Conspiracy beliefs and perceptual inference in times of political uncertainty.

Sociopolitical crises causing uncertainty have accumulated in recent years, providing fertile ground for the emergence of conspiracy ideations. Computational models constitute valuable tools for understanding the mechanisms at play in the formation and rigidification of these unshakeable beliefs. Here, the Circular Inference model was used to capture associations between changes in perceptual inference and the dynamics of conspiracy ideations in times of uncertainty. A bistable perception task and conspiracy belief assessment focused on major sociopolitical events were administered to large populations from three polarized countries. We show that when uncertainty peaks, an overweighting of sensory information is associated with conspiracy ideations. Progressively, this exploration strategy gives way to an exploitation strategy in which increased adherence to conspiracy theories is associated with the amplification of prior information. Overall, the Circular Inference model sheds new light on the possible mechanisms underlying the progressive strengthening of conspiracy theories when individuals face highly uncertain situations.

Examining the relationships between cognition and auditory hallucinations: A systematic review.

OBJECTIVE: Auditory hallucinations (hearing voices) have been associated with a range of altered cognitive functions, pertaining to signal detection, source-monitoring, memory, inhibition and language processes. Yet, empirical results are inconsistent. Despite this, several theoretical models of auditory hallucinations persist, alongside increasing emphasis on the utility of a multidimensional framework. Thus, clarification of current evidence across the broad scope of proposed mechanisms is warranted. METHOD: A systematic search of the Web of Science, PubMed and Scopus databases was conducted. Records were screened to confirm the use of an objective behavioural cognitive task, and valid measurement of hallucinations specific to the auditory modality. RESULTS: Auditory hallucinations were primarily associated with difficulties in perceptual decision-making (i.e. reduced sensitivity/accuracy for signal-noise discrimination; liberal responding to ambiguity), source-monitoring (i.e. self-other and temporal context confusion), working memory and language function (i.e. reduced verbal fluency). Mixed or limited support was observed for perceptual feature discrimination, imagery vividness/illusion susceptibility, source-monitoring for stimulus form and spatial context, recognition and recall memory, executive functions (e.g. attention, inhibition), emotion processing and language comprehension/hemispheric organisation. CONCLUSIONS: Findings were considered within predictive coding and self-monitoring frameworks. Of concern was the portion of studies which - despite offering auditory-hallucination-specific aims and inferences - employed modality-general measures, and/or diagnostic-based contrasts with psychologically healthy individuals. This review highlights disparities within the literature between theoretical conceptualisations of auditory hallucinations and the body of rigorous empirical evidence supporting such inferences. Future cognitive investigations, beyond the schizophrenia-spectrum, which explicitly define and measure the timeframe and sensory modality of hallucinations, are recommended.

Can computational models help elucidate the link between complex trauma and hallucinations?

Recently, a number of predictive coding models have been proposed to account for post-traumatic stress disorder (PTSD)'s symptomatology, including intrusions, flashbacks and hallucinations. These models were usually developed to account for traditional/type-1 PTSD. We here discuss whether these models also apply or can be translated to the case of complex/type-2 PTSD and childhood trauma (cPTSD). The distinction between PTSD and cPTSD is important because the disorders differ in terms of symptomatology and potential mechanisms, how they relate to developmental stages, but also in terms of illness trajectory and treatment. Models of complex trauma could give us insights on hallucinations in physiological/pathological conditions or more generally on the development of intrusive experiences across diagnostic classes.

fMRI-based neurofeedback strategies and the way forward to treating phasic psychiatric symptoms.

Auditory verbal hallucinations (AVH) are the perfect illustration of phasic symptoms in psychiatric disorders. For some patients and in some situations, AVH cannot be relieved by standard therapeutic approaches. More advanced treatments are needed, among which neurofeedback, and more specifically fMRI-based neurofeedback, has been considered. This paper discusses the different possibilities to approach neurofeedback in the specific context of phasic symptoms, by highlighting the strengths and weaknesses of the available neurofeedback options. It concludes with the added value of the recently introduced information-based neurofeedback. Although requiring an online fMRI signal classifier, which can be quite complex to implement, this neurofeedback strategy opens a door toward an alternative treatment option for complex phasic symptomatology.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Functional connectivity and glutamate levels of the medial prefrontal cortex in schizotypy are related to sensory amplification in a probabilistic reasoning task.

