Feasibility and Validation of a Robotic-Based Multisensory Integration Assessment in Healthy Controls and a Stroke Patient.

After experiencing brain damage, stroke patients commonly suffer from motor and sensory impairments that impact their ability to perform volitional movements. Visuo-proprioceptive integration is a critical component of voluntary movement, allowing for accurate movements and a sense of ownership over one's body. While recent studies have increased our understanding of the balance between visual compensation and proprioceptive deficits in stroke patients, quantitative methods for studying multisensory integration are still lacking. This study aimed to evaluate the feasibility of adapting a 3D visuo-proprioceptive disparity (VPD) task into a 2D setting using an upper-limb robotic platform for moderate to severe chronic stroke patients. To assess the implementation of the 2D task, a cohort of unimpaired healthy participants performed the VPD task in both a 3D and 2D environment. We used a computational Bayesian model to predict errors in visuo-proprioceptive integration and compared the model's predictions to real behavioral data. Our findings indicated that the behavioral trends observed in the 2D and 3D tasks were similar, and the model accurately predicted behavior. We then evaluated the feasibility of our task to assess post-stroke deficits in a patient with severe motor and sensory deficits. Ultimately, this work may help to improve our understanding of the significance of visuo-proprioceptive integration and aid in the development of better rehabilitation therapies for improving sensorimotor outcomes in stroke patients.

The self and the Bayesian brain: Testing probabilistic models of body ownership through a self-localization task.

Simple multisensory manipulations can induce the illusory misattribution of external objects to one's own body, allowing to experimentally investigate body ownership. In this context, body ownership has been conceptualized as the result of the online Bayesian optimal estimation of the probability that one object belongs to the body from the congruence of multisensory inputs. This idea has been highly influential, as it provided a quantitative basis to bottom-up accounts of self-consciousness. However, empirical evidence fully supporting this view is scarce, as the optimality of the putative inference process has not been assessed rigorously. This pre-registered study aimed at filling this gap by testing a Bayesian model of hand ownership based on spatial and temporal visuo-proprioceptive congruences. Model predictions were compared to data from a virtual-reality reaching task, whereby reaching errors induced by a spatio-temporally mismatching virtual hand have been used as an implicit proxy of hand ownership. To rigorously test optimality, we compared the Bayesian model versus alternative non-Bayesian models of multisensory integration, and independently assess unisensory components and compare them to model estimates. We found that individually measured values of proprioceptive precision correlated with those fitted from our reaching task, providing compelling evidence that the underlying visuo-proprioceptive integration process approximates Bayesian optimality. Furthermore, reaching errors correlated with explicit ownership ratings at the single individual and trial level. Taken together, these results provide novel evidence that body ownership, a key component of self-consciousness, can be truly described as the bottom-up, behaviourally optimal processing of multisensory inputs.

A Quantitative, Digital Method to Analyze Human Figure Drawings as a Tool to Assess Body Representations Distortions in Stroke Patients.

OBJECTIVE: Human figure drawings are widely used in clinical practice as a qualitative indication of Body Representations (BRs) alterations in stroke patients. The objective of this study is to present and validate the use of a new app called QDraw for the quantitative analysis of drawings and to investigate whether this analysis can reveal distortions of BRs in chronic stroke patients. RESULTS: QDraw has proven to generate reliable data as compared to manual scoring and in terms of inter-rater reliability, as shown by the high correlation coefficients. Moreover, human figure drawings from chronic stroke patients demonstrated a distortion of upper limb perception, as shown by a significantly higher arm length asymmetry compared to legs, whereas no difference was found in healthy controls. CONCLUSIONS: The present study supports the use of quantitative, digital methods (the QDraw app) to analyze human figure drawings as a tool to evaluate BRs distortions in stroke patients.

Assess and rehabilitate body representations via (neuro)robotics: An emergent perspective.

