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Background and Hypotheses: Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode., Study Design: We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button., Study Results: We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode., Conclusions: The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Olfactory hallucinations referring to olfactory perceptions in the absence of chemical stimuli, occur in non-clinical and clinical populations. Few studies have investigated their prevalence in the general population and little is known about factors triggering and maintaining them such as substance use, severe life events, and mood. We analyzed self-report data from 2500 community dwelling Norwegians, aged 18-96 years, for occurrence of olfactory hallucinations and co-occurring hallucinations in other modalities (auditory, visual, tactile). Analyses included age, sex, self-reported symptoms of depression and anxiety, mental health status, and experience of severe life-events. The results show that 4.2% (95% CI 3.5-5.1%) reported having experienced olfactory hallucinations, and 56% of individuals experiencing olfactory hallucinations also reported these in combination with hallucinations in other modalities. Prevalence varied significantly in terms of age and sex, in that olfactory hallucinations were most frequently reported by young individuals and females. Self-reported symptoms of anxiety and experience of stressful life events were significantly associated with olfactory hallucinations, suggesting that experiencing olfactory hallucinations may negatively affect functioning and may increase the likelihood of developing psychopathology. Findings underline the need to continue to examine olfactory hallucinations albeit with a more comprehensive assessment in order to increase knowledge on this experience., (Copyright © 2021. Published by Elsevier B.V.)

Source monitoring refers to the ability to identify the origin of a memory, for example, whether you remember saying something or thinking about it, and confusions of these sources have been associated with the experience of auditory verbal hallucinations (AVHs). Both AVHs and source confusions are reported to originate from dysfunctional brain activations in the prefrontal cortex (PFC) and the superior temporal gyrus (STG); specifically, it is assumed that a hypoactive PFC and a hyperactive STG gives rise to AVHs and source confusions. We set out to test this assumption by trying to mimic this hypertemporal/hypofrontal model in healthy individuals with transcranial direct current stimulation (tDCS): the inhibitory cathode was placed over the left PFC and the excitatory anode over the left dorsolateral STG. Participants completed a reality monitoring task (distinguishing between external and internal memory sources) and an internal source monitoring task (distinguishing between two or more internal memory sources) in two separate experiments (offline vs. online tDCS). In the offline experiment (n = 34), both source monitoring tasks were completed after tDCS stimulation, and in the online experiment (n = 27) source monitoring tasks were completed while simultaneously being stimulated with tDCS. We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation in both experiments. We speculate, based on combining the present findings with previous studies, that there might be different brain areas involved in reality and internal source monitoring. While internal source monitoring seems to involve speech production areas, specifically Broca's area, as suggested in the present study, reality monitoring seems to rely more on the STG and DLPFC, as shown in other studies of the field., Competing Interests: Author KH has shares in NordicNeuroLab (NNL) AS, which produced MR accessories used during data acquisition. All authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants ( N = 1,394 across 11 data-collection sites and online) completed assessments of hallucinatory experiences, a measure of adverse childhood experiences, and four tasks: source memory, dichotic listening, backward digit span, and auditory signal detection. We found that hallucinatory experiences were associated with a higher false-alarm rate on the signal detection task and a greater number of reported adverse childhood experiences but not with any of the other cognitive measures employed. These findings are an important step in improving reproducibility in hallucinations research and suggest that the replicability of some findings regarding cognition in clinical samples needs to be investigated.

Background: Few studies have investigated hallucinations that occur at the onset/offset of sleep (called hypnagogic/hypnopompic hallucinations; HHHs), despite the fact that their prevalence in the general population is reported to be higher than the prevalence of daytime hallucinations. We utilized data from an epidemiological study to explore the prevalence of HHHs in various modalities. We also investigated phenomenological differences between sleep-related (HHHs) and daytime hallucinations in the auditory modality. We hypothesized that individuals with only HHHs would not differ from controls on a range of mental health and wellbeing measures, but that if they occur together with daytime hallucinations will pose a greater burden on the individual experiencing them. We also hypothesize that HHHs are qualitatively different (i.e. less severe) from daytime hallucinations., Methods: This study utilized data from a cross-sectional epidemiological study on the prevalence of hallucinations in the Norwegian general population. The sample (n = 2533) was divided into a control group without hallucinations (n = 2303), a group only experiencing sleep-related hallucinations (n = 62), a group only experiencing daytime hallucinations (n = 57), and a group experiencing both sleep-related as well as daytime hallucinations (n = 111). Prevalence rates were calculated and groups were compared using analyses of variance and chi-square tests where applicable., Results: The prevalence for HHHs in the auditory domain was found to be 6.8%, whereas 12.3% reported multimodal HHHs, and 32.2% indicated out-of-body experiences at the onset/offset of sleep. Group comparisons of hallucinations in the auditory modality showed that individuals that experienced only auditory HHHs scored significantly (p < 0.05) lower than those who also experienced daytime auditory hallucinations on a range of variables including mental health, anxiety, childhood happiness, and wellbeing. In addition, individuals with only auditory HHHs reported significantly (p < 0.05) less frequent hallucinations, less disturbing hallucinations, more neutral (in terms of content) hallucinations, hallucinations with less influence over their behavior, and less hallucination-related interference with social life compared to those individuals that experience daytime hallucinations. We also found that purely auditory HHHs had a significantly higher age of first onset of hallucinations than the purely daytime and the combined daytime and auditory HHHs groups (28.2 years>20.9 > 19.1)., Conclusions: Sleep-related hallucinations are common experiences in the general population, with the auditory modality being the least common. They occur mostly in combination with daytime hallucinations. However, some individuals (2.4%) experience only (auditory) sleep-related hallucinations and this group can be seen as more closely related, on a range of health-related factors, to non-hallucinating individuals than individuals who experience daytime hallucinations. Finally, there is a clear need for more research in this field, and ideas for future studies are presented., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically different antipsychotics: olanzapine, amisulpride, and aripiprazole., Methods: The present study is part of the Bergen-Stavanger-Innsbruck-Trondheim study, a 12-month prospective, randomized, pragmatic antipsychotic drug trial in active-phase schizophrenia spectrum disorders. The primary outcome of the present study was change of hallucinations as measured by item P3 (hallucinatory behavior) from the Positive and Negative Syndrome Scale in the subgroup with hallucinations at baseline. Primary analyses were intention to treat., Results: A total of 144 participants were included in the study, where 105 (72%) had a score of 3 or more on the Positive and Negative Syndrome Scale P3 item at baseline, indicating the presence of hallucinations (HALL subgroup).In the HALL subgroup, a significantly less reduction of hallucinations was revealed for participants using olanzapine in weeks 12, 26, 39, and 52 when compared with amisulpride and in weeks 26 and 52 when compared with aripiprazole. In subanalyses for participants never exposed to antipsychotic drugs (antipsychotic-naive) and those who had used antipsychotics before entering the study, antihallucinatory differences were revealed only in the latter group., Conclusions: A differential antihallucinatory effect of the 3 study drugs was present. The inferior effect of olanzapine seems to be driven by the subgroup of participants exposed to antipsychotic treatment before entering the study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Suggestions have been made that psychotic-like experiences (PLEs), such as hallucinatory and delusional experiences, exist on a continuum from healthy individuals to patients with a diagnosis of schizophrenia. We used the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately, to assess PLEs in Norway. Based on data from an online survey in a sample of more than 1,400 participants, we demonstrated that the QPE screening questions show satisfactory psychometric properties. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders. Childhood experiences were rather low and ranged from 0.7% to 5.2%. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, a binomial regression revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of the present study support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. Moreover, we demonstrated that the QPE screening questions can be used by themselves as a complementary tool to the full QPE interview., (© 2020 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P < 0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P = 0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum.

