Traditional models of speech perception posit that neural activity encodes speech through a hierarchy of cognitive processes, from low-level representations of acoustic and phonetic features to high-level semantic encoding. Yet it remains unknown how neural representations are transformed across levels of the speech hierarchy. Here, we analyzed unique microelectrode array recordings of neuronal spiking activity from the human left anterior superior temporal gyrus, a brain region at the interface between phonetic and semantic speech processing, during a semantic categorization task and natural speech perception. We identified distinct neural manifolds for semantic and phonetic features, with a functional separation of the corresponding low-dimensional trajectories. Moreover, phonetic and semantic representations were encoded concurrently and reflected in power increases in the beta and low-gamma local field potentials, suggesting top-down predictive and bottom-up cumulative processes. Our results are the first to demonstrate mechanisms for hierarchical speech transformations that are specific to neuronal population dynamics.

Background: Deficits in self are commonly described through different neuro-pathologies, based on clinical evaluations and experimental paradigms. However, currently available approaches lack appropriate clinical validation, making objective evaluation and discrimination of self-related deficits challenging. Methods: We applied a statistical standardized method to assess the clinical discriminatory capacity of a Self-Other Voice Discrimination (SOVD) task. This task, validated experimentally as a marker for self-related deficits, was administered to 17 patients eligible for neurosurgery due to focal hemispheric brain tumors or epileptic lesions. Results: The clinical discriminatory capacity of the SOVD task was evident in three patients who exhibited impairments for self-voice perception that could not be predicted by other neuropsychological deficits. Impairments in other-voice perception were linked to inhibitory neuropsychological deficits, suggesting a potential association with executive deficits in voice recognition. Conclusions: This exploratory study highlights the clinical discriminatory potential of the SOVD task and suggests that it could complement the standard neuropsychological assessment, paving the way for enhanced diagnoses and tailored treatments for self-related deficits.

Self-voice plays an important role in our everyday lives. Apart from being used for communication, our own voice defines our identity, as it is the sound that is most intimately related to ourselves. Disturbances in self-voice recognition have been related to certain psychotic symptoms such as auditory-verbal hallucinations, colloquially called ‘hearing voices’, and to a distorted sense of self more generally. Recent research has indicated that a specific self-other voice discrimination procedure combining psychophysics, voice morphing technology, as well as air-and bone-conducted voice stimuli can be of clinical significance as a biomarker for detecting pathological alterations in self-consciousness. However, there are several limitations with the existing approach, mainly in not being simple to use and difficult to apply in different clinical contexts. To address these drawbacks, we adapted the current methodology and developed a self-other voice discrimination solution with a graphical user interface, automated voice morphing with personalized voice selection tool, and results visualization. This improves the usability of the task, shortens the procedure duration, and provides a patient-tailored approach. This paper demonstrates the technological advantages and scientific potential of the new methodology, with sample data from two different participant groups in clinical and non-clinical settings.

Traditional models of speech perception posit that neural activity encodes speech through a hierarchy of cognitive processes, from low-level representations of acoustic and phonetic features to high-level semantic encoding. Yet it remains unknown how neural representations are transformed across levels of the speech hierarchy. Here, we analyzed unique microelectrode array recordings of neuronal spiking activity from the human left anterior superior temporal gyrus, a brain region at the interface between phonetic and semantic speech processing, during a semantic categorization task and natural speech perception. We identified distinct neural manifolds for semantic and phonetic features, with a functional separation of the corresponding low-dimensional trajectories. Moreover, phonetic and semantic representations were encoded concurrently and reflected in power increases in the beta and low-gamma local field potentials, suggesting top-down predictive and bottom-up cumulative processes. Our results are the first to demonstrate mechanisms for hierarchical speech transformations that are specific to neuronal population dynamics.

Background Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented toward understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors. Methods In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e. feeling the presence of a non-existing another person). Results Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, quantified as an increase in false alarm rate in a voice detection task. Robotically-induced AVH-like sensations were further associated with delusional ideation and to both AVH accounts. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors). Conclusions By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

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.

One's own voice is one of the most important and most frequently heard voices. Although it is the sound we associate most with ourselves, it is perceived as strange when played back in a recording. One of the main reasons is the lack of bone conduction that is inevitably present when hearing one's own voice while speaking. The resulting discrepancy between experimental and natural self-voice stimuli has significantly impeded self-voice research, rendering it one of the least investigated aspects of self-consciousness. Accordingly, factors that contribute to self-voice perception remain largely unknown. In a series of three studies, we rectified this ecological discrepancy by augmenting experimental self-voice stimuli with bone-conducted vibrotactile stimulation that is present during natural self-voice perception. Combining voice morphing with psychophysics, we demonstrate that specifically self-other but not familiar-other voice discrimination improved for stimuli presented using bone as compared with air conduction. Furthermore, our data outline independent contributions of familiarity and acoustic processing to separating the own from another's voice: although vocal differences increased general voice discrimination, self-voices were more confused with familiar than unfamiliar voices, regardless of their acoustic similarity. Collectively, our findings show that concomitant vibrotactile stimulation improves auditory self-identification, thereby portraying self-voice as a fundamentally multi-modal construct.

