This study will evaluate the effectiveness of MRI-guided transcranial magnetic stimulation in improving the "voices" and other symptoms experienced by people with schizophrenia.

Schizophrenia is a severely disabling brain disorder that affects about 1% of the United States population. Approximately 50 to 80% of people with schizophrenia experience auditory hallucinations, also known as "voices." These hallucinations consist of spoken dialogue, which is usually unrecognizable, but sometimes resembles the voices of familiar people. The voices may comment, cajole, criticize, and, in some cases, command the patient. They are highly distressing, and can disrupt one's ability to interact with others, work, study, and sleep. In about 25% of cases, medication treatment is either completely ineffective or only partially effective in relieving voices. Effective treatment alternatives are necessary to improve this troubling symptom.

Recent studies have suggested that voices arise from parts of the brain that are ordinarily involved in perceiving spoken word. Low frequency transcranial magnetic stimulation (TMS), a technique that uses an electromagnet to induce reductions in cortical brain activity, may be effective in quieting hallucinated voices. To determine the effectiveness of TMS in reducing auditory hallucinations, this study will use magnetic resonance imaging (MRI) to locate areas of the brain involved in speech perception and then target TMS directly at those areas.

Participants in this double blind study will be randomly assigned to receive either left-sided TMS, right-sided TMS, or placebo stimulation, which feels similar to TMS, but does not produce direct brain effects. Depending on group assignment, participation may last 4 to 8 weeks. Over the first 2 weeks, all participants will undergo five daily sessions of TMS, lasting approximately 16 minutes each. During the third week, participants will attend five additional sessions, in which stimulation will be focused on whichever left- or right-sided site that appeared to produce the greatest clinical improvement. All participants will then be informed as to whether they received real or placebo stimulation. Participants who received real stimulation will be offered 5 additional days of stimulation at the brain site that achieved the best response. Participants who received placebo stimulation will be offered real stimulation for up to twenty sessions over 4 weeks using the same schedule described above. Outcomes will be assessed after every fifth rTMS session. Neuropsychological testing will also be done before and after the trial.

Inclusion Criteria:

• Auditory hallucinations that occur at least five times per day, on average
• Diagnosis of schizophrenia or schizoaffective disorder

Exclusion Criteria:

• Pregnant
• History of seizure that is not drug-induced or secondary to alcohol withdrawal
• Drug or alcohol abuse within 6 weeks of study entry (prior history of drug or alcohol abuse is not an exclusion)
• Changes in antipsychotic drug dosages within 4 weeks of study entry (patients do not need to be on antipsychotic medication to be included)
• Current significant untreated or unstable medical illness (e.g., poorly controlled diabetes mellitus, severe hypertension, unstable cardiac arrhythmia)
• Inability to understand the nature of the study due to severe psychotic disorganization, mental retardation, etc.
• Significant neurological condition (e.g., traumatic brain injury, multiple sclerosis)
• Factors that would preclude an MRI scan (e.g., severe obesity, claustrophobia, certain surgical implants with metallic components, metal shavings in the eye acquired while working as machinist)
• Cardiac pacemaker