An immersive virtual reality tool for assessing left and right unilateral spatial neglect.

The reported rate of the occurrence of unilateral spatial neglect (USN) is highly variable likely due to the lack of validity and low sensitivity of classical tools used to assess it. Virtual reality (VR) assessments try to overcome these limitations by proposing immersive and complex environments. Nevertheless, existing VR-based tasks are mostly focused only on near space and lack analysis of psychometric properties and/or clinical validation. The present study evaluates the clinical validity and sensitivity of a new immersive VR-based task to assess USN in the extra-personal space and examines the neuronal correlates of deficits of far space exploration. The task was administrated to two groups of patients with right (N = 28) or left (N = 11) hemispheric brain lesions, also undergoing classical paper-and-pencil assessment, as well as a group of healthy participants. Our VR-based task detected 44% of neglect cases compared to 31% by paper-and-pencil tests in the total sample. Importantly, 30% of the patients (with right or left brain lesions) with no clear sign of USN on the paper-and-pencil tests performed outside the normal range in the VR-based task. Voxel lesion-symptom mapping revealed that deficits detected in VR were associated with lesions in insular and temporal cortex, part of the neural network involved in spatial processing. These results show that our immersive VR-based task is efficient and sensitive in detecting mild to strong manifestations of USN affecting the extra-personal space, which may be undetected using standard tools.

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 effect of visual perspective on episodic memory in aging: A virtual reality study.

The possibility of flexibly retrieving our memories using a first-person or a third-person perspective (1PP or 3PP) has been extensively investigated in episodic memory research. Here, we used a Virtual Reality-based paradigm to manipulate the visual perspective used during the encoding stage to investigate age-related differences in the formation of memories experienced from 1PP vs. 3PP. 32 young adults and 32 seniors participated in the study. Participants navigated through two virtual cities to encode complex real-life virtual events, from either a 1PP (as if from their egocentric viewpoint) or a 3PP, while actively controlling an avatar. While recognition accuracy was higher in young adults after encoding in 1PP compared to 3PP, there was no benefit in memory formation in 1PP for older adults. These findings are discussed in terms of both age-related changes in episodic memory functioning and self-referencing processes.

Space for power: feeling powerful over others' behavior affects peri-personal space representation.

We investigated whether and how social power affects the representation of peri-personal space (PPS). We applied a multisensory interaction task to assess PPS representation and the Personal Sense of Power Scale to assess participants' feelings of power over others' behaviors and over others' opinions. In Study 1, we probed PPS representation in a virtual social context. Participants with a higher sense of power showed a less defined differentiation between the close and far space as compared to participants with a lower sense of power. This effect was replicated in Study 2 when participants performed the task in a non-social context (with no person in the scene), but only after they were reminded of an episode of power. Thus, social power-the perception of power over others' behavior-affects the multisensory representation of the self in space by blurring the differentiation between one's own PPS and the space of others.

Human primary motor cortex indexes the onset of subjective intention in brain-machine-interface mediated actions.

Self-initiated behavior is accompanied by the experience of willing our actions. Here, we leverage the unique opportunity to examine the full intentional chain - from will (W) to action (A) to environmental effects (E) - in a tetraplegic person fitted with a primary motor cortex (M1) brain machine interface (BMI) generating hand movements via neuromuscular electrical stimulation (NMES). This combined BMI-NMES approach allowed us to selectively manipulate each element of the intentional chain (W, A, and E) while performing extra-cellular recordings and probing subjective experience. Our results reveal single-cell, multi-unit, and population-level dynamics in human M1 that encode W and may predict its subjective onset. Further, we show that the proficiency of a neural decoder in M1 reflects the degree of W-A binding, tracking the participant's subjective experience of intention in (near) real time. These results point to M1 as a critical node in forming the subjective experience of intention and demonstrate the relevance of intention-related signals for translational neuroprosthetics.

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.

An immersive virtual reality system for ecological assessment of peripersonal and extrapersonal unilateral spatial neglect.

