Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia

Study Overview
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Brief Summary
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This trial attempts to investigate whether 10 sessions of tACS improves cognitive function, especially which domains of cognitive function are most improved and to investigate whether 10 sessions of tACS affecting brain activation during a working memory task and changes patterns of brain connectivity networks.Subjects will be divided into 2 groups 2:1, active and sham tACS. 50 subjects will be in the active group, and 25 subjects in the sham group (specific numbers to be decided on later).

Detailed Description
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Schizophrenia patients (SZ) show profound and persistent cognitive deficits in attention, executive processing, and verbal and visuospatial memory, which persist even after psychotic symptoms are ameliorated. Cognitive deficits may be more important in preventing functional, occupational, and social recovery in SZ than other symptom domains and are not effectively treated by current pharmacological approaches. Alternating current stimulation (tACS) is less expensive than other modalities (e.g. repetitive transcranial magnetic stimulation; rTMS), easily available, and has a good safety profile in healthy controls (HC) and SZ. The ability to entrain γ oscillations with 40Hz tACS, might compensate more specifically for this deficit in γ oscillations in schizophrenia, and, may therefore, produce more robust behavioral improvements in working memory and other aspects of cognition.However, no studies have looked at the effects of multiple daily tACS stimulation at a 40HZ γ frequency on cognitive function and symptoms in schizophrenia. This provides a rationale for the current study, which proposes to investigate the effects of 10 sessions of 40HZ tACS on cognitive functions, symptoms in schizophrenia. Active vs. sham treatment will be randomly assigned in a 2:1 fashion (A:S) in groups using computer generated lists. Subjects and tDCS testers or evaluators will be blind to treatment. Subjects will be evaluated with cognitive, symptom and functional measures at baseline, within 1 day ( or 2 days fro some measures) after 10 sessions, 2 weeks after 10 sessions, 1 month after 10 sessions, and 2 months after 10 sessions.After the 1 month evaluation, subjects in the initial active tACS group will be randomly assigned to receive either 5 booster sessions of either active or sham tACS ( 25 subjects each), following parameters used in the initial treatment. Subjects in the initial Sham group will receive 5 booster session Sham tACS. Participants will be scanned once prior to tACS sessions, and within 3 days after the 10th tACS session, using our Siemens 3T Tim Verio MRI scanner with a standard 32-channel phased-array head coil.

Official Title
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Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia: a Randomized Controlled Trial

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: Active tACS
* Device: Sham tACS
* Device: Active boosting
* Device: Sham boosting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have cognitive deficits as indicated by a score of < 85 on RBANS, and meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA), or schizophreniform disorder (SZF), and who are stably treated with antipsychotic medications and are not in acute exacerbation of illness symptoms. Exclusion Criteria: Patients with risk factors for an MRI scan, seizure disorder, and for women of childbearing age who are pregnant or regularly engaging in sexual activity and not regularly using an acceptable birth control method (systemic or double-barrier).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tACS & active boosting group<br>The active tACS & active boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of active tACS. | Device: Active tACS<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.<br>Device: Active boosting<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of active tACS.The active boosting group will be stimulated with a 2 mA current for 20 minutes.<br>|
| Other: Active tACS & sham boosting group<br>The active tACS & sham boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of sham tACS. | Device: Active tACS<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.<br>Device: Sham boosting<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.<br>|
| Sham Comparator: Sham tACS & sham boosting group<br>The sham tACS & sham boosting group will be stimulated with 10 sessions of sham alternating current stimulation (tACS) and 5 booster sessions of sham tACS. | Device: Sham tACS<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 sham tACS sessions.The sham tACS group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.<br>Device: Sham boosting<br>* Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in The MATRICS Consensus Cognitive Battery (MCCB) |  | Change from Baseline MCCB at 2 weeks. | 
| changes in Neuroimage changes in Magnetic Resonance Imaging (MRI) | Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI) | Change from Baseline at 2 weeks. | 
| changes in Gamma oscillation intensity ( 40-80 Hz) over the left and right frontal lobe | measured by electroencephalogram (EEG) | Change from Baseline at 2 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| N-back task | to test working memory | At baseline,1-week, 2-week, 4-week, and 8-week follow-up. | 
| The Paced Auditory Serial Addition Task (PASAT) | to test Verbal Working memory | At baseline,2-week, 4-week, and 8-week follow-up. | 
| The Positive and Negative Syndrome Scale (PANSS) | PANSS was assessed using 30 basic items to form three subscales: positive, negative, and general psychopathological scales.The value of each item is ranging from 1 to 7, higher values represent more serious symptoms of schizophrenia. | At baseline,2-week, 4-week, and 8-week follow-up. | 
| The USCD Performance- Based Skills Assessment Battery (UPSA) |  | At baseline,2-week, 4-week, and 8-week follow-up. | 
| Side-effects of tACS |  | At each stimulation session,up to 2 weeks. | 
| The MATRICS Consensus Cognitive Battery (MCCB) |  | At 4-week and 8-week follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tACS, schizophrenia, cognition, fMRI