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on the constrains for interaction between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer reconstructed tracks along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer tracks in the left compared to the right side. In addition, there were significant positive correlations between PANSS scores and track length, track volume, and number of track streamlines for the posterior AF segment on the left side. It is concluded that the present DTI results may have implications for interpretations of functional imaging results., Competing Interests: Declaration of Competing Interests Co-authors Kenneth Hugdahl and Lars Ersland owns shares in the company NordicNeurolab Inc. (https://nordicneurolab.com/) that produced add-on equipment for the acquisition of the MR data. Kenneth Hugdahl and Lars Ersland declare no conflict of interest, as do all other co-authors., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Glutamate (Glu), gamma amino-butyric acid (GABA), and excitatory/inhibitory (E/I) imbalance have inconsistently been implicated in the etiology of schizophrenia. Elevated Glu levels in language regions have been suggested to mediate auditory verbal hallucinations (AVH), the same regions previously associated with neuronal hyperactivity during AVHs. It is, however, not known whether alterations in Glu levels are accompanied by corresponding GABA alterations, nor is it known if Glu levels are affected in brain regions with known neuronal hypo-activity. Using magnetic resonance spectroscopy (MRS), we measured Glx (Glu+glutamine) and GABA+ levels in the anterior cingulate cortex (ACC), left and right superior temporal gyrus (STG), and left inferior frontal gyrus (IFG), in a sample of 77 schizophrenia patients and 77 healthy controls. Two MRS-protocols were used. Results showed a marginally significant positive correlation in the left STG between Glx and AVHs, whereas a significant negative correlation was found in the ACC. In addition, high-hallucinating patients as a group showed decreased ACC and increased left STG Glx levels compared to low-hallucinating patients, with the healthy controls in between the 2 hallucinating groups. No significant differences were found for GABA+ levels. It is discussed that reduced ACC Glx levels reflect an inability of AVH patients to cognitively inhibit their "voices" through neuronal hypo-activity, which in turn originates from increased left STG Glu levels and neuronal hyperactivity. A revised E/I-imbalance model is proposed where Glu-Glu imbalance between brain regions is emphasized rather than Glu-GABA imbalance within regions, for the understanding of the underlying neurochemistry of AVHs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

That trauma can play a significant role in the onset and maintenance of voice-hearing is one of the most striking and important developments in the recent study of psychosis. Yet the finding that trauma increases the risk for hallucination and for psychosis is quite different from the claim that trauma is necessary for either to occur. Trauma is often but not always associated with voice-hearing in populations with psychosis; voice-hearing is sometimes associated with willful training and cultivation in nonclinical populations. This article uses ethnographic data among other data to explore the possibility of multiple pathways to voice-hearing for clinical and nonclinical individuals whose voices are not due to known etiological factors such as drugs, sensory deprivation, epilepsy, and so forth. We suggest that trauma sometimes plays a major role in hallucinations, sometimes a minor role, and sometimes no role at all. Our work also finds seemingly distinct phenomenological patterns for voice-hearing, which may reflect the different salience of trauma for those who hear voices.

The field of digital mental health is rapidly expanding with digital tools being used in assessment, intervention, and supporting self-help. The application of digital mental health to hallucinations is, however, at a very early stage. This report from a working group of the International Consortium on Hallucinations Research considers particular synergies between the phenomenon of hallucinations and digital tools that are being developed. Highlighted uses include monitoring and managing intermittently occurring hallucinations in daily life; therapeutic applications of audio and video media including virtual and augmented reality; targeting verbal aspects of hallucinations; and using avatars to represent hallucinatory voices. Although there is a well-established Internet-based peer support network, digital resources for hallucinations have yet to be implemented in routine practice. Implementation may benefit from identifying how to market resources to the broad range of populations who experience hallucinations and identifying sustainable funding models. It is envisaged that digital tools will contribute to improved self-management and service provision for people experiencing hallucinations.

