Auditory Verbal Hallucinations In Patients Research Articles

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.

Discrimination of auditory verbal hallucination in schizophrenia based on EEG brain networks

Auditory verbal hallucinations (AVH) are a core positive symptom of schizophrenia and are regarded as a consequence of the functional breakdown in the related sensory process. Yet, the potential mechanism of AVH is still lacking. In the present study, we explored the difference between AVHs (n = 23) and non-AVHs (n = 19) in schizophrenia and healthy controls (n = 29) by using multidimensional electroencephalograms data during an auditory oddball task. Compared to healthy controls, both AVH and non-AVH groups showed reduced P300 amplitudes. Additionally, the results from brain networks analysis revealed that AVH patients showed reduced left frontal to posterior parietal/temporal connectivity compared to non-AVH patients. Moreover, using the fused network properties of both delta and theta bands as features for in-depth learning made it possible to identify the AVH from non-AVH patients at an accuracy of 80.95%. The left frontal-parietal/temporal networks seen in the auditory oddball paradigm might be underlying biomarkers of AVH in schizophrenia. This study demonstrated for the first time the functional breakdown of the auditory processing pathway in the AVH patients, leading to a better understanding of the atypical brain network of the AVH patients.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study

Introduction: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. Methods: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. Results: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. Conclusion: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Нейрокогнитивные модели вербальных галлюцинаций при шизофрении: обзор

Recent studies at the interface between psychiatry and neuroscience demonstrate a trend towards the investigation of single significant clinical characteristics of mental disorders in contrast to the analysis of a mental disorder as a homogeneous nosological unit. Thus, a large body of studies is focused on auditory verbal hallucinations (AVH) in schizophrenia, which are one of the core positive symptoms of the disorder and an important diagnostic criterion. Nevertheless, the neuropsychological and neurophysiological mechanisms of AVH in patients with schizophrenia remain debatable. In this paper, we will review the main neurocognitive models of AVH in schizophrenia, including models of intrusive cognitions and poor inhibitory control, a model of attentional shift to inner auditory stimuli and an inability to reallocate its resources, a model of expectation maximization, a model of working memory deficit, a model of poor source-monitoring, models of AVH within cultural-historical approach, and a model of impaired verbal self-monitoring in inner speech. The results of several neuroimaging and neurophysiological studies relevant to the models are also highlighted. We conclude that schizophrenia patients with AVH demonstrate deficits in executive functions and language, or rather a poor cross-functional interaction between them.

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

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

Negative content in auditory verbal hallucinations: a natural language processing approach

ABSTRACT Introduction Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. Methods Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. Results The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. Conclusions Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.

Inhibitory Top-Down Control Deficits in Schizophrenia With Auditory Verbal Hallucinations: A Go/NoGo Task.

Objective: Auditory verbal hallucinations (AVH), with unclear mechanisms, cause extreme distresses to schizophrenia patients. Deficits of inhibitory top-down control may be linked to AVH. Therefore, in this study, we focused on inhibitory top-down control in schizophrenia patients with AVH.Method: The present study recruited 40 schizophrenia patients, including 20 AVH patients and 20 non-AVH patients, and 23 healthy controls. We employed event-related potentials to investigate the N2 and P3 amplitude and latency differences among these participants during a Go/NoGo task.Results: Relative to healthy controls, the two patient groups observed longer reaction time (RT) and reduced accuracy. The two patient groups had smaller NoGo P3 amplitude than the healthy controls, and the AVH patients showed smaller NoGo P3 amplitude than the non-AVH patients. In all the groups, the parietal area showed smaller NoGo P3 than frontal and central areas. However, no significant difference was found in N2 and Go P3 amplitude between the three groups.Conclusions: AVH patients might have worse inhibitory top-down control, which might be involved in the occurrence of AVH. Hopefully, our results could enhance understanding of the pathology of AVH.

Frontotemporal Transcranial Direct Current Stimulation Decreases Serum Mature Brain-Derived Neurotrophic Factor in Schizophrenia.

