Synchronous Stimulation Research Articles

How His bundle pacing prevents and reverses heart failure induced by right ventricular pacing.

Ideal heart performance demands vigorous systolic contractions and rapid diastolic relaxation. These sequential events are precisely timed and interdependent and require the rapid synchronous electrical stimulation provided by the His-Purkinje system. Right ventricular (RV) pacing creates slow asynchronous electrical stimulation that disrupts the timing of the cardiac cycle and results in left ventricular (LV) mechanical asynchrony. Long-term mechanical asynchrony produces LV dysfunction, remodeling, and clinical heart failure. His bundle pacing preserves synchronous electrical and mechanical LV function, prevents or reverses RV pacemaker-induced remodeling, and reduces heart failure.

Investigating the Hand Ownership Illusion With Two Views Merged in.

Researchers investigating virtual/augmented reality have shown humans' marked adaptability, especially regarding our sense of body ownership; their cumulative findings have expanded the concept of what it means to have a body. Herein, we report the hand ownership illusion during “two views merged in.” In our experiment, participants were presented two first-person perspective views of their arm overlapped, one was the live feed from a camera and the other was a playback video of the same situation, slightly shifted toward one side. The relative visibility of these two views and synchrony of tactile stimulation were manipulated. Participants' level of embodiment was evaluated using a questionnaire and proprioceptive drift. The results show that the likelihood of embodying the virtual hand is affected by the relative visibility of the two views and synchrony of the tactile events. We observed especially strong hand ownership of the virtual hand in the context of high virtual hand visibility with synchronous tactile stimulation.

Effects of Rubber Hand Illusion and Excitatory Theta Burst Stimulation on Tactile Sensation: A Pilot Study.

Synchronous visuotactile stimulation on the own hidden hand and a visible fake limb can alter bodily self-perception and influence spontaneous neuroplasticity. The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. The aim of this cross-over, placebo-controlled, single-blind study was to assess whether RHI, in combination with high-frequency repetitive transcranial magnetic stimulation (rTMS) given as intermittent (excitatory) theta burst stimulation (iTBS) applied over the hand area of the primary sensory region (S1) can enhance tactile sensation in a group of 21 healthy subjects and one patient with cervical spinal cord injury. Four sessions covered all combinations of real and sham stimulations of the RHI and the TBS: real TBS and real RHI, real TBS and sham RHI, sham TBS and real RHI, and both conditions sham. The condition sham TBS and real RHI shows the greatest effect on the proprioceptive drift (median 2.3 cm, IQR 2) and on the score of RHI questionnaires (median 3, IQR 2) in the control group as well as in the real-real condition (median 2, IQR 2). The sham TBS and real RHI condition also shows the best results in the electrical perception test of the patient (median 1.9 mA). Conversely, the upregulation of the cortical excitability of S1 via TBS seems to impair the effect of the RHI. This might be due to a strengthening of the top-down connection between the central nervous system and the periphery, diminishing the RHI. This finding helps in understanding the mechanisms of top-down and bottom-up mechanisms in healthy subjects and patients with spinal cord injury. The RHI paradigm could represent an interesting therapeutic approach in improving tactile sensation and rTMS techniques could modulate these effects. Yet, further studies are needed, to examine the direction of the interaction effect of TMS and RH.

Visual appearance of the virtual hand affects embodiment in the virtual hand illusion

Body ownership (the feeling that one’s body belongs to oneself) is commonly studied with Rubber hand illusion (RHI) paradigm that allows inducing a temporary illusory feeling of ownership of a life-sized rubber hand. However, it remains unclear whether illusory ownership of the fake hand relies on the same mechanisms as ownership of one’s own real hand. Here, we directly compared ownership of the own hand (OH) and fake hand (FH) in the same set of conditions within immersive virtual reality. We obtained behavioral (proprioceptive drift) and subjective (questionnaire) measures of ownership and disownership for virtual OH, FH and object (Obj) that were located congruently or incongruently with the participant’s real hand and were stimulated synchronously or asynchronously with the real hand. Both OH and FH (but not Obj) were embodied after synchronous stimulation in both locations. Crucially, subjective ownership of the OH was stronger than of the FH in congruent location after synchronous stimulation. It was also present after asynchronous stimulation, being stronger when the virtual OH was subjectively more similar to the real hand. The results suggest that the detailed appearance of the body might act as an additional component in the construction of body ownership.

