Active self-touch restores bodily proprioceptive spatial awareness following disruption by 'rubber hand illusion'.

Bodily self-awareness relies on a constant integration of visual, tactile, proprioceptive, and motor signals. In the 'rubber hand illusion' (RHI), conflicting visuo-tactile stimuli lead to changes in self-awareness. It remains unclear whether other, somatic signals could compensate for the alterations in self-awareness caused by visual information about the body. Here, we used the RHI in combination with robot-mediated self-touch to systematically investigate the role of tactile, proprioceptive and motor signals in maintaining and restoring bodily self-awareness. Participants moved the handle of a leader robot with their right hand and simultaneously received corresponding tactile feedback on their left hand from a follower robot. This self-touch stimulation was performed either before or after the induction of a classical RHI. Across three experiments, active self-touch delivered after-but not before-the RHI, significantly reduced the proprioceptive drift caused by RHI, supporting a restorative role of active self-touch on bodily self-awareness. The effect was not present during involuntary self-touch. Unimodal control conditions confirmed that both tactile and motor components of self-touch were necessary to restore bodily self-awareness. We hypothesize that active self-touch transiently boosts the precision of proprioceptive representation of the touched body part, thus counteracting the visual capture effects that underlie the RHI.

Quantifying spatial acuity of frequency resolved midair ultrasound vibrotactile stimuli.

Spatial acuity is a fundamental property of any sensory system. In the case of the somatosensory system, the two-point discrimination (2PD) test has long been used to investigate tactile spatial resolution. However, the somatosensory system comprises three main mechanoreceptive channels: the slowly adapting channel (SA) responds to steady pressure, the rapidly adapting channel (RA) responds to low-frequency vibration, and the Pacinian channel (PC) responds to high-frequency vibration. The use of mechanical stimuli in the classical 2PD test means that previous studies on tactile acuity have primarily focussed on the pressure-sensitive channel alone, while neglecting other submodalities. Here, we used a novel ultrasound stimulation to systematically investigate the spatial resolution of the two main vibrotactile channels. Contrary to the textbook view of poor spatial resolution for PC-like stimuli, across four experiments we found that high-frequency vibration produced surprisingly good spatial acuity. This effect remained after controlling for interchannel differences in stimulus detectability and perceived intensity. Laser doppler vibrometry experiments confirmed that the acuity of the PC channel was not simply an artifact of the skin's resonance to high-frequency mechanical stimulation. Thus, PC receptors may transmit substantial spatial information, despite their sparse distribution, deep location, and large receptive fields.

Erratum: Touching with the eyes: Oculomotor self-touch induces illusory body ownership.

[This corrects the article DOI: 10.1016/j.isci.2023.106180.].

Touching with the eyes: Oculomotor self-touch induces illusory body ownership.

Self-touch plays a central role in the construction and plasticity of the bodily self. But which mechanisms support this role? Previous accounts emphasize the convergence of proprioceptive and tactile signals from the touching and the touched body parts. Here, we hypothesise that proprioceptive information is not necessary for self-touch modulation of body-ownership. Because eye movements do not rely on proprioceptive signals as limb movements do, we developed a novel oculomotor self-touch paradigm where voluntary eye movements generated corresponding tactile sensations. We then compared the effectiveness of eye versus hand self-touch movements in generating an illusion of owning a rubber hand. Voluntary oculomotor self-touch was as effective as hand-driven self-touch, suggesting that proprioception does not contribute to body ownership during self-touch. Self-touch may contribute to a unified sense of bodily self by binding voluntary actions toward our own body with their tactile consequences.

Resistin-like beta reduction is associated to low survival rate and is downregulated by adjuvant therapy in colorectal cancer patients.

Colorectal Cancer (CRC) is one of the most common cancers accounting for 1.8 million new cases worldwide every year. Therefore, the identification of new potential therapeutic targets represents a continuous challenge to improve survival and quality of CRC patient's life. We performed a microarray analysis dataset consisting of colon biopsies of healthy subjects (HS) and CRC patients. These results were further confirmed in a clinical setting evaluating a series of CRC patients to assess the expression of Resistin-Like Beta (RETNLB) and to correlate it with their clinical data. Our results showed a significant reduction of RETNLB expression in CRC biopsies compared to the HS mucosa. Furthermore, such reduction was significantly associated with the TNM grade and patients' age. Furthermore, a significantly positive correlation was found within mutated subjects for KRAS, TP53, and BRAF. In particular, patients with poor prognosis at 5 years exhibited RETNLB lower levels. In-silico analysis data were confirmed by histochemical analysis in a series of CRC patients recruited by our group. The results obtained provided that RETNLB low levels are associated with an unfavorable prognosis in CRC patients and its expression is also dependent on adjuvant therapy. Further studies are warranted in order to evaluate the molecular mechanisms underlying the role of RETNLB in CRC progression.