Although transcranial direct current stimulation (tDCS) shows promise as a treatment for auditory verbal hallucinations in patients with schizophrenia, mechanisms through which tDCS may induce beneficial effects remain unclear. Evidence points to the involvement of neuronal plasticity mechanisms that are underpinned, amongst others, by brain-derived neurotrophic factor (BDNF) in its two main forms: pro and mature peptides. Here, we aimed to investigate whether tDCS modulates neural plasticity by measuring the acute effects of tDCS on peripheral mature BDNF levels in patients with schizophrenia. Blood samples were collected in 24 patients with schizophrenia before and after they received a single session of either active (20 min, 2 mA, n = 13) or sham (n = 11) frontotemporal tDCS with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. We compared the tDCS-induced changes in serum mature BDNF (mBDNF) levels adjusted for baseline values between the two groups. The results showed that active tDCS was associated with a significantly larger decrease in mBDNF levels (mean −20% ± standard deviation 14) than sham tDCS (−8% ± 21) (F = 5.387; p = 0.030; η2 = 0.205). Thus, mature BDNF may be involved in the beneficial effects of frontotemporal tDCS observed in patients with schizophrenia.

T134. THE ROLE OF THE DEFAULT MODE NETWORK IN SCHIZOPHRENIA AND AUDITORY VERBAL HALLUCINATIONS – AN INVESTIGATION OF DYNAMIC FMRI RESTING STATE CONNECTIVITY

BackgroundThere is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed information on connectivity abnormalities in psychiatric disorders such as schizophrenia.MethodsThe current study investigated dynamic FC in a sample of 80 schizophrenia patients and 80 matched healthy control subjects. Furthermore, relationships with auditory verbal hallucinations (AVH), a core symptom of schizophrenia, were explored. Two measures of AVH were used, one measure of current AVH severity assessed on the day of scanning, and one trait-measure where AVH were assessed repeatedly over the course of one year.ResultsCompared to healthy controls, schizophrenia patients showed increased dwell times in states with high connectivity within the default mode network (DMN). Current AVH severity did not show a significant relationship with dynamic FC. However, the trait-measure of AVH proneness over one year showed a significant relationship with dynamic FC. Patients with high AVH proneness spent less time in connectivity states characterized by strong anti-correlation between the DMN and task-positive networks.DiscussionThe results provide further evidence for a DMN dysfunction in schizophrenia, which could be linked to thought disturbances in relation to an increased internal focus of cognitive processing. The effects of AVH proneness on dynamic FC support theoretical models of AVH which have proposed an instability of the DMN and impaired cognitive control in AVH patients. The results also point to AVH proneness as a potential marker for identifying distinct subgroups of schizophrenia patients.

Intra-Regional Glu-GABA vs Inter-Regional Glu-Glu Imbalance: A 1H-MRS Study of the Neurochemistry of Auditory Verbal Hallucinations in Schizophrenia.

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.

Sensory processing deficiencies in patients with borderline personality disorder who experience auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are common in patients with borderline personality disorder (BPD). We examined two candidate mechanisms of AVH in patients with BPD, suggested to underlie sensory processing systems that contribute to psychotic symptoms in patients with schizophrenia; sensory gating (P50 ratio and P50 difference) and change detection (mismatch negativity; MMN). Via electroencephalographic recordings P50 amplitude, P50 ratio, P50 difference and MMN amplitude were compared between 23 borderline patients with and 25 without AVH, and 26 healthy controls. Borderline patients with AVH had a significantly lower P50 difference compared with healthy controls, whereas no difference was found between borderline patients without AVH and healthy controls. The groups did not differ on MMN amplitude.The impaired sensory gating in patients with borderline personality disorder who experience AVH implies that P50 sensory gating deficiencies may underlie psychotic vulnerability in this specific patient group. Patients with borderline personality disorder with or without AVH did not have problems with auditory change detection. This may explain why they are spared from the poor outcome associated with negative symptoms and symptoms of disorganization in patients with chronic schizophrenia.

RTMS and auditory verbal hallucinations in patients with schizophrenia: Should left-handers be treated the same as right-handers?