Mechanisms of the breathing contribution to bodily self-consciousness in healthy humans: Lessons from machine-assisted breathing?

Previous studies investigated bodily self‐consciousness (BSC) by experimentally exposing subjects to multisensory conflicts (i.e., visuo‐tactile, audio‐tactile, visuo‐cardiac) in virtual reality (VR) that involve the participant's torso in a paradigm known as the full‐body illusion (FBI). Using a modified FBI paradigm, we found that synchrony of visuo‐respiratory stimulation (i.e., a flashing outline surrounding an avatar in VR; the flash intensity depending on breathing), is also able to modulate BSC by increasing self‐location and breathing agency toward the virtual body. Our aim was to investigate such visuo‐respiratory effects and determine whether respiratory motor commands contributes to BSC, using non‐invasive mechanical ventilation (i.e., machine‐delivered breathing). Seventeen healthy participants took part in a visuo‐respiratory FBI paradigm and performed the FBI during two breathing conditions: (a) “active breathing” (i.e., participants actively initiate machine‐delivered breaths) and (b) “passive breathing” (i.e., breaths’ timing was determined by the machine). Respiration rate, tidal volume, and their variability were recorded. In line with previous results, participants experienced subjective changes in self‐location, breathing agency, and self‐identification toward the avatar's body, when presented with synchronous visuo‐respiratory stimulation. Moreover, drift in self‐location was reduced and tidal volume variability were increased by asynchronous visuo‐respiratory stimulations. Such effects were not modulated by breathing control manipulations. Our results extend previous FBI findings showing that visuo‐respiratory stimulation affects BSC, independently from breathing motor command initiation. Also, variability of respiratory parameters was influenced by visuo‐respiratory feedback and might reduce breathing discomfort. Further exploration of such findings might inform the development of respiratory therapeutic tools using VR in patients.

Synchronous stimulation in the rubber hand illusion task boosts the subsequent sense of ownership on the vicarious agency task

The relationship between sense of agency and sense of ownership remains unclear. Here we investigated this relationship by manipulating ownership using the rubber hand illusion and assessing the resulting impact on self-experiences during the vicarious agency illusion. We tested whether modulating ownership towards another limb using the rubber hand illusion would subsequently influence the illusory experience of ownership and agency towards a similar-looking limb in the vicarious agency task. Crucially, the vicarious agency task measures both sense of agency and sense of ownership at the same time, while removing the confounding influence of motor signals. Our results replicated the well-established effects of both paradigms. We also found that manipulating the sense of ownership with the rubber hand illusion influenced the subsequent vicarious experience of ownership but not the vicarious experience of agency. This supports the idea that sense of agency and sense of ownership are, at least partially, independent experiences.

Altered self-recognition in patients with schizophrenia

Self-alienation is a common characterization of various disturbing experiences in patients with schizophrenia. A vivid example comes from patient reports of not recognizing themselves when inspecting their specular image in the mirror. By applying the multisensory paradigm of the Enfacement Illusion, this study empirically addresses the specular Self-Other discrimination in patients with schizophrenia. 35 patients diagnosed with schizophrenia and 35 healthy matched controls were enrolled in the study. Results found that the group of patients with schizophrenia had a significant skewed self-other discrimination towards the other at baseline. Furthermore, the effect of visuo-tactile stimulation on self-recognition in the schizophrenia patients was significantly altered after both synchronous and asynchronous stimulation compared to baseline. This contrasted with healthy controls which in line with earlier studies only had significantly different self-recognition after synchronous stimulation. The study thus suggests that patients with schizophrenia have deviations in their specular self-recognition compared to healthy controls. Moreover, that temporal factors in multisensory integration may contribute to alterations of self-related stimuli in patients with schizophrenia.

