes become functional immediately after hatching [8, 9], semicircular canal-dependent vestibulo-ocular reflexes (VORs) appear later [10]. Thus, small semicircular canals are unable to detect swimming-related head oscillations, despite the fact that corresponding acceleration components are well-suited to trigger an angular VOR [11]. This leaves the utricle as the sole vestibular origin for swimming-related compensatory eye movements [12, 13]. We report a remarkable ontogenetic plasticity of swimming-related head kinematics and vestibular end organ recruitment in Xenopus tadpoles with beneficial consequences for gaze-stabilization. Swimming of older larvae generates sinusoidal head undulations with small, similar curvature angles on the left and right side that optimally activate horizontal semicircular canals. Young larvae swimming causes left-right head undulations with narrow curvatures and strong, bilaterally dissimilar centripetal acceleration components well suited to activate utricular hair cells and to substitute the absent semicircular canal function at this stage. The capacity of utricular signals to supplant semicircular canal function was confirmed by recordings of eye movements and extraocular motoneurons during off-center rotations in control and semicircular canal-deficient tadpoles. Strong alternating curvature angles and thus linear acceleration profiles during swimming in young larvae therefore represents a technically elegant solution to compensate for the incapacity of small semicircular canals to detect angular acceleration components.

No Gain No Pain: Relations Between Vestibulo-Ocular Reflexes and Motion Sickness in Mice.

Motion sickness occurs when the vestibular system is subjected to conflicting sensory information or overstimulation. Despite the lack of knowledge about the actual underlying mechanisms, several drugs, among which scopolamine, are known to prevent or alleviate the symptoms. Here, we aim at better understanding how motion sickness affects the vestibular system, as well as how scopolamine prevents motion sickness at the behavioral and cellular levels. We induced motion sickness in adult mice and tested the vestibulo-ocular responses to specific stimulations of the semi-circular canals and of the otoliths, with or without scopolamine, as well as the effects of scopolamine and muscarine on central vestibular neurons recorded on brainstem slices. We found that both motion sickness and scopolamine decrease the efficacy of the vestibulo-ocular reflexes and propose that this decrease in efficacy might be a protective mechanism to prevent later occurrences of motion sickness. To test this hypothesis, we used a behavioral paradigm based on visuo-vestibular interactions which reduces the efficacy of the vestibulo-ocular reflexes. This paradigm also offers protection against motion sickness, without requiring any drug. At the cellular level, we find that depending on the neuron, scopolamine can have opposite effects on the polarization level and firing frequency, indicating the presence of at least two types of muscarinic receptors in the medial vestibular nucleus. The present results set the basis for future studies of motion sickness counter-measures in the mouse model and offers translational perspectives for improving the treatment of affected patients.

The visual encoding of purely proprioceptive intermanual tasks is due to the need of transforming joint signals, not to their interhemispheric transfer.

To perform goal-oriented hand movement, humans combine multiple sensory signals (e.g., vision and proprioception) that can be encoded in various reference frames (body centered and/or exo-centered). In a previous study (Tagliabue M, McIntyre J. PLoS One 8: e68438, 2013), we showed that, when aligning a hand to a remembered target orientation, the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due 1) to the necessity of transferring sensory information across the brain hemispheres, or 2) to the necessity, due to the arms' anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other. To answer this question, we asked subjects to perform purely proprioceptive tasks in different conditions: Intra, the same arm sensing the target and performing the movement; Inter/Parallel, one arm sensing the target and the other reproducing its orientation; and Inter/Mirror, one arm sensing the target and the other mirroring its orientation. Performance was very similar between Intra and Inter/Mirror (conditions not requiring joint-signal transformations), while both differed from Inter/Parallel. Manipulation of the visual scene in a virtual reality paradigm showed visual encoding of proprioceptive information only in the latter condition. These results suggest that the visual encoding of purely proprioceptive tasks is not due to interhemispheric transfer of the proprioceptive information per se, but to the necessity of transforming joint signals between mirror-symmetric limbs.NEW & NOTEWORTHY Why does the brain encode goal-oriented, intermanual tasks in a visual space, even in the absence of visual feedback about the target and the hand? We show that the visual encoding is not due to the transfer of proprioceptive signals between brain hemispheres per se, but to the need, due to the mirror symmetry of the two limbs, of transforming joint angle signals of one arm in different joint signals of the other.

Differences between kinematic synergies and muscle synergies during two-digit grasping.

