Auditory verbal hallucinations and the brain

Abstract

Auditory verbal hallucinations (AVH), or perceptions of speech when there is no actual auditory stimulation, are a core symptom of schizophrenia. These voices can be highly distressing, often severely affect quality of life, and increase risk for suicide. Although AVH are prevalent in schizophrenia and several other psychiatric and neurologic disorders, they are not inevitably associated with disease. A minority of people in the general population also experiences AVH without a need for care. These non-clinical individuals provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. In this thesis, the pathophysiological mechanism underlying AVH was investigated in schizophrenia patients and a non-clinical population. In the “state” studies, brain activity during AVH episodes was contrasted with brain activity during non-AVH episodes. This approach can inform us about the neural activity associated with AVH. In the “trait” studies, brain activity was compared between individuals with and without AVH. This approach provides information about neural mechanisms predisposing individuals to experience AVH. Furthermore, the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of AVH was studied. A review of electroencephalography (EEG) and magnetoencephalography (MEG) studies revealed that the left superior temporal cortex is consistently reported to be involved in this symptom. Moreover, the review showed evidence that a failure in corollary discharge, i.e. a neural signal originating in frontal speech areas that indicates to sensory areas that forthcoming thought is self-generated, may underlie the experience of auditory hallucinations. In the first state study of this thesis, it was found that activity observed in the left inferior frontal gyrus and Heschl’s gyrus during AVH in schizophrenia patients as measured with fMRI may be related to stimulus detection and motor activity. Several other areas were suggested to be more specifically involved in the genesis of AVH, including the thalamus and parahippocampal gyrus. These latter structures may provide important targets for neuromodulation to alleviate AVH symptoms. In the second state study, it was found that AVH in schizophrenia patients were related to activity in auditory and language areas. AVH onset corresponded with a decrease in theta-band power in the right hippocampus, suggesting that AVH onset may be triggered by memory processes. The first trait study revealed that individuals with non-clinical AVH exhibited increased psychophysiological measures of effortful attention, suggesting that attention to auditory channels may be related to the predisposition to hallucinate in this population. The second trait study showed that non-psychotic individuals with AVH exhibited increased functional connectivity from auditory and default mode areas during the resting state compared to controls. Finally, a repetitive transcranial magnetic stimulation (rTMS) study revealed that the effect of rTMS observed in some studies may be reliant on a placebo effect. In sum, these findings highlight the importance of attention and auditory processes as well as the involvement of language and memory structures in the genesis of AVH. In addition, these results question the efficacy of rTMS as a treatment tool for AVH.