"Fake it till You Make it"! Contaminating Rubber Hands ("Multisensory Stimulation Therapy") to Treat Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a deeply enigmatic psychiatric condition associated with immense suffering worldwide. Efficacious therapies for OCD, like exposure and response prevention (ERP), are sometimes poorly tolerated by patients. As many as 25% of patients refuse to initiate ERP mainly because they are too anxious to follow exposure procedures. Accordingly, we proposed a simple and tolerable (immersive yet indirect) low-cost technique for treating OCD that we call “multisensory stimulation therapy.” This method involves contaminating a rubber hand during the so-called “rubber hand illusion” (RHI) in which tactile sensations may be perceived as arising from a fake hand. Notably, Jalal et al. (2015) showed that such fake hand contamination during the RHI provokes powerful disgust reactions in healthy volunteers. In the current study, we explored the therapeutic potential of this novel approach. OCD patients (n = 29) watched as their hidden real hand was being stroked together with a visible fake hand; either synchronously (inducing the RHI; i.e., the experimental condition; n = 16) or asynchronously (i.e., the control condition; n = 13). After 5 min of tactile stimulation, the rubber hand was contaminated with fake feces, simulating conventional exposure therapy. Intriguingly, results suggested sensory assimilation of contamination sensations into the body image via the RHI: patients undergoing synchronous stimulation did not report greater contamination sensations when the fake hand was initially contaminated relative to asynchronous stroking. But contrary to expectations, they did so after the rubber hand had been contaminated for 5 min, as assessed via disgust facial expressions (a secondary outcome) and in vivo exposure (upon discontinuing the illusion). Further, to our surprise, synchronous and asynchronous stroking induced an equally vivid and fast-emerging illusion, which helps explain why both conditions initially (5 min after initiating tactile stimulation) provoked contamination reactions of equal magnitude. This study is the first to suggest heightened malleability of body image in OCD. Importantly, it may pave the way for a tolerable technique for the treatment of OCD—highly suitable for poorly resourced and emergency settings, including low-income and developing countries with minimal access to high-tech solutions like virtual reality.

Getting closer: Synchronous interpersonal multisensory stimulation increases closeness and attraction toward an opposite-sex other in female participants.

Experiencing tactile facial stimulation while seeing synchronous stimulations delivered to another's face induces enfacement, i.e. the subjective experience of ownership over the other's face. The synchronous Interpersonal Multisensory Stimulation (IMS) procedure leading to enfacement induces changes beyond the bodily sense of self, such as increased feeling of closeness between self and other. However, evidence for such an influence of IMS on higher-level self-other representations remains limited. Moreover, research has been restricted to settings involving a same-sex other. The current study tested, in female participants, whether IMS could promote social closeness and attraction toward an opposite-sex other. Across two experiments, enfacement with an opposite-sex face was successfully obtained. Synchronous (vs. asynchronous) IMS yielded greater closeness with the other and induced greater Liking and Attraction scores. These novel findings add further evidence to the existence of a link between body representation and social cognition. Implications for interpersonal attraction are discussed.

Synchronous Stimulation With Light and Heat Induces Body Ownership and Reduces Pain Perception

In this study, we investigated whether illusionary body ownership over artificial hands and non-corporeal objects modulates pain perception. Previous research has yielded to mixed results, but has separated painful stimulation used to test pain perception from the stimulation that was used to induce the illusion. Here, we used a variant of the rubber hand illusion (RHI) paradigm and induced the illusion directly via a combination of visual and painful stimuli. We presented heat pain stimuli at the real hand and visual stimuli beneath a rubber hand (part1), or a glass ball (part2). Illusion ratings were higher and pain ratings were lower in the synchronous compared to the asynchronous condition in both parts of the experiment. This study demonstrated the successful induction of a body illusion using a new visual–thermal method with painful stimuli. We showed that the RHI and interestingly also the glass ball has an analgesic effect on the perception of the heat pain stimuli. Our data suggests that induced ownership over artificial limbs but also over non-corporeal objects can reduce the perceived pain perception. This might be mediated via a partial referral of the perceived location of pain or respectively a distribution of pain over 2 locations. PerspectiveThis article presents a new visual–thermal method with painful stimuli for the induction of the Rubber Hand Illusion. An illusionary body ownership over artificial hands and non-corporeal has an analgesic effects on the perception of pain. Similar approaches might be useful to alleviate chronic pain, but needs further testing.

