Treatment-refractory auditory verbal hallucinations in patients with schizophrenia – Neurofunctional correlates of attention and working memory

Abstract

This doctoral thesis was interested in the neural correlates underlying treatment-refractory AVH in schizophrenia and potential associations with clinical symptoms and cognitive processes. AVH are defined as a sensory experience of hearing voices in the absence of a corresponding external stimulus with a compelling sense of reality. They are one of the core symptoms of schizophrenia with 50-80% of patients experiencing AVH (Andreasen & Flaum, 1991). Treatment-refractory AVH, i.e., persisting hallucinations despite an adequate treatment which should be sufficient in intensity and duration (Berman et al., 1997), cause major distress and affect the lives of patients substantially (Vauth & Stieglitz, 2007). To date, the precise neurocognitive and neurobiological mechanisms contributing to AVH occurrence are still largely unknown with different studies providing inconsistent results. So far, the neuroscientific state of evidence regarding AVH in schizophrenic patients points to morphological and functional changes in frontal, temporal and parietal regions as well as abnormal network connectivity in the brain. The current study was designed as a ‘piece of the puzzle’ to add to the existing literature and answer the question whether AVH in schizophrenia are associated with different neural activation in known brain areas of interest. In addition, the relationship between these functional neural activation patterns and performance on the on-line activation paradigms, neuropsychological measures of cognitive functioning, as well as psychopathology was assessed. Participants underwent one-time assessment of cognition, psychopathology, and neuroimaging on two or three dates each lasting approximately 1-1.5 hours. Four hypotheses were evaluated regarding confirmatory indicators of evidence: (1) Groups will differ in functional neural activation patterns. In specific and in accordance with the symptom interference idea, reduced neural activation in hallucinating patients when compared with both control groups was hypothesized. (2) AVH-related neural activation will interfere with task performance on-line. The direction of correlation was predicted to be negative. (3) AVH-related neural activation will be correlated with neuropsychological performance off-line. And (4) AVH-related neural dysfunction will be negatively correlated with general psychopathology. The statistical analyses revealed that none of the initially formulated hypotheses could be confirmed with regard to the hypothesized direction of effect. However, both fMRI activation paradigms, the alertness task and the n-back task, lead to significant AVH-related neural activation at p k (expected voxels per cluster) in contrast to the predicted hypoactivation. The results are discussed in the context of the Predictive Processing Framework.