Increased Functional Connectivity of the Intraparietal Sulcus Underlies the Attenuation of Numerosity Estimations for Self-Generated Words.

Previous studies have shown that self-generated stimuli in auditory, visual, and somatosensory domains are attenuated, producing decreased behavioral and neural responses compared with the same stimuli that are externally generated. Yet, whether such attenuation also occurs for higher-level cognitive functions beyond sensorimotor processing remains unknown. In this study, we assessed whether cognitive functions such as numerosity estimations are subject to attenuation in 56 healthy participants (32 women). We designed a task allowing the controlled comparison of numerosity estimations for self-generated (active condition) and externally generated (passive condition) words. Our behavioral results showed a larger underestimation of self-generated compared with externally generated words, suggesting that numerosity estimations for self-generated words are attenuated. Moreover, the linear relationship between the reported and actual number of words was stronger for self-generated words, although the ability to track errors about numerosity estimations was similar across conditions. Neuroimaging results revealed that numerosity underestimation involved increased functional connectivity between the right intraparietal sulcus and an extended network (bilateral supplementary motor area, left inferior parietal lobule, and left superior temporal gyrus) when estimating the number of self-generated versus externally generated words. We interpret our results in light of two models of attenuation and discuss their perceptual versus cognitive origins.SIGNIFICANCE STATEMENT We perceive sensory events as less intense when they are self-generated compared with when they are externally generated. This phenomenon, called attenuation, enables us to distinguish sensory events from self and external origins. Here, we designed a novel fMRI paradigm to assess whether cognitive processes such as numerosity estimations are also subject to attenuation. When asking participants to estimate the number of words they had generated or passively heard, we found bigger underestimation in the former case, providing behavioral evidence of attenuation. Attenuation was associated with increased functional connectivity of the intraparietal sulcus, a region involved in numerosity processing. Together, our results indicate that the attenuation of self-generated stimuli is not limited to sensory consequences but is also impact cognitive processes such as numerosity estimations.

Robotically-induced hallucination triggers subtle changes in brain network transitions.

The perception that someone is nearby, although nobody can be seen or heard, is called presence hallucination (PH). Being a frequent hallucination in patients with Parkinson's disease, it has been argued to be indicative of a more severe and rapidly advancing form of the disease, associated with psychosis and cognitive decline. PH may also occur in healthy individuals and has recently been experimentally induced, in a controlled manner during fMRI, using MR-compatible robotics and sensorimotor stimulation. Previous neuroimaging correlates of such robot-induced PH, based on conventional time-averaged fMRI analysis, identified altered activity in the posterior superior temporal sulcus and inferior frontal gyrus in healthy individuals. However, no link with the strength of the robot-induced PH was observed, and such activations were also associated with other sensations induced by robotic stimulation. Here we leverage recent advances in dynamic functional connectivity, which have been applied to different psychiatric conditions, to decompose fMRI data during PH-induction into a set of co-activation patterns that are tracked over time, as to characterize their occupancies, durations, and transitions. Our results reveal that, when PH is induced, the identified brain patterns significantly and selectively increase their transition probabilities towards a specific brain pattern, centred on the posterior superior temporal sulcus, angular gyrus, dorso-lateral prefrontal cortex, and middle prefrontal cortex. This change is not observed in any other control conditions, nor is it observed in association with other sensations induced by robotic stimulation. The present findings describe the neural mechanisms of PH in healthy individuals and identify a specific disruption of the dynamics of network interactions, extending previously reported network dysfunctions in psychotic patients with hallucinations to an induced robot-controlled specific hallucination in healthy individuals.

Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation.

Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

Force feedback facilitates multisensory integration during robotic tool use.

The present study investigated the effects of force feedback in relation to tool use on the multisensory integration of visuo-tactile information. Participants learned to control a robotic tool through a surgical robotic interface. Following tool-use training, participants performed a crossmodal congruency task, by responding to tactile vibrations applied to their hands, while ignoring visual distractors superimposed on the robotic tools. In the first experiment it was found that tool-use training with force feedback facilitates multisensory integration of signals from the tool, as reflected in a stronger crossmodal congruency effect with the force feedback training compared to training without force feedback and to no training. The second experiment extends these findings by showing that training with realistic online force feedback resulted in a stronger crossmodal congruency effect compared to training in which force feedback was delayed. The present study highlights the importance of haptic information for multisensory integration and extends findings from classical tool-use studies to the domain of robotic tools. We argue that such crossmodal congruency effects are an objective measure of robotic tool integration and propose some potential applications in surgical robotics, robotic tools, and human-tool interaction.

Restoration of natural thermal sensation in upper-limb amputees.

