Sensorimotor Induction of Auditory Misattribution in Psychosis is Linked to Neural Disconnectivity

Background: Schneiderian first rank symptoms (FRS) are characterized by a diminished demarcation of self-other boundaries, causing misattribution of self-generated thoughts and actions to external sources. We have shown that introducing sensorimotor prediction error (SPE) by a robotic device in healthy subjects can induce a Feeling of a Presence (FoP) which is related to the FRS (Blanke et al. 2014). Here, we tested if SPE may induce auditory misattribution in psychotic patients and if this is related to neural connectivity in the temporoparietal cortex, insular cortex and fronto-parietal cortex (FoP Network). Methods: Participants manipulated a haptic robotic system inducing a sensorimotor conflict while performing a self-other auditory discrimination task. 31 early psychotic patients (19 with and 12 without FRS) and 20 controls participated in the experiment. We measured accuracy (d′) on auditory self-other discrimination task during sensorimotor conflict induction or control condition, functional connectivity magnitude in a priori FoP network, and calculated correlation between the two measures. Results: Patients with FRS had reduced accuracy in auditory self-other discrimination when sensorimotor conflict was induced (F(2, 44)=6.68, p=.002). rsfMRI connectivity analysis indicated lower connectivity for these patients in regions of the FoP network compared to the non-first rank and control groups (p=.015, p=.014). The level of functional connectivity in the FoP network correlated with the reduction of self-other discrimination in the FRS+ group (r=-0.56, p=.03). Conclusions: Experimental induction of SPE can cause self-other confusion in the auditory domain. This deficit in self-other discrimination was correlated to specifically reduced connectivity in the FoP network related to sensorimotor self-representation.

Sensorimotor Induction of Auditory Misattribution in Early Psychosis

Fosco Bernasconi, Olaf Blanke, Alessandra Griffa, Patric Hagmann, Silvia Marchesotti, Pierre Progin, Giulio Rognini, Roy Salomon, Andrea Serino

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.

2020

Hallucination Engineering: From Neuroscience Robotics to Hallucinations in Health and Disease

Eva Blondiaux

My thesis focuses on a psychotic symptom called the presence hallucination (PH). PHs are defined as the false perception that someone is nearby when no one is actually present. PHs can occur in various populations, ranging from healthy subjects (when exposed to extreme conditions) to neurological (e.g. epileptic, Parkinsonâs disease patients) and psychiatric patients (e.g. schizophrenia). Our group has designed a robotic device that allows to safely induce PH in healthy subjects, in a controlled manner, using different sensorimotor conflicts (Blanke et al., 2014). The aim of my thesis was to unravel the brain regions and mechanisms associated with PH and explore how the neuroscientific understanding of PH can improve diagnostics of different clinical populations with hallucinations. In Chapter 2, I investigated the brain networks associated with a category of complex phenomena named autoscopic phenomena (AP). AP include PHs and three other forms: autoscopic hallucinations, heautoscopies, and out-of-body experiences. AP are rare phenomena, defined as illusory reduplication involving a double of oneâs own body seen or felt in extrapersonal space. Lesion network mapping analysis was used to identify the brain networks associated to each AP. My data showed that each AP is characterised by specific connectivity networks consistent with their phenomenology. All AP also share common brain connectivity. In Chapter 3, using an MR-compatible robot able to induce PH, I investigated the brain regions and mechanisms of robot-induced PH in healthy subjects using fMRI. I combined these data with the results of my lesion network mapping analysis in neurological patients with focal brain damage associated with PH (Chapter 3). Both networks (i.e. robot-induced PH-network in healthy subjects and symptomatic PH-network) were merged together to identify the key regions involved in PH, defining a common PH-network. The relevance of this common PH-network was then assessed and confirmed in patients with Parkinsonâs disease (PD), revealing a difference in functional connectivity within this network between PD patients experiencing symptomatic PH compared to patients without such symptoms. Further, I studied the functional connectivity within the common PH-network in 22q11.2 deletion syndrome (DS) subjects (i.e. subjects with high risks (30%) of developing schizophrenia) (Chapter 4) and in psychotic patients with passivity experiences (Chapter 5). Studying PH in these population is relevant since PH is frequent in schizophrenia. In both populations, a reduced functional connectivity in the common PH-network was revealed. In Chapter 4, I also assessed the sensitivity to the sensorimotor conflicts and the proneness to experience robot-induced PH in 22q11DS subjects and age-matched controls. Results showed a lack of sensitivity in sensorimotor modulation for the sense of agency, further corroborated by a lack of delay dependency in experiencing robot-induced PH in 22q11DS subjects compared to controls. In summary, by coupling robotic technology with neuroimaging, a common PH-network was delineated and was found relevant in different clinical populations. These findings are important since PH can be present at early stages before the apparition of more severe symptoms. Therefore, our results can lead to more robust diagnostic tools and early treatment intervention, which might significantly improve prognosis in those patients.