Interhemispheric communication during haptic self-perception.

During the haptic exploration of a planar surface, slight resistances against the hand's movement are illusorily perceived as asperities (bumps) in the surface. If the surface being touched is one's own skin, an actual bump would also produce increased tactile pressure from the moving finger onto the skin. We investigated how kinaesthetic and tactile signals combine to produce haptic perceptions during self-touch. Participants performed two successive movements with the right hand. A haptic force-control robot applied resistances to both movements, and participants judged which movement was felt to contain the larger bump. An additional robot delivered simultaneous but task-irrelevant tactile stroking to the left forearm. These strokes contained either increased or decreased tactile pressure synchronized with the resistance-induced illusory bump encountered by the right hand. We found that the size of bumps perceived by the right hand was enhanced by an increase in left tactile pressure, but also by a decrease. Tactile event detection was thus transferred interhemispherically, but the sign of the tactile information was not respected. Randomizing (rather than blocking) the presentation order of left tactile stimuli abolished these interhemispheric enhancement effects. Thus, interhemispheric transfer during bimanual self-touch requires a stable model of temporally synchronized events, but does not require geometric consistency between hemispheric information, nor between tactile and kinaesthetic representations of a single common object.

Multiple primary malignances managed with surgical excision: a case report with next generation sequencing analysis.

BACKGROUND: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases. METHODS AND RESULTS: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers. CONCLUSIONS: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development.

Interplay of tactile and motor information in constructing spatial self-perception.

During active movement, there is normally a tight relation between motor command and sensory representation about the resulting spatial displacement of the body. Indeed, some theories of space perception emphasize the topographic layout of sensory receptor surfaces, while others emphasize implicit spatial information provided by the intensity of motor command signals. To identify which has the primary role in spatial perception, we developed experiments based on everyday self-touch, in which the right hand strokes the left arm. We used a robot-mediated form of self-touch to decouple the spatial extent of active or passive right hand movements from their tactile consequences. Participants made active movements of the right hand between unpredictable, haptically defined start and stop positions, or the hand was passively moved between the same positions. These movements caused a stroking tactile motion by a brush along the left forearm, with minimal delay, but with an unpredictable spatial gain factor. Participants judged the spatial extent of either the right hand's movement, or of the resulting tactile stimulation to their left forearm. Across five experiments, we found that movement extent strongly interfered with tactile extent perception, and vice versa. Crucially, interference in both directions was stronger during active than passive movements. Thus, voluntary motor commands produced stronger integration of multiple sensorimotor signals underpinning the perception of personal space. Our results prompt a reappraisal of classical theories that reduce space perception to motor command information.

Touch inhibits touch: sanshool-induced paradoxical tingling reveals perceptual interaction between somatosensory submodalities.

Human perception of touch is mediated by inputs from multiple channels. Classical theories postulate independent contributions of each channel to each tactile feature, with little or no interaction between channels. In contrast to this view, we show that inputs from two sub-modalities of mechanical input channels interact to determine tactile perception. The flutter-range vibration channel was activated anomalously using hydroxy-α-sanshool, a bioactive compound of Szechuan pepper, which chemically induces vibration-like tingling sensations. We tested whether this tingling sensation on the lips was modulated by sustained mechanical pressure. Across four experiments, we show that sustained touch inhibits sanshool tingling sensations in a location-specific, pressure-level and time-dependent manner. Additional experiments ruled out the mediation of this interaction by nociceptive or affective (C-tactile) channels. These results reveal novel inhibitory influence from steady pressure onto flutter-range tactile perceptual channels, consistent with early-stage interactions between mechanoreceptor inputs within the somatosensory pathway.

Sensorimotor signals underlying space perception: An investigation based on self-touch.

