Effect of Repetitive Transcranial Magnetic Stimulation on Resting State Brain Activity in Schizophrenia
|Schizophrenia||Device: Active Repetitive Transcranial Magnetic Stimulation 1 Hz Device: Active Repetitive Transcranial Magnetic Stimulation 10 Hz Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz Device: Sham control site Repetitive Transcranial Magnetic Stimulation Device: Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
|Official Title:||Effect of Repetitive Transcranial Magnetic Stimulation (RTMS) on Resting State Brain Activity in Schizophrenia|
- Changes in Auditory Hallucinations Questionnaire (AHQ). [ Time Frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)" ]The Auditory Hallucinations Questionnaire (AHQ) will be used to determine the patient's perceptions of change in auditory hallucinations(s). Normal controls do not fill out this measure because they do not have auditory hallucinations. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured. The range of scores is 0-70, higher scores mean more symptoms.
- Overall Change in the Percent Habituation of the P50 Evoked Response Potential at 250 Inter Stimulus Interval (ISI) Between the Control and Active Treatments (1 and 10 Hz). [ Time Frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)" ]Percent habituation refers to change in the amplitude of the P50 evoked response potential following a 250 ms inter stimulus interval. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured.
- Depression Level Changes as Measured by the Hamilton Depression Inventory (HAMD). [ Time Frame: change between the baseline time point and 4 days of active treatment (patients) or 2 days of sham or active treatment (controls)" ]HAM-D is a multiple choice questionnaire that clinicians administer to rate the severity of a subject's depression. There are 17 questions; each question has between 3-5 possible responses which increase in severity (range 0 to 52). The clinician chooses the correct response by interviewing the subject and by observing the symptoms. A score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression. Change in the average results of this test between the baseline and active treatment weeks (1 and 10 Hz) will be measured.
|Study Start Date:||June 2012|
|Study Completion Date:||August 2015|
|Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Patients with Schizophrenia who meet entry criteria for the study and first receive active repetitive transcranial magnetic stimulation for four days over a control site located at the vertex and then are randomized to receive repetitive Transcranial Magnetic Stimulation for four days over the temporal cortex at both 1 Hz and 10 Hz.
Device: Active Repetitive Transcranial Magnetic Stimulation 1 Hz
active rTMS delivered at 1Hz frequency over temporal cortex
Other Name: rTMSDevice: Active Repetitive Transcranial Magnetic Stimulation 10 Hz
active rTMS delivered at 10 Hz frequency over temporal cortex
Other Name: rTMSDevice: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz
active rTMS delivered at either 1 Hz frequency over the vertexDevice: Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz
Active 10 Hz rTMS delivered over the vertex
These subjects are normal controls without schizophrenia who receive sham, repetitive transcranial magnetic stimulation at 1 Hz for two days and then receive active, repetitive Transcranial Magnetic stimulation for two days. All stimulation is delivered at the control site located over the vertex.
Device: Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz
active rTMS delivered at either 1 Hz frequency over the vertexDevice: Sham control site Repetitive Transcranial Magnetic Stimulation
sham rTMS delivered at 1Hz frequency over the vertex
Background. The sub-Investigator Dr. Mennemeier has been using repetitive transcranial magnetic stimulation (rTMS) to treat phantom sound perception in subjects with tinnitus. The Principal Investigator (PI), Dr. Messias, now aims to team up with Drs. Mennemeier and James, to learn how rTMS influences phantom sound perception in schizophrenia. rTMS has already been shown to be an effective treatment for both tinnitus and schizophrenia. rTMS is a non-invasive method of regional brain stimulation that can significantly reduce phantom sound perception temporarily in 50% of subjects with tinnitus and schizophrenia. This study will go further than previous investigations by analyzing how different frequencies of rTMS influence not only auditory hallucinations (AH) in schizophrenia but also brain connectivity in schizophrenia. The investigators want to learn if rTMS decreases AH by normalizing brain connectivity. Whereas this study focuses on schizophrenic subjects with AH, the design is very similar to ongoing work on tinnitus so the findings will be comparable.
Tinnitus and AH in schizophrenia are prevalent and disabling disorders of sound perception. The investigators understanding of the precise mechanisms of these disorders is lacking. Interestingly, the symptoms of both disorders respond positively to rTMS of the temporal cortex in ways that defy contemporary understanding of the nature of these symptoms and of how rTMS should work to improve them. For example, phantom sound perception in both tinnitus and schizophrenia are linked to maladaptive, hyperactivity of auditory processing regions of temporal cortex; however, it is increasingly clear that these pathological changes alone are insufficient to explain the pronounced intrusiveness and negative emotional valance of symptoms in each disorder. Therefore, a barrier to understanding these disorders lies in understanding how changes in auditory cortex are synchronized with changes in other cortical regions that regulate perception and emotion. Additionally, at present, the decision of which rTMS frequency to apply as a treatment for phantom sound perception has no firm theoretical or empirical basis. Whereas, low frequency rTMS has traditionally been used, based upon contemporary models, to "inhibit" hyperactivity in auditory cortex; high frequency rTMS, which should induce an opposite effect on neuronal processing, not only works to improve symptoms but may be more effective for some subjects than low frequency rTMS. Therefore, contemporary models designed to explain how the frequency of rTMS influences neuronal activity immediate following stimulation are insufficient to explain how low and high frequencies of rTMS can mitigate phantom sound perception for days, weeks and months following a single course of treatment.
Hypothesis. The investigators propose that phantom sound perception in schizophrenia result from an imbalance of excitatory and inhibitory neural process in auditory networks and from synchronized, maladaptive changes in linked brain regions that regulate perception and emotion. Treating auditory cortex with repetitive, external magnetic stimulation can decrease phantom sound perception and distress by reversing the maladaptive brain reorganization that is set in motion by these underlying neural imbalances.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01620086
|United States, Arkansas|
|University of Arkansas for Medical Sciences|
|Little Rock, Arkansas, United States, 72205|
|Principal Investigator:||Erick Messias, MD, MPH, PhD||University of Arkansas|