The enfacement illusion boosts facial mimicry

Facial mimicry, the automatic imitation of another person's emotion, is a mechanism underlying emotion recognition and emotional contagion, a phylogenetically conserved form of empathy that precedes later developing empathic skills. We tested the possibility to increase facial mimicry by blurring self-other distinction via the enfacement illusion. To do so we delivered synchronous, versus asynchronous, visuo-tactile interpersonal multisensory stimulation on the observer and expresser's faces and then recorded surface facial EMG while participants observed videos of happy and sad facial expressions displayed by the expresser. Our results show that synchronous visuo-tactile stimulation can indeed enhance facial mimicry and that this depends on participants' baseline tendency to mimic.. Our findings could set the basis for developing novel interventions for conditions characterized by reduced empathic and emotion recognition skills, including autism and schizophrenia.

Self-Concept Clarity and the Bodily Self: Malleability Across Modalities.

The self has fascinated scholars for centuries. Although theory suggests that the self-concept (cognitive self-understanding) and bodily self (pre-reflective awareness of one's body) are related, little work has examined this notion. To this end, in Study 1, participants reported on self-concept clarity (SCC) and completed the rubber hand illusion (RHI), a paradigm in which synchronous (vs. asynchronous) stimulation between a prosthetic hand and one's own hand leads one to "embody" the prosthetic hand. Whereas participants were equally susceptible to the RHI during synchronous stroking, low-SCC individuals were more vulnerable to the illusion during asynchronous stroking, when the effect is unwarranted. Conceptually replicating and extending this finding, in Study 2, low-SCC individuals were more susceptible to the body-swap illusion-the impression that another person's body is one's own. These findings suggest that a clear sense of self implies clarity and stability of both the self-concept and the bodily self.

A visual-haptic neurofeedback training improves sensorimotor cortical activations and BCI performance.

Neurofeedback training (NFT) could provide a novel way to investigate or restore the impaired brain function and neuroplasticity. However, it remains unclear how much the different feedback modes can contribute to NFT training. Specifically, whether they can enhance the cortical activations for motor training. To this end, our study proposed a brain-computer interface (BCI) based visual-haptic NFT incorporating synchronous visual scene and proprioceptive electrical stimulation feedback. By comparison between previous and posterior control sessions, the cortical activations measured by multi-band (i.e. alpha_1: 8-10Hz, alpha_2: 11-13Hz, beta_1: 15-20Hz and beta_2: 22-28Hz) lateralized relative event-related desynchronization (lrERD) patterns were significantly enhanced after NFT. And the classification performance was also significantly improved, achieving a ~9% improvement and reaching ~85% in mean classification accuracy from a relatively low MI-BCI performance. These findings validate the feasibility of our proposed visual- haptic NFT approach to improve sensorimotor cortical activations and BCI performance during motor training.

Multisensory Facial Stimulation Implicitly Improves Evaluations of the Goodness of Attractive Others.

It has been well demonstrated that shared multisensory experiences between the self and others can influence the social perception of out-group members. Previous research has shown that the illusion of ownership over a dark-skinned rubber hand or full virtual body generated less negative implicit bias against people with dark skin. However, less is known about how perceived attractiveness difference between self and other affects social perception toward those others after shared multisensory experience. The present study assessed whether shared multisensory experience between the self and attractive others would affect the implicit evaluation of goodness of others. Seventy-three women participated in the study. After the visuotactile multisensory stimulation procedure, participants were administered the Single Category Implicit Association Test (SC-IAT), which presents two attributes (good and bad) and one concept (other). Results showed that the more attractive the faces are, the more positive their implicit evaluation becomes after the synchronous tactile stimulation. This result suggests that shared multisensory experience makes people feel more positive toward others who have positive attribute. This finding suggests that self-other blurring in social contexts might be a compelling factor in evaluating other people positively.