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

ABSTRACT Personality changes following neurosurgical procedures pose a major concern for patients and remain poorly understood both by clinicians and neuroscientists. Here we report a case of a female patient in her 50s 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 and symptoms resembling the Gastaut-Geschwind syndrome. Clinical observations were further reflected and experimentally quantified with a series of behavioral and neuroimaging tasks assessing self-other voice discrimination, one of the established markers for self-consciousness. In all tasks, the patient consistently confused self- and other voices – i.e., she misattributed other-voice stimuli to herself and self-voice stimuli to others. Moreover, behavioral findings were corroborated with scalp EEG results. Specifically, the same EEG microstate, that was in healthy participants associated with hearing their own voice, in this patient occurred more often for other-voice stimuli. We hypothesize that the patient’s preexisting psychological problems were significantly aggravated by postoperative decompensation of a fragile steady-state combination of direct frontal lobe compression and preoperative development of a large venous collateral hemodynamic network that followed gradual occlusion of the superior sagittal sinus. Resection of the sagittal sinus together with the tumor impacted venous drainage of brain areas associated with self-consciousness. These findings are of high relevance for developing experimental biomarkers of post-surgical personality alterations.

Background and Objectives The identification of cognitive biomarkers in preoperative counselling and their monitoring during brain surgery is of growing interest for the safe conduction of resective intracranial procedures with potential impact on the patients’ personality. The conscious experience of identifying with the body (self-identification) and of where ‘I’ am in space(self-location) are central for bodily self-consciousness (BSC). In a virtual reality (VR) paradigm using multisensory feedback, illusory self-identification and self-location over a virtual body can be induced, by manipulating the synchrony of visuo-tactile inputs. To date, no studies applied lesion network mapping (LNM) to investigate networks underlying BSC components with VR.Methods Fifteen neurosurgical patients with intra-axial and extra-axial brain lesions(8 pre-resection, 9 post-resection) performed the visuo-tactile VR paradigm. Patients subjectively rated their self-identification and self-location, after being exposed to synchronous or asynchronous visuo-tactile stimulations. We applied LNM analysis using functional data from 1015 healthy subjects and determined functional connectivity patterns related to each measure.Results In the post-surgery group, the self-identification network included the right inferior frontal, superior frontal and inferior temporal gyri. The self-location network encompassed the right parahippocampal gyrus, superior temporal gyrus, bilateral cerebellum and brainstem. No clusters survived for the pre-surgery group.Discussion Our LNM findings reveal the existence of two distinct networks for self-identification and self-location, including structures playing key roles in self-recognition or self-other distinction as well as in spatial navigation or memory processes, respectively. Such networks should be added to the portfolio of presurgical surveillance of functions related to the sense of self to improve future surgical outcomes.What is already known on this topic The development of extra- and intraoperative cognitive biomarkers is of importance for monitoring the personality of patients during cranial surgical procedures, as that may allow for individualized pre-operative counselling and intraoperative decision making. Such guidance may ultimately help to improve neuropsychological outcomes following brain surgery.Bodily self-consciousness refers to a perceptual form of the sense of self, related to multisensory bodily inputs, which can be disrupted in neurological, psychiatric, or neurosurgical conditions.What this study adds In this study, we investigated networks associated with changes in two components bodily self-consciousness (self-identification, self-location) that we manipulated in real-time using multisensory stimulation and virtual reality in neurosurgical patients, who underwent resective surgery for brain tumors or lesions (gliomas, meningiomas, epileptic foci).Our lesion network mapping findings reveal the existence of two distinct networks of bodily self-consciousness, including structures playing key roles in self-recognition or self-other distinction for self-identification, and in spatial navigation or memory processes for self-location.How this study might affect research, practice or policy Ideally, such networks should be identified, and their individual anatomical allocation be integrated in the surgical plan, to make them potentially amenable for functional mapping and monitoring during resective brain surgery. Ultimately, that assessment of functions related to the sense of self and personality should help.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by the Bertarelli Foundation, the Pictet Foundation, and the Swiss National Science Foundation (no. 320030_182497, FNS-Project 17548).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Cantonal Ethical Committee of Geneva (CCER) gave ethical approval for this workI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

One’s own voice is one of the most important and most frequently heard voices and the sound we associate most with ourselves, and yet, it is perceived as strange when played back in a recording. One of the main reasons is the lack of bone conduction that is inevitably present when hearing own voice while speaking. The resulting discrepancy between experimental and natural self-voice stimuli has significantly impeded self-voice research, rendering it one of the least investigated aspects of self-consciousness. Accordingly, factors that contribute to self-voice perception remain largely unknown. In a series of three studies, we rectified this ecological discrepancy by augmenting experimental self-voice stimuli with bone-conducted vibrotactile stimulation that is present during natural self-voice perception. Combining voice-morphing with psychophysics, we demonstrate that specifically self-other but not familiar-other voice discrimination improved for stimuli presented using bone as compared to air conduction. Furthermore, our data outline independent contributions of familiarity and acoustic processing to separating the own from another’s voice: although vocal differences increased general voice discrimination, self-voices were more confused with familiar than unfamiliar voices, regardless of their acoustic similarity. Collectively, our findings show that concomitant vibrotactile stimulation improves auditory self-identification, thereby portraying self-voice as a fundamentally multimodal construct.

