Effect of Repetitive Transcranial Magnetic Stimulation on Resting State Brain Activity in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      This study compares the efficacy of low and high frequency repetitive transcranial magnetic
      stimulation (rTMS) as a means of treating subjects with schizophrenia. Magnetic pulses
      delivered over the scalp cause brain activity. This activity has been shown to help decrease
      the intensity and frequency of auditory hallucinations (AH) in schizophrenia. The
      investigators will compare whether low or high frequencies work best. The investigators will
      also examine what changes occur in the brain that are related to improvement.
    

Detailed description: 
      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.
    

Intervention name(s): Active Repetitive Transcranial Magnetic Stimulation 1 Hz; Active Repetitive Transcranial Magnetic Stimulation 10 Hz; Active control site Repetitive Transcranial Magnetic Stimulation at 1Hz; Sham control site Repetitive Transcranial Magnetic Stimulation; Active control site Repetitive Transcranial Magnetic Stimulation at 10 Hz
Intervention type(s): Device; Device; Device; Device; Device
Intervention description(s): active rTMS delivered at 1Hz frequency over temporal cortex; active rTMS delivered at 10 Hz frequency over temporal cortex; active rTMS delivered at either 1 Hz frequency over the vertex; sham rTMS delivered at 1Hz frequency over the vertex; Active 10 Hz rTMS delivered over the vertex
Other intervention name(s): rTMS; rTMS
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Schizophrenia; Auditory hallucinations (AH); Phantom sound perception; repetitive transcranial magnetic stimulation (rTMS); Percent habituation in the P50 amplitude with 250 ms ISI