The use of hands for gathering rich sensory information is essential for proper interaction with the environment; therefore, the restoration of sensation is critical for reestablishing the sense of embodiment in hand amputees. Here, we show that a noninvasive wearable device can be used to provide thermal sensations on amputees' phantom hands. The device delivers thermal stimuli to specific regions of skin on their residual limb. These sensations were phenomenologically similar to those on the intact limbs and were stable over time. Using the device, the subjects could successfully exploit the thermal phantom hand maps to detect and discriminate different thermal stimuli. The use of a wearable device that provides thermal sensation can increase the sense of embodiment and improve life quality in hand amputees.

Haptic handles for robotic surgery.

Robotic surgery, i.e. master-slave telemanipulators for surgery, is rapidly developing. One of the key components is the surgeon's console, and, within the console, especially the "handles" (the "joysticks") for manipulation control. Two examples of haptic (force-feedback) handle designs developed and realized at the LSRO lab are briefly presented along with design considerations (ergonomics, usability). Incidence on patient safety and patient benefit and future trends in this field are hinted at, especially the possibilities offered VR in this context.

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.

Neuroscience robotics for controlled induction and real-time assessment of hallucinations.

Although hallucinations are important and frequent symptoms in major psychiatric and neurological diseases, little is known about their brain mechanisms. Hallucinations are unpredictable and private experiences, making their investigation, quantification and assessment highly challenging. A major shortcoming in hallucination research is the absence of methods able to induce specific and short-lasting hallucinations, which resemble clinical hallucinations, can be elicited repeatedly and vary across experimental conditions. By integrating clinical observations and recent advances in cognitive neuroscience with robotics, we have designed a novel device and sensorimotor method able to repeatedly induce a specific, clinically relevant hallucination: presence hallucination. Presence hallucinations are induced by applying specific conflicting (spatiotemporal) sensorimotor stimulation including an upper extremity and the torso of the participant. Another, MRI-compatible, robotic device using similar sensorimotor stimulation permitted the identification of the brain mechanisms of these hallucinations. Enabling the identification of behavioral and a frontotemporal neural biomarkers of hallucinations, under fully controlled experimental conditions and in real-time, this method can be applied in healthy participants as well as patients with schizophrenia, neurodegenerative disease or other hallucinations. The execution of these protocols requires intermediate-level skills in cognitive neuroscience and MRI processing, as well as minimal coding experience to control the robotic device. These protocols take ~3 h to be completed.

Neural signatures of visuo-motor integration during human-robot interactions.

Visuo-motor integration shapes our daily experience and underpins the sense of feeling in control over our actions. The last decade has seen a surge in robotically and virtually mediated interactions, whereby bodily actions ultimately result in an artificial movement. But despite the growing number of applications, the neurophysiological correlates of visuo-motor processing during human-machine interactions under dynamic conditions remain scarce. Here we address this issue by employing a bimanual robotic interface able to track voluntary hands movement, rendered in real-time into the motion of two virtual hands. We experimentally manipulated the visual feedback in the virtual reality with spatial and temporal conflicts and investigated their impact on (1) visuo-motor integration and (2) the subjective experience of being the author of one's action (i.e., sense of agency). Using somatosensory evoked responses measured with electroencephalography, we investigated neural differences occurring when the integration between motor commands and visual feedback is disrupted. Our results show that the right posterior parietal cortex encodes for differences between congruent and spatially-incongruent interactions. The experimental manipulations also induced a decrease in the sense of agency over the robotically-mediated actions. These findings offer solid neurophysiological grounds that can be used in the future to monitor integration mechanisms during movements and ultimately enhance subjective experience during human-machine interactions.

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.

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.

Thought consciousness and source monitoring depend on robotically controlled sensorimotor conflicts and illusory states.

Thought insertion (TI) is characterized by the experience that certain thoughts, occurring in one's mind, are not one's own, but the thoughts of somebody else and suggestive of a psychotic disorder. We report a robotics-based method able to investigate the behavioral and subjective mechanisms of TI in healthy participants. We used a robotic device to alter body perception by providing online sensorimotor stimulation, while participants performed cognitive tasks implying source monitoring of mental states attributed to either oneself or another person. Across several experiments, conflicting sensorimotor stimulation reduced the distinction between self- and other-generated thoughts and was, moreover, associated with the experimentally generated feeling of being in the presence of an alien agent and subjective aspects of TI. Introducing a new robotics-based approach that enables the experimental study of the brain mechanisms of TI, these results link TI to predictable self-other shifts in source monitoring and specific sensorimotor processes.

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson's disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl's gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Sensorimotor Induction of Auditory Misattribution in Early Psychosis.

