Auditory Verbal Hallucinations In Schizophrenia Research Articles

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

BackgroundAuditory 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. ObjectiveThis 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. MethodFunctional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. ResultsThe 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. ConclusionLow-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.

Soundless voices, silenced selves: are auditory verbal hallucinations in schizophrenia truly perceptual?

In much contemporary psychiatric training and practice, there is a strong emphasis on the audible or perceptual quality and externality of auditory verbal hallucinations in clinical assessments. A typical question during clinical assessment is asking whether the voices that a person hears sound identical to the way the clinician's voice is heard. In this Personal View, we argue that the most important factor in auditory verbal hallucinations in schizophrenia spectrum psychoses is a loss of first-person authority, and that a perceptual quality is not required for it to be this kind of hallucination. We draw on evidence from cognitive neuroscience showing that the activation of brain networks retrieved during capture of auditory verbal hallucinations that were experienced when a patient was in a functional MRI scanner does not match activation of networks retrieved during auditory perception. We propose that, despite early writings by Esquirol and Schneider that defined auditory verbal hallucinations as beliefs in perception rather than true perception, cognitive neuroscience, psychiatric training and practice, and patients adopting clinical vocabulary have been strongly influenced by the progression of the diagnostic criteria for schizophrenia, which increasingly place emphasis on language, such as the "full force" of a true perception. We hold that this change has resulted in an unhelpful top-down influence on the field, imposing perceptual qualities on auditory verbal hallucinations, and leading to misunderstandings and inaccuracies in clinical practice and patients' self-reports, and misinterpretations in cognitive neuroscience. We encourage a revision of the definition of auditory verbal hallucinations to move away from the necessity for auditory perception, and towards beliefs in perception due to the loss of first-person authority.

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

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. 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. 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. 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.

Functional Connectivity of Language-Related Cerebellar Regions Is Reduced in Schizophrenia Patients.

Schizophrenia (SZ) is a widespread psychiatric disorder that is traditionally characterized by positive and negative symptoms. However, recent focus has shifted to cognitive deficits as a crucial aspect. The cerebellum, conventionally tied to motor coordination, is now recognized as pivotal in the pathophysiology of SZ cognitive impairments. Proposed disruptions in the cortico-cerebellar-thalamic-cortico circuit contribute to these deficits. Despite evidence of cerebellar abnormalities, within-cerebellum functional connectivity is often overlooked. This study explores spontaneous functional interactions within the cerebellum and their link to cognitive deficits in SZ. Using a multi-domain task battery (MDTB) parcellation, fMRI data from SZ patients and healthy controls were analyzed. Significant differences in cerebellar connectivity emerged, particularly in regions related to attention, language, and memory processing. Correlations between connectivity values and SZ symptomatology were identified. A post hoc analysis, considering the patients' hallucination vulnerability, revealed distinct connectivity patterns. Non-hallucinating and low-hallucinating SZ patients exhibited higher cerebellar connectivity than high-hallucinating patients, especially in language and motor control regions. These findings suggest a gradient of cerebellar connectivity alterations corresponding to hallucination vulnerability in SZ patients. This study offers novel insights into cerebellar impairments in SZ, highlighting the role of within-cerebellum connectivity in cognitive deficits. The observed connectivity patterns in language-related regions contribute to understanding language development and auditory verbal hallucinations in SZ.

A detailed examination of pitch discrimination deficits associated with auditory verbal hallucinations in schizophrenia.

Individuals with schizophrenia spectrum disorders (SSD) and a history of experiencing auditory verbal hallucinations (AVH) exhibit poor pitch discrimination relative to those with an SSD but no AVH history. The present study extended this research, asking if a lifetime history, and the current presence, of AVH exacerbated the pitch discrimination challenges that are seen in SSD. Participants completed a pitch discrimination task, where the tones presented differed in pitch by either 2%, 5%, 10%, 25% or 50%. Pitch discrimination accuracy, sensitivity, reaction time (RT) and intra-individual RT variability (IIV) were examined in individuals with SSD and AVHs (AVH+; n=46), or without AVHs (AVH-; n=31), and healthy controls (HC; n=131). Secondary analyses split the AVH+ group into state (i.e., actively experiencing AVH; n=32) and trait hallucinators (i.e., a history of, but not actively experiencing, AVH; n=16). Relative to HC, significantly poorer accuracy and sensitivity was detected in individuals with SSD at 2% and 5% pitch deviants, and in hallucinators at 10%; however, no significant differences in accuracy, sensitivity, RT nor IIV were found between AVH+ and AVH- groups. No differences between state and trait hallucinators were observed. A general SSD deficit drove the current findings. The findings may inform future research into the auditory processing capabilities of AVH+ individuals.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brainperfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.

