Out-of-body illusion induced by visual-vestibular stimulation.

Out-of-body experiences (OBEs) are characterized by the subjective feeling of being located outside one's physical body and perceiving one's own body from an elevated perspective looking downwards. OBEs have been correlated with abnormal integration of bodily signals, including visual and vestibular information. In two studies, we used mixed reality combined with a motion platform to manipulate visual and vestibular integration in healthy participants. Behavioral data and questionnaires show that congruent visual-vestibular stimulation in a self-centered reference frame induced an OBE-like illusion characterized by elevated self-location and feelings of disembodiment and lightness. The OBE-like illusion was also modulated by individuals' visual field dependency assessed by the Rod and Frame Test. These results show that the manipulation of visual-vestibular stimulation in the present study induces various aspects of OBEs and further link OBE to congruency mechanisms between visual and vestibular gravitational and self-motion cues.

Virtual reality intervention alleviates dyspnoea in patients recovering from COVID-19 pneumonia.

Background: Immersive virtual reality (iVR)-based digital therapeutics are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnoea, we investigated the effects of visual respiratory feedback on persistent dyspnoea in patients recovering from coronavirus disease 2019 (COVID-19) pneumonia. Methods: We performed a controlled, randomised, single-blind, crossover proof-of-concept study (feasibility and initial clinical efficacy) to evaluate an iVR-based intervention to alleviate dyspnoea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnoea (≥5 on a 10-point scale) and preserved cognitive function (Montreal Cognitive Assessment score >24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. The virtual body flashed in a waxing and waning visual effect that could be synchronous or asynchronous to the patient's respiratory movements. Outcomes were assessed using questionnaires and breathing recordings. Results: Study enrolment was open between November 2020 and April 2021. 26 patients were enrolled (27% women; median age 55 years, interquartile range (IQR) 18 years). Data were available for 24 of 26 patients. The median rating on a 7-point Likert scale of breathing comfort improved from 1 (IQR 2) at baseline to 2 (IQR 1) for synchronous feedback, but remained unchanged at 1 (IQR 1.5) for asynchronous feedback (p<0.05 between iVR conditions). Moreover, 91.2% of all patients were satisfied with the intervention (p<0.0001) and 66.7% perceived it as beneficial for their breathing (p<0.05). Conclusion: Our iVR-based digital therapy presents a feasible and safe respiratory rehabilitation tool that improves breathing comfort in patients recovering from COVID-19 infection presenting with persistent dyspnoea. Future research should investigate the intervention's generalisability to persistent dyspnoea with other aetiologies and its potential for preventing chronification.

Experimentally-evidenced personality alterations following meningioma resection: A case report.

Personality changes following neurosurgical procedures remain poorly understood and pose a major concern for patients, rendering a strong need for predictive biomarkers. Here we report a case of a female patient in her 40s who underwent resection of a large sagittal sinus meningioma with bilateral extension, including resection and ligation of the superior sagittal sinus, that resulted in borderline personality disorder. Importantly, we captured clinically-observed personality changes in a series of experiments assessing self-other voice discrimination, one of the experimental markers for self-consciousness. In all experiments, the patient consistently confused self- and other voices - i.e., she misattributed other-voice stimuli to herself and self-voice stimuli to others. Moreover, the electroencephalogram (EEG) microstate, that was in healthy participants observed when hearing their own voice, in this patient occurred for other-voice stimuli. We hypothesize that the patient's personality alterations resulted from a gradual development of a venous collateral hemodynamic network that impacted venous drainage of brain areas associated with self-consciousness. In addition, resection and ligation of the superior sagittal sinus significantly aggravated personality alterations through postoperative decompensation of a direct frontal lobe compression. Experimentally mirroring clinical observations, these findings are of high relevance for developing biomarkers of post-surgical personality alterations.

ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.

The full-body illusion changes visual depth perception.

