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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH063326-01
Application #
6323603
Study Section
Special Emphasis Panel (ZMH1-ITV-D (01))
Program Officer
Rudorfer, Matthew V
Project Start
2001-03-01
Project End
2004-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$192,575
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hoffman, Ralph E (2010) Revisiting Arieti's ""listening attitude"" and hallucinated voices. Schizophr Bull 36:440-2
Hoffman, R E; Varanko, M; Gilmore, J et al. (2008) Experiential features used by patients with schizophrenia to differentiate 'voices'from ordinary verbal thought. Psychol Med 38:1167-76
Hoffman, Ralph E (2008) Auditory/Verbal hallucinations, speech perception neurocircuitry, and the social deafferentation hypothesis. Clin EEG Neurosci 39:87-90
Hoffman, R E; Varanko, M (2006) ""Seeing voices"": fused visual/auditory verbal hallucinations reported by three persons with schizophrenia-spectrum disorder. Acta Psychiatr Scand 114:290-2; discussion 292
Hoffman, R E; McGlashan, T H (2006) Using a speech perception neural network computer simulation to contrast neuroanatomic versus neuromodulatory models of auditory hallucinations. Pharmacopsychiatry 39 Suppl 1:S54-64
Hoffman, Ralph E; Gueorguieva, Ralitza; Hawkins, Keith A et al. (2005) Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry 58:97-104
Hoffman, Ralph E; Hawkins, Keith A; Gueorguieva, Ralitza et al. (2003) Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations. Arch Gen Psychiatry 60:49-56
Hoffman, Ralph E; Cavus, Idil (2002) Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. Am J Psychiatry 159:1093-102