The perceptions of our own body (e.g., size and shape) do not always coincide with its real characteristics (e.g., dimension). To track the complexity of our perception, the concept of mental representations (model) of the body has been conceived. Body representations (BRs) are stored in the brain and are maintained and updated through multiple sensory information. Despite being altered in different clinical conditions and being tightly linked with self-consciousness, which is one of the most astonishing features of the human mind, the BRs and, especially, the underlying mechanisms and functions are still unclear. In this vein, here we suggest that (neuro)robotics can make an important contribution to the study of BRs. The first section of the study highlights the potential impact of robotics devices in investigating BRs. Far to be exhaustive, we illustrate major examples of its possible exploitation to further improve the assessment of motor, haptic, and multisensory information building up the BRs. In the second section, we review the main evidence showing the contribution of neurorobotics-based (multi)sensory stimulation in reducing BRs distortions in various clinical conditions (e.g., stroke, amputees). The present study illustrates an emergent multidisciplinary perspective combining the neuroscience of BRs and (neuro)robotics to understand and modulate the perception and experience of one's own body. We suggest that (neuro)robotics can enhance the study of BRs by improving experimental rigor and introducing new experimental conditions. Furthermore, it might pave the way for the rehabilitation of altered body perceptions.

Body and peripersonal space representations in chronic stroke patients with upper limb motor deficits.

The continuous stream of multisensory information between the brain and the body during body-environment interactions is crucial to maintain the updated representation of the perceived dimensions of body parts (metric body representation) and the space around the body (the peripersonal space). Such flow of multisensory signals is often limited by upper limb sensorimotor deficits after stroke. This would suggest the presence of systematic distortions of metric body representation and peripersonal space in chronic patients with persistent sensorimotor deficits. We assessed metric body representation and peripersonal space representation in 60 chronic stroke patients with unilateral upper limb motor deficits, in comparison with age-matched healthy controls. We also administered a questionnaire capturing explicit feelings towards the affected limb. These novel measures were analysed with respect to patients' clinical profiles and brain lesions to investigate the neural and functional origin of putative deficits. Stroke patients showed distortions in metric body representation of the affected limb, characterized by an underestimation of the arm length and an alteration of the arm global shape. A descriptive lesion analysis (subtraction analysis) suggests that these distortions may be more frequently associated with lesions involving the superior corona radiata and the superior frontal gyrus. Peripersonal space representation was also altered, with reduced multisensory facilitation for stimuli presented around the affected limb. These deficits were more common in patients reporting pain during motion. Explorative lesion analyses (subtraction analysis, disconnection maps) suggest that the peripersonal space distortions would be more frequently associated with lesions involving the parietal operculum and white matter frontoparietal connections. Moreover, patients reported altered feelings towards the affected limb, which were associated with right brain damage, proprioceptive deficits and a lower cognitive profile. These results reveal implicit and explicit distortions involving metric body representation, peripersonal space representation and the perception of the affected limb in chronic stroke patients. These findings might have important clinical implications for the longitudinal monitoring and the treatments of often-neglected deficits in body perception and representation.

Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors.

BACKGROUND: A conventional treatment outcome is suboptimal for sensory impairments in stroke patients. Novel approaches based on electrical stimulation or robotics are proposed as an adjuvant for rehabilitation, though their efficacy for motor, sensory, and body representation recovery have not been tested. METHODS: Sixty chronic stroke patients with unilateral motor deficits were included in a pseudo-randomized open-label multi-arm control trial (ClinicalTrials.gov: NCT03349138). We tested the effects of a robotic glove (GloReha [GR]) and a new neuromuscular electrical stimulation system (Helping Hand [HH]) and compared them with conventional treatment (CT) in restoring motor and sensory functions and the affected limb perception. HH was designed to concurrently deliver peripheral motor activation and enhanced cutaneous sensation. Patients were split in four dose-matched groups: CT, GR, HH, and GRHH (receiving 50% GR and 50% HH). Assessments were performed at inclusion, halfway, end of treatment (week 9), and follow-up (week 13). FINDINGS: HH provided an earlier benefit, quantified by the Motricity Index (MI), than GR. At the end of the treatment, the amelioration was higher in groups GRHH and HH and extended to somatosensory functions. These benefits persisted at the follow-up. GRHH and HH also improved the perceived dimensions and altered feeling toward the affected limb. Interestingly, the reduction of altered feelings correlated with MI improvements and depended on the amount of HH. CONCLUSIONS: We suggest that HH concurrently stimulates sensory and motor systems by generating an enhanced cutaneous sensation, coherent in location with the elicited motor recruitment, leading to ameliorated sensorimotor functions and bodily perceptions in stroke patients. FUNDING: This work was supported by a Foundation advised by CARIGEST, by Fondazione CARIPLO, by the SNSF NCCR Robotics, and by the Bertarelli Foundation.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

