Targeting the superior temporal gyrus with real-time fMRI neurofeedback: A pilot study of the indirect effects on self-referential processes in schizophrenia.

BACKGROUND: Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs. METHODS: In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network. RESULTS: Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex). CONCLUSIONS: STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ. CLINICALTRIALS: GOV: Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579.

Associations of Cognitive Expectancies With Auditory Hallucinations and Hallucinatory-Like Experiences in Patients With Schizophrenia.

BACKGROUND: Various neurocognitive models explore perceptual distortions and hallucinations in schizophrenia and the general population. A variant of predictive coding account suggests that strong priors, like cognitive expectancy, may influence perception. This study examines if stronger cognitive expectancies result in more auditory false percepts in clinical and healthy control groups, investigates group differences, and explores the association between false percepts and hallucinations. STUDY DESIGN: Patients diagnosed with schizophrenia with current auditory hallucinations (n = 51) and without hallucinations (n = 66) and healthy controls (n = 51) underwent the False Perception Task under various expectancy conditions. All groups were examined for the presence and severity of hallucinations or hallucinatory-like experiences. STUDY RESULTS: We observed a main effect of condition across all groups, ie, the stronger the cognitive expectancy, the greater the ratio of auditory false percepts. However, there was no group effect for the ratio of auditory false percepts. Despite modest pairwise correlations in the hallucinating group, the ratio of auditory false percepts was not predicted by levels of hallucinations and hallucinatory-like experiences in a linear mixed model. CONCLUSIONS: The current study demonstrates that strong priors in the form of cognitive expectancies affect perception and play a role in perceptual disturbances. There is also a tentative possibility that overreliance on strong priors may be associated with hallucinations in currently hallucinating subjects. Possible, avoidable confounding factors are discussed in detail.

Functional connectivity of the auditory cortex in women with trauma-related disorders who hear voices.

BACKGROUND: 'Voice-hearing' (VH) is a transdiagnostic experience that is common in trauma-related disorders (trauma-D). However, the neural substrates underlying trauma-related VH remain largely unexplored. While auditory perceptual dysfunction is among the abnormalities implicated in schizophrenia VH, whether VH in trauma-D also involves auditory perceptual alterations is unknown. METHODS: We investigated auditory cortex (AC)-related functional connectivity (FC) in n=65 women with trauma-D related to childhood abuse with varying severities of VH. Using a novel, computationally-driven and individual-specific method of functionally parcellating the brain, we calculated the FC of two distinct AC subregions-Heschl's gyrus (HG, corresponding to primary AC) and lateral superior temporal gyrus (lSTG, in non-primary AC)- with both the cerebrum and cerebellum. We then measured the association between VH severity and FC using leave-one-out cross validation within the cerebrum, and voxel-wise multiple regression analyses in the cerebellum. RESULTS: We found that VH severity positively correlated with left lSTG-frontoparietal network FC, while it negatively correlated with FC between left lSTG and both cerebral and cerebellar representations of the default mode network. VH severity was not predicted by FC of left HG or right AC subregions. CONCLUSIONS: Our findings point to altered interactions between auditory perceptual processing and higher-level processes related to self-reference and executive functioning. This is the first study to show alterations in auditory cortical connectivity in trauma-related VH. While VH in trauma-D appears to be mediated by brain networks that are also implicated in schizophrenia VH, the results suggest a unique mechanism that could distinguish VH in trauma-D.

Recent social stress and severity of auditory hallucinations.