The large number of mechanical degrees of freedom of the hand is not fully exploited during actual movements such as grasping. Usually, angular movements in various joints tend to be coupled, and EMG activities in different hand muscles tend to be correlated. The occurrence of covariation in the former was termed kinematic synergies, in the latter muscle synergies. This study addresses two questions: (i) Whether kinematic and muscle synergies can simultaneously accommodate for kinematic and kinetic constraints. (ii) If so, whether there is an interrelation between kinematic and muscle synergies. We used a reach-grasp-and-pull paradigm and recorded the hand kinematics as well as eight surface EMGs. Subjects had to either perform a precision grip or side grip and had to modify their grip force in order to displace an object against a low or high load. The analysis was subdivided into three epochs: reach, grasp-and-pull, and static hold. Principal component analysis (PCA, temporal or static) was performed separately for all three epochs, in the kinematic and in the EMG domain. PCA revealed that (i) Kinematic- and muscle-synergies can simultaneously accommodate kinematic (grip type) and kinetic task constraints (load condition). (ii) Upcoming grip and load conditions of the grasp are represented in kinematic- and muscle-synergies already during reach. Phase plane plots of the principal muscle-synergy against the principal kinematic synergy revealed (iii) that the muscle-synergy is linked (correlated, and in phase advance) to the kinematic synergy during reach and during grasp-and-pull. Furthermore (iv), pair-wise correlations of EMGs during hold suggest that muscle-synergies are (in part) implemented by coactivation of muscles through common input. Together, these results suggest that kinematic synergies have (at least in part) their origin not just in muscular activation, but in synergistic muscle activation. In short: kinematic synergies may result from muscle synergies.

A modular theory of multisensory integration for motor control.

To control targeted movements, such as reaching to grasp an object or hammering a nail, the brain can use divers sources of sensory information, such as vision and proprioception. Although a variety of studies have shown that sensory signals are optimally combined according to principles of maximum likelihood, increasing evidence indicates that the CNS does not compute a single, optimal estimation of the target's position to be compared with a single optimal estimation of the hand. Rather, it employs a more modular approach in which the overall behavior is built by computing multiple concurrent comparisons carried out simultaneously in a number of different reference frames. The results of these individual comparisons are then optimally combined in order to drive the hand. In this article we examine at a computational level two formulations of concurrent models for sensory integration and compare this to the more conventional model of converging multi-sensory signals. Through a review of published studies, both our own and those performed by others, we produce evidence favoring the concurrent formulations. We then examine in detail the effects of additive signal noise as information flows through the sensorimotor system. By taking into account the noise added by sensorimotor transformations, one can explain why the CNS may shift its reliance on one sensory modality toward a greater reliance on another and investigate under what conditions those sensory transformations occur. Careful consideration of how transformed signals will co-vary with the original source also provides insight into how the CNS chooses one sensory modality over another. These concepts can be used to explain why the CNS might, for instance, create a visual representation of a task that is otherwise limited to the kinesthetic domain (e.g., pointing with one hand to a finger on the other) and why the CNS might choose to recode sensory information in an external reference frame.

When kinesthesia becomes visual: a theoretical justification for executing motor tasks in visual space.

Several experimental studies in the literature have shown that even when performing purely kinesthetic tasks, such as reaching for a kinesthetically felt target with a hidden hand, the brain reconstructs a visual representation of the movement. In our previous studies, however, we did not observe any role of a visual representation of the movement in a purely kinesthetic task. This apparent contradiction could be related to a fundamental difference between the studied tasks. In our study subjects used the same hand to both feel the target and to perform the movement, whereas in most other studies, pointing to a kinesthetic target consisted of pointing with one hand to the finger of the other, or to some other body part. We hypothesize, therefore, that it is the necessity of performing inter-limb transformations that induces a visual representation of purely kinesthetic tasks. To test this hypothesis we asked subjects to perform the same purely kinesthetic task in two conditions: INTRA and INTER. In the former they used the right hand to both perceive the target and to reproduce its orientation. In the latter, subjects perceived the target with the left hand and responded with the right. To quantify the use of a visual representation of the movement we measured deviations induced by an imperceptible conflict that was generated between visual and kinesthetic reference frames. Our hypothesis was confirmed by the observed deviations of responses due to the conflict in the INTER, but not in the INTRA, condition. To reconcile these observations with recent theories of sensori-motor integration based on maximum likelihood estimation, we propose here a new model formulation that explicitly considers the effects of covariance between sensory signals that are directly available and internal representations that are 'reconstructed' from those inputs through sensori-motor transformations.

Eye-hand coordination when the body moves: dynamic egocentric and exocentric sensory encoding.

We investigated whether the human brain encodes and memorizes object orientations with respect to external references, such as gravity and visual landmarks, or whether it uses egocentric representations of the task. To this end, we applied a new analysis to a previously reported experiment on a reach-to-grasp-like movement, in which we used sensory conflict to identify how the CNS encodes target and hand orientation. Whereas in the preceding study deviations of responses provoked by the conflict provided evidence for the simultaneous use of visual and kinesthetic representations of target and hand (Tagliabue and McIntyre, 2011 [20]), here we used an analysis of response variability in the presence of conflict to test for ego- versus exo-centric encoding within each sensory modality. Our results show an increase of response variability with the amplitude of the head rotation, indicative of errors that accumulate when updating egocentric representations during head movements. In addition, the effect of conflict on error accumulation showed that the brain selects different information about the head movement for the updating, depending on the modality of the egocentric representation (visual or kinesthetic) that is retained. In particular, the CNS appears to privilege the sensory information about head movement that can most easily be combined with each internal representation. Moreover, a combined analysis of response variability and response deviations induced by the conflict suggests the coexistence of independent ego- and exo-centered internal representations within each sensory modality.