BACKGROUND: Unilateral spatial neglect (USN) is a debilitating neuropsychological syndrome that often follows brain injury, in particular a stroke affecting the right hemisphere. In current clinical practice, the assessment of neglect is based on old-fashioned paper-and-pencil and behavioral tasks, and sometimes relies on the examiner's subjective judgment. Therefore, there is a need for more exhaustive, objective and ecological assessments of USN. METHODS: In this paper, we present two tasks in immersive virtual reality to assess peripersonal and extrapersonal USN. The tasks are designed with several levels of difficulty to increase sensitivity of the assessment. We then validate the feasibility of both assessments in a group of healthy adult participants. RESULTS: We report data from a study with a group of neurologically unimpaired participants (N = 39). The results yield positive feedback on comfort, usability and design of the tasks. We propose new objective scores based on participant's performance captured by head gaze and hand position information, including, for instance, time of exploration, moving time towards left/right and time-to-reach, which could be used for the evaluation of the attentional spatial bias with neurological patients. Together with the number of omissions, the new proposed parameters can result in lateralized index ratios as a measure of asymmetry in space exploration. CONCLUSIONS: We presented two innovative assessments for USN based on immersive virtual reality, evaluating the far and the near space, using ecological tasks in multimodal, realistic environments. The proposed protocols and objective scores can help distinguish neurological patients with and without USN.

My social comfort zone: Attachment anxiety shapes peripersonal and interpersonal space.

Following positive social exchanges, the neural representation of interactive space around the body (peripersonal space; PPS) expands, whereas we also feel consciously more comfortable being closer to others (interpersonal distance; ID). However, it is unclear how relational traits, such as attachment styles, interact with the social malleability of our PPS and ID. A first, exploratory study (N=48) using a visuo-tactile, augmented reality task, found that PPS depended on the combined effects of social context and attachment anxiety. A follow-up preregistered study (N = 68), showed that those with high attachment anxiety demonstrated a sharper differentiation between peripersonal and extrapersonal space, even in a non-social context. A final, preregistered large-scale survey (N = 19,417) found that people scoring high in attachment anxiety prefer closer ID and differentiate their ID less based on feelings of social closeness. We conclude that attachment anxiety reduces the social malleability of both peripersonal and interpersonal space.

Morphology, Connectivity, and Encoding Features of Tactile and Motor Representations of the Fingers in the Human Precentral and Postcentral Gyrus.

Despite the tight coupling between sensory and motor processing for fine manipulation in humans, it is not yet totally clear which specific properties of the fingers are mapped in the precentral and postcentral gyrus. We used fMRI to compare the morphology, connectivity, and encoding of the motor and tactile finger representations (FRs) in the precentral and postcentral gyrus of 25 5-fingered participants (8 females). Multivoxel pattern and structural and functional connectivity analyses demonstrated the existence of distinct motor and tactile FRs within both the precentral and postcentral gyrus, integrating finger-specific motor and tactile information. Using representational similarity analysis, we found that the motor and tactile FRs in the sensorimotor cortex were described by the perceived structure of the hand better than by the actual hand anatomy or other functional models (finger kinematics, muscles synergies). We then studied a polydactyly individual (i.e., with a congenital 6-fingered hand) showing superior manipulation abilities and divergent anatomic-functional hand properties. The perceived hand model was still the best model for tactile representations in the precentral and postcentral gyrus, while finger kinematics better described motor representations in the precentral gyrus. We suggest that, under normal conditions (i.e., in subjects with a standard hand anatomy), the sensorimotor representations of the 5 fingers in humans converge toward a model of perceived hand anatomy, deviating from the real hand structure, as the best synthesis between functional and structural features of the hand.SIGNIFICANCE STATEMENT Distinct motor and tactile finger representations exist in both the precentral and postcentral gyrus, supported by a finger-specific pattern of anatomic and functional connectivity across modalities. At the representational level, finger representations reflect the perceived structure of the hand, which might result from an adapting process harmonizing (i.e., uniformizing) the encoding of hand function and structure in the precentral and postcentral gyrus. The same analyses performed in an extremely rare polydactyly subject showed that the emergence of such representational geometry is also found in neuromechanical variants with different hand anatomy and function. However, the harmonization process across the precentral and postcentral gyrus might not be possible because of divergent functional-structural properties of the hand and associated superior manipulation abilities.

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity.

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory 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.

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.

Acute stress affects peripersonal space representation in cortisol stress responders.