BACKGROUND AND HYPOTHESIS: Hearing voices is a common and often distressing experience for people with psychosis, and many individuals experience medication-resistant auditory verbal hallucinations (AVH). Psychosocial interventions are often employed to address distress over hearing voices. However, although links have been made between adverse social experiences and psychosis broadly, no work has yet delineated the relationship between day-to-day social stress and hallucination severity. We aimed to define that relationship in both clinical and non-clinical voice-hearers. STUDY DESIGN: A sample of 278 participants with a history of hearing voices was selected from the Yale Control Over Perceptual Experiences (COPE) Project. They were administered self-report measures of recent stress and recent auditory experiences within a cross-sectional design. Regression models were used to evaluate whether self-reported aspects of recent stress-and social stress in particular-were related to recent frequency of and distress over hearing voices. Related demographics and clinical characteristics were included as covariates. STUDY RESULTS: A significant relationship was observed between recent social stress and both recent frequency of and distress over hearing voices. While other aspects of recent stress were also related to recent distress over voices, social stressors uniquely predicted distress over voice-hearing, beyond the influence of other stressors. Depressive symptom severity was also related to distress over voices. CONCLUSIONS: Results suggest that daily social stress may be an important consideration and a potential treatment target for individuals experiencing clinical distress over auditory hallucinations.

The efficacy of low frequency repetitive transcial magnetic stimulation for treating auditory verbal hallucinations in schizophrenia: Insights from functional gradient analyses.

Background: Auditory Verbal Hallucinations (AVH) constitute a prominent feature of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic benefits in ameliorating AVH, the underlying mechanisms of its efficacy necessitate further elucidation. Objective: This study investigated the cortical gradient characteristics and their associations with clinical responses in schizophrenia patients with AVH, mediated through 1 Hz rTMS targeting the left temporoparietal junction. Method: Functional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. Results: The 1 Hz rTMS treatment effectively ameliorated the positive symptoms in patients, specifically targeting AVH. Initial evaluations revealed expanded global gradient distribution patterns and specific principal gradient variations in certain brain regions in patients at baseline compared to a control cohort. Following treatment, these divergent global and local patterns showed signs of normalizing. Furthermore, there was observed a closer alignment in between-network dispersion among various networks after treatment, including the somatomotor, attention, and limbic networks, indicating a potential harmonization of brain functionality. Conclusion: Low-frequency rTMS induces alternations in principal functional gradient patterns, may serve as imaging markers to elucidate the mechanisms underpinning the therapeutic efficacy of rTMS on AVH in schizophrenia.

Grey matter volume reduction in the frontotemporal cortex associated with persistent verbal auditory hallucinations in Chinese patients with chronic schizophrenia: Insights from a 3 T magnetic resonance imaging study.

BACKGROUND: Persistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ. METHODS: 76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups. RESULTS: Compared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (ß = -0.29, p = 0.001) and right fusiform (ß = -0.21, p = 0.01) were significantly associated with the severity of pAVHs. CONCLUSIONS: Widespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ.

Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

BACKGROUND AND HYPOTHESIS: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. STUDY DESIGN: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. STUDY RESULTS: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). CONCLUSIONS: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Functional and structural effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations in schizophrenia: A systematic review.

BACKGROUND: Auditory verbal hallucinations (AVH) are a disabling symptom for people with schizophrenia (SCZ), and do not always respond to antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for medication-refractory AVH, though the underlying neural mechanisms by which rTMS produces these effects remain unclear. This systematic review evaluated the structural and functional impact of rTMS for AVH in SCZ, and its association with clinical outcomes. METHODS: A systematic search was conducted in Medline, PsychINFO, and PubMed using terms for four key concepts: AVH, SCZ, rTMS, neuroimaging. Using PRISMA guidelines, 18 studies were identified that collected neuroimaging data of an rTMS intervention for AVH in SCZ. Risk of bias assessments was conducted. RESULTS: Low frequency (<5 Hz) rTMS targeting left hemispheric language processing regions may normalize brain abnormalities in AVH patients at structural, functional, electrophysiological, and topological levels, with concurrent symptom improvement. Amelioration of aberrant neural activity in frontotemporal networks associated with speech and auditory processing was commonly observed, as well as in cerebellar and emotion regulation regions. Neuroimaging analyses identified neural substrates with direct correlations to post-rTMS AVH severity, propounding their use as therapeutic targets. DISCUSSION: Combined rTMS-neuroimaging highlights the multidimensional alterations of rTMS on brain activity and structure in treatment-resistant AVH, which may be used to develop more efficacious therapies. Larger randomized, sham-controlled studies are needed. Future studies should explore alternate stimulation targets, investigate the neural effects of high-frequency rTMS and evaluate long-term neuroimaging outcomes.