Reaching while standing in microgravity: a new postural solution to oversimplify movement control.

Many studies showed that both arm movements and postural control are characterized by strong invariants. Besides, when a movement requires simultaneous control of the hand trajectory and balance maintenance, these two movement components are highly coordinated. It is well known that the focal and postural invariants are individually tightly linked to gravity, much less is known about the role of gravity in their coordination. It is not clear whether the effect of gravity on different movement components is such as to keep a strong movement-posture coordination even in different gravitational conditions or whether gravitational information is necessary for maintaining motor synergism. We thus set out to analyze the movements of eleven standing subjects reaching for a target in front of them beyond arm's length in normal conditions and in microgravity. The results showed that subjects quickly adapted to microgravity and were able to successfully accomplish the task. In contrast to the hand trajectory, the postural strategy was strongly affected by microgravity, so to become incompatible with normo-gravity balance constraints. The distinct effects of gravity on the focal and postural components determined a significant decrease in their reciprocal coordination. This finding suggests that movement-posture coupling is affected by gravity, and thus, it does not represent a unique hardwired and invariant mode of control. Additional kinematic and dynamic analyses suggest that the new motor strategy corresponds to a global oversimplification of movement control, fulfilling the mechanical and sensory constraints of the microgravity environment.

Necessity is the mother of invention: reconstructing missing sensory information in multiple, concurrent reference frames for eye-hand coordination.

When aligning the hand to grasp an object, the CNS combines multiple sensory inputs encoded in multiple reference frames. Previous studies suggest that when a direct comparison of target and hand is possible via a single sensory modality, the CNS avoids performing unnecessary coordinate transformations that add noise. But when target and hand do not share a common sensory modality (e.g., aligning the unseen hand to a visual target), at least one coordinate transformation is required. Similarly, body movements may occur between target acquisition and manual response, requiring that egocentric target information be updated or transformed to external reference frames to compensate. Here, we asked subjects to align the hand to an external target, where the target could be presented visually or kinesthetically and feedback about the hand was visual, kinesthetic, or both. We used a novel technique of imposing conflict between external visual and gravito-kinesthetic reference frames when subjects tilted the head during an instructed memory delay. By comparing experimental results to analytical models based on principles of maximum likelihood, we showed that multiple transformations above the strict minimum may be performed, but only if the task precludes a unimodal comparison of egocentric target and hand information. Thus, for cross-modal tasks, or when head movements are involved, the CNS creates and uses both kinesthetic and visual representations. We conclude that the necessity of producing at least one coordinate transformation activates multiple, concurrent internal representations, the functionality of which depends on the alignment of the head with respect to gravity.

A methodology to quantify alterations in human upper limb movement during co-manipulation with an exoskeleton.

While a large number of robotic exoskeletons have been designed by research teams for rehabilitation, it remains rather difficult to analyse their ability to finely interact with a human limb: no performance indicators or general methodology to characterize this capacity really exist. This is particularly regretful at a time when robotics are becoming a recognized rehabilitation method and when complex problems such as 3-D movement rehabilitation and joint rotation coordination are being addressed. The aim of this paper is to propose a general methodology to evaluate, through a reduced set of simple indicators, the ability of an exoskeleton to interact finely and in a controlled way with a human. The method involves measurement and recording of positions and forces during 3-D point to point tasks. It is applied to a 4 degrees-of-freedom limb exoskeleton by way of example.

A mathematical tool to generate complex whole body motor tasks and test hypotheses on underlying motor planning.

In spite of the complexity of human motor behavior, difficulties in mathematical modeling have restricted to rather simple movements attempts to identify the motor planning criterion used by the central nervous system. This paper presents a novel-simulation technique able to predict the "desired trajectory" corresponding to a wide range of kinematic and kinetic optimality criteria for tasks involving many degrees of freedom and the coordination between goal achievement and balance maintenance. Employment of proper time discretization, inverse dynamic methods and constrained optimization technique are combined. The application of this simulator to a planar whole body pointing movement shows its effectiveness in managing system nonlinearities and instability as well as in ensuring the anatomo-physiological feasibility of predicted motor plans. In addition, the simulator's capability to simultaneously optimize competing movement aspects represents an interesting opportunity for the motor control community, in which the coexistence of several controlled variables has been hypothesized.

Whole body pointing movements in transient microgravity: preliminary results.

The aim of the present study is a better comprehension of strategies of motor coordination during complex movements. In this field of research microgravity represent a unique experimental condition for the investigation of the role of equilibrium control in movement planning. Namely, here we focus on two important issues: the centre of mass control and the endpoint trajectory. Preliminary results of the center of mass position and the finger path curvature during pointing movements performed under normal and transient microgravity conditions are presented.