A growing number of studies have focused on identifying cognitive processes that are modulated by interoceptive signals. Here we investigated whether interoception affects self-processing, by assessing changes in self-voice perception as a function of respiratory and cardiac cycles. Considering the fundamental role interoception plays in bodily self-consciousness, we additionally applied conflicting sensorimotor stimulation inducing a state characterized by a loss of self and increased otherness, and investigated its effects in self-other voice perception. Our data reveal that breathing, but not heartbeat, affects self-voice perception, by showing that participants (N = 30) discriminated self-voice from other voices better during inspiration, while being in the state of increased otherness and especially when hearing voices of other people. Loudness judgement of equivalent self-related stimuli was unaffected by breathing. Combining interoception and voice perception with self-monitoring framework, these data extend recent findings on breathing-dependent cognition to self-processing.

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

There is growing evidence showing that the representation of the human "self" recruits special systems across different functions and modalities. Compared to self-face and self-body representations, few studies have investigated neural underpinnings specific to self-voice. Moreover, self-voice stimuli in those studies were consistently presented through air and lacking bone conduction, rendering the sound of self-voice stimuli different to the self-voice heard during natural speech. Here, we combined psychophysics, voice-morphing technology, and high-density EEG in order to identify the spatiotemporal patterns underlying self-other voice discrimination (SOVD) in a population of 26 healthy participants, both with air- and bone-conducted stimuli. We identified a self-voice-specific EEG topographic map occurring around 345 ms post-stimulus and activating a network involving insula, cingulate cortex, and medial temporal lobe structures. Occurrence of this map was modulated both with SOVD task performance and bone conduction. Specifically, the better participants performed at SOVD task, the less frequently they activated this network. In addition, the same network was recruited less frequently with bone conduction, which, accordingly, increased the SOVD task performance. This work could have an important clinical impact. Indeed, it reveals neural correlates of SOVD impairments, believed to account for auditory-verbal hallucinations, a common and highly distressing psychiatric symptom.

Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, sometimes requiring addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatio-temporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, fifteen patients with severe chronic pain and an SCS implant underwent congruent SCS-VR (personalized visual feedback of the perceived SCS-induced paresthesia displayed on the patient's virtual body) and two control conditions (incongruent SCS-VR; VR alone). We demonstrate the efficacy of neuromodulation-enhanced VR for the treatment of chronic pain by showing that congruent SCS-VR reduced pain ratings on average by 44%. SCS-VR analgesia was stronger than in both control conditions (enabling stronger analgesic effects than incongruent SCS-VR analgesia or VR alone), and kept increasing over successive stimulations, revealing the selectivity and consistency of the observed effects. We also show that analgesia persists after congruent SCS-VR had stopped, indicating carry over effects and underlining its therapeutic potential. Linking latest VR technology with recent insights from the neuroscience of body perception and SCS-neuromodulation, our personalized new SCS-VR platform highlights the impact of immersive digiceutical therapies for chronic pain.

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.

Sensorimotor conflicts are known to alter the perception of accompanying sensory signals, and deficits in sensory attenuation have been observed in schizophrenia. In the auditory domain, self-generated tones or voices (compared to tones or voices presented passively or with temporal delays) have been associated with changes in loudness perception and attenuated neural responses. It has been argued that for sensory signals to be attenuated, predicted and sensory consequences must have a consistent spatiotemporal relationship, between button presses and reafferent signals, via predictive sensory signaling, a process altered in schizophrenia. Here, we investigated auditory sensory attenuation for a series of morphed voices while healthy participants applied sensorimotor stimulations that had no spatiotemporal relationship to the voice stimuli and that have been shown to induce mild psychosis-like phenomena. In two independent groups of participants, we report a loudening of silent voices and found this effect only during maximal sensorimotor conflicts (versus several control conditions). Importantly, conflicting sensorimotor stimulation also induced a mild psychosis-like state in the form of somatic passivity and participants who experienced stronger passivity lacked the sensorimotor loudening effect. We argue that this conflict-related sensorimotor loudness amplification may represent a reduction of auditory self-attenuation that is lacking in participants experiencing a concomitant mild psychosis-like state. We interpret our results within the framework of the comparator model of sensorimotor control, and discuss the implications of our findings regarding passivity experiences and hallucinations in schizophrenia.