Exciting links: imaging and modulation of neural networks underlying key symptoms of schizophrenia

Despite regular treatment, a major part of patients with schizophrenia suffers from auditory verbal hallucinations and/or negative symptoms (reduced energy and motivation, flat affect). To effectively treat these symptoms, it is important to understand the underlying brain mechanisms of these symptoms. Symptoms of schizophrenia are considered a result of disrupted functioning within and between brain networks. The investigation of the brain networks that are involved in the processing of auditory verbal information can give us information about the way patients with auditory verbal hallucinations use these networks in comparison with patients without auditory verbal hallucination. The studies in this thesis show that these networks do not function optimally. Specifically, the network that processes auditory information appears to be too active. In addition, it is known that patients with negative symptoms demonstrate less activation in frontal brain areas, which are closely connected to many other brain regions. In theory, important networks can be stimulated with Transcranial Magnetic Stimulation, such that it can reduce symptomatology. Two placebo controlled clinical trials that applied this technique have been described in this thesis. In the first study, the efficacy of low frequency stimulation of an area that is involved in the processing of auditory verbal information has been investigated. Although on average the active as well as the placebo groups improved, on a symptom level the active treatment did not appear to be more effective than the placebo treatment. However, on a brain level we observed that the active treatment did cause differences. Possibly, optimization of treatment parameters may result in stronger treatment effects. In a second placebo controlled trial, we investigated the effect of high frequency Transcranial Magnetic Stimulation on negative symptoms of schizophrenia. The group that received active treatment improved significantly more on a symptom level than the group that received placebo treatment. In both trials, there were large inter-individual differences in treatment response. Future research should therefore focus on the identification of factors that are related to treatment response, such as demographic variables and brain characteristics (e.g. anatomy and baseline connectivity). The results of this thesis are a good basis for further research on the treatment of auditory verbal hallucinations and negative symptoms in schizophrenia.