Cerebral Cortex Advance Access published online on February 13, 2007
Cerebral Cortex, doi:10.1093/cercor/bhl183
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Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation
1 Department of Psychiatry, 2 Department of Diagnostic Radiology, 3 Department of Neurosurgery, Yale School of Medicine, New Haven CT, USA, 4 Department of Biomedical Engineering, 5 Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville TN, USA, 6 Department of Neurosurgery, University of Texas, Health Science Center at San Antonio, Texas, USA
Address correspondence to Ralph Hoffman, MD, Yale-New Haven Psychiatric Hospital, 184 Liberty Street LV108, New Haven CT 06519. Email: ralph.hoffman{at}yale.edu.
Functional magnetic resonance imaging and repetitive transcranial magnetic stimulation (rTMS) were used to explore the pathophysiology of auditory/verbal hallucinations (AVHs). Sixteen patients with schizophrenia-spectrum disorder were studied with continuous or near continuous AVHs. For patients with intermittent hallucinations (N = 8), blood oxygenation level–dependent (BOLD) activation maps comparing hallucination and nonhallucination periods were generated. For patients with continuous hallucinations (N = 8) correlations between BOLD signal time course in Wernicke's area, and other regions were used to map functional coupling to the former. These maps were used to identify 3–6 cortical sites per patient that were probed with 1-Hz rTMS and sham stimulation. Delivering rTMS to left temporoparietal sites in Wernicke's area and the adjacent supramarginal gyrus was accompanied by a greater rate of AVH improvement compared with sham stimulation and rTMS delivered to anterior temporal sites. For intermittent hallucinators, lower levels of hallucination-related activation in Broca's area strongly predicted greater rate of response to left temporoparietal rTMS. For continuous hallucinators, reduced coupling between Wernicke's and a right homologue of Broca's area strongly predicted greater left temporoparietal rTMS rate of response. These findings suggest that dominant hemisphere temporoparietal areas are involved in expressing AVHs, with higher levels of coactivation and/or coupling involving inferior frontal regions reinforcing underlying pathophysiology.
Key Words: Broca's area • hallucinations • language • schizophrenia • Wernicke's area
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