The circular inference (CI) computational model assumes a corruption of sensory data by prior information and vice versa, leading at the extremes to 'see what we expect' (through prior amplification) and/or to 'expect what we see' (through sensory amplification). Although a CI mechanism has been reported in a schizophrenia population, it has not been investigated in individuals experiencing psychosis-like experiences, such as people with high schizotypy traits. Furthermore, the neurobiological basis of CI, such as the link between hierarchical amplifications, excitatory neurotransmission, and resting state functional connectivity (RSFC), remains untested. The participants included in the present study consisted of a subsample of those recruited in a study previously published by our group, Kozhuharova et al. (2021b). We included 36 participants with High (n=18) and Low (n=18) levels of schizotypy who completed a probabilistic reasoning task (the Fisher task) for which individual confidence levels were obtained and fitted to the CI model. Participants also underwent a 1H-Magnetic Resonance Spectroscopy (MRS) scan to measure medial prefrontal cortex (mPFC) glutamate metabolite levels, and a functional Magnetic Resonance Imaging (fMRI) scan to measure RSFC of the medial prefrontal cortex (mPFC). People with high levels of schizotypy exhibited changes in CI parameters, altered cortical excitatory neurotransmission and RSFC that were all associated with sensory amplification. Our findings capture a multimodal signature of CI that is observable in people early in the psychosis spectrum.

The neural signature of reality-monitoring: A meta-analysis of functional neuroimaging studies.

Distinguishing imagination and thoughts from information we perceived from the environment, a process called reality-monitoring, is important in everyday situations. Although reality monitoring seems to overlap with the concept of self-monitoring, which allows one to distinguish self-generated actions or thoughts from those generated by others, the two concepts remain largely separate cognitive domains and their common brain substrates have received little attention. We investigated the brain regions involved in these two cognitive processes and explored the common brain regions they share. To do this, we conducted two separate coordinate-based meta-analyses of functional magnetic resonance imaging studies assessing the brain regions involved in reality- and self-monitoring. Few brain regions survived threshold-free cluster enhancement family-wise multiple comparison correction (p < .05), likely owing to the small number of studies identified. Using uncorrected statistical thresholds recommended by Signed Differential Mapping with Permutation of Subject Images, the meta-analysis of reality-monitoring studies (k = 9 studies including 172 healthy subjects) revealed clusters in the lobule VI of the cerebellum, the right anterior medial prefrontal cortex and anterior thalamic projections. The meta-analysis of self-monitoring studies (k = 12 studies including 192 healthy subjects) highlighted the involvement of a set of brain regions including the lobule VI of the left cerebellum and fronto-temporo-parietal regions. We showed with a conjunction analysis that the lobule VI of the cerebellum was consistently engaged in both reality- and self-monitoring. The current findings offer new insights into the common brain regions underlying reality-monitoring and self-monitoring, and suggest that the neural signature of the self that may occur during self-production should persist in memories.

Understanding visual hallucinations: A new synthesis.

Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active Inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations.

Admission to jail and psychotic symptoms: a study of the psychotic continuum in a sample of recently incarcerated men.

PURPOSE: We sought to measure the prevalence of psychotic symptoms (PSs) and psychotic disorders (PDs) in a sample of men entering jail and to compare these prevalences with those observed in the general population. We also aimed to explore the sociodemographic and clinical factors associated with PSs and PDs. METHODS: The Mental Health in the Prison Population (MHPP) survey interviewed 630 incarcerated men upon admission to jail, using the Mini International Neuropsychiatric Interview. We looked for associations between sociodemographic and clinical characteristics and the presence of lifetime PSs and PDs in the MHPP and Mental Health in the General Population (MHGP) surveys, which used the same methodology to collect data from the jail and general populations of the same geographical area. RESULTS: A higher proportion of PSs without PDs was found in the MHGP group (25.3% vs. 17.8%, p < 0.001), whereas a higher prevalence of PDs was found in the MHPP group (7.0% vs. 2.6%, p < 0.001). The multivariable model indicated that subjects who were single or separated/divorced/widowed and had a history of trauma exposure were at joint risk of PSs and PDs, whereas entering jail was not associated with either PSs or PDs after adjustment for all covariates. CONCLUSION: The present study shows that PDs, but not PSs, are more prevalent in men entering jail than in the general population. This overrepresentation could be further explained by the exposure to vulnerability factors found in this population rather than by any specificity related to entering jail.

Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study.

BACKGROUND: Aripiprazole is a second-generation antipsychotic, efficacious in patients with schizophrenia during acute episodes. Due to its pharmacological profile, aripiprazole may be of interest in patients with specific clinical profiles who have not been studied extensively in randomised clinical trials. OBJECTIVES: To capture experience with aripiprazole in everyday psychiatric practice using the Delphi method in order to inform decision-making on the use of aripiprazole for the treatment of patients with schizophrenia in clinical situations where robust evidence from clinical trials is lacking. METHODS: The scope of the survey was defined as the management of schizophrenia in adults. A systematic literature review was performed to identify the different clinical situations in which aripiprazole has been studied, and to describe the level of clinical evidence. Clinical profiles to include in the Delphi survey were selected if there was a clear interest in terms of medical need but uncertainty over the efficacy of aripiprazole. For each clinical profile retained, five to seven specific statements were generated and included in a questionnaire. The final 41-item questionnaire was proposed to a panel of 406 French psychiatrists with experience in the treatment of schizophrenia. Panellists rated their level of agreement using a Likert scale. A second round of voting on eleven items was organised to clarify points for which a consensus was not obtained in the first round. RESULTS: Five clinical profiles were identified in the literature review (persistent negative symptoms, pregnancy, cognitive dysfunction, addictive comorbidity and clozapine resistance). Sixty-two psychiatrists participated in the first round of the Delphi survey and 33 in the second round. A consensus was obtained for 11 out of 41 items in the first round and for 9/11 items in the second round. According to the panellists' clinical experience, aripiprazole can be used as maintenance treatment for pregnant women, is relevant to preserve cognitive function and can be considered an option in patients with a comorbid addictive disorder or with persistent negative symptoms. CONCLUSION: These findings may help physicians in choosing relevant ways to use aripiprazole and highlight areas where more research is needed to widen the evidence base.

Intrusive experiences in posttraumatic stress disorder: Treatment response induces changes in the directed functional connectivity of the anterior insula.

BACKGROUND: One of the core features of posttraumatic stress disorder (PTSD) is re-experiencing trauma. The anterior insula (AI) has been proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in re-experiencing trauma and its putative modulation by effective therapy need to be specified. METHODS: Thirty PTSD patients were enrolled and exposed to traumatic memory reactivation therapy. Resting-state functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment. To explore AI-directed influences over the rest of the brain, we referred to a mixed model using pre-/posttreatment Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of re-experiencing trauma, we investigated how intrusive severity affected (i) causality maps and (ii) the spatial stability of other intrinsic brain networks. RESULTS: We observed changes in AI-directed functional connectivity patterns in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found to be positively correlated with re-experiencing symptoms, while they were linked with a stronger default mode network (DMN) and more unstable central executive network (CEN) connectivity. CONCLUSION: We showed that directed changes in AI signaling to the DMN and CEN at rest may underlie the degree of re-experiencing symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.

From hallucinations to synaesthesia: A circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis.

Psychedelics distort perception and induce visual and multimodal hallucinations as well as synaesthesia. This is in contradiction with the high prevalence of distressing voices in schizophrenia. Here we introduce a unifying account of unimodal and multimodal erroneous percepts based on circular inference. We show that amplification of top-down predictions (descending loops) leads to an excessive reliance on priors and aberrant levels of integration of the sensory representations, resulting in crossmodal percepts and stronger illusions. By contrast, amplification of bottom-up information (ascending loops) results in overinterpretation of unreliable sensory inputs and high levels of segregation between sensory modalities, bringing about unimodal hallucinations and reduced vulnerability to illusions. We delineate a canonical microcircuit in which layer-specific inhibition controls the propagation of information across hierarchical levels: inhibitory interneurons in the deep layers exert control over priors, removing descending loops. Conversely, inhibition in the supragranular layers counterbalances the effects of the ascending loops. Overall, we put forward a multiscale and transnosographic account of erroneous percepts with important theoretical, conceptual and clinical implications.