Phenomenology of auditory verbal hallucination in schizophrenia: An erroneous perception or something else?

This study presents phenomenological features of auditory verbal hallucinations (AVH) in schizophrenia and associated anomalies of experience. The purpose is to compare the lived experience of AVH to the official definition of hallucinations as a perception without object. Furthermore, we wish to explore the clinical and research implication of the phenomenological approach to AVH. Our exposition is based on classic texts on AVH, recent phenomenological studies and our clinical experience. AVH differ on several dimensions from ordinary perception. Only a minority of schizophrenia patients experiences AVH localized externally. Thus, the official definition of hallucinations does not fit the AVH in schizophrenia. AVH are associated with several anomalies of subjective experiences (self-disorders) and the AVH must be considered as a product of self-fragmentation. We discuss the implications with respect to the definition of hallucination, clinical interview, conceptualization of a psychotic state and potential target of pathogenetic research.

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.

Self-assessment of auditory verbal hallucinations in schizophrenia; validation of a digital device

IntroductionAuditory verbal hallucinations (AVH) are experienced by approximately 70% of patients with schizophrenia. At the present time, there are no self-evaluation scales for auditory verbal hallucinations. They would allow the patient to self-assess their hallucinations when they occur, taking into account the great variability over time. Moreover, self-assessment allows the patients to better recognize their symptoms and to be more engaged in their treatment. In this context, we have developed a digital device (MIMO) allowing the patient to self-evaluate his/her AVH and to declare his/her hallucinatory crisis at any time. This device contains a self-assessment of auditory verbal hallucinations (SAVH) with 13 questions, 9 of which concern the frequency, the severity, the content and the impact of hallucinations. These 9 questions are rated on a 5-point scale ranging from 0 (absent) to 5 (severe). The patients and practitioners can have an online feedback on the scores as well as on their temporal changes.ObjectivesThe aim of this study was to validate the SAVH scale as well the digital tool, to demonstrate the acceptability by the patients and to prove the feasibility in using such a digital device (mobile phone or tablet).MethodsForty one patients with schizophrenia or schizoaffective disorder (DSM-5) with AVH loaded this application on their own mobile or on a loaned one. AVH was also assessed with the Auditory Hallucination Rating Scale associated with the Brief Psychiatric Rating Scale and the self-assessment of insight. Moreover, a questionnaire included a visual analogic scale on the global satisfaction of the device scoring from 0 (“Not at all satisfied”) to 10 (“Very satisfied”) and 22 questions concerning the conditions of use, the acceptability and the content of the app, its impact on mental health, and questions related to the declaration of hallucinatory crisis. Moreover, statistical analyses were carried out testing internal, external and construct validities of the SAVH.Results56.1% and 36.6% of patients found the app to be easy and very easy to use, respectively. 61% and 29.3% of the patients considered that the questions were respectively rather adapted and very adapted to the evaluation of auditory hallucinations. 46.3% of patients found the questions quite easy to understand. The majority of patients felt that the MIMO app could be useful to them. Overall satisfaction was 8.073+-3.8 indicating very good overall patient satisfaction of the app. Statistical tests revealed significant convergence and divergence validities as well as good internal consistency of the SAVH.ConclusionsThis study demonstrated good psychometric properties of the SAVH and very good acceptability of this kind of assessment by digital device in patients with schizophrenia. Such a device can be quite useful to assess the efficacy of the treatment of AVH and to increase the patient’s empowerment.Disclosure of InterestNone Declared

Structural brain abnormalities in schizophrenia patients with a history and presence of auditory verbal hallucination

