A source-monitoring account of auditory verbal hallucinations in patients with schizophrenia

Auditory verbal hallucinations are a common and distressing symptom experienced by patients with schizophrenia. They can be understood as arising from an impairment in reality monitoring-the process by which internally and externally generated events are distinguished. This impairment might arise through primary abnormalities in the reality-monitoring mechanism or through secondary mechanisms (abnormalities in the perceptual characteristics of internally generated events or in the perception of externally generated events). This article examines evidence for and against an association between abnormalities in reality monitoring and auditory verbal hallucinations in schizophrenia. A comprehensive review of the psychological literature suggests that there is little evidence for an association between auditory verbal hallucinations and secondary mechanisms leading to abnormalities in reality monitoring. There is some evidence suggesting that hallucinators show a primary reality-monitoring abnormality that is most apparent when patients are required to distinguish self from other in real time. To draw firmer conclusions, however, it is imperative that future studies select patient populations precisely, match control groups, and use consistent criteria for defining hallucinators.     

Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non‐psychotic individuals

The pathophysiology of auditory verbal hallucinations (AVH) is still unclear. Cognitive as well as electrophysiological studies indicate that a defect in sensory feedback (corollary discharge) may contribute to the experience of AVH. This could result from disruption of the arcuate fasciculus, the major tract connecting frontal and temporo‐parietal language areas. Previous diffusion tensor imaging studies indeed demonstrated abnormalities of this tract in schizophrenia patients with AVH. It is, however, difficult to disentangle specific associations with AVH in this patient group as many other factors, such as other positive and negative symptoms, medication or halted education could likewise have affected tract integrity. We therefore investigated AVH in relative isolation and studied a group of non‐psychotic individuals with AVH as well as patients with AVH and non‐hallucinating matched controls. We compared tract integrity of the arcuate fasiculus and of three other control tracts, between 35 non‐psychotic individuals with AVH, 35 schizophrenia patients with AVH, and 36 controls using diffusion tensor imaging and magnetization transfer imaging. Both groups with AVH showed an increase in magnetization transfer ratio (MTR) in the arcuate fasciculus, but not in the other control tracts. In addition, a general decrease in fractional anisotropy (FA) for almost all bundles was observed in the patient group, but not in the non‐psychotic individuals with AVH. As increased MTR in the arcuate fasciculus was present in both hallucinating groups, a specific association with AVH seems plausible. Decreases in FA, on the other hand, seem to be related to other disease processes of schizophrenia. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Decreased integrity of the fronto-temporal fibers of the left inferior occipito-frontal fasciculus associated with auditory verbal hallucinations in schizophrenia

Auditory verbal hallucinations (AVH) have been proposed to result from altered connectivity between frontal speech production regions and temporal speech perception regions. Whilst the dorsal language pathway, serviced by the arcuate fasciculus, has been extensively studied in relation to AVH, the ventral language pathway, serviced by the inferior occipito-frontal fasciculus (IOFF) has been rarely studied in relation to AVH. This study examined whether structural changes in anatomically defined subregions of the IOFF were associated with AVH in patients with schizophrenia. Diffusion tensor imaging scans and clinical data were obtained from the Australian Schizophrenia Research Bank for 113 schizophrenia patients, of whom 39 had lifetime experience of AVH (18 had current AVH, 21 had remitted AVH), 74 had no lifetime experience of AVH, and 40 healthy controls. Schizophrenia patients with a lifetime experience of AVH exhibited reduced fractional anisotropy (FA) in the fronto-temporal fibers of the left IOFF compared to both healthy controls and schizophrenia patients without AVH. In contrast, structural abnormalities in the temporal and occipital regions of the IOFF were observed bilaterally in both patient groups, relative to the healthy controls. These results suggest that while changes in the structural integrity of the bilateral IOFF are associated with schizophrenia per se, integrity reductions in the fronto-temporal fibers of the left IOFF may be specifically associated with AVH.     