Introduction Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising therapeutic option for schizophrenia patients suffering from treatment-resistant auditory verbal hallucinations. Nevertheless, most rTMS studies exclude left-handed patients. This subpopulation of patients is therefore poorly represented in clinical trials using rTMS whereas they represent nearly 14% of the schizophrenic population. Objectives We will attempt to address two issues in this regard: – should we systematically exclude left-handed patients from rTMS studies? – should the same rTMS treatment method be used for left- and right-handed patients? Methods A literature search was carried out from the MEDLINE database with the following keywords: “repetitive transcranial magnetic stimulation”; “schizophrenia” and “auditory hallucinations”. From the 148 articles found, 8 publications including left-handed patients were selected for the literature review. Most studies highlighted a statistically significant therapeutic effect of rTMS for the treatment of resistant auditory verbal hallucinations. However, none specifically compared the difference in efficacy between left- and right-handed patients. Results Literature data was very limited in this field. Handedness appeared to be an important factor that can influence rTMS treatment because handedness is associated with some cognitive functions such as language. Moreover, auditory verbal hallucinations are strongly associated with cerebral activations in language areas. Thus, the rTMS treatment efficacy can vary between subjects depending on handedness and the stimulated target area. Conclusion Even though handedness (left-handed/right-handed) may be considered as a confounding bias for rTMS studies, left-handed patients should not be systematically excluded from clinical trials. Although few studies have reported opposite effects of rTMS in left- and right-handed patients, further studies are needed to determine whether left-handed psychiatric patients should be treated differently to right-handed ones.

P56-F Auditory-motor task triggers gamma and beta oscillations in patients with schizophrenia and auditory verbal hallucinations

Background In a study with intracranial recordings, auditory-verbal stimuli elicited augmented gamma-oscillations in the posterior portion of the superior temporal gyrus, whereas hand-motor responses elicited gamma-augmentation in the pre- and postcentral gyri (Nagasawa et al., 2010). We aimed to investigate if motor cortical activation (MCA) during an auditory-motor (AM) task is affected by laterality of hand motor responses in healthy subjects (HS) and in patients with auditory verbal hallucinations (AVH). Methods Eight HS and ten patients were asked to press a button using the thumb of both hands independently, during two sessions of 3 min. Each session contained 40 trials; 20 auditory-verbal commands saying “Press” and 20 commands saying “Do not press” (Nagasawa et al., 2010). MCA analysis epochs had duration of 500 ms following the button “press”. We used high-density 256 EEG ANT Neuro. Here we show preliminary results of MCA in HS and AVH patients using power spectral density (PSD) and topographical frequency maps including both hands sensory-motor regions. Results The preliminary data show that the laterality of the cortical activation related to the AM task may not be affected to a large degree by the motor reaction. Resting state EEG and AM task brain maps showed fragmented EEG topography in patients with schizophrenia for all analyzed band frequencies. Conclusions With this method we were able to trigger high beta and gamma bands activity in regions related to sensory-motor cortex. The topography of these frequencies remained stable when the participant used the right or the left hand.

Long-Term Changes in Self-Report Auditory Verbal Hallucinations in Patients with Schizophrenia Using Clozapine.

This study explored long-term changes in self-report auditory verbal hallucinations (AVHs) among patients with schizophrenia taking clozapine. Forty-four patients who were evaluated more than twice and were above the mild severity category on the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) were enrolled. The mean observation period was 492.5±350.1 days (median, 452 days). The mean total, physical, and emotional factor scores on the HPSVQ were significantly reduced from baseline to the final observations except for one item “interference with life,” which was not significantly reduced. Regarding the time-dependent longitudinal changes modeled using linear mixed-effect regression, the total and physical factor scores showed significant changes during the first year, but the emotional factor score did not satisfy a more stringent level of significance. Female gender was negatively associated with the reduction in total and physical factor scores. The duration of treatment with clozapine also had a negative relationship with the reductions in all three scores.

Feasibility of EMDR for posttraumatic stress disorder in patients with personality disorders: a pilot study