Rubber tail illusion is weakened in Ca2+-dependent activator protein for secretion 2 (Caps2)-knockout mice

Body ownership is a fundamental aspect of self-consciousness. Illusion of body ownership is caused by updating body representation through multisensory integration. Synchronous visuotactile stimulation of a hand and rubber hand leads to illusory changes in body ownership in humans, but this is impaired in individuals with autism spectrum disorder (ASD). We previously reported that mice also exhibit body ownership illusion. With synchronous stroking of a tail and rubber tail, mice responded as if their own tails were being touched when the rubber tails were grasped (‘rubber tail illusion’). However, it remains unknown whether deficits in illusion of body ownership occur in mouse models of autism. Here, we examined whether the ‘rubber tail illusion’ occurred in Ca2+-dependent activator protein for secretion 2-knockout (Caps2-KO) mice, which exhibit autistic-like phenotypes. During the synchronous stroking, response rates were significantly lower in Caps2-KO mice than in wild-type mice. There were no significant differences between the response rates of wild-type and Caps2-KO mice during the asynchronous stroking. The ‘rubber tail illusion’ was weak in Caps2-KO mice, suggesting that Caps2-KO mice experienced weaker visuotactile integration during the task. The rubber tail task will be a useful tool in mouse models of autism to evaluate atypical sensory processing.

Rubber hands in space: the role of distance and relative position in the rubber hand illusion

The rubber hand illusion (RHI) is a perceptual phenomenon in which participants experience ownership over a fake model hand through synchronous visuotactile stimulation. Several studies have shown that the illusion occurs only when both hands are in close proximity to each other. In the present study, we systematically examined the role of relative position (lateral, distal) and distance (13–75 cm) of the model hand (with respect to participants’ real hand) on illusion experience across both lateral and distal positions. Furthermore, we also compared different facets of the subjective illusion experience; the experience of the model hand being part of one’s body (i.e., ownership) and the perceptual fusion of vision and touch (i.e., referral of touch). In two experiments we observed indications for a stronger illusion experiences in distal compared to lateral positions of identical distances, indicating that the illusory effects may vary as a function of the relative position of the hand. Our results also showed that manipulations of distance differently modulated both facets of the illusion. While ownership was restricted to near distances, referral of touch sensations remained stable at farther distances. These results are interpreted in relation to variations in sensory weighting across different planes.

Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement

G protein-coupled receptors (GPCRs) are key biological switches that transmit both internal and external stimuli into the cell interior. Among the GPCRs, the "light receptor" rhodopsin has been shown to activate with a rearrangement of the transmembrane (TM) helix bundle within ∼1 ms, while all other receptors are thought to become activated within ∼50 ms to seconds at saturating concentrations. Here, we investigate synchronous stimulation of a dimeric GPCR, the metabotropic glutamate receptor type 1 (mGluR1), by two entirely different methods: (i) UV light-triggered uncaging of glutamate in intact cells or (ii) piezo-driven solution exchange in outside-out patches. Submillisecond FRET recordings between labels at intracellular receptor sites were used to record conformational changes in the mGluR1. At millimolar ligand concentrations, the initial rearrangement between the mGluR1 subunits occurs at a speed of τ1 ∼ 1-2 ms and requires the occupancy of both binding sites in the mGluR1 dimer. These rapid changes were followed by significantly slower conformational changes in the TM domain (τ2 ∼ 20 ms). Receptor deactivation occurred with time constants of ∼40 and ∼900 ms for the inter- and intrasubunit conformational changes, respectively. Together, these data show that, at high glutamate concentrations, the initial intersubunit activation of mGluR1 proceeds with millisecond speed, that there is loose coupling between this initial step and activation of the TM domain, and that activation and deactivation follow a cyclic pathway, including-in addition to the inactive and active states-at least two metastable intermediate states.