Childhood traumatic events and types of auditory verbal hallucinations in first-episode schizophrenia patients

ObjectiveEvidence is accumulating that childhood trauma might be associated with higher severity of positive symptoms in patients with psychosis and higher incidence of psychotic experiences in non-clinical populations. However, it remains unknown whether the history of childhood trauma might be associated with particular types of auditory verbal hallucinations (AVH).MethodWe assessed childhood trauma using the Early Trauma Inventory Self-Report — Short Form (ETISR-SF) in 94 first-episode schizophrenia (FES) patients. Lifetime psychopathology was evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist, while symptoms on the day of assessment were examined using the Positive and Negative Syndrome Scale (PANSS). Based on ETISR-SF, patients were divided into those with and without the history of childhood trauma: FES(+) and FES(−) patients.ResultsFES(+) patients had significantly higher total number of AVH types and Schneiderian first-rank AVH as well as significantly higher PANSS P3 item score (hallucinatory behavior) in comparison with FES(−) patients. They experienced significantly more frequently third person AVH and abusive/accusatory/persecutory voices. These differences remained significant after controlling for education, PANSS depression factor score and chlorpromazine equivalent. Linear regression analysis revealed that the total number of AVH types was predicted by sexual abuse score after controlling for above mentioned confounders. This effect was significant only in females.ConclusionOur results indicate that the history of childhood trauma, especially sexual abuse, is associated with higher number AVH in females but not in males. Third person AVH and abusive/accusatory/persecutory voices, representing Schneiderian first-rank symptoms, might be particularly related to childhood traumatic events.     

Dysconnectivity of multiple resting-state networks in patients with schizophrenia who have persistent auditory verbal hallucinations

Background

Functional neuroimaging studies on schizophrenia have suggested abnormal task-related functional connectivity in patients with schizophrenia who have auditory verbal hallucinations (AVHs). However, little is known about intrinsic functional connectivity in these patients.

Methods

Between January 2009 and February 2010, we studied patients with schizophrenia who had persistent and treatment-refractory AVHs in comparison with healthy controls. Using functional magnetic resonance imaging, we studied the functional connectivity of multiple resting state networks (RSNs) and their relation to symptom severity. We analyzed the data using a spatial group independent component analysis, and we used random-effects t tests to compare spatial components between groups.

Results

There were 10 patients and 14 controls enrolled in this study. In total, 16 RSNs were identified, from which we selected 4 networks of interest for further analyses. Within a speech-related network, patients showed increased connectivity in bilateral temporal regions and decreased connectivity in the cingulate cortex. Within 2 additional RSNs associated with attention and executive control, respectively, patients exhibited abnormal connectivity in the precuneus and right lateral prefrontal areas. We found correlations between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and right lateral prefrontal cortex.

Limitations

The relatively small sample size, the patients’ use of antipsychotic medication and the lack of a clinical control group have to be considered as potential limitations.

Conclusion

Our findings indicate that disrupted intrinsic connectivity of a speech-related network could underlie persistent AVHs in patients with schizophrenia. In addition, the occurrence of hallucinatory symptoms seems to modulate RSNs associated with attention and executive control.     

Auditory verbal hallucinations and the interhemispheric auditory pathway in chronic schizophrenia

Objectives. The interhemispheric auditory pathway has been shown to play a crucial role in the processing of acoustic stimuli, and alterations of structural and functional connectivity between bilateral auditory areas are likely relevant to the pathogenesis of auditory verbal hallucinations (AVHs). The aim of this study was to examine this pathway in patients with chronic schizophrenia regarding their lifetime history of AVHs. Methods. DTI scans were acquired from 33 healthy controls (HC), 24 schizophrenia patients with a history of AVHs (LT-AVH) and nine schizophrenia patients without any lifetime hallucinations (N-LT-AVH). The interhemispheric auditory fibre bundles were extracted using streamline tractography. Subsequently, diffusivity indices, namely Fractional Anisotropy (FA), Trace, Mode, Axial and Radial diffusivity, were calculated. Results. FA was decreased over the entire pathway in LT-AVH compared with N-LT-AVH. Moreover, LT-AVH displayed decreased FA and Mode as well as increased radial diffusivity in the midsagittal section of the fibre tract. Conclusions. These findings indicate complex microstructural changes in the interhemispheric auditory pathway of schizophrenia patients with a history of AVHs. Alterations appear to be absent in patients who have never hallucinated.     

Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.     