Epidemiological studies have repeatedly shown that a significant minority of the general population have experienced hallucinations, however, a potential effect of age on the prevalence of hallucinations in the general population has never been previously examined in a specific study. The aim of the present study was thus to examine the effects of age and sensory modality on hallucination prevalence in a general population sample. A large, randomly selected and representative sample of the Norwegian population completed measures assessing different hallucination modalities (auditory, visual, olfactory, and tactile) and types (sensed presence and hypnagogic/hypnopompic hallucinations). Three age groups were identified and compared: young (19-30 years), middle (31-60) and old (61-96). There was a significant main-effect of age for all hallucination modalities and types, whereby hallucination prevalence significantly decreased with age. We also found that anxiety partially mediated the effect of age on hallucinations whilst depression was a partial suppressor. Concerning the co-occurrence of hallucination modalities, there was very little co-occurrence of auditory and visual hallucinations in all three age groups. In summary, a main-effect of age for hallucination prevalence was observed. Furthermore, individuals reported a more diverse variety of hallucination modalities compared to what is commonly reported in clinical populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose of Review: Hallucinations are common and often stressful experiences, occurring in all sensory modalities. They frequently complicate many disorders or situations, such as Parkinson's disease, schizophrenia, hearing or vision loss, intoxications and delirium. Although psychoeducation, coping techniques and psychotherapy may be broadly applicable, they do not address a specific underlying brain mechanism. Pharmacotherapy may effectively alleviate hallucinations if the corresponding mechanism is present, whereas in its absence, may only cause harmful side effects. Therefore, pharmacotherapy needs input about underlying brain mechanisms., Recent Findings: Recent findings suggest new underlying neurobiological mechanisms as possible therapeutic targets in selected patients, for example increased glutamate levels. In addition, neuronavigation can guide repetitive transcranial magnetic stimulation treatment of auditory verbal hallucinations to target-specific cortical regions., Summary: We propose the use of neuroimaging methods to better understand the interaction of different mechanisms underlying hallucinations and to use this knowledge to guide pharmacotherapy or focal brain stimulation in a personalized manner. In addition, we suggest evidence from various imaging modalities should converge to answer a research question. We believe this 'convergence of evidence' avoids the problem of overreliance on single and isolated findings.

Understanding what happens at first onset of auditory verbal hallucinations (AVHs) is extremely important on a clinical and theoretical level. Previous studies have only focused on age with regard to first onset of AVHs. In the current epidemiological study, we examined a number of aspects relating to first onset of AVHs, such as the role of adverse life events at first onset of AVHs on symptom severity and general mental health. For this purpose, we compared participants who reported adverse life events at first onset of AHVs (adverse-trigger group; N = 76) to those that did not report any specific events at first onset of AVHs (no-adverse-trigger group; N = 59) on a large array of variables. Results showed that AVHs in the adverse-trigger group were experienced as more emotional compared to the no-adverse-trigger group. In addition, the adverse-trigger group more often reported hallucinations in other (non-auditory) sensory modalities (e.g. visual) compared to the no-adverse-trigger group. Furthermore, the adverse-trigger group reported poorer general mental health, reported having contact with mental health professionals more often, and also reported more frequently taking medication for psychological problems in general. The implications of these findings are discussed., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

In the present article, we present a "Levels of Explanation" (LoE) approach to auditory verbal hallucinations (AVHs) in schizophrenia. Mental phenomena can be understood at different levels of explanation, including cultural, clinical, cognitive, brain imaging, cellular, and molecular levels. Current research on AVHs is characterized by accumulation of data at all levels, but with little or no interaction of findings between levels. A second advantage with a Levels of Explanation approach is that it fosters interdisciplinarity and collaboration across traditional borders, facilitating a real breakthrough in future research. We exemplify a Levels of Explanation approach with data from 3 levels where findings at 1 level provide predictions for another level. More specifically, we show how functional neuroimaging data at the brain level correspond with behavioral data at the cognitive level, and how data at these 2 levels correspond with recent findings of changes in neurotransmitter function at the cellular level. We further discuss implications for new therapeutic interventions, and the article is ended by suggestion how future research could incorporate genetic influences on AVHs at the molecular level of explanation by providing examples for animal work.

Hallucinated voices are common across psychiatric and non-clinical groups. The predominant cognitive theory about the impact of voices posits that beliefs about voice power ('Omnipotence') and voice intent ('Malevolence'/'Benevolence') play a key role in determining emotional and behavioral reactions. The revised Beliefs about Voices Questionnaire (BAVQ-R) was designed to assess these constructs, together with two styles of responding (Engagement and Resistance). The BAVQ-R is widely used in clinical and research settings, yet it has not received validation of its constructs and factor structure. This study examined the factor structure of the BAVQ-R by combining datasets from five study centers, comprising 450 participants (belief constructs) and 269 participants (response styles), and using confirmatory and exploratory factor analysis. Findings failed to support a three factor belief model, instead showing a two-factor structure ('Persecutory beliefs' combining Omnipotence and Malevolence constructs, and a Benevolent construct). Emotional and behavioral items did not separate. Overall, results showed that (i) a two-factor model of beliefs (Persecutory and Benevolent beliefs) provides a better fit to the data than a three-factor model, and (ii) emotional and behavioral modes of responding items should not be separated. Theoretical implications of this finding are discussed in relation to the research and therapy., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

In this invited review article, I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway, with a focus on the neuronal mechanisms underlying the phenomenology of experiencing "hearing voices". An auditory verbal hallucination (i.e. hearing a voice) is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations, called Levels of Explanation. Using a Levels of Explanation approach, mental phenomena can be described and explained at different levels (cultural, clinical, cognitive, brain-imaging, cellular and molecular). Another way of saying this is that, to advance knowledge in a research field, it is not only necessary to replicate findings, but also to show how evidence obtained with one method, and at one level of explanation, converges with evidence obtained with another method at another level. To achieve breakthroughs in our understanding of auditory verbal hallucinations, we have to advance vertically through the various levels, rather than the more common approach of staying at our favourite level and advancing horizontally (e.g., more advanced techniques and data acquisition analyses). The horizontal expansion will, however, not advance a deeper understanding of how an auditory verbal hallucination spontaneously starts and stops. Finally, I present data from the clinical, cognitive, brain-imaging, and cellular levels, where data from one level validate and support data at another level, called converging of evidence. Using a translational approach, the current status of auditory verbal hallucinations is that they implicate speech perception areas in the left temporal lobe, impairing perception of and attention to external sounds. Preliminary results also show that amygdala is implicated in the emotional «colouring» of the voices and that excitatory neurotransmitters might be involved. What we do not know is why hallucinatory episodes occur spontaneously, why they fluctuate over time, and what makes them spontaneously stop. Moreover, is voice hearing a category or dimension in its own right, independent of diagnosis, and why is the auditory modality predominantly implicated in psychotic disorders, while the visual modality dominates in, for example, neurological diseases?

