Balancing the Senses: Electrophysiological Responses Reveal the Interplay between Somatosensory and Visual Processing During Body-Related Multisensory Conflict.

In the study of bodily awareness, the predictive coding theory has revealed that our brain continuously modulates sensory experiences to integrate them into a unitary body representation. Indeed, during multisensory illusions (e.g., the rubber hand illusion, RHI), the synchronous stroking of the participant's concealed hand and a fake visible one creates a visuotactile conflict, generating a prediction error. Within the predictive coding framework, through sensory processing modulation, prediction errors are solved, inducing participants to feel as if touches originated from the fake hand, thus ascribing the fake hand to their own body. Here, we aimed to address sensory processing modulation under multisensory conflict, by disentangling somatosensory and visual stimuli processing that are intrinsically associated during the illusion induction. To this aim, we designed two EEG experiments, in which somatosensory- (SEPs; Experiment 1; N = 18; F = 10) and visual-evoked potentials (VEPs; Experiment 2; N = 18; F = 9) were recorded in human males and females following the RHI. Our results show that, in both experiments, ERP amplitude is significantly modulated in the illusion as compared with both control and baseline conditions, with a modality-dependent diametrical pattern showing decreased SEP amplitude and increased VEP amplitude. Importantly, both somatosensory and visual modulations occur in long-latency time windows previously associated with tactile and visual awareness, thus explaining the illusion of perceiving touch at the sight location. In conclusion, we describe a diametrical modulation of somatosensory and visual processing as the neural mechanism that allows maintaining a stable body representation, by restoring visuotactile congruency under the occurrence of multisensory conflicts.

Bodily self-recognition in patients with pathological embodiment.

The ability to discriminate between one's own and others' body parts can be lost after brain damage, as in patients who misidentify someone else's hand as their own (pathological embodiment). Surprisingly, these patients do not use visual information to discriminate between the own and the alien hand. We asked whether this impaired visual discrimination emerges only in the ecological evaluation when the pathological embodiment is triggered by the physical alien hand (the examiner's one) or whether it emerges also when hand images are displayed on a screen. Forty right brain-damaged patients, with (E+ = 20) and without (E- = 20) pathological embodiment, and 24 healthy controls underwent two tasks in which stimuli depicting self and other hands was adopted. In the Implicit task, where participants judged which of two images matched a central target, the self-advantage (better performance with Self than Other stimuli) selectively emerges in controls, but not in patients. Moreover, E+ patients show a significantly lower performance with respect to both controls and E- patients, whereas E- patients were comparable to controls. In the Explicit task, where participants judged which stimuli belonged to themselves, both E- and E+ patients performed worst when compared to controls, but only E+ patients hyper-attributed others' hand to themselves (i.e., false alarms) as observed during the ecological evaluation. The VLSM revealed that SLF damage was significantly associated with the tendency of committing false alarm errors. We demonstrate that, in E+ patients, the ability to visually recognize the own body is lost, at both implicit and explicit level.

Tonic somatosensory responses and deficits of tactile awareness converge in the parietal operculum.

Although clinical neuroscience and the neuroscience of consciousness have long sought mechanistic explanations of tactile-awareness disorders, mechanistic insights are rare, mainly because of the difficulty of depicting the fine-grained neural dynamics underlying somatosensory processes. Here, we combined the stereo-EEG responses to somatosensory stimulation with the lesion mapping of patients with a tactile-awareness disorder, namely tactile extinction. Whereas stereo-EEG responses present different temporal patterns, including early/phasic and long-lasting/tonic activities, tactile-extinction lesion mapping co-localizes only with the latter. Overlaps are limited to the posterior part of the perisylvian regions, suggesting that tonic activities may play a role in sustaining tactile awareness. To assess this hypothesis further, we correlated the prevalence of tonic responses with the tactile-extinction lesion mapping, showing that they follow the same topographical gradient. Finally, in parallel with the notion that visuotactile stimulation improves detection in tactile-extinction patients, we demonstrated an enhancement of tonic responses to visuotactile stimuli, with a strong voxel-wise correlation with the lesion mapping. The combination of these results establishes tonic responses in the parietal operculum as the ideal neural correlate of tactile awareness.

