Cerebellar Modulation of Cognition in Psychosis

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks). Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

Detailed Description
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Psychotic disorders including schizophrenia, bipolar disorder, and related illnesses are severe, debilitating, and often fatal. Cognitive impairments in psychosis are among the leading predictors of disability and poor quality of life; despite this, there are no first-line interventions to target these symptoms. This trial will test the hypothesis that cognitive performance in these disorders is modifiable and specifically that it can be modified non-invasively. Transcranial magnetic stimulation (TMS) is a neuromodulation technique that utilizes magnets to alter brain activity non-invasively. TMS has received FDA approval as a therapeutic intervention for multiple psychiatric disorders. In this study, we will use different forms of TMS to modulate a specific brain circuit and we will measure the outcomes of this circuit manipulation. These outcomes include performance on cognitive tests and also changes to the circuit itself that we can measure using magnetic resonance imaging (MRI).

Official Title
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Cerebellar Modulation of Cognition in Psychosis

Conditions
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Schizophrenia, Schizoaffective Disorder, Bipolar Disorder I, Psychosis

Intervention / Treatment
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* Device: intermittant theta burst stimulation (iTBS)
* Device: continuous theta burst stimulation (cTBS)
* Device: sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-55 years Diagnosis of a psychotic disorder (i.e. schizophrenia or schizoaffective disorder or bipolar disorder type I) Must be able to read, speak and understand English Must be judged by study staff to be capable of completing the study procedures Participants will be in stable outpatient treatment with no recent (within the past 30 days) hospitalizations or changes in their medication regimens. Exclusion Criteria: Diagnostic and Statistical Manual 5 diagnosis of moderate substance use disorder within the past month Conditions that might result in increased risks of side effects or complications from rTMS or MRI, including: Intracranial pathology from a known genetic disorder (e.g., Neurofibromatosis 1, tuberous sclerosis) or from acquired neurologic disease (e.g. stroke, tumor), cerebral palsy, history of severe head injury, or significant dysmorphology; History of fainting spells of unknown or undetermined etiology that might constitute seizures History of multiple seizures or diagnosis of epilepsy Any progressive (e.g., neurodegenerative) neurological disorder such as multiple sclerosis or Parkinson's disease Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) Metal implants (excluding dental fillings) unless cleared by the responsible covering MD (i.e. MRI compatible joint replacement) Pacemaker Implanted medication pump Vagal nerve stimulator Deep brain stimulator or transcutaneous electric nerve stimulation unit Ventriculo-peritoneal shunt Signs of increased intracranial pressure Intracranial lesion History of head injury resulting in prolonged loss of consciousness (>15minutes) or neurological sequelae Pregnancy: All participants capable of becoming pregnant will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intermittent theta burst stimulation (iTBS)<br>Participants complete MRI scanning and cognitive testing followed by rTMS (iTBS pattern) followed by repeat cognitive testing and MRI scanning | Device: intermittant theta burst stimulation (iTBS)<br>* iTBS consists of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.<br>|
| Active Comparator: continuous theta burst stimulation (cTBS)<br>Participants complete MRI scanning and cognitive testing followed by rTMS (cTBS pattern) followed by repeat cognitive testing and MRI scanning | Device: continuous theta burst stimulation (cTBS)<br>* cTBS consists of 3 pulses at 50 Hz repeated at 5 Hz (every 200ms) continuously for a total of 600 pulses<br>|
| Sham Comparator: sham rTMS<br>Participants complete MRI scanning and cognitive testing followed by sham rTMS followed by repeat cognitive testing and MRI scanning | Device: sham rTMS<br>* sham rTMS does not deliver a significant change in magnetic field strength<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BACS Symbol Coding test | The BACS Symbol coding test is a test of information processing speed | eight minutes before TMS and one minute after TMS on each of the three TMS visit days | 
| BACS Digit Sequence test | The BACS digit sequence test is a test of working memory performance | five minutes before TMS and four minutes after TMS on each of the three TMS visit days | 
| functional Magnetic Resonance Imaging | resting-state (task free) functional connectivity | fifteen minutes before TMS and nine minutes after TMS on each of the three TMS visit days |