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This study is dedicated to exploring the brain mechanism of medication-resistant auditory hallucinations and developing effective treatment methods for them by using both cross-sectional and longitudinal designs. The continuous theta burst stimulation(cTBS) treatment mode, with the left cerebellum Crus II as the stimulation target, is applied to treat the schizophrenia patients with the medication-resistant auditory hallucinations. At the same time, the first-episode schizophrenia patients with auditory hallucinations were recruited as a test cohort to examine that brain mechanism of general auditory hallucinations in schizophrenia may be the structural and functional abnormalities in the temporoparietal circuit.
Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) targeted at the temporal-parietal junction can effectively treat genenal auditory hallucinations in schizophrenia, but it is not the case for medication-resistant auditory hallucinations. Studies suggested that rTMS targeted at the left Crus II might be effective for medication-resistant auditory hallucinations. This study is dedicated to exploring the brain mechanism of medication-resistant auditory hallucinations and developing effective treatment methods for them by using both cross-sectional and longitudinal designs. The continuous theta burst stimulation(cTBS) treatment mode, with the left cerebellum Crus II as the stimulation target, is applied to treat the schizophrenia patients with the medication-resistant auditory hallucinations. Assessment with symptomatology, neuropsychology, neuroimaging, and machine learning methods is utilized to examine the investigators hypothesis that structural and functional abnormalities of the cerebral cortico-cerebellar-thalamic-cortical circuit (CCTCC) may contribute to brain mechanism of medication-resistant auditory hallucinations in schizophrenia. At the same time, the first-episode schizophrenia patients with auditory hallucinations were recruited as a test cohort to examine that brain mechanism of general auditory hallucinations in schizophrenia may be the structural and functional abnormalities in the temporoparietal circuit, whereas structural and functional abnormalities of the CCTCC may contribute to brain mechanism of medication-resistant auditory hallucinations in schizophrenia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The schizophrenia patients with medication-resistant auditory hallucinations | Experimental | Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) |
|
| The schizophrenia patients with general auditory hallucinations | Active Comparator | Drug intervention |
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| The healthy controls | No Intervention | MRI scan at baseline and no drugs treatment | |
| Drug + cTBS intervention: the first-episode schizophrenia patients with auditory hallucinations | Experimental | Drug + cTBS intervention (the left temporoparietal cortex as the stimulation target) |
|
| Drug intervention: the first-episode schizophrenia patients with auditory hallucinations | Active Comparator | Drug intervention |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antipsychotic drugs | Drug | Stable antipsychotic medication 4 weeks before and during the treatment. Chlorpromazine (CPZ) equivalent dosages were calculated for second- and first-generation antipsychotic drugs |
| Measure | Description | Time Frame |
|---|---|---|
| Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH) | The Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH) is an instrument designed to quantify the severity of hallucinations before and after treatment at different follow up point. Raw score range is 0-44. A higher score indicates a worse outcome. | From baseline to 10 weeks |
| Structural and Function MRI data | A 3.0 T Siemens scanner was used to obtain the fMRI images in the Second Xiangya Hospital of Central South University.The MRI data wii be obtained before and after treatment at different follow up point. | From baseline to 10 weeks |
| Positive and Negative Syndrome Scale (PANSS) | The PANSS total scores, subscale scores were used to evaluate the severity of psychotic symptoms for schizophrenia before and after treatment at different follow up point.The total score of the PANSS was more than 60.The higher scores mean a worse outcome. | From baseline to 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | Pre-post assessment of cognitive function via Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | From baseline to 10 weeks |
| The Stroop test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wenbin Guo | Central South University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Xiangya Hospital of Central South University | Changsha | China |
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| The schizophrenia patients with medication-resistant auditory hallucinations from the fourth arm |
| Experimental |
Drug + cTBS intervention (the left cerebellum Crus II as the stimulation target) |
|
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| cTBS（the left temporoparietal cortex as the stimulation target） | Device | Participants received 3 daily sessions of cTBS treatment. One session of cTBS was 40 seconds in duration and consisted of 3-pulse bursts at 50 Hz repeated every 200 milliseconds (5 Hz) until a total of 600 pulses was reached. To achieve cumulative aftereffects, this protocol was repeated 3 times and (1800 pulses in total) separated by two 15 minute breaks |
|
|
| cTBS （the left cerebellum Crus II as the stimulation target） | Device | Participants received 3 daily sessions of cTBS treatment. One session of cTBS was 40 seconds in duration and consisted of 3-pulse bursts at 50 Hz repeated every 200 milliseconds (5 Hz) until a total of 600 pulses was reached. To achieve cumulative aftereffects, this protocol was repeated 3 times and (1800 pulses in total) separated by two 15 minute breaks |
|
|
Pre-post assessment of cognitive function via the Stroop test
| From baseline to 10 weeks |
| Wisconsin Card Sorting Test (WCST) | Pre-post assessment of cognitive function via Wisconsin Card Sorting Test (WCST) | From baseline to 10 weeks |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D014150 | Antipsychotic Agents |
| D009682 | Magnetic Resonance Spectroscopy |
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D014149 | Tranquilizing Agents |
| D002492 | Central Nervous System Depressants |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D002491 | Central Nervous System Agents |
| D045506 | Therapeutic Uses |
| D011619 | Psychotropic Drugs |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D014054 | Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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