Robotically-induced auditory-verbal hallucinations: combining self-monitoring and strong perceptual priors.

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.

Neural manifolds carry reactivation of phonetic representations during semantic processing.

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.

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.

Human primary motor cortex indexes the onset of subjective intention in brain-machine-interface mediated actions.

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.

Bone conduction facilitates self-other voice discrimination.

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.

Breathing affects self-other voice discrimination in a bodily state associated with somatic passivity.

A growing number of studies have focused on identifying cognitive processes that are modulated by interoceptive signals, particularly in relation to the respiratory or cardiac cycle. Considering the fundamental role of interoception in bodily self-consciousness, we here investigated whether interoceptive signals also impact self-voice perception. We applied an interactive, robotic paradigm associated with somatic passivity (a bodily state characterized by illusory misattribution of self-generated touches to someone else) to investigate whether somatic passivity impacts self-voice perception as a function of concurrent interoceptive signals. Participants' breathing and heartbeat signals were recorded while they performed two self-voice tasks (self-other voice discrimination and loudness perception) and while simultaneously experiencing two robotic conditions (somatic passivity condition; control condition). Our data reveal that respiration, but not cardiac activity, affects self-voice perception: participants were better at discriminating self-voice from another person's voice during the inspiration phase of the respiration cycle. Moreover, breathing effects were prominent in participants experiencing somatic passivity and a different task with the same stimuli (i.e., judging the loudness and not identity of the voices) was unaffected by breathing. Combining interoception and voice perception with self-monitoring framework, these data extend findings on breathing-dependent changes in perception and cognition to self-related processing.

Sense of agency for intracortical brain-machine interfaces.

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.

EEG Spatiotemporal Patterns Underlying Self-other Voice Discrimination.

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.

Sensorimotor conflicts induce somatic passivity and louden quiet voices in healthy listeners.

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.

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.

Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality.

ABSTRACT: 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, requiring sometimes the 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 spatiotemporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, 15 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 2 control conditions (incongruent SCS-VR and 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%. Spinal cord stimulation-VR analgesia was stronger than that 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.Registration: clinicaltrials.gov, Identifier: NCT02970006.