Although many studies have demonstrated structural brain abnormalities associated with auditory verbal hallucinations (AVH) in schizophrenia, the results remain inconsistent because of the small sample sizes and the reliability of clinical interviews. We compared brain morphometries in 204 participants, including 58 schizophrenia patients with a history of AVH (AVH + ), 29 without a history of AVH (AVH−), and 117 healthy controls (HCs) based on a detailed inspection of medical records. We further divided the AVH+ group into 37 patients with and 21 patients without hallucinations at the time of the MRI scans (AVH++ and AVH+−, respectively) via clinical interviews to explore the morphological differences according to the persistence of AVH. The AVH + group had a smaller surface area in the left caudal middle frontal gyrus (F = 7.28, FDR-corrected p = 0.0008) and precentral gyrus (F = 7.68, FDR-corrected p = 0.0006) compared to the AVH− group. The AVH+ patients had a smaller surface area in the left insula (F = 7.06, FDR-corrected p = 0.001) and a smaller subcortical volume in the bilateral hippocampus (right: F = 13.34, FDR-corrected p = 0.00003; left: F = 6.80, FDR-corrected p = 0.001) compared to the HC group. Of these significantly altered areas, the AVH++ group showed significantly smaller bilateral hippocampal volumes compared to the AVH+− group, and a smaller surface area in the left precentral gyrus and caudal middle frontal gyrus compared to the AVH- group. Our findings highlighted the distinct pattern of structural alteration between the history and presence of AVH in schizophrenia, and the importance of integrating multiple criteria to elucidate the neuroanatomical mechanisms.

Auditory verbal hallucination can be evoked by prefrontal epileptic seizure

Auditory verbal hallucinations (AVHs) have been reported in neocortical temporal epileptic seizures and have been considered highly associated with implication of auditory cortex by epileptic discharges or electrical stimulation. Herein, we report two rare frontal epilepsy cases in which AVHs featured the habitual seizures. The epileptogenic zones of these two patients were localized in the dorsal and orbitomedial prefrontal cortex, respectively by stereoelectroencephalography (SEEG) monitoring. Comparing with the AVHs in schizophrenia, we postulated that the phenomenological similarities between the two sets of AVHs imply homology in mechanisms. Ictal SEEG confirmed that the wide involvement of prefrontal–cingulate–auditory cortical network by low-voltage fast activity corresponded the occurrence with AVHs during frontal epileptic seizures. Electrical stimulation study of one of the two cases highlighted the causal role of prefrontal–cingulate cortex in the emergence of AVHs. Based on our clinical observation, SEEG findings, and electrical cortical stimulation, we supposed that wide implication of prefrontal–cingulate–auditory cortical network during epileptic seizure underlie the emergence of AVHs, and further hypothesized that AVHs could be yielded by transient deficit of self-monitoring for inner speech in focal epileptic seizures.

The phenomenology of auditory verbal hallucinations in schizophrenia and the challenge from pseudohallucinations.

In trying to make sense of the extensive phenomenological variation of first-personal reports on auditory verbal hallucinations, the concept of pseudohallucination is originally introduced to designate any hallucinatory-like phenomena not exhibiting some of the paradigmatic features of “genuine” hallucinations. After its introduction, Karl Jaspers locates the notion of pseudohallucinations into the auditory domain, appealing to a distinction between hallucinatory voices heard within the subjective inner space (pseudohallucination) and voices heard in the outer external space (real hallucinations) with differences in their sensory richness. Jaspers' characterization of the term has been the target of a number of phenomenological, conceptual and empirically-based criticisms. From this latter point of view, it has been claimed that the concept cannot capture distinct phenomena at the neurobiological level. Over the last years, the notion of pseudohallucination seems to be falling into disuse as no major diagnostic system seems to refer to it. In this paper, we propose that even if the concept of pseudohallucination is not helpful to differentiate distinct phenomena at the neurobiological level, the inner/outer distinction highlighted by Jaspers' characterization of the term still remains an open explanatory challenge for dominant theories about the neurocognitive origin of auditory verbal hallucinations. We call this, “the challenge from pseudohallucinations”. After exploring this issue in detail, we propose some phenomenological, conceptual, and empirical paths for future research that might help to build up a more contextualized and dynamic view of auditory verbal hallucinatory phenomena.

A Decrease in Hemodynamic Response in the Right Postcentral Cortex Is Associated With Treatment-Resistant Auditory Verbal Hallucinations in Schizophrenia: An NIRS Study.

