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Imaging and modulation of brain networks underlying key symptoms of schizophrenia
PhD ceremony:Ms L. (Leonie) Bais
When:February 08, 2017
Supervisor:prof. dr. A. (Andre) Aleman
Co-supervisor:dr. H. Knegtering
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
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Despite regular treatment, many patients with schizophrenia suffer 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. Thus, investigation of brain networks involved in the processing of auditory verbal information can inform us how patients with auditory verbal hallucinations use these networks in comparison with patients without them. 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 (TMS), such that it can reduce symptomatology. Two placebo controlled clinical trials that applied this technique are described in this thesis. In the first study we investigated the efficacy of low frequency stimulation of an area that is involved in the processing of auditory verbal information. Although on average the treatment as well as the placebo groups improved, on a symptom level we did not find differences between the groups. In contrast, a brain level we observed that the active treatment did cause differences. Potentially optimization of treatment parameters may result in stronger treatment effects. In a second placebo controlled trial, we investigated the effect of high frequency TMS on negative symptoms of schizophrenia. The group receiving active treatment improved significantly more on a symptom level than the group on placebo. In both trials, we found large inter-individual differences in treatment response. We recommend that future research focuses on identification of factors related to treatment response, such as demographic variables and brain characteristics (e.g. anatomy and baseline connectivity).