EPFL2020

Unraveling neural and behavioral mechanisms of cognitive self-attenuation and alienation

Giedre Stripeikyte

The present thesis aimed at investigating behavioral and neural underpinnings of the mechanisms related to the different aspects of self-monitoring. The first aim was to study functional connectivity alterations related to the mechanisms accounting for the alienation in psychotic patients and those at high-risk to develop it. The second aim was to extend the fundamental knowledge of whether higher-level cognitive processes beyond sensorimotor involvement are subject to attenuation and whether it is affected in psychotic patients with thought insertion. In Part I of the thesis, I have studied whether the neural mechanisms (PH-network) accounting for the presence hallucination (PH), the experience that someone is here when no one is around, could also be relevant to understand alienation experienced in psychotic patients. In Study 1, I have investigated psychotic patients with passivity experiences where one's own actions, thoughts and emotions are perceived as not self-generated and caused by an external entity. In Study 2, individuals with 22q11 deletion syndrome who are at high-risk for psychosis development were investigated. In both populations, reduced functional connectivity between fronto-temporal connections within the PH-network was revealed. Taken together, these studies show that PH-network is affected not only when psychosis manifests but also in individuals prone to develop psychosis. The current findings strengthen the relevance of PH mechanisms to explain the occurrence of psychotic symptoms, specifically the alienation, and potentially could provide a biomarker for the disease development. In Part II of the thesis, I have investigated self-attenuation, an important aspect for the sense of agency, during the cognitive function of numerosity estimations in healthy individuals and psychotic patients with thought insertion. In Study 3, a novel fMRI task was designed, allowing a controlled comparison of numerosity estimations for self and externally generated words in healthy volunteers. For the first time, self-attenuation during cognitive function beyond sensorimotor processing was reported. It was linked to the functional network involving intraparietal sulcus (key numerosity region) and extended areas more generally associated with attenuation processes. This work was continued in Study 4, where psychotic patients with thought insertion were studied. I showed that cognitive self-attenuation during numerosity estimations can be observed in patients with thought insertion and is related to altered executive functioning. Importantly, increased functional connectivity within the network related to attenuation processing during numerosity estimations was found in patients with thought insertion suggesting insufficient attenuation at the neural level. Lastly, I found the association between the altered functional connectivity within the PH-network and cognitive self-attenuation, providing a link between two different aspects related to the self-monitoring in patients with thought insertion. To summarize, I present new insights into the different mechanisms related to self-monitoring, which would help to understand the manifestation of psychotic symptoms and develop prevention strategies.

EPFL2020

Unraveling neural and behavioral mechanisms of cognitive self-attenuation and alienation

Giedre Stripeikyte

EPFL2020

Hallucination Engineering: From Neuroscience Robotics to Hallucinations in Health and Disease

Eva Blondiaux

EPFL2020