Diametrical modulation of tactile and visual perceptual thresholds during the rubber hand illusion: a predictive coding account.

During the rubber hand illusion (RHI), the synchronous stroking of the participants' concealed hand and a visible rubber hand induces a conflict among visuo-tactile inputs, leading healthy subjects to perceive the illusion of being touched on the rubber hand, as if it were part of their body. The predictive coding theory suggests that the RHI emerges to settle the conflict, attenuating somatosensory inputs in favour of visual ones, which "capture" tactile sensations. Here, we employed the psychophysical measure of perceptual threshold to measure a behavioural correlate of the somatosensory and visual modulations, to better understand the mechanisms underpinning the illusion. Before and after the RHI, participants underwent a tactile (Experiment 1) and a visual (Experiment 2) task, wherein they had to detect stimuli slightly above the perceptual threshold. According to the predictive coding framework, we found a significant decrease of tactile detection (i.e. increased tactile perceptual threshold) and a significant increase of visual detection (i.e.  decreased visual perceptual threshold), suggesting a diametrical modulation of somatosensory and visual perceptual processes. These findings provide evidence of how our system plastically adapts to uncertainty, attributing different weights to sensory inputs to restore a coherent representation of the own body.

Face-like configurations modulate electrophysiological mismatch responses.

The human face is one of the most salient stimuli in the environment. It has been suggested that even basic face-like configurations (three dots composing a downward pointing triangle) may convey salience. Interestingly, stimulus salience can be signaled by mismatch detection phenomena, characterized by greater amplitudes of event-related potentials (ERPs) in response to relevant novel stimulation as compared to non-relevant repeated events. Here, we investigate whether basic face-like stimuli are salient enough to modulate mismatch detection phenomena. ERPs are elicited by a pair of sequentially presented visual stimuli (S1-S2), delivered at a constant 1-s interval, representing either a face-like stimulus (Upright configuration) or three neutral configurations (Inverted, Leftwards, and Rightwards configurations), that are obtained by rotating the Upright configuration along the three different axes. In pairs including a canonical face-like stimulus, we observe a more effective mismatch detection mechanism, with significantly larger N270 and P300 components when S2 is different from S1 as compared to when S2 is identical to S1. This ERP modulation, not significant in pairs excluding face-like stimuli, reveals that mismatch detection phenomena are significantly affected by basic face-like configurations. Even though further experiments are needed to ascertain whether this effect is specifically elicited by face-like configuration rather than by particular orientation changes, our findings suggest that face essential, structural attributes are salient enough to affect change detection processes.

Long-term limb immobilization modulates inhibition-related electrophysiological brain activity.

The effect of long-term immobilization on the motor system has been described during motor preparation, imagination or execution, when the movement has to be performed. But, what happens when the movement has to be suppressed? Does long-term limb immobilization modulate physiological responses underlying motor inhibition? Event-related potentials (ERPs) were recorded in healthy participants performing a Go/Nogo task, either with both hands free to respond (T1/T4: before/after the immobilization) or when left-hand movements were prevented by a cast (T2: as soon as the cast was positioned; T3: after one week of immobilization). In the right (control) side, N140, N2, and P3 components showed the expected greater amplitude in Nogo than in Go trials, irrespective of the timepoint. On the contrary, in the left (manipulated) side, each component of the ERP responses to Nogo trials showed specific differences across timepoints, suggesting that the inhibition-related EEG activity is significantly reduced by the presence of the cast and the duration of the immobilization. Furthermore, inhibition-related theta band activity to Nogo stimuli decreased at post-immobilization blocked session (T3-blocked). Altogether these findings can be interpreted as a consequence of the plastic changes induced by the immobilization, as also demonstrated by the cast-related corticospinal excitability modulation (investigated by using TMS) and by the decreased beta band in response to Go and Nogo trials. Thus, only if we are free to move, then inhibitory responses are fully implemented. After one week of immobilization, the amount of inhibition necessary to block the movement is lower and, consequently, inhibitory-related responses are reduced.