Perception of space has puzzled scientists since antiquity, and is among the foundational questions of scientific psychology. Classical "local sign" theories assert that perception of spatial extent ultimately derives from efferent signals specifying the intensity of motor commands. Everyday cases of self-touch, such as stroking the left forearm with the right index fingertip, provide an important platform for studying spatial perception, because of the tight correlation between motor and tactile extents. Nevertheless, if the motor and sensory information in self-touch were artificially decoupled, these classical theories would clearly predict that motor signals - especially if self-generated rather than passive - should influence spatial perceptual judgements, but not vice versa. We tested this hypothesis by quantifying the contribution of tactile, kinaesthetic, and motor information to judgements of spatial extent. In a self-touch paradigm involving two coupled robots in master-slave configuration, voluntary movements of the right-hand produced simultaneous tactile stroking on the left forearm. Crucially, the coupling between robots was manipulated so that tactile stimulation could be shorter, equal, or longer in extent than the movement that caused it. Participants judged either the extent of the movement, or the extent of the tactile stroke. By controlling sensorimotor gains in this way, we quantified how motor signals influence tactile spatial perception, and vice versa. Perception of tactile extent was strongly biased by the amplitude of the movement performed. Importantly, touch also affected the perceived extent of movement. Finally, the effect of movement on touch was significantly stronger when movements were actively-generated compared to when the participant's right hand was passively moved by the experimenter. Overall, these results suggest that motor signals indeed dominate the construction of spatial percepts, at least when the normal tight correlation between motor and sensory signals is broken. Importantly, however, this dominance is not total, as classical theory might suggest.

Giant hepatic hemangioma case report: When is it time for surgery?

We describe a case of a 30-year-old man who complained intermitted pain in right abdominal flank; a large cavernoumatos hemangioma - up to 6 cm in size - was revealed in the fifth hepatic segment using Ultrasonography and MRI (Magnetic Resonance Imaging). Indications for treatment - based on imaging features and clinical data - are briefly discussed in our report, providing also a review of existing literature.

The Detached Self: Investigating the Effect of Depersonalisation on Self-Bias in the Visual Remapping of Touch.

There is a growing consensus that our most fundamental sense of self is structured by the ongoing integration of sensory and motor information related to our own body. Depersonalisation (DP) is an intriguing form of altered subjective experience in which people report feelings of unreality and detachment from their sense of self. The current study used the visual remapping of touch (VRT) paradigm to explore self-bias in visual-tactile integration in non-clinical participants reporting high and low levels of depersonalisation experiences. We found that the high-DP group showed an increased overall VRT effect but a no-self-face bias, instead showing a greater VRT effect when observing the face of another person. In addition, across all participants, self-bias was negatively predicted by the occurrence of anomalous body experiences. These results indicate disrupted integration of tactile and visual representations of the bodily self in those experiencing high levels of DP and provide greater understanding of how disruptions in multisensory perception of the self may underlie the phenomenology of depersonalisation.

Effects of GIT-27NO, a NO-donating compound, on hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (H2O2), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the H2O2 on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.

Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor. CONCLUSION: This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.

Why the whole is more than the sum of its parts: Salience-driven overestimation in aggregated tactile sensations.

Experimental psychology often studies perception analytically, reducing its focus to minimal sensory units, such as thresholds or just noticeable differences in a single stimulus. Here, in contrast, we examine a synthetic aspect: how multiple inputs to a sensory system are aggregated into an overall percept. Participants in three experiments judged the total stimulus intensity for simultaneous electrical shocks to two digits. We tested whether the integration of component somatosensory stimuli into a total percept occurs automatically, or rather depends on the ability to consciously perceive discrepancy among components (Experiment 1), whether the discrepancy among these components influences sensitivity or/and perceptual bias in judging totals (Experiment 2), and whether the salience of each individual component stimulus affects perception of total intensity (Experiment 3). Perceptual aggregation of two simultaneous component events occurred both when participants could perceptually discriminate the two intensities, and also when they could not. Further, the actual discrepancy between the stimuli modulated both participants' sensitivity and perceptual bias: increasing discrepancies produced a systematic and progressive overestimation of total intensity. The degree of this bias depended primarily on the salience of the stronger stimulus in the pair. Overall, our results suggest that important nonlinear mechanisms contribute to sensory aggregation. The mind aggregates component inputs into a coherent and synthetic perceptual experience in a salience-weighted fashion that is not based on simple summation of inputs.