Background: Neuroimaging studies have demonstrated associations between smaller auditory cortex volume and auditory hallucinations (AH) in schizophrenia. Reduced cortical volume can result from a reduction of either cortical thickness or cortical surface area, which may reflect different neuropathology. We investigate for the first time how thickness and surface area of the auditory cortex relate to AH in a large sample of schizophrenia spectrum patients., Methods: Schizophrenia spectrum (n = 194) patients underwent magnetic resonance imaging. Mean cortical thickness and surface area in auditory cortex regions (Heschl's gyrus [HG], planum temporale [PT], and superior temporal gyrus [STG]) were compared between patients with (AH+, n = 145) and without (AH-, n = 49) a lifetime history of AH and 279 healthy controls., Results: AH+ patients showed significantly thinner cortex in the left HG compared to AH- patients (d = 0.43, P = .0096). There were no significant differences between AH+ and AH- patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication., Conclusions: AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This review from the International Consortium on Hallucinations Research intends to question the pertinence of the excitatory-to-inhibitory (E/I) imbalance hypothesis as a model for hallucinations. A large number of studies suggest that subtle impairments of the E/I balance are involved in neurological and psychiatric conditions, such as schizophrenia. Emerging evidence also points to a role of the E/I balance in maintaining stable perceptual representations, suggesting it may be a plausible model for hallucinations. In support, hallucinations have been linked to inhibitory deficits as shown with impairment of gamma-aminobutyric acid transmission, N-methyl-d-aspartate receptor plasticity, reductions in gamma-frequency oscillations, hyperactivity in sensory cortices, and cognitive inhibition deficits. However, the mechanisms by which E/I dysfunctions at the cellular level might relate to clinical symptoms and cognitive deficits remain unclear. Given recent data advances in the field of clinical neuroscience, it is now possible to conduct a synthesis of available data specifically related to hallucinations. These findings are integrated with the latest computational frameworks of hallucinations, and recommendations for future research are provided., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The present study was specifically designed to investigate the prevalence of auditory verbal hallucinations (AVH) in the general population, and sought to compare similarities and differences regarding socio-demographics, mental health and severe life events between individuals who have never experienced AVH with those who had. The study also aimed to compare those who sought professional help for their experience of AVH with those who had not sought help. Through a postal questionnaire, 2,533 participants ages 18 and over from a national survey completed the Launay-Slade Hallucinations Scale and other measures examining AVH characteristics and other areas related to AVH. In total, 7.3% of the sample reported a life-time prevalence of AVH. Those with AVH were more likely to be single and unemployed, reported higher levels of depression and anxiety, and experienced a higher number of severe life events compared with those without AVH. Only 16% of those who experienced AVH in the general population sought professional help for these experiences. Compared to those who did not seek professional help, participants that had were more likely to experience AVH with a negative content, experience them on a daily basis, undergo negative reactions when experiencing AVH, and resist AVH. In conclusion, the prevalence of AVH was found to be relatively high. The results also revealed higher levels of reduced mental health for individuals who sought professional help, followed by those who did not, compared with those who had never experienced AVH., (© 2015 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

This is a (1)H MR spectroscopy (MRS) study of glutamate (Glu), measured as Glx, levels in temporal and frontal lobe regions in patients with schizophrenia compared with a healthy control group with the objective of revealing aspects of the underlying neurochemistry of auditory hallucinations. We further compared and correlated Glu(Glx) levels for the patients-only against frequency and severity of auditory hallucinations and the sum of Positive symptoms, and also for frequency and severity of emotional withdrawal, and sum of Negative symptoms. The sample included 23 patients with an ICD-10 and DSM-IV diagnosis of schizophrenia, and 26 healthy control subjects without any known psychiatric or neurological disorders. Symptom scores were obtained from the Positive and Negative Syndrome Scale (PANSS). (1)H MRS data were acquired on a 3T MR scanner from two temporal and two frontal voxels, using standard sequences and analysis parameters. The results showed that schizophrenia patients as a group had reduced Glu(Glx) levels in the voxels of interest compared to the healthy control subjects, while increased levels were found for patients with frequent and severe auditory hallucinations, relative to patients with less frequent and severe hallucination. We further found significant positive correlations between frequency and severity of auditory hallucinations, and for sum Positive symptoms, and Glu(Glx) levels in all regions, not seen when the analysis was done for negative symptoms. It is concluded that the results show for the first time that glutamate may be a mediating factor in auditory hallucinations in schizophrenia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up., Methods: Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS)., Results: A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group., Conclusions: Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category., Trial Registration: ClinicalTrials.gov ID; NCT00932529.