Self-assessment scale of auditory verbal hallucinations (SAVH): A novel tool for patients with schizophrenia.

BACKGROUND: A scale for self-assessment of auditory verbal hallucinations (SAVH) was developed for patients, and this study aimed to validate the scale by investigating its psychometric properties. METHODS: Forty one patients with schizophrenia or schizoaffective disorders (DSM-5) self-assessed their hallucinations using nine SAVH questions. Each question was scored from 0 to 5, indicating the severity of the symptoms. Patients were also evaluated with the Brief Psychiatric Rating Scale (BPRS), Auditory Hallucination Rating Scale (AHRS), and Birchwood Insight Scale (BIS). The psychometric properties of the SAVH were assessed by the face, internal consistency, construct, convergent and discriminant validities. RESULTS: SAVH scores were used to examine the psychometric properties. Cronbach's α and Guttman's Lambda-6 were 0.67 and 0.73 respectively. Significant correlations were observed between SAVH and AHRS total scores, as well as BPRS hallucinatory behavior subscores. No significant correlations were found between total SAVH scores and (i) levels of insight or (ii) negative BPRS subscores. Factor analysis on SAVH revealed three factors accounting for 59.3 % of the variance. Most patients found the questions clear, appropriate, and of adequate length. CONCLUSIONS: SAVH demonstrated good psychometric properties, suggesting its utility in assessing auditory verbal hallucinations (AVH). This self-assessment could be valuable in evaluating AVH treatment efficacy, monitoring AVH, and empowering patients.

Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Neuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks. STUDY DESIGN: We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks. STUDY RESULTS: The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance. CONCLUSIONS: Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.

Abnormal effective connectivity of reward network in first-episode schizophrenia with auditory verbal hallucinations.

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging. Group-level connection coefficients, between-group differences and correlation analysis between image measures and symptoms were performed. RESULT: DCM revealed weaker effective connectivity (EC) from right ventral striatum (RVS) to ventral tegmental area (VTA) in AVH compared to NAVH. AVH showed stronger EC from left anterior insula (AI) to RVS, stronger EC from RVS to anterior cingulate cortex (ACC), and stronger EC from VTA to posterior cingulate cortex (PCC) compared to NC. The correlation analysis results were mostly visible in the negative correlation between EC from right AI to ACC and positive sub-score, P1 sub-score, and P3 sub-score of PNASS in group-level. CONCLUSION: These findings suggest that neural causal interactions between the reward network associated with AVHs are disrupted, expanding the evidence for potential neurobiological mechanisms of AVHs. Particularly, dopamine-dependent salience attribution and top-down monitoring impairments and compensatory effects of enhanced excitatory afferents to ACC, which may provide evidence for a therapeutic target based on direct in vivo of AVHs in schizophrenia.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

Functional Connectivity Between Auditory and Medial Temporal Lobe Networks in Antipsychotic-Naïve Patients With First-Episode Schizophrenia Predicts the Effects of Dopamine Antagonism on Auditory Verbal Hallucinations.

Background: Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVHs) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response. Methods: This case-control study included examinations at baseline and at follow-up after 6 weeks. Initially, antipsychotic-naïve patients with first-episode schizophrenia who were experiencing AVHs were recruited together with healthy control participants. Antipsychotic treatment with the relatively selective D2 receptor antagonist amisulpride was administered as monotherapy. Functional connectivity measured by resting-state functional magnetic resonance imaging between networks of interest was used to study the effects of D2 blockade on brain circuitry and predict clinical treatment response. Hallucinations were rated with the Positive and Negative Syndrome Scale. Results: Thirty-two patients experiencing AVHs and 34 healthy control participants were scanned at baseline. Twenty-two patients and 34 healthy control participants were rescanned at follow-up. Connectivity between the auditory network and the medial temporal lobe network was increased in patients at baseline (p = .002) and normalized within 6 weeks of D2 blockade (p = .018). At baseline, the connectivity between these networks was positively correlated with ratings of hallucinations (t = 2.67, p = .013). Moreover, baseline connectivity between the auditory network and the medial temporal lobe network predicted reduction in hallucinations (t = 2.34, p = .032). Conclusions: Functional connectivity between the auditory network and the medial temporal lobe predicted response to initial antipsychotic treatment. These findings demonstrate that connectivity between networks involved in auditory processing, internal monitoring, and memory is associated with the clinical effect of dopamine antagonism.