ABSTRACT Background: Trauma and posttraumatic stress disorder (PTSD) are prevalent in patients with personality disorders. Despite the established efficacy of eye movement desensitisation and reprocessing (EMDR) for PTSD, EMDR has barely been examined in patients with comorbid PTSD and personality disorders. Objective: The aim of this study was to explore what changes occur in symptom severity of PTSD, dissociative symptoms, insomnia, non-suicidal self-injurious behaviour and auditory verbal hallucinations in patients with personality disorders during treatment with EMDR. Method: This uncontrolled open feasibility study on EMDR for PTSD was an addition to treatment-as-usual for personality disorders. The outcome measures were the severity of PTSD symptoms, dissociation, insomnia, non-suicidal self-injury, and auditory verbal hallucinations. Results: Forty-seven participants (22 with a borderline personality disorder, 25 with other personality disorders) were included. A significant reduction in the severity of symptoms of PTSD, dissociation and insomnia was observed after EMDR treatment (median of four sessions), and 40% of the participants scored below the threshold for PTSD diagnosis. No differences in efficacy were found between patients with borderline personality disorder and other personality disorders. EMDR treatment was completed by 68% of the participants. Conclusions: The addition of EMDR techniques to treatment, as usual, may be beneficial in the treatment of PTSD in patients with personality disorders in order to reduce symptoms of PTSD, dissociation and insomnia. Although one-third of these patients did not complete the additional EMDR treatment, no severe complications (e.g. suicidal behaviour or hospitalisation) occurred. Controlled studies are needed to further investigate the validity of these findings.

Add-on atypical anti-psychotic treatment alleviates auditory verbal hallucinations in patients with chronic post-traumatic stress disorder

Auditory verbal hallucinations are common symptoms of post traumatic distress disorder. Previous studies have demonstrated alterations in the salience network (SN) in patients with post traumatic distress disorder and that hyperactivity of the SN is associated with AVHs in patients with psychosis. Patients with post traumatic distress disorder may benefit from aripiprazole; however, studies investigating the effect of aripiprazole on AVHs and activity in the SN in patients with post traumatic distress disorder are scarce. Therefore, we conducted an outcomes analysis using functional magnetic resonance imaging to explore the effects of add-on aripiprazole treatment on AVHs and brain functional connectivity in patients with post traumatic distress disorder. AVHs were alleviated by add-on aripiprazole treatment (Auditory Hallucination Rating Scale [AHRS] score reduced by ≥ 50%) in 22.7% of patients. Functional activity in the SN was obviously decreased in patients in whom AHRS scores were reduced ≥ 50% following add-on aripiprazole treatment compared to patients in whom AHRS scores were reduced by <50%. The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AHRS scores. Although this study was associated with several limitations, the findings suggest that add-on aripiprazole treatment can alleviate AVHs in patients with post traumatic distress disorder by reducing activity in the SN.

A Review of the Effects of Transcranial Direct Current Stimulation for the Treatment of Hallucinations in Patients With Schizophrenia.

Some 25% to 30% of patients with schizophrenia report auditory verbal hallucinations (AVHs) that fail to respond adequately to antipsychotic treatments. In such cases, transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option. Here, we aim to provide an exhaustive review of the literature examining the clinical effects of tDCS on AVH in patients with schizophrenia. A systematic search in the PubMed and Web of Science databases yielded 14 results, 7 randomized controlled trials (RCTs) and 7 open-label studies. Among them, 4 RCTs and 7 open-label studies reported a significant reduction of AVH after repeated sessions of tDCS, whereas 3 RCTs did not show any advantage of active tDCS over sham tDCS. Altogether, current studies showed an overall decrease of approximately 26% of AVH after active tDCS and 11% after sham tDCS. One suitable approach to decreasing AVH was to deliver twice-daily sessions of tDCS over 5 consecutive days (10 sessions at 20 minutes each, 2 mA) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Demographic and clinical parameters such as young age, nonsmoking status, and higher frequencies of AVH occurrence seemed to be predictors of clinical improvement. Further RCTs, with larger sample sizes, are needed to confirm the usefulness of tDCS for AVH.

Auditory Verbal Hallucinations in Borderline Personality Disorder and the Efficacy of Antipsychotics: A Systematic Review.

