Transcranial Magnetic Stimulation for "Voices"

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 "voices,"
also known as auditory hallucinations. These hallucinations consist of spoken speech, which
sometimes replicates the speaking voice of a familiar person, and sometimes reflects a
speaking voice that is not known but becomes highly recognizable. The phrases and sentences
expressed by "voices" are often highly disruptive, and may comment, cajole, criticize, and,
in some cases, command the patient. They are often but not invariably 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 needed to improve this troubling
and often disabling symptom.

Recent studies have suggested that auditory hallucinations arise from parts of the brain
that are ordinarily involved in perceiving actual spoken speech. Low frequency repetitive
transcranial magnetic stimulation (rTMS), a technique that uses an electromagnet to induce
reductions in cortical brain activity, may therefore be effective in quieting auditory
hallucinations. The potential usefulness of this approach has been demonstrated by previous
studies conducted at our medical center. This new study uses magnetic resonance imaging
(MRI) to locate two areas of the brain involved in speech perception. These areas are in
Wernicke's area in the left superior temporal gyrus, and in the right hemisphere in an
analogous site in the superior temporal gyrus. Repetitive TMS is specifically positioned to
reduce cortical excitability or reactivity at these two brain regions.

Participants in this double blind study will be randomly assigned to receive either real
rTMS, or placebo stimulation, which feels similar to real rTMS 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 two sequences of rTMS, each consisting of five
16-minute sessions. One sequence is directed to left Wernicke's area and the other sequence
is directed to the right-sided equivalent area. During the third week, participants will
receive five additional sessions to the left or right site that appeared to produce greater
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 stimulation sessions 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. Assessments of
severity of hallucinations and other clinical symptoms will be conducted after every fifth
rTMS session by a clinician who does not know whether the participant is receiving real or
placebo stimulation.

Neuropsychological testing will also be done before, during, and after the trial. Our
previous trial demonstrated some improvement in verbal processing with no significant
impairments in terms of memory, language or cognitive function. However, insofar as this
trial involves a greater total "dose" of rTMS, careful monitoring of these functions is
conducted throughout the trial.

In addition, the study will determine the degree to which improvement obtained during the
course of trial is sustained over the ensuing months. This is accomplished via on-going
monthly contact with study participants for up to 1 year after the last rTMS stimulation
session.