Auditory hallucinations of speech reported by patients with schizophrenia are often resistant to psychotropic drugs and can cause significant distress, functional disability and behavioral dyscontrol. The long-term objective of this application is to develop an alternative somatic intervention for these patients using repetitive transcranial magnetic stimulation (rTMS). The PI has completed a pilot study of twelve schizophrenic patients showing that 1 hertz rTMS delivered to left temporoparietal cortex, a brain region underlying speech perception, can curtail auditory hallucinations. A more extended trial where patients receive nine instances of 1 Hz rTMS has now been initiated. Early data from this second study suggest that active rTMS robustly reduces auditory hallucinations when compared to sham stimulation in 60-70% of patients with a sustained duration of at least many months.
Specific Aim #1 of our study application is to undertake a preliminary test of the efficacy of our extended rTMS protocol. Forty patients reporting AHs will be enrolled in a randomized double-blind, parallel design. Procedures for monitoring patients for emergence of cognitive impairments will be implemented and tested. Pilot data will be used to estimate effect size, statistical power, rates of adverse effects and attrition, and rate and duration of clinical response. One-year follow-along assessments of symptoms and treatment course will be conducted to ascertain longer-terms effects of active rTMS.
Specific Aim #2 is to test an alternative method for positioning rTMS using [18F] fluorodeoxyglucose positron emission tomography (FDG PET) for an intervention trial in a subgroup of schizophrenic patients with constant auditory hallucinations. PET metabolic brain maps will be used to identify the region of maximum abnormal cortical activation for individual patients. A computerized frameless stereotaxy system will then be used to position the rTMS coil based on patient-specific neuroimaging data. We hypothesize that rTMS positioned according to PET findings will be superior to rTMS positioned at our standard stimulation site (left temporoparietal cortex) and sham stimulation in reducing hallucinations and other symptoms. Fifteen schizophrenic patients with constant auditory hallucinations will be studied using a randomized, double blind, crossover design to test this hypothesis. The results of these studies will be used to design an intervention algorithm for a full-scale trial of rTMS in a larger group of schizophrenic patients with medication-resistant AHs.
