The hallucinating brain

Background Although auditory verbal hallucinations (AVH) or 'voices' present a debilitating symptom of schizophrenia, they can also be observed in healthy individuals in the general population. As the origin of AVH remains largely unknown, the aim of the present thesis was to shed more light on the neurobiological basis of this symptom. With this aim, the studies presented in this thesis investigated brain activation in relation to AVH. The first part of this thesis consists of state studies which investigated brain activation during the experience of AVH. The second part describes trait studies which focussed at comparing brain activation between individuals with and without AVH. These trait studies may reveal specific mechanisms predisposing a person to experience AVH. Methods To identify brain activation related to the state of AVH, participants were instructed to indicate the presence of AVH while functional MRI scans were acquired continuously. Using this set-up, the first study investigated brain activation during AVH and compared the resulting pattern of activation to brain activation during inner speech, in a group of psychotic patients. Subsequently, the second study investigated brain activation preceding AVH and the third study focussed on calculating the reliability of AVH-related brain activation in psychotic patients. In the fourth state study, brain activation during AVH was compared between psychotic patients and a group of healthy control subjects. In addition to these state studies, two trait studies were conducted in which language lateralization and resting state connectivity were compared between individuals who presented with AVH and a group of healthy control subjects. Results These studies showed that the state of AVH is related to activation in language regions. However, in contrast to normal inner speech, AVH primarily involved activation of right hemisphere instead of left hemisphere language regions. In addition, it was shown that shortly before patients experienced AVH, changes in brain activation could be observed in the left parahippocampal gyrus which fulfils an important role in memory retrieval. Moreover, it was found that brain activation during AVH could be considered reliable. Furthermore, the last state study showed that pyschotic patients and healthy individuals showed similar activation during the experience of AVH. The first trait study revealed that although psychotic patients display decreased language lateralization, this could not be observed in healthy individuals with AVH. Finally, the second trait study showed that healthy individuals with AVH display dysfunctional resting state connectivity within the language network and between language and memory regions. Conclusion From these studies it can be concluded that AVH may be initiated by spontaneous memory retrieval. This may lead to activation of language areas, as observed during the experience of AVH, which is likely to be related to the re-experience of the retrieved memory. The observation of dysfunctional connectivity of language and memory regions during resting state provides further support for the hypothesis that dysfunction of these regions underlies AVH. In addition, the finding of common areas of activation in psychotic patients and healthy individuals suggest that AVH represent a similar phenomenon in both groups.