Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders

BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different etiologies.The pathomechanisms of MH encompass various conditions.The etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of MH.Over the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of MH.Functional imaging studies reveal that MH activates a wide array of brain regions.An up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is warranted.AIM To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of MH.METHODS Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of Science.MH cases were collected and categorized based on their etiologies.The t-test and ANOVA were employed(P<0.05)to compare the age differences of MH different etiological groups.Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed.RESULTS Among the 357 yielded publications,294 MH cases were collected.The average age of MH cases was 67.9 years,with a predominance of females(66.8%females vs 33.2%males).MH was classified into eight groups based on their etiological mechanisms.Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses.CONCLUSION We carried out a more comprehensive review of MH studies.For the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.

Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Cognitive behavioural therapy for auditory hallucinations in schizophrenia:A review

AIM To provide an updated of recent findings about efficacy of cognitive-behavior therapy(CBT) in reduction of command hallucinations.METHODS Pub Med/MEDLINE,Cochrane Library,the Cumulative Index to Nursing and Allied Health Literature,PsycI NFO,Clinical Trial.gov searches were performed using the keywords "hallucinations","behavioural therapy" and " cognitive therapy" in order to identify relevant articles published during the years of 2011 to 2016.No language limits were used.Studies conducted within control group,reviews,editorials,were excluded.Data on efficacy,acceptability and tolerability were extracted by three authors independently.Disagreements were resolved in a consensus meeting or by another reviewer.RESULTS A total of eight articles were eligible for inclusion.Two are randomized clinical trials(RCTs) and six are observational studies.The two RCTs included showed a greater efficacy of CBT compared to standard care on auditory hallucinations(AHs).Nevertheless,they considered different CBT models,particularly Treatment of Resistant Command Hallucinations and Cognitive Therapy for Command Hallucinations.As regards non RCT-studies,all papers included showed reduction on frequency and severity of AHs and distress related to them.However,the lack of content details within non-RCTs studies decreased their comparability.In terms of predictive variables,our findings show that negative symptoms at baseline appeared to be the strongest predictor of the treatment efficacy.Indeed,negative symptoms showed a significant negative correlation on outcome.CONCLUSION Although more conclusive studies are still needed,we found some preliminary evidence for the efficacy of CBT in the treatment of command hallucinations.

Auditory hallucinations: A review of the ERC “VOICE” project

In this invited review I provide a selective overview of recent research on brain mechanisms and cognitive processes involved in auditory hallucinations. The review is focused on research carried out in the "VOICE" ERC Advanced Grant Project, funded by the European Research Council, but I also review and discuss the literature in general. Auditory hallucinations are suggested to be perceptual phenomena, with a neuronal origin in the speech perception areas in the temporal lobe. The phenomenology of auditory hallucinations is conceptualized along three domains, or dimensions; a perceptual dimension, experienced as someone speaking to the patient; a cognitive dimension, experienced as an inability to inhibit, or ignore the voices, and an emotional dimension, experienced as the "voices" having primarily a negative, or sinister, emotional tone. I will review cognitive, imaging, and neurochemistry data related to these dimensions, primarily the first two. The reviewed data are summarized in a model that sees auditory hallucinations as initiated from temporal lobe neuronal hyper-activation that draws attentional focus inward, and which is not inhibited due to frontal lobe hypo-activation. It is further suggested that this is maintained through abnormal glutamate and possibly gamma-amino-butyric-acid transmitter mediation, which could point towards new pathways for pharmacological treatment. A final section discusses new methods of acquiring quantitative data on the phenomenology and subjective experience of auditory hallucination that goes beyond standard interview questionnaires, by suggesting an iP hone/iP od app.

