Studies suggest that speech processing areas of the brain play an important role in producing auditory hallucinations (AHs). The PI has reported that delivering 1-Hertz repetitive transcranial magnetic stimulation (rTMS) to the left temporoparietal cortex - a brain region underlying speech perception - produces statistically significant improvements in AHs relative to sham simulation. In a follow-up study, the PI used individualized fMRI maps of abnormal speech processing neurocircuitry to position rTMS in multiple cortical sites, and has found that targeting Wernicke's region and a homologous right-sided region in the superior temporal gyrus (STG) optimized clinical improvement of AHs. The proposed study will enroll 90 patients with a diagnosis of schizophrenia and medication-resistant AHs in a more extended, double- masked rTMS trial. Stimulation will be positioned using structural MRI over the left Wernicke's site and right-sided STG site previously found to have optimized clinical response.
Specific Aim #1 is to demonstrate that MRI-positioned 1-Hz rTMS, delivered to the Wernicke's and right STG sites, each for 5 sessions in randomized order, results in greater clinical improvement in AHs compared to sham stimulation.
Specific Aim #2 is to determine if alterations in cerebral laterality predict optimal hemisphere of stimulation in reducing AHs, and the degree of improvement elicited by rTMS at each of the two sites.
Specific Aim #3 is to demonstrate that a third 5-session series of active rTMS directed to the left/right site found to optimize clinical improvement in the first 10 sessions produces greater improvements in AHs compared to sham stimulation positioned according to the same algorithm.
Specific Aim #4 is to demonstrate prospectively that a higher level of hallucination frequency at baseline is a statistical moderator of 1-Hz rTMS in reducing AHs. This study will provide critical information regarding positioning strategies that optimize rTMS for AHs, as well as new insights regarding underlying pathophysiology. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH073673-03
Application #
7343162
Study Section
Special Emphasis Panel (ZMH1-ERB-D (06))
Program Officer
Hillefors, MI
Project Start
2006-02-01
Project End
2011-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
3
Fiscal Year
2008
Total Cost
$424,822
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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