Understanding the Language of Schizophrenia: Neuronal Correlates of Formal Thought Disorder (FTD) and Auditory Verbal Hallucinations (AVH)

Abstract

Schizophrenia is a disease manifesting in symptoms in cognition, language, emotion, and motor behavior. Treatment is available but some symptoms are associated with residual impaired functioning and low treatment response. Neuroimaging studies suggest several structural and functional brain aberrations connected to schizophrenia. However, our knowledge about the fundamental neurobiological mechanisms of the pathogenesis in schizophrenia is still limited. This thesis aims to advance knowledge about the neuronal correlates of two clinical core features in the language domain of schizophrenia, formal thought disorder (FTD) and auditory verbal hallucinations (AVH). In the first study, we investigated structural and functional neuronal correlates of positive and negative FTD. Positive FTD is characterized by pressured speech, derailment, illogicality, and incoherence, while negative FTD is characterized by poverty of speech and content. Neuronal correlates of patients with either positive or negative FTD were assessed by evaluation of cortical thickness, subcortical volumes and cortical resting-state perfusion. Perfusion in the right middle temporal gyrus and the right insula predicted negative FTD and proposes a potential starting point for new treatment options in FTD. The second study investigated functional differences in blood-oxygen-level-dependent (BOLD) brain activation between patients with and without AVH during a language task. Higher activation in fusiform gyrus/cortex in patients without AVH points to a compensatory strategy for deficits in task performance. In the third study, we investigated the effects of a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS) over the left posterior superior temporal cortex to target the auditory cortex (AC). AC is suggested to be involved in AVH generation. However, evidence for tDCS over the temporal cortex as a treatment for AVH is inconclusive due to missing randomized-controlled trials encompassing larger study populations. Thus, we aimed to proof the principle of tDCS modulating auditory processing in the AC. We applied anodal tDCS over the left posterior superior temporal cortex and recorded EEG to investigate effects of tDCS on auditory-evoked potentials (AEP). In contrast to our hypothesis, we did not find a modulatory effect of tDCS on AEP. However, we only assessed immediate effects of tDCS. With our design, we might have missed long-term effects of tDCS on auditory processing. In conclusion, our findings demonstrate unique neurobiological alterations for patients in the separately studied groups, i.e. the perfusion differences allowed differentiation between positive and negative FTD, and between patients with and without hallucinations. Our results are in favor of a symptom-based approach to investigate schizophrenia. This is in line with the findings that treatment outcome can be symptom-specific, e.g. AVH remain even if other symptoms improve or negative FTD predicts a poor functional outcome but not positive FTD. Therefore, our results provide potential starting points for the development of new treatment options in the future and towards a better understanding of the concept of schizophrenia. In addition, the negative findings of the third study leave doubt about the capability of tDCS to modulate AC. However, several factors are discussed that might have influenced our results. Further analyses in the future will follow to get insight into potential mechanisms of tDCS on short-term dynamic changes in the brain (microstates) of healthy subjects and patients with AVH, and a broader understanding of the potential of tDCS.