Relationship of auditory verbal hallucinations with cerebral asymmetry in patients with schizophrenia: an event-related fMRI study

The purpose of this study was to explore whether there are differences in cerebral asymmetry between subgroups of schizophrenic patients with or without auditory verbal hallucinations (AVHs) and normal controls by using event-related functional magnetic resonance imaging (efMRI). A total of 26 Chinese Han male patients with paranoid schizophrenia (diagnosed by DSM IV, including 13 patients with AVHs and 13 patients without) and 13 matched normal controls were recruited for the present study. The participants had been instructed to listen to short sentences from left or right side and to indicate laterality during efMRI scanning. Functional data were acquired using a 1.5T MR, and were analyzed using statistical parametric mapping. A random-effect model was employed to asses the difference in blood oxygen level dependent response between "left-sided" and "right-sided" conditions. The results from the present study have shown (1) within group comparisons: right precuneus and right superior parietal lobule were significantly activated showed significantly greater activation by left-sided voices than right-sided ones in controls. However, no significant difference in activation was found in any brain region between left and right-sided voices in either of the two patient subgroups, (2) between group comparisons: in comparison with AVHs patients, right middle frontal gyrus (MFG) was markedly activated when control subjects were differentiating right-sided voices. In comparison with patients without AVHs, right-side stimuli significantly activated bilateral MFG and left postcentral gyrus in control group. Furthermore, compared to the non-hallucination group, left Wernicke's area, including supramarginal gyrus, angular gyrus and superior temporal gyrus, was significantly activated by both left and right-sided voices in the hallucination group. In summary, auditory-related asymmetry in control subjects is attenuated in schizophrenic patients. The symptoms of AVHs in schizophrenia are possibly correlated with left hemispheric, particularly auditory and language-related areas dysfunction.     

rTMS in the management of auditory hallucinations in patients with schizophrenia

Schizophrenia spectrum disorders can be accompanied by hallucinations in any of the sensory modalities. They are auditory in nature in 70% of cases, resulting in functional disability and a low quality of life. The pathophysiological basis of auditory verbal hallucinations （AVH） remains unclear; functional brain imaging studies suggest the involvement of frontal and temporal cortical regions as well as deep brain structures and the limbic system. The regions associated with the perception and production of speech within the temporoparietal （TP） cortex are of particular i nte re st.     

Misattribution of speech and impaired connectivity in patients with auditory verbal hallucinations

Several studies report that patients with schizophrenia who experience auditory verbal hallucinations (AVH) tend to misidentify their own speech as that of somebody else. We tested the hypothesis that this tendency is associated with poor functional integration within the network of regions that mediate the evaluation of speech. Using functional magnetic resonance imaging, we measured brain responses from 11 schizophrenics with AVH, 10 schizophrenics without AVH, and 10 healthy controls. Stimuli comprised prerecorded words, which varied for their source (self, alien) and acoustic quality (undistorted, distorted). Participants had to indicate whether each word was spoken in their own or another person's voice via a button press. Using dynamic causal modeling, we estimated the impact of one region over another ("effective connectivity") and how this was modulated by source and distortion. In controls and in patients without AVH, the connectivity between left superior temporal and anterior cingulate cortex was significantly greater for alien- than for self-generated speech; in contrast, the reverse trend was found in schizophrenic patients with AVH. In conclusion, when patients with AVH appraise their own speech we find impaired functional integration between left superior temporal and anterior cingulate cortex. Although this finding is based on external rather than internal speech, the same mechanism may contribute to the faulty appraisal of inner speech that putatively underlies AVH.     

Working memory predicts presence of auditory verbal hallucinations in schizophrenia and bipolar disorder with psychosis

Objective: The recent dramatic increase in research investigating auditory verbal hallucinations (AVHs) has broadened the former narrow focus on schizophrenia to incorporate additional populations that experience these symptoms. However, an understanding of potential shared mechanisms remains elusive. Based on theories suggesting a failure of top-down cognitive control, we aimed to compare the relationship between AVHs and cognition in two categorical diagnoses of psychosis, schizophrenia and psychotic bipolar disorder. Method: A total of 124 adults aged 21–60 participated, of whom 76 had present-state psychosis (schizophrenia, n = 53; bipolar disorder with psychosis, n = 23), and 48 were non-clinical controls. Diagnosis and hallucination presence was determined using the Structured Clinical Diagnostic Interview for DSM-IV TR. AVHs severity was assessed using the Positive and Negative Syndrome Scale. Participants also completed the MATRICS cognitive battery. Results: The bipolar disorder with psychosis group performed better than the schizophrenia group for cognitive domains of Processing speed, Attention, Working memory (WM), and Visual memory. Hierarchical binary logistic regression found that WM significantly predicted presence of AVHs in both psychotic groups, but diagnosis did not significantly increase the predictive value of the model. A hierarchical multiple linear regression found that schizophrenia diagnosis was the only significant predictor of hallucination severity. Conclusions: The findings of this study—the first, to our knowledge, to compare the relationship between AVHs and MATRICS domains across schizophrenia and bipolar disorder with psychosis—support theories that deficits in WM underly the genesis of AVHs. WM potentially represents a shared mechanism of AVHs across diagnoses, supporting dimensional classifications of these psychotic disorders. However, non-cognitive factors predictive of hallucination severity may be specific to schizophrenia.     