Peripersonal space is the representation of the space near the body. It is implemented by a dedicated multisensory-motor network, whose purpose is to predict and plan interactions with the environment, and which can vary depending on environmental circumstances. Here, we investigated the effect on the PPS representation of an experimentally induced stress response and compared it to a control, non-stressful, manipulation. We assessed PPS representation in healthy humans, before and after a stressful manipulation, by quantifying visuotactile interactions as a function of the distance from the body, while monitoring salivary cortisol concentration. While PPS representation was not significantly different between the control and experimental group, a relation between cortisol response and changes in PPS emerged within the experimental group. Participants who showed a cortisol stress response presented enhanced visuotactile integration for stimuli close to the body and reduced for far stimuli. Conversely, individuals with a less pronounced cortisol response showed a reduced difference in visuotactile integration between the near and the far space. In our interpretation, physiological stress resulted in a freezing-like response, where multisensory-motor resources are allocated only to the area immediately surrounding the body.

Sense of agency for intracortical brain-machine interfaces.

Intracortical brain-machine interfaces decode motor commands from neural signals and translate them into actions, enabling movement for paralysed individuals. The subjective sense of agency associated with actions generated via intracortical brain-machine interfaces, the neural mechanisms involved and its clinical relevance are currently unknown. By experimentally manipulating the coherence between decoded motor commands and sensory feedback in a tetraplegic individual using a brain-machine interface, we provide evidence that primary motor cortex processes sensory feedback, sensorimotor conflicts and subjective states of actions generated via the brain-machine interface. Neural signals processing the sense of agency affected the proficiency of the brain-machine interface, underlining the clinical potential of the present approach. These findings show that primary motor cortex encodes information related to action and sensing, but also sensorimotor and subjective agency signals, which in turn are relevant for clinical applications of brain-machine interfaces.

Contribution of interaction force to the sense of hand ownership and the sense of hand agency.

When performing willed actions, we have the unified and coherent experience of owning and controlling our body. Body ownership is believed to emerge from the integration of coherent multisensory signals, while agency is believed to emerge from the coherence between predicted and perceived outcomes of actions. As a consequence, body ownership and agency can both be modulated by multisensory conflicts. The contribution of active movement generation to ownership and agency has not been parametrically explored. Here, we investigated the contribution of interaction force between the agent and the environment to the sense of hand ownership (SO) and the sense of hand agency (SA). By combining robotics and virtual reality, we manipulated the sensorimotor and visual information during immersive scenarios to induce and quantify altered states of SO and SA. First, we demonstrated that SO and SA could be successfully manipulated by our experimental paradigms. Second, we showed that interaction force strongly contributes to SA, but to a lesser extent to SO. Finally, we showed that SO and SA interact beyond their common multisensory basis. Our results, based on two independent studies, provide a direct link between sensorimotor interactions and subjective body experience and demonstrate a new dissociation between SO and SA.

Disentangling the percepts of illusory movement and sensory stimulation during tendon vibration in the EEG.

Mechanical vibration of muscle tendons in specific frequencies - termed functional proprioceptive stimulation (FPS) - has the ability to induce the illusion of a movement which is congruent with a lengthening of the vibrated tendon and muscle. The majority of previous reports of the brain correlates of this illusion are based on functional neuroimaging. Contrary to the electroencephalogram (EEG) however, such technologies are not suitable for bedside or ambulant use. While a handful of studies have shown EEG changes during FPS, it remains underinvestigated whether these changes were due to the perceived illusion or the perceived vibration. Here, we aimed at disentangling the neural correlates of the illusory movement from those produced by the vibration sensation by comparing the neural responses to two vibration types, one that did and one that did not elicit an illusion. We recruited 40 naïve participants, 20 for the EEG experiment and 20 for a supporting behavioral study, who received functional tendon co-vibration on the biceps and triceps tendon at their left elbow, pseudo-randomly switching between the illusion and non-illusion trials. Time-frequency decomposition uncovered a strong and lasting event-related desynchronization (ERD) in the mu and beta band in both conditions, suggesting a strong somatosensory response to the vibration. Additionally, the analysis of the evoked potentials revealed a significant difference between the two experimental conditions from 310 to 990ms post stimulus onset. Training classifiers on the frequency-based and voltage-based correlates of illusion perception yielded above chance accuracies for 17 and 13 out of the 20 subjects respectively. Our findings show that FPS-induced illusions produce EEG correlates that are distinct from a vibration-based control and which can be classified reliably in a large number of participants. These results encourage pursuing EEG-based detection of kinesthetic illusions as a tool for clinical use, e.g., to uncover aspects of cognitive perception in unresponsive patients.