Auditory verbal hallucinations (AVHs) are speech perceptions that lack an external source, phenomenologically experienced as "hearing voices". A perceptual origin of an AVH experience in patients with schizophrenia can however not explain why the "voices" drain the attentional and cognitive capacity of the patients, making them unable to direct attention away from the "voices" and to cognitively suppress the experience. We recently reported how AVHs interfere with the perception of speech sounds, using a dichotic listening experimental paradigm. We now extend this finding by reporting on the interference caused by AVHs on attention and cognitive control, using a slight variation of the same dichotic listening paradigm. The patients (N=148) were instructed to pay attention to and report from either the right or left ear syllable of the dichotic pair. We then correlated their PANSS score for the hallucination item (P3) with the performance score on the dichotic listening task. The results showed that AVHs interfered with the ability to report the right ear syllable when instructed to pay attention to the right side, which is a marker of inability to attend to an external speech stimulus. When instructed to pay attention to the left side, AVHs interfered with the ability to report the left ear syllable, which is a marker of inability to use cognitive control to suppress attending to the "voices". The corresponding correlations for the emotional withdrawal (N2) negative symptom were all non-significant. The correlations were substantiated in an ANOVA with corresponding significant group differences between high versus low symptom score groups. The results thus extend our previous findings of a perceptual origination for AVHs by showing that AVHs interfere with the ability to attend to the outer world around the patient, and the ability to inhibit, or suppress, the "voices" once they occur. Future research should pin down the neuronal basis of both the origination and the attentional and cognitive control aspects of AVHs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Inattention in people with schizophrenia is common. However, there has been little research on the association between inattention and auditory hallucinations. The aim of the study was to investigate how inattention is affected by beliefs about voices as benevolent and malevolent and perceived control of voices. A total of 31 patients who experienced auditory hallucinations and who met the criteria for schizophrenia or other psychosis completed the attention subscale of the Scale for the Assessment of Negative Symptoms (SANS) and the Connors' Continuous Performance Test II (CCPT-II). The revised Beliefs About Voices Questionnaire (BAVQ-R) was used to assess malevolent and benevolent beliefs about voices, and severity of auditory hallucinations (the Psychotic Symptom Rating Scales; PSYRATS) was used to assess perceived control of voices and frequency of voices. Levels of depression (the Beck Depression Inventory; BDI), anxiety (the Beck Anxiety Inventory; BAI), severity of overall psychiatric symptoms (the Brief Psychiatric Rating Scale; BPRS), and severity of negative symptoms (SANS) were assessed to control for their potential confounding effects. The relations between the variables were explored with correlations and multiple hierarchical regression analyses. The results indicated that more malevolent, but not more benevolent, beliefs about voices predicted lower levels of attention, independently of general psychiatric symptoms and various other psychotic symptoms such as frequency of and perceived control of voices. These findings suggest an important relationship between malevolent beliefs about voices and levels of inattention. The possible impact of changing beliefs about voices to improve attentional functioning is discussed., (© 2013 The Authors. Scandinavian Journal of Psychology © 2013 The Scandinavian Psychological Associations.)

Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = -0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = -0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population.

Experiencing auditory verbal hallucinations is a prominent symptom in schizophrenia that also occurs in subjects at enhanced risk for psychosis and in the general population. Drug treatment of auditory hallucinations is challenging, because the current understanding is limited with respect to the neural mechanisms involved, as well as how CNS drugs, such as antipsychotics, influence the subjective experience and neurophysiology of hallucinations. In this article, the authors review studies of the effect of antipsychotic medication on brain activation as measured with functional MRI in patients with auditory verbal hallucinations. First, the authors examine the neural correlates of ongoing auditory hallucinations. Then, the authors critically discuss studies addressing the antipsychotic effect on the neural correlates of complex cognitive tasks. Current evidence suggests that blood oxygen level-dependant effects of antipsychotic drugs reflect specific, regional effects but studies on the neuropharmacology of auditory hallucinations are scarce. Future directions for pharmacological neuroimaging of auditory hallucinations are discussed.

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonant-vowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interfere with correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reports with the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scores with the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlations were close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Despite a growing interest in auditory verbal hallucinations (AVHs) in different clinical and nonclinical groups, the phenomenological characteristics of such experiences have not yet been reviewed and contrasted, limiting our understanding of these phenomena on multiple empirical, theoretical, and clinical levels. We look at some of the most prominent descriptive features of AVHs in schizophrenia (SZ). These are then examined in clinical conditions including substance abuse, Parkinson's disease, epilepsy, dementia, late-onset SZ, mood disorders, borderline personality disorder, hearing impairment, and dissociative disorders. The phenomenological changes linked to AVHs in prepsychotic stages are also outlined, together with a review of AVHs in healthy persons. A discussion of key issues and future research directions concludes the review.

The continuum model of psychosis has been extremely influential. It assumes that psychotic symptoms, such as auditory verbal hallucinations (AVH), are not limited to patients with psychosis but also occur in healthy, non-clinical individuals - suggesting similar mechanisms of origin. Recent debate surrounding this model has highlighted certain differences, as well as similarities, in the phenomenology of AVH in clinical and non-clinical populations. These findings imply that there may, in fact, be only partial overlap of the mechanism(s) involved in generating AVH in these groups. We review evidence of continuity or similarity, and dissimilarity, in cognitive, and related neural processes, underlying AVH in clinical and non-clinical samples. The results reveal some shared (intrusive cognitions, inhibitory deficits) and some distinct (aspects of source memory and cerebral lateralization) mechanisms in these groups. The evidence, therefore, supports both continuous and categorical models of positive psychotic symptoms. The review considers potential risks of uncritical acceptance of the continuum model and highlights some important methodological issues for future research., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The existing literature on neuroimaging studies of auditory verbal hallucinations (AVHs) in patients with schizophrenia contains an apparent "paradox" in that the same areas in the auditory cortex seem to be both activated and deactivated in relation to AVHs, depending on whether an external auditory stimulus is present or not. We performed meta-analyses of neuroimaging studies examining patients with schizophrenia during the processing of auditory stimuli and in individuals experiencing hallucinations in the absence of auditory stimuli to examine whether the auditory cortex shows the paradoxical decrease/increase pattern across studies. Databases PubMed and ISI Web of Knowledge were queried with the combination of the keywords "auditory verbal hallucinations", "auditory hallucinations", "fMRI", "PET", "imaging", yielding 11 studies involving comparison between schizophrenia and control group during external auditory stimulation, and 12 studies of hallucinating subjects experiencing AVHs and resting in the absence of auditory stimulation. The data were analyzed using Activation Likelihood Estimation method. The results showed overlapping increased activation in the absence of an external stimulus, and decreased activation in the presence of an external auditory stimulus in the left primary auditory cortex and in the right rostral prefrontal cortex, confirming the "paradoxical" brain activation in relation to AVHs. It is suggested that the "paradox" may be caused by an attentional bias towards internally generated information and failure of down- and up-regulation of the default mode and auditory processing networks, respectively, with the consequence that the spontaneous activation in the absence of an external stimulus shuts down the perceptual apparatus for further processing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: The aim of the study was to investigate behavioral and brain activation in nonpsychotic hallucinating individuals. Auditory hallucinations are reported by patients with epilepsy, although less frequent than visual hallucinations are. If behavioral and neuronal activation patterns in hallucinating patients with epilepsy are found to be similar to what has been found in hallucinating patients with schizophrenia, this would support a unique neuronal representation for auditory hallucinations cutting across diagnostic groups., Methods: We report behavioral and functional magnetic resonance imaging (fMRI) data from six epilepsy patients experiencing auditory hallucinations compared with six healthy control subjects. The participants had to report which of two simultaneously presented simple speech sounds they perceived on each trial, using a dichotic stimulus presentation mode., Results: The results showed that the patients failed to show an expected right ear advantage on the task, and they also showed significantly reduced activation in temporal, frontal, and cingulate cortex areas., Discussion: The results are discussed in relation to a view that neuropsychological and functional neuroimaging indices of auditory hallucinations may be orthogonal to diagnostic category and not unique to patients with schizophrenia.