Musical hallucinations in schizophrenia. 2. Relations with verbal hallucinations

The musical hallucinations reported by 33 schizophrenics who fulfilled ICD-10 diagnostic criteria were assessed semiologically. The subjects were 24 men and 9 women. The duration of 48 episodes of musical hallucinations varied. They occurred at all times during the course of schizophrenia, and 9 of them (18.8%) occurred before the diagnosis was made. All of the episodes could be divided into three stages: 17 (35.4%) were first stage, close to obsession, 5 (10.4%) were second stage, close to Schneiderian first-rank symptoms, and 26 (54.2%) were third stage, which is the autochthonous experience. The sounds were in a subjective space in 38 episodes and in the majority of cases, their content was familiar. The second stage was associated with xenopathic experience ("gemachtes Erlebnis") and audition of thought, and words were added to melodies that normally had no lyrics. Musical hallucinations in schizophrenia are pseudohallucinations that originate in memory representations, and they may undergo a transition to true hallucinations. The authors think that the three stages are related to the severity of the disease.     

Neurophysiological studies of auditory verbal hallucinations

We discuss 3 neurophysiological approaches to study auditory verbal hallucinations (AVH). First, we describe "state" (or symptom capture) studies where periods with and without hallucinations are compared "within" a patient. These studies take 2 forms: passive studies, where brain activity during these states is compared, and probe studies, where brain responses to sounds during these states are compared. EEG (electroencephalography) and MEG (magnetoencephalography) data point to frontal and temporal lobe activity, the latter resulting in competition with external sounds for auditory resources. Second, we discuss "trait" studies where EEG and MEG responses to sounds are recorded from patients who hallucinate and those who do not. They suggest a tendency to hallucinate is associated with competition for auditory processing resources. Third, we discuss studies addressing possible mechanisms of AVH, including spontaneous neural activity, abnormal self-monitoring, and dysfunctional interregional communication. While most studies show differences in EEG and MEG responses between patients and controls, far fewer show symptom relationships. We conclude that efforts to understand the pathophysiology of AVH using EEG and MEG have been hindered by poor anatomical resolution of the EEG and MEG measures, poor assessment of symptoms, poor understanding of the phenomenon, poor models of the phenomenon, decoupling of the symptoms from the neurophysiology due to medications and comorbidites, and the possibility that the schizophrenia diagnosis breeds truer than the symptoms it comprises. These problems are common to studies of other psychiatric symptoms and should be considered when attempting to understand the basic neural mechanisms responsible for them.     

Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia

Auditory verbal hallucinations (AVHs) have a high prevalence in schizophrenic patients. An array of studies have explored the neural correlates of AVHs by means of functional neuroimaging and have associated AVHs with diverse brain regions, some of which have been shown to be involved in speech generation, speech perception, and auditory stimulus processing. We divided these studies into "state" studies comparing periods of presence and absence of AVHs within-subject and "trait" studies comparing patients experiencing AVHs with patients without AVHs or healthy controls during tasks with verbal material. We set out to test the internal consistency and possible dissociations of the neural correlates of AVHs. We used activation likelihood estimation to perform quantitative meta-analyses on brain regions reported in state and trait studies on AVHs to assess significant concordance across studies. State studies were associated with activation in bilateral inferior frontal gyrus, bilateral postcentral gyrus, and left parietal operculum. Trait studies on the other hand showed convergence of decreases in hallucinating subjects in left superior temporal gyrus, left middle temporal gyrus, anterior cingulate cortex, and left premotor cortex activity. Based on the clear dissociation of brain regions that show convergence across state in comparison to trait studies, we conclude that the state of experiencing AVHs is primarily related brain regions that have been implicated in speech production ie, Broca's area, whereas the general trait that makes humans prone to AVHs seems to be related to brain areas involved in auditory stimuli processing and speech perception, ie, auditory cortex.     

言语性幻听的现象学特征

言语性幻听是一种复杂的精神病性症状,广泛存在于神经精神疾病患者和健康人群中,多见于精神分裂症。本文从感知觉特征、幻听的频率、声音的身份、幻听的内容及患者的情绪反应、对幻听的评估和控制五个方面描述言语性幻听的现象学特点,并阐述不同人群症状连续谱的现象,以期增进对言语性幻听的认识,为进一步研究其产生机制提供参考。