Fluordeoxyglucose-PET study in first-episode schizophrenic patients during the hallucinatory state, after remission and during linguistic-auditory activation

Objectives We tested the hypothesis that endogenous auditory verbal hallucinations (AVH) involve activation of auditory/linguistic association cortices that are usually activated by externally presented speech. Methods Nine neuroleptic-naive patients with first-episode schizophrenia (Diagnostic and Statistical Manual for Mental Disorders-IV criteria) with prominent AVH underwent three PET scans using F-18-fluordeoxyglucose (FDG): (i) shortly after presentation, while experiencing prominent and frequent AVH; (ii) after medication-induced remission (R), using a stable dose of risperidone; (iii) also in remission, during bilateral linguistic auditory activation (LAA) induced by spoken text mimicking the content of the hallucinations experienced while the first PET was performed, using headphones. PET scans were acquired using an Advanced-Nxi Scanner (GE Healthcare). Intrasubject realignment, spatial normalization and statistical analysis of PET images were carried out using statistical parametric mapping. Differences between AVH and R and between LAA and R were statistically evaluated using a voxel-wise paired t-test. A voxel level threshold of P < 0.01 was used to determine which regions underwent the most significant changes in F-18-FDG uptake. Results During AVH, patients demonstrated a significant activation of the supplementary motor area, anterior cingulum, medial superior frontal area and cerebelum. Activation was also observed in the left superior frontal area, right superior temporal pole and right orbitofrontal region. During LAA, greater FDG uptake was observed in the right and left superior and middle temporal cortices, left hippocampus and parahippocampal regions. Conclusion Our findings show a different pattern of regional cerebral glucose metabolism between AVH and physiological auditory activation. This feature does not support the hypothesis that AVH in acute schizophrenic patients reflects an abnormal activation of auditory-linguistic pathways. However, it does suggest that cortical regions implicated in the generation of inner speech could be involved.