Effects on voice hearing distress and social functioning of unguided application of a smartphone app - A randomized controlled trial.

Background: Temstem is a smartphone app developed with and for clinical voice hearing individuals with the aim to reduce their voice hearing distress and improve social functioning. Methods: A randomized controlled trial with adult outpatients suffering from distressing and frequent auditory verbal hallucinations (AVH) was conducted. Participants were randomized to unguided 'Temstem+AVH monitoring' or unguided 'AVH monitoring only' (control condition). Assessments were performed at baseline, post-intervention (week 5-6), and follow-up (week 9-10). Primary outcomes were voice hearing distress and social functioning, as measured with Experience Sampling Method (ESM), consisting of multiple daily questionnaires during six days. In addition, voices and mood were self-monitored with help of a daily reflective questionnaire. Analyses were linear regression models (intention-to-treat). Results: 44 Participants were allocated to Temstem and 45 to the control condition. No significant differences between the groups were found on both primary outcomes. Conclusion: Our results do not support the effectiveness of stand-alone use of Temstem versus symptom monitoring on voice hearing distress or social functioning in voice hearing individuals. In order to potentially improve effectiveness of an mHealth tool in a population of people with frequent and distressing voices, we recommend to involve persons with lived experience in all stages of development and research; to thoroughly test the (technological) usability before performing an RCT; to test whether guidance of a therapist is needed to optimize effectiveness; and to provide prompts to remind the user to actually use the tool.

Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA.

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

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

BACKGROUND: Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented toward understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors. METHODS: In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e. feeling the presence of a non-existing another person). RESULTS: Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, quantified as an increase in false alarm rate in a voice detection task. Robotically-induced AVH-like sensations were further associated with delusional ideation and to both AVH accounts. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors). CONCLUSIONS: By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

Intersections of phenomenology, voice beliefs and distress in bipolar disorder: a comparison with schizophrenia.

BACKGROUND: Auditory verbal hallucinations (AVH), or voice-hearing, can be a prominent symptom during fluctuating mood states in bipolar disorder (BD). AIMS: The current study aimed to: (i) compare AVH-related distress in BD relative to schizophrenia (SCZ), (ii) examine correlations between phenomenology and voice beliefs across each group, and (iii) explore how voice beliefs may uniquely contribute to distress in BD and SCZ. METHOD: Participants were recruited from two international sites in Australia (BD=31; SCZ=50) and the UK (BD=17). Basic demographic-clinical information was collected, and mood symptoms were assessed. To document AVH characteristics, a 4-factor model of the Psychotic Symptoms Rating Scale and the Beliefs about Voices Questionnaire-Revised were used. Statistical analyses consisted of group-wise comparisons, Pearson's correlations and multiple hierarchical regressions. RESULTS: It was found that AVH-related distress was not significantly higher in BD than SCZ, but those with BD made significantly more internal attributions for their voices. In the BD group, AVH-related distress was significantly positively correlated with malevolence, omnipotence and resistance, However, only resistance, alongside mania and depressive symptoms, significantly contributed to AVH-related distress in BD. DISCUSSION: Our findings have several clinical implications, including identification of voice resistance as a potential therapeutic target to prioritise in BD. Factoring in the influence of mood symptoms on AVH-related distress as well as adopting more acceptance-oriented therapies may also be of benefit.