Background: Auditory verbal hallucinations (AVH) are experienced more frequently by patients with borderline personality disorder (BPD) than previously assumed. However, consensus is lacking on how to treat them.Objective: To provide a systematic review of studies reporting on AVH in patients with BPD, with a focus on the efficacy of treatment of psychotic symptoms.Methods: For this review a systematic search was made in the PubMed and Ovid databases, and mean weighted prevalence rates, adjusted for sample size, were computed.Results: The search yielded 36 studies describing a total of 1,263 patients. Auditory hallucinations (including AVH) were reported in 27% of hospitalized BPD patients; AVH were reported in 25% of all patients and in 24% of outpatients. Of the hallucinating patients, 78% experienced AVH at least once per day, for a duration of several days to many years. On the whole, patients with BPD regarded their voices as malevolent and omnipotent in nature. Compared to patients with schizophrenia, the phenomenological characteristics of AVH were similar and the ensuing distress was equal or even higher, whereas scores for other positive symptoms were lower. The presence of AVH in BPD was associated with an increase of suicide plans and attempts, and more frequent hospitalization. Moreover, AVH in the context of BPD were associated with higher prevalence rates for post-traumatic stress disorder and emotional abuse. The efficacy of antipsychotics was investigated in 21 studies. Based on these studies, we conclude that both typical and atypical antipsychotics tend to have positive effects on AVH experienced in the context of BPD. The efficacy of cognitive-behavioral therapy and non-invasive brain stimulation has not yet been systematically assessed.Conclusions: These findings indicate that AVH experienced in the context of BPD are in need of proper diagnosis and treatment, and that antipsychotics tend to be beneficial in treating these (and other psychotic) symptoms.There is an urgent need for studies assessing the efficacy of cognitive-behavioral therapy and non-invasive brain stimulation in this underdiagnosed and undertreated group.

Neural Correlates of Auditory Verbal Hallucinations in Schizophrenia and the Therapeutic Response to Theta-Burst Transcranial Magnetic Stimulation.

Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia, and resistant to antipsychotic medication in a substantial proportion of patients. This study aimed to investigate the neural correlates of AVHs in schizophrenia patients and its response to a modified continuous theta-burst stimulation (cTBS) by transcranial magnetic stimulation. In a cross-sectional experiment, resting-state functional magnetic resonance images were collected from 31 AVH schizophrenia patients, 26 non-AVH schizophrenia patients, and 33 sex-/age-matched healthy controls (HCs). Functional connectivity strength (FCS) maps were compared among groups by 1-way analysis of variance (ANOVA). In a longitudinal experiment, 16 and 11 AVH patients received real and sham cTBS treatment for 15 days, respectively. Notably, this was not a randomized control trail. Changes in AVH and FCS were analyzed by 2-way ANOVA and 2-sample t-test, respectively. In the cross-sectional experiment, comparison of FCS maps identified 8 clusters among groups, but only one cluster (in left cerebellum) differed significantly in AVH patients compared to both HCs and non-AVH patients. In the longitudinal experiment, the real cTBS group showed a greater improvement in symptoms and a larger FCS decrease in left cerebellum than the sham group. Pearson’s correlation analysis indicated that baseline FCS of the overlapping cerebellum cluster (between the cross-sectional and longitudinal findings) was negatively correlated with symptom improvement in the real treatment group. These findings emphasize the role of the left cerebellum in both the pathophysiology and clinical treatment of AVHs in schizophrenia patients.

O2.7. CAN THEY HEAR IT? DO PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS HAVE AUDITORY PROCESSING DEFICITS?

BackgroundIt has been well established for over half a century that patients with a diagnosis of schizophrenia have auditory processing deficits. More recently, there has been a small body of work that has suggested patients with a history of auditory hallucinations have particularly pertinent auditory processing deficits, with the importance of pitch perception being noted in a single study. This current body of work has systematically investigated whether auditory perception, using a tone detection task, are related to auditory verbal hallucinations (AVH).MethodsFour studies will be presented each of which used a tone detection task that manipulated pitch, with the study 1 also have a tone duration manipulation.ResultsStudy 1 compared 15 AVH with 15 non-AVH patients with schizophrenia with 34 healthy controls, AVH patients demonstrated the greatest impairments on pitch and tone duration deficits compared to the other two groups. Study 2 compared 99 patients with schizophrenia (65 with a history of AVH and 34 without) with 95 healthy controls and confirmed pitch deficits in schizophrenia, specifically those with AVH. Study 3 established in 100 healthy controls that unusual experiences or auditory hallucination proneness were significantly correlated to pitch perception performance. Lastly, study 4 demonstrated that relatives of patients with schizophrenia also showed a significant correlation between usual experiences and pitch perception.DiscussionThis research indicates auditory processing deficits are a core feature of AVH in schizophrenia, and potentially represent an endophenotype for AVH. The authors will discuss a potential cognitive model which explains the relationship between AVH and pitch perception. There are clear translational elements to this research, and we suggest there might be some utility in using auditory training as an intervention to reduce the impact of AVH.