How ageing shapes body and space representations: A comparison study between healthy young and older adults.

To efficiently interact with the external world, the brain needs to represent the size of the involved body parts - body representations (BR) - and the space around the body in which the interactions with the environment take place - peripersonal space representation (PPS). BR and PPS are both highly flexible, being updated by the continuous flow of sensorimotor signals between the brain and the body, as observed for example after tool-use or immobilization. The progressive decline of sensorimotor abilities typically described in ageing could thus influence BR and PPS representations in the older adults. To explore this hypothesis, we compared BR and PPS in healthy young and older participants. By focusing on the upper limb, we adapted tasks previously used to evaluate BR and PPS plasticity, i.e., the body-landmarks localization task and audio-tactile interaction task, together with a new task targeting explicit BR (avatar adjustment task, AAT). Results show significantly higher distortions in the older rather than young participants in the perceived metric characteristic of the upper limbs. We found significant modifications in the implicit BR of the global shape (length and width) of both upper limbs, together with an underestimation in the arm length. Similar effects were also observed in the AAT task. Finally, both young and older adults showed equivalent multisensory facilitation in the space close to the hand, suggesting an intact PPS representation. Together, these findings demonstrated significant alterations of implicit and explicit BR in the older participants, probably associated with a less efficient contribution of bodily information typically subjected to age-related decline, whereas the comparable PPS representation in both groups could be supported by preserved multisensory abilities in older participants. These results provide novel empirical insight on how multiple representations of the body in space, subserving actions and perception, are shaped by the normal course of life.

Disownership of body parts as revealed by a visual scale evaluation. An observational study.

The disownership of body parts, that most frequently occurs on the left side of the body, contralateral to right-hemispheric lesions, is an infrequent disorder, as usually assessed by interviews asking for dichotomic "yes/no" responses. This observational study in right-brain-damaged stroke patients investigated the efficacy of a continuous Visual Analog Scale (VAS) to detect body disownership after right brain damage, compared to dichotomic questions. Thirty-two right-handed right-brain-damaged stroke patients were given a Standardized Interview (SI), asking "Whose hand/arm/leg is this?", followed by a VAS (asking patients to mark on a vertical line their agreement with the statement that a body part belonged to them). The neural correlates of this disorder and measures of extra-personal and personal spatial neglect were also assessed. Control data were recorded from 18 neurologically unimpaired right-handed participants. During the interview, no patient showed disownership of body parts. Conversely, on the VAS eight out of 32 (25%) patients' scores, but none of the controls' scores, indicated a judgement of disownership for left body parts, with a left-right difference larger than that of control participants. VAS-detected disownership was not systematically associated with extra-personal and personal unilateral spatial neglect. Lesion sites associated with disownership of left body parts included the caudate nucleus and the anterior part of the internal capsule. To conclude, the VAS task, compared to the interview, is a novel tool to detect disownership of left body parts in right brain-damaged patients. A revised classification of body-ownership disorders is proposed. The present variant, assessed and detected by the VAS task, is termed Covert disownership and distinguished from the Overt disownership assessed by a SI.

You or me? Disentangling perspectival, perceptual, and integrative mechanisms in heterotopagnosia.