Hand blink reflex in virtual reality: The role of vision and proprioception in modulating defensive responses.

Our research focused on the role of vision and proprioception in modulating a defensive reflex (hand blink reflex, HBR) whose magnitude is enhanced when the threatened hand is inside the peripersonal space of the face. We capitalized on virtual reality, which allows dissociating vision and proprioception by presenting a virtual limb in congruent/incongruent positions with respect to the participants' limb. In experiment 1, participants placed their own stimulated hand in far/near positions with respect to their face (postural manipulation task), while observing a virtual empty scenario. Vision was not informative, but the HBR was significantly enhanced in near compared with far position, suggesting that proprioception is sufficient for the HBR modulation to occur. In experiment 2, participants did not perform the postural manipulation but they (passively) observed the avatar's virtual limb performing it. Proprioceptive signals were not informative, but the HBR was significantly enhanced when the observed virtual limb was near to the face, suggesting that visual information plays a role in modulating the HBR. In experiment 3, both participants and avatar performed the postural manipulation, either congruently (both of them far/near) or incongruently (one of them far, the other near). The HBR modulation was present only in congruent conditions. In incongruent conditions, the conflict between vision and proprioception confounded the system, abolishing the difference between far and near positions. Taken together, these findings promote the view that observing a virtual limb modulates the HBR, providing also new evidence on the role of vision and proprioception in modulating this subcortical reflex.

To Move or Not to Move? Functional Role of Ventral Premotor Cortex in Motor Monitoring During Limb Immobilization.

Anatomo-clinical evidence from motor-awareness disorders after brain-damages suggests that the premotor cortex (PMC) is involved in motor-monitoring of voluntary actions. Indeed, PMC lesions prevent patients from detecting the mismatch between intended, but not executed, movements with the paralyzed limb. This functional magnetic resonance imaging study compared, in healthy subjects, free movements against blocked movements, precluded by a cast. Cast-related corticospinal excitability changes were investigated by using transcranial magnetic stimulation. Immediately after the immobilization, when the cast prevented the execution of left-hand movements, the contralateral right (ventral) vPMC showed both increased hemodynamic activity and increased functional connectivity with the hand area in the right somatosensory cortex, suggesting a vPMC involvement in detecting the mismatch between planned and executed movements. Crucially, after 1 week of immobilization, when the motor system had likely learned that no movement could be executed and, therefore, predictions about motor consequences were changed, vPMC did not show the enhanced activity as if no incongruence has to be detected. This can be interpreted as a consequence of the plastic changes induced by long-lasting immobilization, as also proved by the cast-related corticospinal excitability modulation in our subjects. The present findings highlight the crucial role of vPMC in the anatomo-functional network generating the human motor-awareness.

Dynamic Shaping of the Defensive Peripersonal Space through Predictive Motor Mechanisms: When the "Near" Becomes "Far".

The hand blink reflex is a subcortical defensive response, known to dramatically increase when the stimulated hand is statically positioned inside the defensive peripersonal space (DPPS) of the face. Here, we tested in a group of healthy human subjects the hand blink reflex in dynamic conditions, investigating whether the direction of the hand movements (up-to/down-from the face) could modulate it. We found that, on equal hand position, the response enhancement was present only when the hand approached to (and not receded from) the DPPS of the face. This means that, when the hand is close to the face but the subject is planning to move the hand down, the predictive motor system can anticipate the consequence of the movement: the "near" becomes "far." We found similar results both in passive movement condition, when only afferent (visual and proprioceptive) information can be used to estimate the final state of the system, and in motor imagery task, when only efferent (intentional) information is available to predict the consequences of the movement. All these findings provide evidence that the DPPS is dynamically shaped by predictive mechanisms run by the motor system and based on the integration of feedforward and sensory feedback signals.SIGNIFICANCE STATEMENT The defensive peripersonal space (DPPS) has a crucial role for survival, and its modulation is fundamental when we interact with the environment, as when we move our arms. Here, we focused on a defensive response, the hand blink reflex, known to increase when a static hand is stimulated inside the DPPS of the face. We tested the hand blink reflex in dynamic conditions (voluntary, passive, and imagined movements) and we found that, on equal hand position, the response enhancement was present only when the hand approached to (and not receded from) the DPPS of the face. This suggests that, through the integration of efferent and afferent signals, the safety boundary around the body is continuously shaped by the predictive motor system.

