Schizophrenia as a network disease: disruption of emergent brain function in patients with auditory hallucinations.
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ABSTRACT:
SUBMITTER: Rish I
PROVIDER: S-EPMC3549920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAuditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology.MethodsTwelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism.ResultsAVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus.ConclusionsThese results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself.
| S-EPMC3402538 | biostudies-literature
Project description:BackgroundInter-hemispheric disconnection is a primary pathological finding in schizophrenia. However, given the inherent complexity of this disease and its development, it remains unclear as to whether associated inter-hemispheric changes play an important role in auditory verbal hallucination (AVH) development. As such, this study was developed to explore inter-hemispheric connectivity in the context of schizophrenia with AVH while excluding positive symptoms and other factors with the potential to confound these results.MethodIn total, resting-state functional magnetic resonance imaging (fMRI) was used to assess 42 patients with AVH (APG), 26 without AVH (NPG), and 82 normal control (NC) individuals. Inter-hemispheric connectivity in these subjects was then assessed through the use of voxel-mirrored homotopic connectivity (VMHC) and Pearson correlation analyses.ResultRelative to HC and NPG subjects, APG individuals exhibited a decrease in VMHC in the superior temporal gyrus (STG) extending into Heschl's gyrus, the insula, and the Rolandic operculum as well as in the fusiform gyrus extending into the para-hippocampus (Corrected p < 0.005, cluster size = 52). Among APG individuals, these observed impairments of inter-hemispheric connectivity were negatively correlated with Hoffman auditory hallucination scores.ConclusionThese results support the schizophrenia hemitropic disconnection hypothesis, and provide novel evidence suggesting that there may be a relationship between reductions in inter-hemispheric connectivity in auditory and memory-related networks and the pathogenesis of AVH in patients with schizophrenia following the exclusion of confounding factors from other positive symptoms.
| S-EPMC9381966 | biostudies-literature
Project description:Purpose:This review reports the current perspectives of brain stimulation techniques in the treatment of auditory verbal hallucinations (AVH) in schizophrenia. Methods:A systematic search of the literature in the PubMed database revealed that the most studied techniques are noninvasive techniques (NIBS), including electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). Results:The results showed that ECT could have great clinical efficacy but is currently underused in practice perhaps due to the costs associated with its limited implementation and potential associated risks. tDCS is still poorly studied and does not demonstrate sufficiently homogeneous or conclusive results yet to prove its efficacy in the treatment of AVH. However, its safe and simple implementation allows us to recommend it to patients who are refractory to other stimulation techniques. Finally, rTMS seems to be the most efficacious NIBS to offer patients with persistent AVH as an add-on therapeutic strategy. Its implementation has a non negligible cost but can be performed by a single practitioner. Great evolution in these techniques with technological progress, robotics and computer science are currently being tested and will undoubtedly improve the clinical efficacy of these procedures, particularly towards more personalized treatments such as individual rTMS targets and intensities. There are also new techniques for deep brain stimulation based on focused ultrasound that could provide much insight into the treatment of AVH in schizophrenia. Conclusion:This review suggests that add-on brain stimulation treatments could play a key role among the therapeutic strategies for auditory hallucinations reduction in schizophrenia.
| S-EPMC6662171 | biostudies-literature
Project description:The pathophysiology of auditory verbal hallucinations remains poorly understood.To characterise the time course of regional brain activity leading to auditory verbal hallucinations.During functional magnetic resonance imaging, 11 patients with schizophrenia or schizoaffective disorder signalled auditory verbal hallucination events by pressing a button. To control for effects of motor behaviour, regional activity associated with hallucination events was scaled against corresponding activity arising from random button-presses produced by 10 patients who did not experience hallucinations.Immediately prior to the hallucinations, motor-adjusted activity in the left inferior frontal gyrus was significantly greater than corresponding activity in the right inferior frontal gyrus. In contrast, motor-adjusted activity in a right posterior temporal region overshadowed corresponding activity in the left homologous temporal region. Robustly elevated motor-adjusted activity in the left temporal region associated with auditory verbal hallucinations was also detected, but only subsequent to hallucination events. At the earliest time shift studied, the correlation between left inferior frontal gyrus and right temporal activity was significantly higher for the hallucination group compared with non-hallucinating patients.Findings suggest that heightened functional coupling between the left inferior frontal gyrus and right temporal regions leads to coactivation in these speech processing regions that is hallucinogenic. Delayed left temporal activation may reflect impaired corollary discharge contributing to source misattribution of resulting verbal images.