Heterotopagnosia-without-Autotopagnosia (HwA) is characterized by the incapacity to point to body parts on others, but not on one's own body. This has been classically interpreted as related to a self-other distinction, with impaired visual representations of other bodies seen in third person perspective (3PP), besides spared own body somatosensory representations in 1PP. However, HwA could be impacted by a deficit in the integration of visual and somatosensory information in space, that are spatially congruent in the case of one's own body, but not for others' body. Here, we test this hypothesis in a rare neurological patient with HwA, H+, as well as in a control patient with a comparable neuropsychological profile, but without HwA, and in age-matched healthy controls, in two experiments. First, we assessed body part recognition in a new task where somatosensory information from the participant's body and visual information from the target body shown in virtual reality was never aligned in space. Results show that, differently from the flawless performance in controls, H+ committed errors for not only the body of others in 3PP, but for all conditions where the information related to the real and the target body was not spatially congruent. Then, we tested whether the integration between these multisensory bodily cues in space, as during visuo-tactile stimulation in the full-body illusion, improves the patient's performance. Data show that after the stimulation prompting visuo-tactile integration, but not in control conditions, the patient's abilities to process body parts improved up to normal level, thus confirming and extending the first findings. Altogether, these results support a new interpretation of HwA as linked to the matching between somatosensory inputs from one's body and visual information from a body seen at a distance, and encourage the application of multisensory stimulation and virtual reality for the treatment of body-related disorders.

Hand perceptions induced by single pulse transcranial magnetic stimulation over the primary motor cortex.

BACKGROUND: When single pulse transcranial magnetic stimulation (TMS) is applied over the primary motor cortex (M1) with sufficient intensity, it evokes muscular contractions (motor-evoked potentials, MEPs) and muscle twitches (TMS-evoked movements). Participants may also report various hand sensations related to TMS, but the perception elicited by TMS and its relationship to MEPs and evoked movements has not been systematically studied. OBJECTIVE: The main aim of this work is to evaluate participants' kinesthetic and somatosensory hand perceptions elicited by single-pulse TMS over M1-hand area at different intensities of stimulation and their relation with MEPs and TMS-evoked movements. METHODS: We compared the number of MEPs (measured by electromyography), TMS-evoked movements (measured by an accelerometer) and participants' hand perception (measured by verbal report) elicited by TMS at different intensity of stimulation. This way, we estimated the amplitude of MEPs and the acceleration of TMS-evoked movements sufficient to trigger TMS evoked hand perceptions. RESULTS: We found that TMS-evoked hand perceptions are induced at 105% of the individual resting motor threshold, a value significantly different from the threshold inducing MEPs (about 100%) and TMS-evoked movements (about 110%). Our data indicate that only MEPs with an amplitude higher than 0.62 mV and TMS-evoked movements with acceleration higher than 0.42 m/s2 were associated with hand perceptions at threshold. CONCLUSIONS: Our data reveal the main features of TMS-evoked hand perception and show that in addition to MEPs and TMS-evoked movements, this is a separate discernible response associated to single-pulse TMS over M1.

Ipsilesional functional recruitment within lower mu band in children with unilateral cerebral palsy, an event-related desynchronization study.

Cerebral palsy (CP) is a group of non-progressive developmental movement disorders inducing a strong brain reorganization in primary and secondary motor areas. Nevertheless, few studies have been dedicated to quantify brain pattern changes and correlate them with motor characteristics in CP children. In this context, it is very important to identify feasible and complementary tools able to enrich the description of motor impairments by considering their neural correlates. To this aim, we recorded the electroencephalographic activity and the corresponding event-related desynchronization (ERD) of a group of mild-to-moderate affected unilateral CP children while performing unilateral reach-to-grasp movements with both their paretic and non-paretic arms. During paretic arm movement execution, we found a reduced ERD in the upper µ band (10-12.5 Hz) over central electrodes, preceded by an increased fronto-central ERD in the lower µ band (7.5-10 Hz) during movement preparation. These changes positively correlated, respectively, with the Modified House Classification scale and the Manual Ability Classification System. The fronto-central activation likely represents an ipsilesional plastic compensatory reorganization, confirming that in not-severely affected CP, the lesioned hemisphere is able to compensate part of the damage effects. These results highlight the importance of analyzing different sub-bands within the classical mu band and suggest that in similar CP population, the lesioned hemisphere should be the target of specific intensive rehabilitation programs.