Intersensory redundancy promotes infant detection of prosody in infant-directed speech

Prosody, or the intonation contours of speech, conveys emotion and intention to the listener and provides infants with an early basis for detecting meaning in speech. Infant-directed speech (IDS) is characterized by exaggerated prosody, slower tempo, and elongated pauses, all amodal properties detectable across the face and voice. Although speech is an audiovisual event, it has been studied primarily as a unimodal auditory stream without the synchronized dynamic face of the speaker. According to the intersensory redundancy hypothesis, redundancy across the senses facilitates perceptual learning of amodal information, including prosody. We predicted that young infants who are still learning to discriminate and categorize prosodic information would detect prosodic changes better in the presence of intersensory redundancy (i.e., synchronous audiovisual speech) than in its absence (i.e., unimodal auditory or asynchronous audiovisual speech). To test this hypothesis, 72 4-month-old infants were habituated to recordings of women reciting passages in IDS with prosody conveying either approval or prohibition and then were tested with recordings of a novel passage with either a change or no change in prosody. Infants who received bimodal synchronous stimulation exhibited significant visual recovery to the novel passage with a change in prosody, but not to a novel passage with no change in prosody. Infants in the unimodal auditory and bimodal asynchronous conditions did not exhibit visual recovery in either condition. Results support the hypothesis that intersensory redundancy facilitates detection and abstraction of invariant prosody across changes in linguistic content and likely serves as an early foundation for the detection of meaning in fluent speech.

Malleability of the self: electrophysiological correlates of the enfacement illusion

Self-face representation is fundamentally important for self-identity and self-consciousness. Given its role in preserving identity over time, self-face processing is considered as a robust and stable process. Yet, recent studies indicate that simple psychophysics manipulations may change how we process our own face. Specifically, experiencing tactile facial stimulation while seeing similar synchronous stimuli delivered to the face of another individual seen as in a mirror, induces ‘enfacement’ illusion, i.e. the subjective experience of ownership of the other’s face and a bias in attributing to the self, facial features of the other person. Here we recorded visual Event-Related Potentials elicited by the presentation of self, other and morphed faces during a self-other discrimination task performed immediately after participants received synchronous and control asynchronous Interpersonal Multisensory Stimulation (IMS). We found that self-face presentation after synchronous as compared to asynchronous stimulation significantly reduced the late positive potential (LPP; 450–750 ms), a reliable electrophysiological marker of self-identification processes. Additionally, enfacement cancelled out the differences in LPP amplitudes produced by self- and other-face during the control condition. These findings represent the first direct neurophysiological evidence that enfacement may affect self-face processing and pave the way to novel paradigms for exploring defective self-representation and self-other interactions.

Dynamic Displacement Vector Interacts with Tactile Localization

SummaryLocating a tactile stimulus on the body seems effortless and straightforward. However, the perceived location of a tactile stimulation can differ from its physical location [1, 2, 3]. Tactile mislocalizations can depend on the timing of successive stimulations [2, 4, 5], tactile motion mechanisms [6], or processes that “remap” stimuli from skin locations to external space coordinates [7, 8, 9, 10, 11]. We report six experiments demonstrating that the perception of tactile localization on a static body part is strongly affected by the displacement between the locations of two successive task-irrelevant actions. Participants moved their index finger between two keys. Each keypress triggered synchronous tactile stimulation at a randomized location on the immobilized wrist or forehead. Participants reported the location of the second tactile stimulation relative to the first. The direction of either active finger movements or passive finger displacements biased participants’ tactile orientation judgements (experiment 1). The effect generalized to tactile stimuli delivered to other body sites (experiment 2). Two successive keypresses, by different fingers at distinct locations, reproduced the effect (experiment 3). The effect remained even when the hand that moved was placed far from the tactile stimulation site (experiments 4 and 5). Temporal synchrony within 600 ms between the movement and tactile stimulations was necessary for the effect (experiment 6). Our results indicate that a dynamic displacement vector, defined as the location of one sensorimotor event relative to the one before, plays a strong role in structuring tactile spatial perception.