Using Transcranial Magnetic Stimulation (TMS) to Understand Hallucinations in Schizophrenia

Study Overview
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Brief Summary
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This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

Detailed Description
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This study tests the hypothesis that hallucinations in schizophrenia are mediated by network pathophysiology, and that network pathophysiology can be quantified by the functional connectivity of a cerebellar-thalamo-cortical circuit. To accomplish this, participants will be recruited who are diagnosed with schizophrenia or schizoaffective disorder who experience auditory hallucinations. Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments of schizophrenia symptom severity. These assessments include reporter-based measures such as the Positive and Negative Syndrome Scale (PANSS). Participants will then undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation. Participants will then undergo five days of twice daily rTMS sessions. One week after the last rTMS session, participants will undergo follow-up MRI imaging and the same study assessments.

Official Title
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Empirical Validation of a Cerebellar-cortical Hallucination Circuit

Conditions
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Schizophrenia, Schizo Affective Disorder

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
* Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder Exclusion Criteria: substance use disorder in past 3 months ambidexterity contraindications for TMS or MRI including : history of neurological disorder history of head trauma resulting in loss of consciousness history of seizures or diagnosis of epilepsy or first degree relative family history of epilepsy metal in brain or skull implanted devices such as a pacemaker, medication pump, nerve stimulator or ventriculoperitoneal shunt claustrophobic in MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active cerebellum rTMS<br>Cerebellar targeted iTBS, twice daily, one week. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses.<br>* Other names: iTBS;|
| Sham Comparator: Sham cerebellum rTMS<br>Cerebellar targeted sham iTBS, twice daily, one week. | Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses. Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head.<br>* Other names: iTBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional connectivity | change in functional connectivity of a putative cerebellar-thalamic-cortical hallucination circuit (cerebellum to thalamus) will be assessed before and after (1 week followup) TMS stimulation. | baseline, 1 week after TMS | 
| Positive and Negative Syndrome Scale (PANSS) | The PANSS is clinical rating scale of symptom severity . Each descriptor is rated on a 7 point scale from 1=(absence of any symptom) to 7=(extremely severe symptoms). | baseline | 
| Scale for the Assessment of Positive Symptoms (SAPS) | The SAPS is clinical rating scale of symptom severity . Each descriptor is rated on a 5 point scale from 1=(absence of any symptom) to 5=(extremely severe symptoms). | baseline | 
| Auditory Hallucination Rating Scale (AHRS) Scale (AHRS) | The AHRS is a 7-item clinical rating scale used to assess auditory hallucinations. | baseline |