Quantifying the role of motor imagery in brain-machine interfaces.

Despite technical advances in brain machine interfaces (BMI), for as-yet unknown reasons the ability to control a BMI remains limited to a subset of users. We investigate whether individual differences in BMI control based on motor imagery (MI) are related to differences in MI ability. We assessed whether differences in kinesthetic and visual MI, in the behavioral accuracy of MI, and in electroencephalographic variables, were able to differentiate between high- versus low-aptitude BMI users. High-aptitude BMI users showed higher MI accuracy as captured by subjective and behavioral measurements, pointing to a prominent role of kinesthetic rather than visual imagery. Additionally, for the first time, we applied mental chronometry, a measure quantifying the degree to which imagined and executed movements share a similar temporal profile. We also identified enhanced lateralized µ-band oscillations over sensorimotor cortices during MI in high- versus low-aptitude BMI users. These findings reveal that subjective, behavioral, and EEG measurements of MI are intimately linked to BMI control. We propose that poor BMI control cannot be ascribed only to intrinsic limitations of EEG recordings and that specific questionnaires and mental chronometry can be used as predictors of BMI performance (without the need to record EEG activity).

Generalization of motor resonance during the observation of hand, mouth, and eye movements.

Transcranial magnetic stimulation (TMS) of the motor cortex shows that hand action observation (AO) modulates corticospinal excitability (CSE). CSE modulation alternatively maps low-level kinematic characteristics or higher-level features, like object-directed action goals. However, action execution is achieved through the control of muscle synergies, consisting of coordinated patterns of muscular activity during natural movements, rather than single muscles or object-directed goals. This synergistic organization of action execution also underlies the ability to produce the same functional output (i.e., grasping an object) using different effectors. We hypothesize that motor system activation during AO may rely on similar principles. To investigate this issue, we recorded both hand CSE and TMS-evoked finger movements which provide a much more complete description of coordinated patterns of muscular activity. Subjects passively watched hand, mouth and eyelid opening or closing, which are performing non-object-directed (intransitive) actions. Hand and mouth share the same potential to grasp objects, whereas eyelid does not allow object-directed (transitive) actions. Hand CSE modulation generalized to all effectors, while TMS evoked finger movements only to mouth AO. Such dissociation suggests that the two techniques may have different sensitivities to fine motor modulations induced by AO. Differently from evoked movements, which are sensitive to the possibility to achieve object-directed action, CSE is generically modulated by "opening" vs. "closing" movements, independently of which effector was observed. We propose that motor activities during AO might exploit the same synergistic mechanisms shown for the neural control of movement and organized around a limited set of motor primitives.

Activating the motor system through action observation: is this an efficient approach in adults and children?

Observing an action performed by another person to learn a new movement is a frequent experience in adult daily life, such as in sports. However, it is an especially common circumstance during the development of motor skills in childhood. Studies on healthy humans indicate that action observation induces a facilitation in the observer's motor system. This effect is supported by an action-perception matching mechanism available both in adults and in children. Because of the simplicity of action observation, it has been proposed to apply this method in clinical contexts. After a brief, non-exhaustive introduction of the essential features underlying action observation in healthy people, we review recent studies reporting beneficial effects of rehabilitative training based on a combination of action perception and execution. We focus on therapeutic interventions for patients with upper-limb motor disabilities such as adults after stroke or children with hemiplegia due to cerebral palsy. Further, we consider data from basic science demonstrating that the facilitation induced by visual perception of the action can be modulated by the combination of multimodal stimuli related to the movement (e.g. visual and acoustic action-related inputs). In line with this, we discuss possible new directions to improve basic knowledge and therapeutic applications of action observation.