BackgroundTreatment-resistant auditory verbal hallucinations (TRAVHs) might cause an increased risk of violence, suicide, and hospitalization in patients with schizophrenia (SCZ). Although neuroimaging studies have identified the neural correlation to the symptom of AVH, functional brain activity that correlates particularly in patients with TRAVH remains limited. Functional near-infrared spectroscopy (fNIRS) is a portable and suitable measurement, particularly in exploring brain activation during related tasks. Hence, our researchers aimed to explore the differences in the cerebral hemodynamic function in SCZ-TRAVH, patients with schizophrenia without AVH (SCZ-nAVH), and healthy controls (HCs), to examine neural abnormalities associated more specifically with TRAVH.MethodsA 52-channel functional near-infrared spectroscopy system was used to monitor hemodynamic changes in patients with SCZ-TRAVH (n = 38), patients with SCZ-nAVH (n = 35), and HC (n = 30) during a verbal fluency task (VFT). VFT performance, clinical history, and symptom severity were also noted. The original fNIRS data were analyzed using MATLAB to obtain the β values (the brain cortical activity response during the VFT task period); these were used to calculate Δβ (VFT β minus baseline β), which represents the degree of change in oxygenated hemoglobin caused by VFT task.ResultOur results showed that there were significant differences in Δβ values among the three groups at 26 channels (ch4, ch13-15, 18, 22, ch25–29, 32, ch35–39, ch43–51, F = 1.70 to 19.10, p < 0.043, FDR-corrected) distributed over the prefrontal–temporal cortical regions. The further pairwise comparisons showed that the Δβ values of 24 channels (ch13–15, 18, 22, 25, ch26–29, ch35–39, ch43–49, ch50–51) were significantly lower in the SCZ group (SCZ-TRAVH and/or SCZ-nAVH) than in the HC group (p < 0.026, FDR-corrected). Additionally, the abnormal activation in the ch22 of right postcentral gyrus was correlated, in turn, with severity of TRAVH.ConclusionOur findings indicate that specific regions of the prefrontal cortex may be associated with TRAVH, which may have implications for early intervention for psychosis.

Auditory Verbal Hallucinations in Schizophrenia, Part II: Phenomenological Qualities and Evolution.

Hallucination is defined in the diagnostic systems as an experience resembling true perception without causal stimulus. In this second report from an in-depth phenomenological study of schizophrenia patients experiencing auditory verbal hallucinations (AVHs), we focused on the phenomenological qualities of AVHs. We found that a substantial proportion of patients could not clearly distinguish between thinking and hallucinating. The emotional tone of the voices increased in negativity. AVHs became more complex. Spatial localization was ambiguous and only 10% experienced only external hallucinations. There was an overlap with passivity phenomena in one third of the cases. The patients occasionally acted upon the content of AVHs. In the discussion section, we criticize the perceptual model of AVHs. We conclude that the definition of AVH in schizophrenia is misleading and exerts negative consequences on the clinical work and empirical research.

Low-frequency rTMS treatment alters the topographical organization of functional brain networks in schizophrenia patients with auditory verbal hallucination

Auditory verbal hallucinations (AVH) are an important characteristic of schizophrenia. Repeated transcranial magnetic stimulation (rTMS) has been evidence to be effective in treating AVH. We evaluated the topological properties of resting-state functional brain networks in schizophrenia patients with AVH (n = 32) who received 1-Hz rTMS treatment and matched healthy controls (n = 33). The results showed that the psychotic symptoms and certain neurocognitive performances in patients were improved by rTMS treatment. Furthermore, the pretreatment patients showed abnormal global topological metrics compared with the controls, including lower global efficiency (Eglob, represents the relative quality of information transmission between all nodes in the network) and higher characteristic path length (Lp, characterizes the mean shortest distance between any two nodes in the network). The pretreament patients also showed decreased local topological metrics relative to the controls, including the nodal shortest path (NLp, quantifies the mean distance between the given node and the other nodes in the network) and nodal efficiency (Ne, measures the information interchange among the neighbor nodes when one node is removed), mainly located in the prefrontal cortex, occipital cortex, and subcortical regions. While the abnormal global and local topological patterns were normalized in patients after rTMS treatment. The multiple linear regression analysis indicated that the baseline topological metrics could be associated with the clinical responses after treatment in the patient group. The results suggested that the topological organization of the functional brain network was globally and regionally altered in schizophrenia patients with AVH after rTMS treatment and may be a potential therapeutic effect for AVH in schizophrenia.

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.

