Exploring function in the hallucinating brain

For many patients with schizophrenia 'hearing voices’ is frightening and severely disruptive symptom of their illness. Recent analysis techniques now offer the possibility to study the complex brain as a communicating network, and in this way develop more realistic models on the origin of hallucinations, which is desperately needed in our search for targeted interventions for hallucinations. In this thesis we present an integrated network model in which we show how the same mathematical principles can be used to explain psychotic symptoms on different levels of human functioning (from nerve cells to brain areas to social networks). In this way we put an end to a fixation on one or several causes of schizophrenia, and we embrace a multi-factorial or (eco)systems approach to this disorder. Derived from data-driven analysis of fMRI data from patients with schizophrenia, we comprehensively describe the neural circuit involved in hallucinations. Specifically, our findings show that miscommunications between two functional networks are central in the occurrence of hallucinations, i.e. linguistic content from the right-sided area of Broca is assigned false salience in the insula. This mechanical insight directly informs us where we can effectively intervene into the hallucination network

An integrated network model of psychotic symptoms

AbstractThe full body of research on the nature of psychosis and its determinants indicates that a considerable number of factors are relevant to the development of hallucinations, delusions, and other positive symptoms, ranging from neurodevelopmental parameters and altered connectivity of brain regions to impaired cognitive functioning and social factors. We aimed to integrate these factors in a single mathematical model based on network theory. At the microscopic level this model explains positive symptoms of psychosis in terms of experiential equivalents of robust, high-frequency attractor states of neural networks. At the mesoscopic level it explains them in relation to global brain states, and at the macroscopic level in relation to social-network structures and dynamics. Due to the scale-free nature of biological networks, all three levels are governed by the same general laws, thereby allowing for an integrated model of biological, psychological, and social phenomena involved in the mediation of positive symptoms of psychosis. This integrated network model of psychotic symptoms (INMOPS) is described together with various possibilities for application in clinical practice

Exploring function in the hallucinating brain

For many patients with schizophrenia 'hearing voices’ is frightening and severely disruptive symptom of their illness. Recent analysis techniques now offer the possibility to study the complex brain as a communicating network, and in this way develop more realistic models on the origin of hallucinations, which is desperately needed in our search for targeted interventions for hallucinations. In this thesis we present an integrated network model in which we show how the same mathematical principles can be used to explain psychotic symptoms on different levels of human functioning (from nerve cells to brain areas to social networks). In this way we put an end to a fixation on one or several causes of schizophrenia, and we embrace a multi-factorial or (eco)systems approach to this disorder. Derived from data-driven analysis of fMRI data from patients with schizophrenia, we comprehensively describe the neural circuit involved in hallucinations. Specifically, our findings show that miscommunications between two functional networks are central in the occurrence of hallucinations, i.e. linguistic content from the right-sided area of Broca is assigned false salience in the insula. This mechanical insight directly informs us where we can effectively intervene into the hallucination network

Draining the pond and catching the fish : Uncovering the ecosystem of auditory verbal hallucinations

The various models proposed for the mediation of auditory verbal hallucinations (AVH) implicate a considerable number of brain areas and mechanisms. To establish which of those mechanisms are actually involved in the mediation of AVH, we developed a novel method to analyze functional MRI data, which allows for the detection of the full network of mutually interacting brain states, and the identification of those states that are relevant to the mediation of AVH, while applying a minimum number of preconceived assumptions. This method is comparable to the draining of a pond to lay bare the full ecosystem that affects the presence of a particular fish species. We used this model to analyze the fMRI data of 85 psychotic patients experiencing AVH. The data were decomposed into 98 independent components (ICs) representing all major functions active in the brain during scanning. ICs involved in mediating AVH were identified by associating their time series with the hallucination time series as provided by subjects within the scanner. Using graph theory, a network of interacting ICs was created, which was clustered into IC modules. We used causal reasoning software to determine the direction of links in this network, and discover the chain of events that leads to the conscious experience of hallucinations. Hallucinatory activity was linked to three of the seven IC clusters and 11 of the 98 ICs. ICs with the most influential roles in producing AVH-related activity were those within the so-called salience network (comprising the anterior cingulate gyrus, right insula, Broca's homologue, premotor cortex, and supramarginal gyrus). Broca's area and the cerebellar regions were significantly, but more distantly involved in the mediation of AVH. These results support the notion that AVH are largely mediated by the salience network. We therefore propose that the mediation of AVH in the context of schizophrenia spectrum disorders involves the attribution of an excess of negative salience by anterior-cingulate areas to linguistic input from Broca's right homologue, followed by subsequent processing errors in areas further ‘downstream’ the causal chain of events. We provide a detailed account of the origin of AVH for this patient group, and make suggestions for selective interventions directed at the most relevant brain areas

Treatment of Alice in Wonderland Syndrome and Verbal Auditory Hallucinations Using Repetitive Transcranial Magnetic Stimulation:A Case Report with fMRI Findings

Background: Alice in Wonderland syndrome (AIWS) is a rare cluster of CNS symptoms characterized by visual distortions (i.e. metamorphopsias), body image distortions, time distortions, and deja experiences. Verbal auditory hallucinations (VAHs) are the most prevalent type of hallucination in adults with or without a history of psychiatric illness. Here, we report the case of a woman with AIWS, long-lasting VAHs, and various additional perceptual and mood symptoms. Methods: Semi-structured interviews were used to assess symptoms, and functional MRI (fMRI) was employed to localize cerebral activity during self-reported VAHs. Treatment consisted of repetitive transcranial magnetic stimulation (rTMS) at a frequency of 1 Hz at T3P3, overlying Brodmann's area 40. Results: Activation during VAHs was observed bilaterally in the basal ganglia, the primary auditory cortex, the association auditory cortex, the temporal poles, and the anterior cingulated gyrus. The left and right inferior frontal gyri (Broca's area and its contralateral homologue) were involved, along with the dorsolateral prefrontal cortex. Interestingly, synchronized activation was observed in the primary visual cortex (areas V1 and V2), and the bilateral dorsal visual cortex. The higher visual association cortex also showed significant, but less prominent, activation. During the second week of rTMS treatment, not only the VAHs, but also the other sensory deceptions/distortions and mood symptoms showed complete remission. The patient remained free of any symptoms during a 4-month follow-up phase. After 8 months, when many of the original symptoms had returned, a second treatment phase with rTMS was again followed by complete remission. Conclusions: This case indicates that VAHs and metamorphopsias in AIWS are associated with synchronized activation in both auditory and visual cortices. It also indicates that local rTMS treatment may have global therapeutic effects, suggesting an effect on multiple brain regions in a distributed network. Although a placebo effect cannot be ruled out, this case warrants further investigation of the effects of rTMS treatment in AIWS. Copyright (C) 2011 S. Karger AG, Base