Executive control of language in schizophrenia patients with history of auditory verbal hallucinations: A neuropsychological and resting-state fMRI study.

BACKGROUND: As demonstrated by a plethora of studies, compromised executive functions (EF) and language are implicated in mechanisms of auditory verbal hallucinations (AVH), but the contribution of their interaction to AVH remains unclear. We hypothesized that schizophrenia patients with history of AVH (AVHh+) vs. without history of AVH (AVHh-) have a specific deficit of executive control of language and alterations in functional connectivity (FC) between the brain regions involved in EF and language, and these neuropsychological and neurophysiological traits are associated with each other. METHODS: To explore the executive control of language and its contribution to AVH, we used an integrative approach involving analysis of neuropsychological and resting-state fMRI data of 34 AVHh+, 16 AVHh-, and 40 healthy controls. We identified the neuropsychological and FC measures that differentiated between AVHh+, AVHh-, and HC, and tested the associations between them. RESULTS: AVHh+ were characterized by decreased category and phonological verbal fluency, utterance length, productivity in the planning tasks, and poorer retelling. AVHh+ had decreased FC between the left inferior frontal gyrus and the anterior cingulate cortex. Productivity in category verbal fluency was associated with the FC between these regions. CONCLUSIONS: Poor executive control of word retrieval and deficient programming of sentence and narrative related to more general deficits of planning may be the neuropsychological traits specific for AVHh+. A neurophysiological trait specific for AVHh+ may be a decreased FC between regions involved in language production and differentiation between alien- vs. self-generated speech and between language production vs. comprehension.

Rich-club reorganization of white matter structural network in schizophrenia patients with auditory verbal hallucinations following 1 Hz rTMS treatment.

The human brain comprises a large-scale structural network of regions and interregional pathways, including a selectively defined set of highly central and interconnected hub regions, often referred to as the "rich club", which may play a pivotal role in the integrative processes of the brain. A quintessential symptom of schizophrenia, auditory verbal hallucinations (AVH) have shown a decrease in severity following low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the underlying mechanism of rTMS in treating AVH remains elusive. This study investigated the effect of low-frequency rTMS on the rich-club organization within the brain in patients diagnosed with schizophrenia who experience AVH using diffusion tensor imaging data. Through by constructing structural connectivity networks, we identified several critical rich hub nodes, which constituted a rich-club subnetwork, predominantly located in the prefrontal cortices. Notably, our findings revealed enhanced connection strength and density within the rich-club subnetwork following rTMS treatment. Furthermore, we found that the decreased connectivity within the subnetwork components, including the rich-club subnetwork, was notably enhanced in patients following rTMS treatment. In particular, the increased connectivity strength of the right median superior frontal gyrus, which functions as a critical local bridge, with the right postcentral gyrus exhibited a significant correlation with improvements in both positive symptoms and AVH. These findings provide valuable insights into the role of rTMS in inducing reorganizational changes within the rich-club structural network in schizophrenia and shed light on potential mechanisms through which rTMS may alleviate AVH.

An exploration of the relationship between voices, dissociation, and post-traumatic stress disorder symptoms.

OBJECTIVES: Extensive research has shown voice hearing to be associated with symptoms of Post-Traumatic Stress Disorder (PTSD) and dissociation. However, most studies have adopted a quantitative design, using cross-sectional data sampling methods, precluding temporal relationships between variables from being defined. DESIGN: Using a qualitative design, this study sought to identify potential symptom relationships by addressing the research question: what is the nature of the temporal relationship between voices, dissociation and PTSD symptoms? METHODS: Seven voice hearers (aged 27 to 68 years) participated in a semi-structured interview exploring voice hearing, PTSD symptoms, and dissociation. The interviews were analysed using Interpretative Phenomenological Analysis. RESULTS: One superordinate theme was identified in the data. Voices were observed to occur in dynamic interrelationship with PTSD symptoms and dissociation, and were frequently experienced before and after PTSD symptoms and dissociative episodes. CONCLUSIONS: Implications for theoretical understandings of voice hearing and future research are discussed.