Multimodal morphometry and functional magnetic resonance imaging in schizophrenia and auditory hallucinations

AIM: To validate a multimodal [structural and functional magnetic resonance (MR)] approach as coincidence brain clusters are hypothesized to correlate with clinical severity of auditory hallucinations. METHODS: Twenty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders (fourth edition, DSM-IV) criteria for schizophrenia and experiencing persistent hallucinations together with 28 healthy controls were evaluated with structural and functional MR imaging with an auditory paradigm designed to replicate those emotions related to the patients’ hallucinatory experiences. Coincidence maps were obtained by combining structural maps of gray matter reduction with emotional functional increased activation. Abnormal areas were correlated with the brief psychiatric rating scale (BPRS) and the psychotic symptom rating scale (PSYRATS) scales. RESULTS: The coincidence analysis showed areas with coexistence gray matter reductions and emotional activation in bilateral middle temporal and superior temporal gyri. Significant negative correlations between BPRS and PSYRATS scales were observed. BPRS scores were negatively correlated in the middle temporal gyrus (right) (t = 6.86, P = 0.001), while negative PSYRATS correlation affected regions in both the superior temporal gyrus (left) (t = 7.85, P = 0.001) and middle temporal gyrus (left) (t = 4.97, P = 0.002). CONCLUSION: Our data identify left superior and middle temporal gyri as relevant areas for the understanding of auditory hallucinations in schizophrenia. The use of multimodal approaches, sharing structural and functional information, may demonstrate areas specifically linked to the severity of auditory hallucinations.

Treatment of refractory auditory hallucinations in schizophrenia by rTMS: Positive impact of negative double blind controlled study

Background: Several studies reported on the effectiveness of 1 Hz repeated transcranial magnetic stimulation (rTMS) over the temporoparietal cortex (TPC) on refractory auditory hallucinations (AH) in schizophrenia but little is known about the long-term therapeutic effect of this tool. Aim: The aim of this study was to evaluate rTMS’ impact on auditory hallucinations (AH) and cognitive functions in patients with schizophrenia with a three-month follow-up. Methods: In a randomized double blind sham controlled study, 26 patients with refractory schizophrenia received 1 Hz rTMS applied on TPC for four weeks. rTMS was given to patients over one month with five rTMS sessions each week. Patients were evaluated via AHRS (Auditory Hallucination Rating Scale, Hoffman et al.), PANSS (Positive and Negative Syndrome Scale, Kay et al. 1988), and CGI (Clinical Global Impression) before treatment by rTMS every week during the first month, and every month until the third month. Results: Neither clinical nor cognitive differences were found between rTMS and placebo. Conclusion: 1 Hz rTMS using parameters mentioned above has no statistically significant effect on AH;although evidences about the potential benefit of rTMS in the treatment of AH negative results suggest the need for further studies in this area.

Abnormal Local Activity and Functional Dysconnectivity in Patients with Schizophrenia Having Auditory Verbal Hallucinations

Auditory verbal hallucination(AVH)is emphasized as a pathological hallmark of schizophrenia.Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks.However,no clear conclusion has still been reached.This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity(LA)and functional connectivity(FC)insights,while excluding confounding factors from other positive symptoms.A total of 42 patients with AVH(AVH patients group,APG),26 without AVH(non-AVH patients group,NPG),and 82 normal controls(NC)underwent resting-state functional magnetic resonance imaging(fMRI).LA measures,including regional homogeneity(ReHo)and fractional amplitude of low-frequency fluctuations(fALFF),and FC measures were evaluated to understand the neuroimaging mechanism of AVH.APG showed increased ReHo and fALFF in the bilateral putamen(Put)compared with NPG and NC.FC analysis(using bilateral putamen as seeds)revealed that all patients showed abnormal FC of multiple resting state network regions,including the anterior and post cingulate cortex,middle frontal gyrus,inferior parietal gyrus,and left angular gyrus.Interestingly,APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC.The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH,providing evidence for the functional disconnection hypothesis of schizophrenia.

40 Hz Auditory Steady State Response to Linguistic Features of Stimuli during Auditory Hallucinations

The auditory steady state response （ASSR） may reflect activity from different regions of the brain, depending on the modulation frequency used. In general, responses induced by low rates （_〈40 Hz） emanate mostly from central structures of the brain, and responses from high rates （〉80 Hz） emanate mostly from the peripheral auditory nerve or brainstem structures. Besides, it was reported that the gamma band ASSR （30-90 Hz） played an important role in working memory, speech understanding and recognition. This paper investigated the 40 Hz ASSR evoked by modulated speech and reversed speech. The speech was Chinese phrase voice, and the noise-like reversed speech was obtained by temporally reversing the speech. Both auditory stimuli were modulated with a frequency of 40 Hz. Ten healthy subjects and 5 patients with hallucination symptom participated in the experiment. Results showed re- duction in left auditory cortex response when healthy subjects listened to the reversed speech compared with the speech. In contrast, when the patients who experienced auditory hallucinations listened to the reversed speech, the auditory cortex of left hemispheric responded more actively. The ASSR results were consistent with the behavior results of patients. Therefore, the gamma band ASSR is expected to be helpful for rapid and objective diagnosis of hallucination in clinic.