| S-EPMC3065772 | biostudies-literature
Project description:Neuroimaging studies have demonstrated associations between smaller auditory cortex volume and auditory hallucinations (AH) in schizophrenia. Reduced cortical volume can result from a reduction of either cortical thickness or cortical surface area, which may reflect different neuropathology. We investigate for the first time how thickness and surface area of the auditory cortex relate to AH in a large sample of schizophrenia spectrum patients.Schizophrenia spectrum (n = 194) patients underwent magnetic resonance imaging. Mean cortical thickness and surface area in auditory cortex regions (Heschl's gyrus [HG], planum temporale [PT], and superior temporal gyrus [STG]) were compared between patients with (AH+, n = 145) and without (AH-, n = 49) a lifetime history of AH and 279 healthy controls.AH+ patients showed significantly thinner cortex in the left HG compared to AH- patients (d = 0.43, P = .0096). There were no significant differences between AH+ and AH- patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication.AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia.
| S-EPMC5216858 | biostudies-other
Project description:Auditory hallucinations (AH), typically hearing voices, are a core symptom in schizophrenia. They may result from deficits in dynamic functional connectivity (FC) between cortical regions supporting speech production and language perception that interfere with the ability to recognize self-generated speech as not coming from external sources. We tested this hypothesis by investigating dynamic connectivity between the frontal cortex region related to language production and the temporal cortex region related to auditory processing.Resting-state fMRI scans were acquired from 18 schizophrenia patients with AH (AH+), 17 schizophrenia patients without AH (AH-) and 22 healthy controls. A multiband sequence with TR?=?427?ms was adopted to provide relatively high temporal resolution data for characterizing dynamic FC. Analysis focused on connectivity between speech production and language comprehension areas, eloquent language cortex in the left hemisphere. Two frequency bands of brain oscillatory activity were evaluated (0.01-0.027?Hz, 0.027-0.08?Hz) in which differential alterations that have been previously linked to schizophrenia. Conventional static FC maps of these seeds were also calculated.Dynamic connectivity analysis indicated that AH+ patients showed not only less temporal variability but transient lower strength in connectivity between speech and auditory areas than healthy controls, while AH- patients not. These findings were restricted to 0.027-0.08?Hz activity. In static connectivity analysis, no significant differences were observed in connectivity between speech production and language comprehension areas in either frequency band.Reduced temporal variability and connectivity strength between key regions of eloquent language cortex may represent a mechanism for AH in schizophrenia.
| S-EPMC6039841 | biostudies-other
Project description:Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.
| S-EPMC4215518 | biostudies-literature
Project description: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 (sDCM) 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-naïve 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. sDCM revealed an increased sensitivity 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 AVH-specific 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.
| S-EPMC5567513 | biostudies-literature
Project description:Existing 67-channel event-related potentials, obtained during recognition and working memory paradigms with words or faces, were used to examine early visual processing in schizophrenia patients prone to auditory hallucinations (AH, n?=?26) or not (NH, n?=?49) and healthy controls (HC, n?=?46). Current source density (CSD) transforms revealed distinct, strongly left- (words) or right-lateralized (faces; N170) inferior-temporal N1 sinks (150?ms) in each group. N1 was quantified by temporal PCA of peak-adjusted CSDs. For words and faces in both paradigms, N1 was substantially reduced in AH compared with NH and HC, who did not differ from each other. The difference in N1 between AH and NH was not due to overall symptom severity or performance accuracy, with both groups showing comparable memory deficits. Our findings extend prior reports of reduced auditory N1 in AH, suggesting a broader early perceptual integration deficit that is not limited to the auditory modality.
| S-EPMC3419781 | biostudies-literature
Project description:BACKGROUND:There have been many attempts at explaining the underlying neuropathological mechanisms of auditory verbal hallucinations (AVH) in schizophrenia on the basis of regional brain changes, with the most consistent findings being that AVH are associated with functional and structural impairments in auditory and speech-related regions. However, the human brain is a complex network and the global topological alterations specific to AVH in schizophrenia remain unclear. METHODS:Thirty-five schizophrenia patients with AVH, 41 patients without AVH, and 50 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). The whole-brain functional and structural networks were constructed and analyzed using graph theoretical approaches. Inter-group differences in global network metrics (including small-world properties and network efficiency) were investigated. RESULTS:We found that three groups had a typical small-world topology in both functional and structural networks. More importantly, schizophrenia patients with and without AVH exhibited common disruptions of functional networks, characterized by decreased clustering coefficient, global efficiency and local efficiency, and increased characteristic path length; structural networks of only schizophrenia patients with AVH showed increased characteristic path length compared with those of healthy controls. CONCLUSION:Our findings suggest that less "small-worldization" and lower network efficiency of functional networks may be an independent trait characteristic of schizophrenia, and regularization of structural networks may be the underlying pathological process engaged in schizophrenic AVH symptom expression.
| S-EPMC4791368 | biostudies-literature