Auditory hallucination is a key characteristic of schizophrenia that seriously debilitates the patient, with consequences for social engagement with others. Hallucinatory experiences are also observed in healthy individuals in the general population who report "hearing voices" in the absence of an external acoustic input. A view on auditory hallucinations and "hearing voices" is presented that regards such phenomena as perceptual processes, originating from speech perception areas in the left temporal lobe. Healthy individuals "hearing voices" are, however, often aware that the experience comes from inner thought processes, which is not reported by hallucinating patients. A perceptual model can therefore, not alone explain the difference in the phenomenology of how the "voices heard" are attributed to either an inner or outer cause. An expanded model is thus presented which takes into account top-down cognitive control, localized to prefrontal cortical areas, to inhibit and re-attribute the perceptual mis-representations. The expanded model is suggested to be empirically validated using a dichotic listening speech perception paradigm with instructions for top-down control of attention focus to either the right or left side in auditory space. It is furthermore suggested to use fMRI to validate the temporal and frontal lobe neuronal correlates of the cognitive processes involved in auditory hallucinations.

Introduction: We propose that auditory hallucinations are internally generated speech misrepresentations that are lateralised to the left temporal lobe. If hallucinations are misrepresentations involving the speech perception area of the left temporal lobe, then hallucinating patients should have problems identifying a simultaneously presented external speech sound, especially when the sound is lateralised to the left hemisphere. Lateralisation of speech perception can be experimentally studied with the dichotic listening task with consonant-vowel syllables. We predicted a negative relation between frequency of auditory hallucinations and performance on the dichotic listening task., Method: We studied 87 right-handed patients with schizophrenia. Hallucination scores were taken from the BPRS symptom scale. Right and left ear scores in the dichotic listening task were recorded. A right ear advantage is expected in healthy individuals, indicating left temporal lobe processing superiority. The patients were compared with 36 right-handed healthy reference subjects., Results: A gradual decrease in the ability to process and report the right ear stimulus with increasing frequency of hallucinations was seen in the schizophrenia patients. No such relationship was found for processing and reporting of the left ear stimulus. There were no significant correlations with negative symptoms. Thus, the results were not the consequence of illness severity. There was however a significant correlation with unusual thought content symptom, pointing to a relationship also between delusions and auditory hallucinations., Conclusion: The results support that auditory hallucinations may be internally generated speech misrepresentations, originating in the left temporal lobe.

The authors used voxel-based morphometry (VBM) to study GM volume differences in the whole brain volume between a group of patients with schizophrenia and a healthy control group. There were 12 patients and 12 control subjects. The subjects were scanned in a 1.5 T MR scanner. The patients had all been evaluated by a senior psychiatrist on the brief psychiatric rating scale (BPRS). The VBM data was correlated with reports of rate and frequency of hallucinations based on their scores on the BPRS hallucination item. There were significant grey matter volume reductions in the schizophrenia patient group in the left superior (transverse) temporal gyrus, the left middle frontal gyrus, and in the right cuneus. Areas of grey matter volume reduction that correlated negatively with hallucinations were found in the left superior (transverse) temporal gyrus, left thalamus, and left and right cerebellum. This article proposes that significant reductions in grey matter volume may be instrumental in generating spontaneous neuronal activity that is associated with speech perception experiences in the absence of an external acoustic stimulus that may cause hallucinations.

Auditory hallucinations (AH) in schizophrenia have been found to be related to both functional and structural brain abnormalities of left temporal lobe language areas. We do not know if these rain abnormalities are state or trait markers for AH. This study tested these alternatives by contrasting schizophrenic patients with ongoing AH and with a previous history of AH. A heterogeneous group of 26 schizophrenic patients was compared with a healthy control group matched for education and age. We used a verbal dichotic listening (DL) test with consonant-vowel syllables to study hemispheric asymmetry and the functional integrity of the left temporal lobe language areas. All subjects were tested during a divided and two focused attention conditions. Our data suggest that abnormal DL asymmetry for language stimuli is a state marker for AH, seen during the perception of AH. In contrast, problems of modulating DL performance by means of attentional control are a trait marker, seen both in patients with ongoing AH and only a history of AH.