Mapping brain structural differences and neuroreceptor correlates in Parkinson's disease visual hallucinations.

Parkinson's psychosis (PDP) describes a spectrum of symptoms that may arise in Parkinson's disease (PD) including visual hallucinations (VH). Imaging studies investigating the neural correlates of PDP have been inconsistent in their findings, due to differences in study design and limitations of scale. Here we use empirical Bayes harmonisation to pool together structural imaging data from multiple research groups into a large-scale mega-analysis, allowing us to identify cortical regions and networks involved in VH and their relation to receptor binding. Differences of morphometrics analysed show a wider cortical involvement underlying VH than previously recognised, including primary visual cortex and surrounding regions, and the hippocampus, independent of its role in cognitive decline. Structural covariance analyses point to the involvement of the attentional control networks in PD-VH, while associations with receptor density maps suggest neurotransmitter loss may be linked to the cortical changes.

Circular inference predicts nonuniform overactivation and dysconnectivity in brain-wide connectomes.

Schizophrenia is a severe mental disorder whose neural basis remains difficult to ascertain. Among the available pathophysiological theories, recent work has pointed towards subtle perturbations in the excitation-inhibition (E/I) balance within different neural circuits. Computational approaches have suggested interesting mechanisms that can account for both E/I imbalances and psychotic symptoms. Based on hierarchical neural networks propagating information through a message-passing algorithm, it was hypothesized that changes in the E/I ratio could cause a "circular belief propagation" in which bottom-up and top-down information reverberate. This circular inference (CI) was proposed to account for the clinical features of schizophrenia. Under this assumption, this paper examined the impact of CI on network dynamics in light of brain imaging findings related to psychosis. Using brain-inspired graphical models, we show that CI causes overconfidence and overactivation most specifically at the level of connector hubs (e.g., nodes with many connections allowing integration across networks). By also measuring functional connectivity in these graphs, we provide evidence that CI is able to predict specific changes in modularity known to be associated with schizophrenia. Altogether, these findings suggest that the CI framework may facilitate behavioral and neural research on the multifaceted nature of psychosis.

Decoding Activity in Broca's Area Predicts the Occurrence of Auditory Hallucinations Across Subjects.

BACKGROUND: Functional magnetic resonance imaging (fMRI) capture aims at detecting auditory-verbal hallucinations (AVHs) from continuously recorded brain activity. Establishing efficient capture methods with low computational cost that easily generalize between patients remains a key objective in precision psychiatry. To address this issue, we developed a novel automatized fMRI-capture procedure for AVHs in patients with schizophrenia (SCZ). METHODS: We used a previously validated but labor-intensive personalized fMRI-capture method to train a linear classifier using machine learning techniques. We benchmarked the performances of this classifier on 2320 AVH periods versus resting-state periods obtained from SCZ patients with frequent symptoms (n = 23). We characterized patterns of blood oxygen level-dependent activity that were predictive of AVH both within and between subjects. Generalizability was assessed with a second independent sample gathering 2000 AVH labels (n = 34 patients with SCZ), while specificity was tested with a nonclinical control sample performing an auditory imagery task (840 labels, n = 20). RESULTS: Our between-subject classifier achieved high decoding accuracy (area under the curve = 0.85) and discriminated AVH from rest and verbal imagery. Optimizing the parameters on the first schizophrenia dataset and testing its performance on the second dataset led to an out-of-sample area under the curve of 0.85 (0.88 for the converse test). We showed that AVH detection critically depends on local blood oxygen level-dependent activity patterns within Broca's area. CONCLUSIONS: Our results demonstrate that it is possible to reliably detect AVH states from fMRI blood oxygen level-dependent signals in patients with SCZ using a multivariate decoder without performing complex preprocessing steps. These findings constitute a crucial step toward brain-based treatments for severe drug-resistant hallucinations.