Sharpening of peripersonal space during the COVID-19 pandemic.

Our social world has been transformed by the COVID-19 pandemic. Beyond the direct impact of the pandemic on physical health, the social distancing measures implemented worldwide to slow down disease transmission have dramatically impacted social interactions1,2. These measures, including orders to stay at home and to maintain a social distance of at least 2 meters, have been essential to limit the spread of the disease, but they have had severe costs for humans as social animals2. Right before and right after the adoption of the most stringent measures in Switzerland in Spring 2020, we were conducting a series of experiments to measure the representation of the so-called peripersonal space - the space immediately surrounding our body, where we normally interact with objects and other individuals3. We found that the introduction of social distancing measures led to a reduction in the extent of the peripersonal space and enhanced its segregation between individuals, as if the presence of others in close space would activate an implicit form of freezing response.

Real-time fMRI and EEG neurofeedback: A perspective on applications for the rehabilitation of spatial neglect.

Spatial neglect is a neuropsychological syndrome characterized by a failure to orient, perceive, and act toward the contralesional side of the space after brain injury. Neglect is one of the most frequent and disabling neuropsychological syndromes following right-hemisphere damage, often persisting in the chronic phase and responsible for a poor functional outcome at hospital discharge. Different rehabilitation approaches have been proposed over the past 60 years, with a variable degree of effectiveness. In this point-of-view article, we describe a new rehabilitation technique for spatial neglect that directly targets brain activity and pathological physiological processes: namely, neurofeedback (NFB) with real-time brain imaging methodologies. In recent proof-of-principle studies, we have demonstrated the potential of this rehabilitation technique. Using real-time functional MRI (rt-fMRI) NFB in chronic neglect, we demonstrated that patients are able to upregulate their right visual cortex activity, a response that is otherwise reduced due to losses in top-down attentional signals. Using real-time electroencephalography NFB in patients with acute or chronic condition, we showed successful regulation with partial restoration of brain rhythm dynamics over the damaged hemisphere. Both approaches were followed by mild, but encouraging, improvement in neglect symptoms. NFB techniques, by training endogenous top-down modulation of attentional control on sensory processing, might induce sustained changes at both the neural and behavioral levels, while being non-invasive and safe. However, more properly powered clinical studies with control groups and longer follow-up are needed to fully establish the effectiveness of the techniques, identify the most suitable candidates, and determine how the techniques can be optimized or combined in the context of rehabilitation.

Spatial tuning of electrophysiological responses to multisensory stimuli reveals a primitive coding of the body boundaries in newborns.

The ability to identify our own body and its boundaries is crucial for survival. Ideally, the sooner we learn to discriminate external stimuli occurring close to our body from those occurring far from it, the better (and safer) we may interact with the sensory environment. However, when this mechanism emerges within ontogeny is unknown. Is it something acquired throughout infancy, or is it already present soon after birth? The presence of a spatial modulation of multisensory integration (MSI) is considered a hallmark of a functioning representation of the body position in space. Here, we investigated whether MSI is present and spatially organized in 18- to 92-h-old newborns. We compared electrophysiological responses to tactile stimulation when concurrent auditory events were delivered close to, as opposed to far from, the body in healthy newborns and in a control group of adult participants. In accordance with previous studies, adult controls showed a clear spatial modulation of MSI, with greater superadditive responses for multisensory stimuli close to the body. In newborns, we demonstrated the presence of a genuine electrophysiological pattern of MSI, with older newborns showing a larger MSI effect. Importantly, as for adults, multisensory superadditive responses were modulated by the proximity to the body. This finding may represent the electrophysiological mechanism responsible for a primitive coding of bodily self boundaries, thus suggesting that even just a few hours after birth, human newborns identify their own body as a distinct entity from the environment.