Background It has been theorized that hallucinations, a common symptom of schizophrenia, are caused by failures in reality monitoring. The paracingulate sulcus (PCS) has been implicated as a brain structure supporting reality monitoring with the absence or shorter length of PCS associated with an occurrence of hallucinations in schizophrenia. The absence or shorter length of PCS has been associated with an occurrence of hallucinations. There are inconsistent findings in the literature regarding the role of the asymmetry of this structure for hallucinations. Here, we investigated the length of the PCS and cortical thickness of surrounding structures in patients with a lifetime history of auditory verbal hallucinations (AVH). Design Seventy-seven patients and twenty-eight healthy controls (HC) underwent an anatomical MRI scan. PCS length and cortical thickness were estimated using Mango brain visualization and FreeSurfer, respectively. Patients with AVH (n = 45) and patients without AVH were compared (n = 32) to the controls. Results PCS length significantly differed between HC and patient groups (F (2,102) = 3.57, P =.032) in the left but not in the right sulcus. We found significantly longer PCS between HC and AVH group but no difference between patient groups. Similarly, we found significant thinning of cortical structures including structures surrounding anterior parts of PCS between HC and patients either in general or per group, but no significant differences were observed between patient groups. Conclusions PCS length in the left hemisphere is shorter in schizophrenia patients with hallucinations as compared to HC subjects. The patient group without hallucinations was in between those 2 groups. Cortical thickness of neighboring areas of PCS is diminished in patient groups relative to the healthy comparison subjects. The role of lateralization and functional involvement of the PCS region in processes underlying hallucinations, such as reality monitoring, needs further clarification. [ABSTRACT FROM AUTHOR]

Functional connectome alterations, including modular network organization, have been related to the experience of hallucinations. It remains to be determined whether individuals with hallucinations across the psychosis continuum exhibit similar alterations in modular brain network organization. This study assessed functional connectivity matrices of 465 individuals with and without hallucinations, including patients with schizophrenia and bipolar disorder, nonclinical individuals with hallucinations, and healthy controls. Modular brain network organization was examined at different scales of network resolution, including (1) global modularity measured as Qmax and Normalised Mutual Information (NMI) scores, and (2) within- and between-module connectivity. Global modular organization was not significantly altered across groups. However, alterations in within- and between-module connectivity were observed for higher-order cognitive (e.g. central-executive salience, memory, default mode), and sensory modules in patients with schizophrenia and nonclinical individuals with hallucinations relative to controls. Dissimilar patterns of altered within- and between-module connectivity were found bipolar disorder patients with hallucinations relative to controls, including the visual, default mode, and memory network, while connectivity patterns between visual, salience, and cognitive control modules were unaltered. Bipolar disorder patients without hallucinations did not show significant alterations relative to controls. This study provides evidence for alterations in the modular organization of the functional connectome in individuals prone to hallucinations, with schizophrenia patients and nonclinical individuals showing similar alterations in sensory and higher-order cognitive modules. Other higher-order cognitive modules were found to relate to hallucinations in bipolar disorder patients, suggesting differential neural mechanisms may underlie hallucinations across the psychosis continuum. [ABSTRACT FROM AUTHOR]

Background: Auditory verbal hallucinations (AVH), the sense of “hearing voices” in the absence of a corresponding auditory source, are a major symptom in schizophrenia. Hemodynamic and electrophysiology studies have shown aberrant activation in fronto-temporal speech and language areas (Curcic-Blake et al., 2017 for review) – indicating neurobiological mediators relating to onset and duration of AVH episodes. However, unanswered is the question of specific neuronal precursors to the spontaneous cessation of an AVH episode. We therefore studied what happens in the brain a few seconds before both the onset and offset of an AVH episode. Methods: Structural and functional MRI data were collected from 44 patients diagnosed with a schizophrenia spectrum disorder, at three sites (University of Bergen, Norway, n=12; Medical University of Plovdiv, Bulgaria, n=13; Utrecht University Medical Center, Netherlands, n=19, total 25m, 19f, age 37.9+/-13.2 years). Symptom severity was assessed with the PANSS; mean total (+/-SD) 64.9+/-16.9; P3 hallucinatory behaviour 4.6+/-1.1. Additional assessments (not reported), scanner hardware and particulars of the MR acquisition varied between sites. Functional data were collected with a “symptom-capture” paradigm (Sommer et al., 2008), where subjects were instructed to press a button when a hallucinatory episode began, and another when the episode ended. Functional data were processed using an FSL FEAT pipeline, with additional filtering using the ICA_AROMA method. Data were then subjected to statistical analysis, contrasting hallucinatory with non-hallucinatory periods; higher-level analysis allowed comparison with findings from previous meta-analyses (Kompus et al. 2011, Jardri et al., 2011). A number of regions of interest were selected based on an initial PCA, in addition to regions nominated in the meta-analyses. For each region, for each start- and end-of-hallucination event, a time-course was extracted for the interval t=-10 to +15sec with respect to button-press onset. Timecourses were aligned and group-averaged (rejecting outliers iteratively) to yield a model time-course for start- and end- hallucinatory events in each region. Permutation analysis (n=5000) was performed to identify differential effects between start and end events. Results: Functional block-analysis revealed several clusters of activation, including among others the left fronto-temporal language areas (superior temporal gyrus and Broca’s area). Similar patterns were present on a per-site basis. Time-course analysis demonstrated a differential effect in the left paracingulate sulcus, characterized by a significant dip in activation (Δ=158iu, p=0.021) at the end-of-hallucination events, in contrast to a significant peak (Δ=35iu, p=0.0142) at the start-of-hallucination events. This activity preceded the motor response for the same events. Discussion: Clusters identified in the block-analysis at group-level were consistent with findings from meta-analyses; this attests to the validity of the source data and initial processing. The novel finding of anticipatory neuronal activity in the paracingulate region, differentiated between onset and offset of AVH- events, complements recent findings of reduced functional connectivity (Alonso-Solís et al., 2015) and morphological differences (Garrison et al., 2019) in the same region. This suggests that the paracingulate region may be crucial in both the initiation and the cessation of an AVH-episode and speaks to a kind of regulatory role for the region. This may in turn point to differential action of excitatory and inhibitory transmitters at a lower level of explanation. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The relation between auditory verbal hallucinations (AVH) and white matter has been studied, but results are still inconsistent. This inconsistency may be related to having only a single time-point of AVH assessment in many studies, not capturing that AVH severity fluctuates over time. In the current study, AVH fluctuations were captured by utilizing a longitudinal design and using repeated (Positive and Negative Symptoms Scale) PANSS questionnaire interviews over a 12 month period. We used a Magnetic Resonance Diffusion Tensor Imaging (MR DTI) sequence and tract-based spatial statistics (TBSS) to explore white matter differences between two subtypes of schizophrenia patients; 44 hallucinating (AVH+) and 13 non-hallucinating (AVH-), compared to 13 AVH- matched controls and 44 AVH+ matched controls. Additionally, we tested for hemispheric fractional anisotropy (FA) asymmetry between the groups. Significant widespread FA-value reduction was found in the AVH+ group in comparison to the AVH- group. Although not significant, the extracted FA-values for the control group were in between the two patient groups, for all clusters. We also found a significant difference in FA-asymmetry between the AVH+ and AVH- groups in two clusters, with significantly higher leftward asymmetry in the AVH- group. The current findings suggest a possible qualitative difference in white matter integrity between AVH+ and AVH- patients. Strengths and limitations of the study are discussed. [ABSTRACT FROM AUTHOR]