Losing my hand. Body ownership attenuation after virtual lesion of the primary motor cortex.

A fundamental component of the self-awareness is the sensation that we are acting with our own body. Thus, a coherent sense of self implies the existence of a tight link between the sense of body ownership and the motor system. Here, we investigated this issue by taking advantage of a well-known experimental manipulation of body ownership, i.e., the rubber hand illusion (RHI), during which the subjects perceive a fake hand as part of their own body. To test the effect of the motor system down-regulation on the RHI susceptibility, we designed a sham-controlled study, where the primary motor cortex (M1) excitability was modulated by off-line low-frequency repetitive transcranial magnetic stimulation (rTMS). After rTMS (real or sham), subjects underwent the RHI either on the right hand, contralateral to the inhibited hemisphere (Experiment 1), or on the left hand, ipsilateral to the inhibited hemisphere (Experiment 2). Only in Experiment 1, the procedure strengthened the illusory experience, as proved by a significant increase, in rTMS compared to Sham, of both subjective (Embodiment/Disembodiment Questionnaires) and objective (Proprioceptive Drift) RHI measures. This evidence demonstrates that, when the M1 activity is down-regulated, the sense of body ownership is attenuated and the subjects become more prone to incorporate an alien body part. This, in turn, supports the existence of a mutual interaction between the sense of body ownership and the motor system, shedding new light on the construction of a coherent sense of self as an acting body.

Empathy or Ownership? Evidence from Corticospinal Excitability Modulation during Pain Observation.

Recent studies show that motor responses similar to those present in one's own pain (freezing effect) occur as a result of observation of pain in others. This finding has been interpreted as the physiological basis of empathy. Alternatively, it can represent the physiological counterpart of an embodiment phenomenon related to the sense of body ownership. We compared the empathy and the ownership hypotheses by manipulating the perspective of the observed hand model receiving pain so that it could be a first-person perspective, the one in which embodiment occurs, or a third-person perspective, the one in which we usually perceive the others. Motor-evoked potentials (MEPs) by TMS over M1 were recorded from first dorsal interosseous muscle, whereas participants observed video clips showing (a) a needle penetrating or (b) a Q-tip touching a hand model, presented either in first-person or in third-person perspective. We found that a pain-specific inhibition of MEP amplitude (a significantly greater MEP reduction in the "pain" compared with the "touch" conditions) only pertains to the first-person perspective, and it is related to the strength of the self-reported embodiment. We interpreted this corticospinal modulation according to an "affective" conception of body ownership, suggesting that the body I feel as my own is the body I care more about.

Sensing the body, representing the body: Evidence from a neurologically based delusion of body ownership.

Humans experience their own body as unitary and monolithic in nature. However, recent findings in cognitive neuroscience seem to suggest that body awareness has a complex and multifaceted structure that can be dissociated in several subcomponents, possibly underpinned by different brain circuits. In the present paper, we focus on a recently reported neuropsychological disorder of body ownership in which patients misattribute to themselves someone else's arm and its movements. As first, we briefly review the clinical and functional features of this disorder. Secondly, we attempt to explain the nature of the delusion and to gain new hints regarding the mechanisms subserving the construction and the maintenance of the sense of body ownership in the intact brain functioning.

Spatial proximity to others induces plastic changes in the neural representation of the peripersonal space.

Peripersonal space (PPS) is a highly plastic "invisible bubble" surrounding the body whose boundaries are mapped through multisensory integration. Yet, it is unclear how the spatial proximity to others alters PPS boundaries. Across five experiments (N = 80), by recording behavioral and electrophysiological responses to visuo-tactile stimuli, we demonstrate that the proximity to others induces plastic changes in the neural PPS representation. The spatial proximity to someone else's hand shrinks the portion of space within which multisensory responses occur, thus reducing the PPS boundaries. This suggests that PPS representation, built from bodily and multisensory signals, plastically adapts to the presence of conspecifics to define the self-other boundaries, so that what is usually coded as "my space" is recoded as "your space". When the space is shared with conspecifics, it seems adaptive to move the other-space away from the self-space to discriminate whether external events pertain to the self-body or to other-bodies.