Knowing where objects are relative to us implies knowing where we are relative to the external world. Here, we investigated whether space perception can be influenced by an experimentally induced change in perceived self-location. To dissociate real and apparent body positions, we used the full-body illusion. In this illusion, participants see a distant avatar being stroked in virtual reality while their own physical back is simultaneously stroked. After experiencing the discrepancy between the seen and the felt location of the stroking, participants report a forward drift in self-location toward the avatar. We wondered whether this illusion-induced forward drift in self-location would affect where we perceive objects in depth. We applied a psychometric measurement in which participants compared the position of a probe against a reference sphere in a two-alternative forced choice task. We found a significant improvement in task performance for the right visual field, indicated by lower just-noticeable differences, i.e., participants were better at judging the differences of the two spheres in depth. Our results suggest that the full-body illusion is able to facilitate depth perception at least unilaterally, implying that depth perception is influenced by perceived self-location.

Breathing control, brain, and bodily self-consciousness: Toward immersive digiceuticals to alleviate respiratory suffering.

Breathing is peculiar among autonomic functions through several characteristics. It generates a very rich afferent traffic from an array of structures belonging to the respiratory system to various areas of the brain. It is intimately associated with bodily movements. It bears particular relationships with consciousness as its efferent motor control can be automatic or voluntary. In this review within the scope of "respiratory neurophysiology" or "respiratory neuroscience", we describe the physiological organisation of breathing control. We then review findings linking breathing and bodily self-consciousness through respiratory manipulations using virtual reality (VR). After discussing the currently admitted neurophysiological model for dyspnea, as well as a new Bayesian model applied to breathing control, we propose that visuo-respiratory paradigms -as developed in cognitive neuroscience- will foster insights into some of the basic mechanisms of the human respiratory system and will also lead to the development of immersive VR-based digital health tools (i.e. digiceuticals).

The perspectives of mapping and monitoring of the sense of self in neurosurgical patients.

Surgical treatment of tumors, epileptic foci or of vascular origin, requires a detailed individual pre-surgical workup and intra-operative surveillance of brain functions to minimize the risk of post-surgical neurological deficits and decline of quality of life. Most attention is attributed to language, motor functions, and perception. However, higher cognitive functions such as social cognition, personality, and the sense of self may be affected by brain surgery. To date, the precise localization and the network patterns of brain regions involved in such functions are not yet fully understood, making the assessment of risks of related post-surgical deficits difficult. It is in the interest of neurosurgeons to understand with which neural systems related to selfhood and personality they are interfering during surgery. Recent neuroscience research using virtual reality and clinical observations suggest that the insular cortex, medial prefrontal cortex, and temporo-parietal junction are important components of a neural system dedicated to self-consciousness based on multisensory bodily processing, including exteroceptive and interoceptive cues (bodily self-consciousness (BSC)). Here, we argue that combined extra- and intra-operative approaches using targeted cognitive testing, functional imaging and EEG, virtual reality, combined with multisensory stimulations, may contribute to the assessment of the BSC and related cognitive aspects. Although the usefulness of particular biomarkers, such as cardiac and respiratory signals linked to virtual reality, and of heartbeat evoked potentials as a surrogate marker for intactness of multisensory integration for intra-operative monitoring has to be proved, systemic and automatized testing of BSC in neurosurgical patients will improve future surgical outcome.

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.

Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome.

Tourette syndrome is characterized by 'unvoluntary' tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyrus is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcortical and motor regions. Although tic suppression in Tourette syndrome also engages the inferior frontal gyrus, it is unclear whether such prefrontal control of action is also dysfunctional: Tic suppression studies do not permit comparison with control groups, and neuroimaging studies of motor inhibition can be confounded by the concurrent expression or suppression of tics. Here, patients with Tourette syndrome were directly compared to control participants when performing an intentional inhibition task during functional MRI. Tic expression was recorded throughout for removal from statistical models. Participants were instructed to make a button press in response to Go cues, withhold responses to NoGo cues, and decide whether to press or withhold to 'Choose' cues. Overall performance was similar between groups, for both intentional inhibition rates (% Choose-Go) and reactive NoGo inhibition commission errors. A subliminal face prime elicited no additional effects on intentional or reactive inhibition. Across participants, the task activated prefrontal and motor cortices and subcortical nuclei, including pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, thalamus and primary motor cortex. In Tourette syndrome, activity was elevated in the inferior frontal gyrus, insula and basal ganglia, most notably within the right inferior frontal gyrus during voluntary action and inhibition (Choose-Go and Choose-NoGo), and reactive inhibition (NoGo-correct). Anatomically, the locus of this inferior frontal gyrus hyperactivation during control of voluntary action matched that previously reported for tic suppression. In Tourette syndrome, activity within the caudate nucleus was also enhanced during both intentional (Choose-NoGo) and reactive (NoGo-correct) inhibition. Strikingly, despite the absence of overt motor behaviour, primary motor cortex activity increased in patients with Tourette syndrome but decreased in controls during both reactive and intentional inhibition. Additionally, severity of premonitory sensations scaled with functional connectivity of the pre-supplementary motor area to the caudate nucleus, globus pallidus and thalamus when choosing to respond (Choose-Go). Together, these results suggest that patients with Tourette syndrome use equivalent prefrontal mechanisms to suppress tics and withhold non-tic actions, but require greater inferior frontal gyrus engagement than controls to overcome motor drive from hyperactive downstream regions, notably primary motor cortex. Moreover, premonitory sensations may cue midline motor regions to generate tics through interactions with the basal ganglia.