Background Auditory Hallucinations (AH) are prevalent in many psychopathologies as well as in a minority of the healthy general population. The literature suggests that people with AH present a signal detection bias, that is, in conditions of uncertainty, they tend to perceive signals that are not actually there– or false perceptions. For example, when listening to white noise, they perceive voices that are not actually in the noise. However, the literature is inconsistent regarding the relation between the number of false perceptions and hallucination proneness. In particular, whereas some studies have reported a significant correlation, other have not. Such inconsistencies may be explained by the lack of understanding of the white noise paradigm and in particular the role of the noise and of the level of expectation. The aim of the present study was thus to disentangle the white noise paradigm and to explore the specific relations with AH and other cognitive mechanisms or personality traits. Methods Twenty-three healthy individuals with a high proneness to AH and 20 with a low proneness were recruited. They were asked to carry out a semantic signal detection task where participants are required to listen to recordings of sentences from which the last word was replaced by a burst of noise alone or by a burst of noise with the last word of the sentence embedded in it. After each sentence, participants were asked to report whether or not they heard the last word. The sentences were created to induce either a high or a low level of expectation regarding the last word. Two different types of noise (that replaced the last word) were created. The first one was composed of white noise in which the language-related frequencies (formants) were predominant – or human noise. The second noise was composed of white noise minus the language-related frequencies – or non-human noise. Participants were also required to complete questionnaires assessing hallucination proneness, fantasy proneness, dissociation, social desirability, mind wandering, suggestibility, aberrant salience, and encoding style. Results Results revealed a significant interaction effect between the level of expectation, the type of noise, and the level of hallucination proneness. In particular, when confronted with both human noise and a high level of expectation, participants with a high proneness towards AH showed a greater signal detection bias than people with a low proneness, i.e. they reported more false alarms. On the contrary, no significant difference was found between the groups for the non-human noise or for a low level of expectation. Finally, regression analyses revealed that hallucination proneness was the best predictor of the signal detection bias. Discussion For the first time in the literature, the present study demonstrated that the signal detection bias frequently observed in people with AH is driven by both the specific language-related frequencies contained in white noise and by a high level of expectation. Moreover, the results showed that the signal detection bias was specifically predicted by a high proneness towards AH. These results are in agreement with the latest cognitive models of AH that claim that AH arise from an interaction between top-down (the human noise) and bottom-up (the high level of expectation) cognitive mechanisms. Futures studies are needed to replicate these findings, nevertheless, the present results suggest that the human noise should be used instead of white noise in order to improve the specificity of the white noise effect. One implication of these findings is that future studies could examine the specificity of this paradigm in terms of detection of ultra-high-risk individuals for psychosis. [ABSTRACT FROM AUTHOR]

Impaired functional brain asymmetry has been shown in schizophrenic patients, in addition to attentional deficits related to this laterality impairment. However, it has usually been shown in older patients with frequent positive symptoms. This is a matter of concern because previous studies have suggested that such deficits interact with subgroup characteristics, especially positive symptoms like hallucinations and age/duration of the illness. Thus, in this study, we tested a homogeneous group of young and stabilised schizophrenic patients. We used a verbal dichotic listening test with consonant–vowel syllables to study brain asymmetry and attentional modulation. Nineteen patients were compared with healthy subjects with the same age, handedness and gender distribution. All subjects were tested during a divided and two focused attention conditions. The patient and reference group showed the same performance pattern. This indicates that young and stabilised patients show normal functional brain asymmetry and normal ability to modulate attention. It is suggested that impairments in functional asymmetry and attentional modulation may follow a continuum related to symptomatology and age/duration of illness. [Copyright &y& Elsevier]

The estrogen hypothesis for schizophrenia suggests neuroprotective effects of estrogen for the development of the disorder and for symptom severity, including auditory hallucinations. Furthermore, estrogen has shown enhancing effects on cognitive control, a function that is also implicated in auditory hallucinations. Whether estrogen affects the tendency to hallucinate in healthy participants, and the potential mediating role of cognitive control, has not yet been studied. Therefore, the current study aimed to test these relationships by using a white noise paradigm in combination with a N-back working memory task in which cognitive load could be manipulated. The paradigm used simulates a hallucinatory state by induction of negative emotions and drainage of cognitive resources. The simultaneous exposure to white noise elicit experiences of hearing voices (false alarms). In a between-subject design, forty-two participants were tested during the menstrual cycle in either the early follicular phase (low estradiol) or late follicular phase (high estradiol). A 2(Cycle Phase) x2(N-back task) ANOVA showed a main-effect of cycle phase on number of experienced hallucinations in the white noise task, with a significantly higher number of reported hallucinations in the early follicular phase. Furthermore, estradiol was found to predict number of hallucinations. No interaction effect of cycle phase and available cognitive resources was found. The results suggest an estradiol-related change in hallucination proneness across the menstrual cycle, but the idea that cognitive functioning mediates this relationship was not supported. Overall, the study supports protective effects of estradiol on hallucination proneness in line with the estrogen-hypothesis of schizophrenia, and that such effects are not specific to the disease. • Estrogen shows antipsychotic effects, but it is unknown if these are disease-specific. • White-noise paradigm can assess hallucination proneness in healthy individuals. • More false alarms were reported during the menstrual phase than follicular phase. • Estradiol levels predicted number of false alarms (hallucinations). • Cognitive resources were not found to be a mediating factor. [ABSTRACT FROM AUTHOR]