Can static Rorschach stimuli perceived as in motion affect corticospinal excitability?

It has been proposed that seeing human movement or activity (M), while trying to say what the static Rorschach inkblot design look like, is accompanied by Mirror Neuron System (MNS)-like mirroring activity in the brain. The present study aimed to investigate whether the Rorschach cards eliciting M responses could affect the excitability of the motor cortex by recording motor evoked potentials (MEPs) elicited by single-pulse TMS over the primary motor cortex (M1). We hypothesized that Rorschach inkblot stimuli triggering the viewer's experience of human movement would increase corticospinal excitability. Twenty-one healthy volunteers (15 women) participated in the preliminary experiment, while another different sample of twenty-two healthy participants (11 women) ranging in age from 21 to 41 years was enrolled in the main experiment. Our results showed that the Rorschach cards known to be associated with a high number of M responses elicited human movement both as automatic internal sensations and as verbal production of responses involving human movement. However, contrary to our hypothesis, the reported internal feeling of human movement had no corresponding physiological counterpart, as the amplitude of MEPs did not increase. Possible and innovative explanations for the involvement of bottom-up and top-down processes were provided.

The role of early attachment experiences in modulating defensive peripersonal space.

Selecting appropriate defensive behaviours for threats approaching the space surrounding the body (peripersonal space, PPS) is crucial for survival. The extent of defensive PPS is measured by recording the hand-blink reflex (HBR), a subcortical defensive response. Higher-order cortical areas involved in PPS representation exert top-down modulation on brainstem circuits subserving HBR. However, it is not yet known whether pre-existing models of social relationships (internal working models, IWM) originating from early attachment experiences influence defensive responses. We hypothesized that organized IWM ensure adequate top-down regulation of brainstem activity mediating HBR, whereas disorganized IWM are associated with altered response patterns. To investigate attachment-dependent modulation on defensive responses, we used the Adult Attachment Interview to determine IWM and recorded HBR in two sessions (with or without the neurobehavioral attachment system activated). As expected, the HBR magnitude in individuals with organized IWM was modulated by the threat proximity to the face, regardless of the session. In contrast, for individuals with disorganized IWM, attachment system activation enhances HBR regardless of the threat position, suggesting that triggering emotional attachment experiences magnifies the threatening valence of external stimuli. Our results indicate that the attachment system exerts a strong modulation on defensive responses and the magnitude of PPS.

Abnormal sense of agency in eating disorders.

The feeling of controlling one's own actions and, through them, impacting the external environment (i.e. Sense of Agency-SoA) can be relevant in the eating disorders (EDs) symptomatology. Yet, it has been poorly investigated. This study aims to implicitly assess SoA exploiting the Sensory Attenuation paradigm in two groups of EDs patients (Anorexia Nervosa Restrictive and Anorexia Nervosa Binge-Purging or Bulimia Nervosa) compared to a control group. We find that controls perceive self-generated stimuli as less intense than other-generated ones showing the classic pattern of sensory attenuation. By contrast, EDs patients show the opposite pattern, with self-generated perceived as more intense than other-generated stimuli. This result indicates an alteration of the implicit component of the feeling of control in EDs patients, thus suggesting a potential implication of these results for the clinical practice and the treatment of EDs symptomatology.

Monochannel Preference in Autism Spectrum Conditions Revealed by a Non-Visual Variant of Rubber Hand Illusion.

Individuals with autism spectrum conditions (ASC) are less susceptible to multisensory delusions, such as rubber hand illusion (RHI). Here, we investigate whether a monochannel variant of RHI is more effective in inducing an illusory feeling of ownership in ASC. To this aim, we exploit a non-visual variant of the RHI that, excluding vision, leverages only on the somatosensory channel. While the visual-tactile RHI does not alter the perceived hand position in ASC individuals, the tacto-tactile RHI effectively modulates proprioception to a similar extent as that found in typical development individuals. These findings suggest a more effective integration of multiple inputs originating from the same sensory channel in ASC, revealing a monochannel preference in this population.