BPSS Award

Trans-cranial magnetic stimulation (TMS) can noninvasively modulate specific brain regions to dissipate auditory verbal hallucinations (AVH) in schizophrenia. Citing critical involvement of temporoparietal cortex (TPC) in AVH, we aimed to study the effect of continuous theta burst stimulation (cTBS) targeting bilateral TPC in schizophrenia subjects with AVH, on a randomized rater blinded placebo control trial. 59 patients were randomly allocated to active and sham groups. They received 20 cTBS sessions (2 per day: first right TPC, then left TPC) 5 days a week for 2 weeks. PANSS (Positive and Negative Syndrome Scale), AVHRS (Auditory vocal hallucination rating scale), PSYRAT-AH (Psychiatric symptoms rating scale- Auditory hallucinations scale), CDSS (Calgary depression scale for schizophrenia), SCoRS (Schizophrenia cognition rating scale), CGI-S (Clinical global impression-severity) were assessed at baseline, immediately post 20th session and 2 weeks post-TBS. 50 patients (25-active, 25-sham) completed the study. Conducting an intention to treat analysis, we found a significant group*time effect for PANSS, AVHRS, PSYRAT-AH, CDSS, SCoRS, CGI-S but when controlled for confounding variables, only PANSS-PS (F=26.617, p<0.001), PANSS-TOTAL (F=23.671, p<0.001), AVHRS (F=17.779, p<0.001), PSYRAT-AH (F=11.385, p<0.001) and CGI-S (F=28.462, p<0.001) retained significance. We conclude that cTBS over TPC is safe and has efficacy in AVH in schizophrenia.

Prof K C Dube Poster Award

Background:Auditory verbal hallucinations (AVH) are one of the core features of schizophrenia. In approximately 25% of patients with schizophrenia, AVH are refractory to psychotropic drug treatment and can chronically persist. Superior temporal cortex is implicated in AVH. Continuous Theta Burst Stimulation (cTBS) can be one of the add on treatment for auditory hallucination in refractory cases. Accelerated cTBS protocols have the advantage of shorter application time and lower stimulation intensity. In addition use of robotized neuronavigation will improve the accuracy of coil placement and thus localization of the stimulation site.Aim:We aimed to evaluate the efficacy of accelerated cTBS over left superior temporal cortex (STC) in improvement of AVH in schizophrenia, using neuronavigation and robotic arm.Methods:40 patients of schizophrenia with AVH, were enrolled for this randomized, sham controlled, double-blind trial. Each participant in the active group received cTBS comprising of 900 pulses (bursts of 3 stimuli at 50 Hz repeated at 5 Hz frequency), twice a day for 5 days per week for 3 consecutive weeks. AVH were assessed with PSYRATS(AHRS), PANSS & CGI. Assessments were carried out at baseline,1st,3rd & 6th weeks.Results:The improvement in AVH in active group at 1st 3rd & 6th week was not statistically significant at 0.05 (p-value) as compared to sham group. Stimulation was well tolerated.Conclusion:Results suggest that accelerated robotized neuronavigated cTBS does not appear to have substantial potential in the treatment of auditory hallucinations and further research should investigate individualised MRI guided neuronavigation with higher sample size.

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS)

Introduction: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients. Methods: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS. Results: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients. Conclusion: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.

Abnormal dynamic resting-state brain network organization in auditory verbal hallucination

Auditory-verbal hallucinations (AVH) are a key symptom of schizophrenia. Recent neuroimaging studies examining dynamic functional connectivity suggest that disrupted dynamic interactions between brain networks characterize complex symptoms in mental illness including schizophrenia. Studying dynamic connectivity may be especially relevant for hallucinations, given their fluctuating phenomenology. Indeed, it remains unknown whether AVH in schizophrenia are directly related to altered dynamic connectivity within and between key brain networks involved in auditory perception and language, emotion processing, and top-down control. In this study, we used dynamic connectivity approaches including sliding window and k-means to examine dynamic interactions among brain networks in schizophrenia patients with and without a recent history of AVH. Dynamic brain network analysis revealed that patients with AVH spent less time in a ‘network-antagonistic’ brain state where the default mode network (DMN) and the language network were anti-correlated, and had lower probability to switch into this brain state. Moreover, patients with AVH showed a lower connectivity within the language network and the auditory network, and lower connectivity was observed between the executive control and the language networks in certain dynamic states. Our study provides the first neuroimaging evidence of altered dynamic brain networks for understanding neural mechanisms of AVH in schizophrenia. The findings may inform and further strengthen cognitive models of AVH that aid the development of new coping strategies for patients.