Moving sounds within the peripersonal space modulate the motor system.

Interactions between ourselves and the external world are mediated by a multisensory representation of the space surrounding the body, i.e. the peripersonal space (PPS). In particular, a special interplay is observed among tactile stimuli delivered on a body part, e.g. the hand, and visual or auditory external inputs presented close, but not far, from the same body part, e.g. within hand PPS. This coding of multisensory stimuli as a function of their distance from the hand has a role in upper limb actions. However, it remains unclear whether PPS representation affects the motor system only when stimuli occur specifically at the hand location or when they move within a continuous portion of space where the hand can potentially act. Here, in order to study these two alternatively hypotheses, we assessed the critical distance at which moving sounds have a direct effect on hand corticospinal excitability by using Transcranial Magnetic Stimulation (TMS). Specifically, TMS single pulses were delivered when a sound source was perceived at six different positions in space: from very close to subjects' hand (15 cm) to far away (90 cm). Moreover, sound direction was manipulated to test if stimuli approaching and receding from the hand might have the same relevance for the motor system. MEPs amplitude was enhanced when sounds were delivered within a limited distance from the hand (around 60 cm) as compared to when the sounds were beyond this space. This effect captures the spatial boundaries within which PPS representation modulates hand cortico-motor excitability. This spatially-dependent modulation of corticospinal activity was not further affected by the sound direction. Such findings support a strict link between the multisensory representation of the space around the body and the motor representation of potential approaching or defensive acts within that space.

Dissociating effect of upper limb non-use and overuse on space and body representations.

Accurate and updated representations of the space where the body acts, i.e. the peripersonal space (PPS), and the location and dimension of body parts (body representation, BR) are essential to perform actions. Because both PPS and BR are involved in motor execution and display the same plastic proprieties after the use of a tool to reach far objects, it has been suggested that they overlap in a unique representation of the body in a space devoted to action. Here we determined whether manipulating actions in space, without modifying body metrics, i.e. through immobilization, induces a dissociation of the plastic properties of PPS and BR. In 39 healthy subjects we evaluated PPS and BR for the non-used right limb and the overused left limb before and after 10 h of right arm immobilization. We observed that non-use reduces PPS representation around the immobilized arm, without affecting the metric representation (i.e. perceived length) of that limb. In contrast, overuse modulates the metric representation of the free arm, leaving PPS unchanged around that limb. These results suggest that the plasticity in PPS and BR depends on different mechanisms; while PPS representation is shaped as a function of the dimension of the acting space, metric characteristics of BR are forged on a complex interplay between visual and sensorimotor information related to the body. This behavioral dissociation between PPS and BR defines a new scenario for the role of action in shaping space and body representations.

Shaping motor cortex plasticity through proprioception.

Short-term upper limb disuse induces a hemispheric unbalance between the primary motor cortices (M1s). However, it is still unclear whether these changes are mainly attributable to the absence of voluntary movements or to the reduction of proprioceptive information. The goal of this work was to investigate the role of proprioception in modulating hemispheric balance during a short-term right arm immobilization. We evaluated the 2 M1s excitability and the interhemispheric inhibition (IHI) between M1s in 3 groups of healthy subjects. Two groups received during the immobilization a proprioceptive (P-VIB, 80 Hz) and tactile (T-VIB, 30 Hz) vibration to the right hand, respectively. Another group did not receive any conditioning sensory inputs (No-VIB). We found that in the No-VIB and in the T-VIB groups immobilization induced a decrease of left M1 excitability and IHI from left to right hemisphere and an increase of right M1 excitability and IHI from right to left hemisphere. Differently, only a partial decrease in left M1 excitability, no change in right M1 excitability and in IHI was observed in the P-VIB group. Our findings demonstrate that the maintenance of dynamic proprioceptive inputs in an immobilized arm through muscle vibration can prevent the hemispheric unbalance induced by short-term limb disuse.