Acute Normalization of Thyroxine Induced Hallucinations and Delusions

The association between disorders of thyroid function and psychiatric symptoms is well established. Generally, hypo-thyroidism is recognized as being able to induce psychotic symptoms. However, psychotic symptoms without affective and cognitive disturbances are rare in hyperthyroidism. We presented a patient with Graves’ disease who suffered from delusions and hallucinations without affective and cognitive disturbances following abrupt normalization of thyroid function. Furthermore, the patient was clinically and biochemically euthyroid when the psychotic symptoms developed. There was resolution of psychotic symptoms in this case. It is suggested that the abrupt change of thyroxine may cause susceptible individuals to become transient psychotic state.

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations： A Resting-state Functional Magnetic Resonance Imaging Study

Background： Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination （AH）. However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods： Auditory hallucinated patients group （n = 42 APG）, no hallucinated patients group （n = 42 NPG） and normal controls （n = 84 NCs） were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index （degree centrality [DC]） across the entire brain networks was calculated and evaluated among three groups. Results： DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG. the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion： Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.

Abnormal Effective Connectivity in the Brain is Involved in Auditory Verbal Hallucinations in Schizophrenia

Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations（AVHs） in schizophrenia（SZ） remains unclear. In this study, we used stochastic dynamic causal modeling（s DCM） to quantify connections among the left dorsolateral prefrontal cortex（inner speech monitoring）, auditory cortex（auditory processing）, hippocampus（memory retrieval）, thalamus（information filtering）, and Broca＇s area（language production） in 17 first-episode drug-na？¨ve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging.Finally, we performed receiver operating characteristic（ROC） analysis and correlation analysis between image measures and symptoms. s DCM revealed an increasedsensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca＇s area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVHspecific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

Impaired brain white matter and functional networks in healthy individuals with auditory verbal hallucinations

To the Editor:Auditory verbal hallucinations (AVHs) are experienced concomitantly with various neuropsychiatric diagnoses including schizophrenia,bipolar disorder,major depression disorder,post-traumatic stress disorder,and borderline personality disorder.

Increased Local Spontaneous Neural Activity in the Left Precuneus Specific to Auditory Verbal Hallucinations of Schizophrenia

Background： Auditory verbal hallucinations （AVHs） of schizophrenia have been associated with structural and functional alterations of some brain regions. However, the brain regional homogeneity （ReHo） alterations specific to AVHs of schizophrenia remain unclear. In the current study, we aimed to investigate ReHo alterations specific to schizophrenic AVHs. Methods： Thirty-five schizophrenic patients with AVH, 41 schizophrenic patients without AVHs, and fifty healthy subjects underwent resting-state functional magnetic resonance imaging. ReHo differences across the three groups were tested using a voxel-wise analysis. Results： Compared with the healthy control group, the two schizophrenia groups showed significantly increased ReHo in the right caudate and inferior temporal gyrus and decreased ReHo in the bilateral postcentral gyrus and thalamus and the right inferior occipital gyrus （false discovery rate corrected, P 〈 0.05）. More importantly, the AVH group exhibited significantly increased ReHo in the left precuneus compared with the non-AVH group. However, using correlation analysis, we did not find any correlation between the auditory hallucination rating scale score and the ReHo of brain regions. Conclusions： Our results suggest that increased ReHo in the left precuneus may be a pathological feature exclusive to schizophrenic AVHs.

Legal and Ethical Perspectives on Artificial Intelligence

People are enormously nervous about Artificial Intelligence.Although many are constructive and want to move forward,many want more answers from a business perspective,a legal perspective,and an economic perspective.Just today,another class action lawsuit was filed in California.This paper will address concerns and hopefully help you understand Artificial Intelligence better.From these perspectives,you may decide how you feel and think about Artificial Intelligence based on the information presented in this paper and other research.