Reach planning with someone else's hand.

To investigate the relationship between the sense of body ownership and motor control, we capitalized on a rare bizarre disorder wherein another person's hand is misattributed to their own body, i.e., a pathological form of embodiment (E+). Importantly, despite E+ is usually associated with motor deficits, we had the opportunity to test two E+ patients with spared motor function, thus able to perform a reaching task. Crucially, these patients had proprioceptive deafferentation, allowing us to purely isolate the embodiment-dependent effect from proprioception-dependent ones that are usually associated in experimental manipulations of body ownership in healthy participants. Previous evidence suggests that the reaching movement vector is attracted towards an embodied hand during the rubber hand illusion (RHI). However, these results are confounded by the spared proprioception, whose modulation alone could explain the effects on reach planning. The neuropsychological approach employed here provides unambiguous evidence about the role of body ownership in reach planning. Indeed, three brain-damaged patients with proprioceptive deafferentation, two E+ and a well-matched control patient without pathological embodiment (E-), and 10 age-matched healthy controls underwent a reaching task wherein they had to reach for a target from a fixed starting point, while an alien hand (the co-experimenter's) was placed on the table. Irrespective of proprioception, damaged in all patients, only in E+ patients reaching errors were significantly more shifted consistently with the pathological belief, i.e., as if they planned movements from the position of the alien (embodied) hand, as compared to controls. Furthermore, with an additional experiment on healthy participants, we demonstrated that reaching errors observed during the RHI correlate with the changes in ownership. In conclusion, our neuropsychological approach suggests that when planning a reach, we do so from where our owned hand is and not from its physical location.

The vision of haptics tunes the somatosensory threshold.

The interaction between different sensory modalities represents a crucial issue in the neuroscience of consciousness: when the processing of one modality is deficient, the concomitant presentation of stimuli of other spared modalities may sustain the restoration of the damaged sensory functions. In this regard, visual enhancement of touch may represent a viable tool in rehabilitating tactile disorders, yet the specific visual features mostly modulating the somatosensory experience remain unsettled. In this study, healthy subjects underwent a tactile detection task during the observation of videos displaying different contents, including static gratings, meaningless motions and natural or point-lights reach-to-grasp-and-manipulate actions. Concurrently, near-threshold stimuli were delivered to the median nerve at different time-points. The subjective report was collected after each trial; the sensory detection rate was computed and compared across video conditions. Our results indicate that the specific presence of haptic contents (i.e., the vision of manipulation), either fully displayed or implied by point-lights, magnifies tactile sensitivity. The notion that such stimuli prompt a conscious tactile experience opens to novel rehabilitation approaches for tactile consciousness disorders.

Multisensory-driven facilitation within the peripersonal space is modulated by the expectations about stimulus location on the body.

Compelling evidence from human and non-human studies suggests that responses to multisensory events are fastened when stimuli occur within the space surrounding the bodily self (i.e., peripersonal space; PPS). However, some human studies did not find such effect. We propose that these dissonant voices might actually uncover a specific mechanism, modulating PPS boundaries according to sensory regularities. We exploited a visuo-tactile paradigm, wherein participants provided speeded responses to tactile stimuli and rated their perceived intensity while ignoring simultaneous visual stimuli, appearing near the stimulated hand (VTNear) or far from it (VTFar; near the non-stimulated hand). Tactile stimuli could be delivered only to one hand (unilateral task) or to both hands randomly (bilateral task). Results revealed that a space-dependent multisensory enhancement (i.e., faster responses and higher perceived intensity in VTNear than VTFar) was present when highly predictable tactile stimulation induced PPS to be circumscribed around the stimulated hand (unilateral task). Conversely, when stimulus location was unpredictable (bilateral task), participants showed a comparable multisensory enhancement in both bimodal conditions, suggesting a PPS widening to include both hands. We propose that the detection of environmental regularities actively shapes PPS boundaries, thus optimizing the detection and reaction to incoming sensory stimuli.