Developing Dual-channel Transcranial Alternating Current Stimulations Targeting Negative Symptoms in Schizophrenia

Study Overview
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Brief Summary
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Negative symptoms are core symptoms in schizophrenia which play an important role in clinical outcomes and impede patients to return to society. Anti-psychotic medicines have shown limited effect in improving negative symptoms and cognitive functioning, whereas non-invasive neuromodulations, i.e. , transcranial alternating current stimulation (tACS), have shown promising potentials. Recently new evidence of brain structural and functional alterations has been provided by neuroimaging studies. Brady RO et al. found cerebellar-prefrontal network connectivity was related to negative symptoms in schizophrenia. It provides clues for developing a new tACS protocol targeting improving negative symptoms, in which dual-channel high-density alternating current stimulations were delivered over both the right dorsolateral prefrontal cortex and cerebellum simultaneously.

Official Title
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Dual-channel Transcranial Alternating Current Stimulations Targeting Negative Symptoms in Schizophrenia Patients: A Randomized Clinical Trial

Conditions
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Negative Symptoms, Schizophrenia, Transcranial Alternating Current Stimulations

Intervention / Treatment
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* Device: transcranial alternating current stimulation (NE Starstim)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meet the DSM-V diagnostic criteria for schizophrenia; present with prominent negative symptoms with PANSS-negative scores >20, at least one score of PANSS N1-N7 >3, and reductive ratio of PANSS-negative in the past two weeks before recruitment <10%; stable usage and dosage of anti-psychotic medicines in the past two weeks and during the tACS intervention. age within 18-60; illness duration >1year; education at least 6 years; written consent of receiving tACS intervention. Exclusion Criteria: Meet any DSM-V diagnostic criteria of any other psychiatric disorders besides schizophrenia ; any history of alcohol or substance dependence in the past 3 months; any other major physical disease (i.e., Sensorimotor disorder, neurological disease); any metal implants or any other tACS contraindication.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tACS<br>Active tACS will be applied twice daily for 5 days. In each session, dual-channel high-density theta(7Hz) tACS stimulations will be delivered over the right DLPFC (one anodal electrode at F4, between -1.2mA and 1.2 mA; two cathodal electrodes at AF4 and FC6, between -0.6mA and 0.6mA) and cerebellum (one anodal electrode at Oz, between -1 mA and 1mA; two cathodal electrodes at PO3 and PO4, between -0.5mA and 0.5mA) lasting 20 minutes. | Device: transcranial alternating current stimulation (NE Starstim)<br>* dual-channel theta-tACS over right DLPFC and cerebellum simultaneously<br>|
| Sham Comparator: Sham tACS<br>Sham tACS will be also applied twice daily for 5 days.The parameters of tACS electrodes numbers, locations, and current duration are all the same with active tACS. But sham tACS begin with a fade in over 3s to the peak, followed immediately by no current stimulation for 20 minutes and a fade out of 3s. | Device: transcranial alternating current stimulation (NE Starstim)<br>* dual-channel theta-tACS over right DLPFC and cerebellum simultaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reductive ratio of PANSS-negative symptoms scores | differences of reductive ratio of PANSS-negative symptoms scores after between active and sham tACS | At 1 week and 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of PANSS total scores | changes of PANSS total scores before and after active or sham tACS | At 1 week and 3 weeks | 
| cognitive functioning changes using MCCB | changes of MCCB scores before and after active or sham tACS | At 1 week | 
| changes of P300 activity | changes of P300 activity at baseline and after 10-session tACS | At 1 week | 
| changes of MMN activity | changes of MMN activity at baseline and after 10-session tACS | At 1 week | 
| changes of power of resting-state EEG activity | changes of power of resting-state EEG activity at baseline, after 1-session tACS and after 10-session tACS | At 1 day and 1 week | 
| centroid value from fNIRS recording before and after active or sham tACS | centroid value from fNIRS recording before and after active or sham tACS | At 1 week | 
| Integral value from fNIRS recording before and after active or sham tACS | Intergral value from fNIRS recording before and after active or sham tACS | At 1 week |