Where the voices come from and how to get rid of them
06 / 2010 - onbekend
NWO VIDI 2009
Background: Auditory verbal hallucinations (AVH) are resistant to standard treatment in 25% of patients. New therapies for these patients are needed and may evolve from better understanding of the pathophysiology of AVH. Method: This study consists of 3 steps: 1. High-resolution functional Magnetic Resonance Imaging (fMRI) of AVH 2. Focal treatment of brain areas active during AVH, with repetitive transcranial magnetic stimulation (rTMS) and ultimately using Extradural Cortical Stimulation (ECS) 3. Positron Emission Tomography (PET) scanning of implanted patients with electrodes switched on and off Step 1: 120 patients with intractable AVH are scanned using a 7 Tesla scanner under 3 conditions: while experiencing AVH as indicated by button presses while hearing the words previously hallucinated while producing these words The first condition shows which areas are active during AVH, and is used to guide rTMS and ECS. Contrasting activity during AVH to activity during the other 2 conditions reveals differences between AVH and normal speech perception and production. Step 2: Patients are treated with fMRI-guided rTMS during 2 weeks in a sham-controlled cross-over design. Patients showing >25% improvement on rTMS, but not on sham, are treated with rTMS during 6 months. From patients who continuously respond to rTMS, a selected group is invited to consider ECS. Six patients will have an electrode implanted at the site of maximal AVH activity, as indicated on fMRI scans. Efficacy of ECS is assessed in a cross-over design by switching stimulation on and off. Step 3: Implanted patients are scanned using 18F-fluordeoxyglucose PET with stimulation alternately switched on and off, to reveal which change in cerebral activity is the critical component of effective ECS. Benefit: This study may identify new treatments for patients to relief intractable AVH and achieve a higher quality of life. In addition, it may unravel the pathophysiology of AVH.