Dysfunction of sensorimotor predictive processing is thought to underlie abnormalities in self-monitoring producing passivity symptoms in psychosis. Experimentally induced sensorimotor conflict can produce a failure in bodily self-monitoring (presence hallucination [PH]), yet it is unclear how this is related to auditory self-monitoring and psychosis symptoms. Here we show that the induction of sensorimotor conflict in early psychosis patients induces PH and impacts auditory-verbal self-monitoring. Participants manipulated a haptic robotic system inducing a bodily sensorimotor conflict. In experiment 1, the PH was measured. In experiment 2, an auditory-verbal self-monitoring task was performed during the conflict. Fifty-one participants (31 early psychosis patients, 20 matched controls) participated in the experiments. The PH was present in all participants. Psychosis patients with passivity experiences (PE+) had reduced accuracy in auditory-verbal self-other discrimination during sensorimotor stimulation, but only when sensorimotor stimulation involved a spatiotemporal conflict (F(2, 44) = 6.68, P = .002). These results show a strong link between robotically controlled alterations in sensorimotor processing and auditory misattribution in psychosis and provide evidence for the role of sensorimotor processes in altered self-monitoring in psychosis.

Modulation of vection latencies in the full-body illusion.

Current neuroscientific models of bodily self-consciousness (BSC) argue that inaccurate integration of sensory signals leads to altered states of BSC. Indeed, using virtual reality technology, observers viewing a fake or virtual body while being exposed to tactile stimulation of the real body, can experience illusory ownership over-and mislocalization towards-the virtual body (Full-Body Illusion, FBI). Among the sensory inputs contributing to BSC, the vestibular system is believed to play a central role due to its importance in estimating self-motion and orientation. This theory is supported by clinical evidence that vestibular loss patients are more prone to altered BSC states, and by recent experimental evidence that visuo-vestibular conflicts can disrupt BSC in healthy individuals. Nevertheless, the contribution of vestibular information and self-motion perception to BSC remains largely unexplored. Here, we investigate the relationship between alterations of BSC and self-motion sensitivity in healthy individuals. Fifteen participants were exposed to visuo-vibrotactile conflicts designed to induce an FBI, and subsequently to visual rotations that evoked illusory self-motion (vection). We found that synchronous visuo-vibrotactile stimulation successfully induced the FBI, and further observed a relationship between the strength of the FBI and the time necessary for complete vection to arise. Specifically, higher self-reported FBI scores across synchronous and asynchronous conditions were associated to shorter vection latencies. Our findings are in agreement with clinical observations that vestibular loss patients have higher FBI susceptibility and lower vection latencies, and argue for increased visual over vestibular dependency during altered states of BSC.

Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis.

Peripheral intraneural stimulation can provide tactile information to amputees. However, efforts are still necessary to identify encoding strategy eliciting percepts that are felt as both natural and effective for prosthesis control. Here we compared the naturalness and efficacy of different encoding strategies to deliver neural stimulation to trans-radial amputees implanted with intraneural electrodes. Biomimetic frequency modulation was perceived as more natural, while amplitude modulation enabled better performance in tasks requiring fine identification of the applied force. Notably, the optimal combination of naturalness and sensitivity of the tactile feedback can be achieved with "hybrid" encoding strategies based on simultaneous biomimetic frequency and amplitude neuromodulation. These strategies improved the gross manual dexterity of the subjects during functional task while maintaining high levels of manual accuracy. They also improved prosthesis embodiment, reducing abnormal phantom limb perceptions ("telescoping effect"). Hybrid strategies are able to provide highly sensitive and natural percepts and should be preferred. VIDEO ABSTRACT.

Cognetics: Robotic Interfaces for the Conscious Mind.

Cognetics joins the cognitive neuroscience of bodily awareness with robotics to study, control, and enhance perception, cognition, and consciousness. We highlight robot-controlled bodily perception, conscious states, and social interactions and sketch how future cognetic interfaces will impact cognitive neuroscience and human enhancement.

Voluntary self-touch increases body ownership.

Experimental manipulations of body ownership have indicated that multisensory integration is central to forming bodily self-representation. Voluntary self-touch is a unique multisensory situation involving corresponding motor, tactile and proprioceptive signals. Yet, even though self-touch is frequent in everyday life, its contribution to the formation of body ownership is not well understood. Here we investigated the role of voluntary self-touch in body ownership using a novel adaptation of the rubber hand illusion (RHI), in which a robotic system and virtual reality allowed participants self-touch of real and virtual hands. In the first experiment, active and passive self-touch were applied in the absence of visual feedback. In the second experiment, we tested the role of visual feedback in this bodily illusion. Finally, in the third experiment, we compared active and passive self-touch to the classical RHI in which the touch is administered by the experimenter. We hypothesized that active self-touch would increase ownership over the virtual hand through the addition of motor signals strengthening the bodily illusion. The results indicated that active self-touch elicited stronger illusory ownership compared to passive self-touch and sensory only stimulation, and show an important role for active self-touch in the formation of bodily self.