Signatures of alcohol use in the structure and neurochemistry of insular cortex: a correlational study.

RATIONALE: Insular cortex supports the representation of motivational feelings through the integration of interoceptive information concerning bodily physiology. Compromised insular integrity is implicated in alcohol and drug use disorders. Alcohol-associated insular dysfunction may arise through aberrant glutamatergic neurotransmission associated with selective neuronal death and atrophy. OBJECTIVE: In a sample of alcohol users, we combined magnetic resonance spectroscopy (MRS) with voxel and surface-based morphometry (VBM, SBM) to test the hypothesis that the neurochemical and structural properties of the insula relate to alcohol use. METHODS: Twenty-three healthy individuals were characterized by measures of alcohol use and subjective craving. Right mid-insula glutamate/glutamine (Glx) and total N-acetylaspartate/N-acetyl-aspartylglutamate (TNAA) concentrations were measured using MRS. Right insular structure was quantified using VBM and SBM parameters. We tested for predictive associations between these neuroimaging and behavioral/psychometric measures using Bayesian statistics. RESULTS: Reduced insular Glx concentration was associated with increased alcohol compulsions and, to a lesser extent, with greater alcohol use severity. Anecdotal evidence for a negative relationship between alcohol use severity and levels of insular gyrification was also observed. CONCLUSIONS: This study is, to date, the first characterization of the neurochemical and morphological integrity of insular cortex in alcohol users. Our data seem to reveal a negative relationship between alcohol use and the neurochemical and structural integrity of the insula, a critical substrate for motivational behavior. These neurobiological characteristics might contribute to loss of control toward compulsive drinking with prolonged and excessive alcohol use.

Validation of an electronic version of the Self-Awareness Questionnaire in English and Italian healthy samples.

OBJECTIVES: Interoception is a general sensitivity to bodily sensations that informs motivational processes and behaviours. Interoceptive abilities seem to be impaired in several clinical conditions, and the development of new pragmatic instruments to assess subjective components of interoception are crucially needed. An easy to use paper and pencil questionnaire measuring sensitivity to bodily sensations was validated in an Italian sample (Self-Awareness Questionnaire; SAQ). METHODS: In the present study, we created and evaluated an electronic version of the SAQ in Italian and English language. RESULTS: Psychometric properties of both electronic versions of the SAQ were validated in an Italian (n = 206) and an English (n = 275) sample, using factorial analyses. Differences in factorial structures observed between the two samples were discussed in terms of cultural impact on emotional regulation and bodily sensations processing. CONCLUSIONS: The electronic version of SAQ in English and Italian provides a pragmatic and validated tool to evaluate bodily signal sensitivity in clinical settings, informing the development of a new therapy targeting interoceptive processes, in a wide range of psychopathological conditions.

Impact of intranasal oxytocin on interoceptive accuracy in alcohol users: an attentional mechanism?

Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the phenomenon of craving, and is reportedly disrupted in alcohol use disorders. The hormone oxytocin influences afferent transmission of bodily signals and, through its potential modulation of craving, is proposed as a possible treatment for alcohol use disorders. However, oxytocin's impact on interoception in alcohol users remains unknown. Healthy alcohol users (n = 32) attended two laboratory sessions to perform tests of interoceptive ability (heartbeat tracking: attending to internal signals and, heartbeat discrimination: integrating internal and external signals) after intranasal administration of oxytocin or placebo. Effects of interoceptive accuracy, oxytocin administration and alcohol intake, were tested using mixed-effects models. On the tracking task, oxytocin reduced interoceptive accuracy, but did not interact with alcohol consumption. On the discrimination task, we found an interaction between oxytocin administration and alcohol intake: Oxytocin, compared with placebo, increased interoceptive accuracy in heavy drinkers, but not in light social drinkers. Our study does not suggest a pure interoceptive impairment in alcohol users but instead potentially highlights reduced flexibility of internal and external attentional resource allocation. Importantly, this impairment seems to be mitigated by oxytocin. This attentional hypothesis needs to be explicitly tested in future research.

How Do Self-Assessment of Alexithymia and Sensitivity to Bodily Sensations Relate to Alcohol Consumption?

BACKGROUND: Alexithymia describes an abnormality of emotional experience that is commonly expressed among individuals with addiction and alcohol abuse disorders. Alexithymic individuals are characterized by difficulties in identifying and describing their emotions. This impairment is linked to the development and maintenance of addiction. Moreover, an emergent theory suggests alexithymia is itself secondary to a failure of interoception (sensitivity to internal bodily signals, including physiological arousal states). METHODS: This study tested for hypothesized contributory roles of alexithymia and dysfunctional interoception in the expression of social drinking. Alexithymia, subjective sensitivity to bodily sensations, and alcohol consumption scores were quantified using the Toronto Alexithymia Scale, the Body Perception Questionnaire, and the Alcohol Use Questionnaire, respectively, in a normative sample (N = 600). Regression and bootstrapping mediation analyses were used to test the hypothesis that alexithymia mediated the association between sensitivity to bodily sensations and alcohol consumption. RESULTS: Alexithymia was positively correlated with sensitivity to bodily sensations and with alcohol consumption. Mediation analysis revealed that alexithymia, and more precisely, difficulty in identifying feelings, mediated the relationship between sensitivity to bodily sensations and alcohol consumption, such that the predictive effect of sensitivity to bodily sensations on alcohol intake became nonsignificant when controlling for alexithymia. CONCLUSIONS: These results indicate that alexithymia is associated with subjective hypersensitivity to bodily sensations. Moreover, our findings support the theoretical proposal that alexithymia is an expression of impaired processing of bodily sensations including physiological arousal, which underpin the development of maladaptive coping strategies, including alcohol use disorders. Our observations extend a growing literature emphasizing the importance of interoception and alexithymia in addiction, which can inform the development of new therapeutic strategies.

Feedback from the heart: Emotional learning and memory is controlled by cardiac cycle, interoceptive accuracy and personality.

Feedback processing is critical to trial-and-error learning. Here, we examined whether interoceptive signals concerning the state of cardiovascular arousal influence the processing of reinforcing feedback during the learning of 'emotional' face-name pairs, with subsequent effects on retrieval. Participants (N=29) engaged in a learning task of face-name pairs (fearful, neutral, happy faces). Correct and incorrect learning decisions were reinforced by auditory feedback, which was delivered either at cardiac systole (on the heartbeat, when baroreceptors signal the contraction of the heart to the brain), or at diastole (between heartbeats during baroreceptor quiescence). We discovered a cardiac influence on feedback processing that enhanced the learning of fearful faces in people with heightened interoceptive ability. Individuals with enhanced accuracy on a heartbeat counting task learned fearful face-name pairs better when feedback was given at systole than at diastole. This effect was not present for neutral and happy faces. At retrieval, we also observed related effects of personality: First, individuals scoring higher for extraversion showed poorer retrieval accuracy. These individuals additionally manifested lower resting heart rate and lower state anxiety, suggesting that attenuated levels of cardiovascular arousal in extraverts underlies poorer performance. Second, higher extraversion scores predicted higher emotional intensity ratings of fearful faces reinforced at systole. Third, individuals scoring higher for neuroticism showed higher retrieval confidence for fearful faces reinforced at diastole. Our results show that cardiac signals shape feedback processing to influence learning of fearful faces, an effect underpinned by personality differences linked to psychophysiological arousal.