Effectiveness of anti-psychiatric treatment on visual and haptic perceptual disorder for a patient with Alzheimer’s disease: A case report

BACKGROUND Perception is frequently impaired in patients with Alzheimer’s disease(AD).Several patients exhibit visual or haptic hallucinations.CASE SUMMARY A 71-year-old Chinese man presented with visual and haptic hallucinations he had been experiencing for 2 weeks.The clinical manifestations were the feeling of insects crawling and biting the limbs and geison.He looked for the insects while itching and scratching,which led to skin breakage on the limbs.He was treated with topical and anti-allergic drugs in several dermatology departments without any significant improvement.After admission,the patient was administered risperidone(0.5 mg)and duloxetine(2 mg/day).One week later,the dose of risperidone was increased to 2 mg/day,and that of duloxetine was increased to 60 mg/day.After 2 weeks of treatment,the patient’s sensation of insects crawling and biting disappeared,and his mood stabilized.CONCLUSION This patient manifested psychiatric behavioral symptoms caused by AD brain atrophy.It was important to re-evaluate the patient’s cognitive-psychological status when the patient repeatedly went to the hospital for treatment.Follow-up attention to cognitive function and the consideration of perceptual deficits as early manifestations of AD should be considered.

Face hallucination via compressive sensing

Face hallucination or super-resolution is an inverse problem which is underdetermined,and the compressive sensing(CS)theory provides an effective way of seeking inverse problem solutions.In this paper,a novel compressive sensing based face hallucination method is presented,which is comprised of three steps:dictionary learning、sparse coding and solving maximum a posteriori(MAP)formulation.In the first step,the K-SVD dictionary learning algorithm is adopted to obtain a dictionary which can sparsely represent high resolution(HR)face image patches.In the second step,we seek the sparsest representation for each low-resolution(LR)face image paches input using the learned dictionary,super resolution image blocks are obtained from the sparsest coefficients and dictionaries,which then are assembled into super-resolution(SR)image.Finally,MAP formulation is introduced to satisfy the consistency restrictive condition and obtain the higher quality HR images.The experimental results demonstrate that our approach can achieve better super-resolution faces compared with other state-of-the-art method.

Emerging role of psychosis in Parkinson's disease:From clinical relevance to molecular mechanisms

Parkinson's disease(PD)is the second most common neurodegenerative disease.Psychosis is one of the common psychiatric presentations in the natural course of PD.PD psychosis is an important non-motor symptom,which is strongly correlated with a poor prognosis.Increasing attention is being given to PD psychosis.In this opinion review,we summarized and analyzed the identification,screening,epidemiology,mechanisms,risk factors,and therapeutic approaches of PD psychosis based on the current clinical evidence.PD psychosis tends to have a negative effect on patients'quality of life and increases the burden of family caregiving.Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome.Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters,structural and network changes,genetic profiles,cognitive impairment,and antiparkinsonian medications.The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug,antipsychotics,cholinesterase inhibitors,and non-pharmacological interventions.Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis.Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

An Analysis of Mystical Experience in Sophy' s Hysterical Hallucination in Darkness Visible

In William Golding' s Darkness Visible,Sophy' s experience of " hysterical hallucination" plays an important role in the the matic expression.They point directly to the evil nature of man.Although the specific content of hallucinations is different,they possess a common characteristic-mystical experience.They worth further research.This paper examines Sophy' s mystical experience in her hyster ical hallucination,so as to find out the functions of mystical experience and its influences on the novel' s thematic expression.

An Analysis of Hysterical Hallucination of Simon in Lord of the Flies

Golding gave hallucination to characters when they are suffering from hysteria.This paper researches the relation between Simon' s hysteria with hallucination and the revelation of the theme,and finds out that this clinical symptom turns to be the window for Golding to tell his theme.

Schizophreniform Disorder after Onset of Menopause

Schizophrenia is one of the psychotic disorders that is a huge concern with prevalence increasing every year. In this case report, we are discussing the case of a 49-year-old female with no prior history of psychiatric illness and a recent diagnosis of menopause, presenting with signs and symptoms of schizophreniform disorder and menopause. After undergoing treatment with estrogen and risperidone, she experienced complete resolution of her delusions and hallucinations.