A Study on Targeted Intervention for Insight in Patients with First Episode and Clinical High Risk of Schizophrenia Based on Theta Oscillation in Anterior Cingulate Cortex
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Change in Resting-state functional brain connectivity between anterior cingulate cortex (ACC) and middle temporal gyrus (MTG)
研究概览
简要总结
Impaired insight is a key factor in the conversion of high-risk individuals to schizophrenia, but there is a lack of targeted interventions. We found that an electroencephalogram (EEG) signal reflecting the function of self monitoring was a potential objective marker of impaired insight. And further functional magnetic resonance imaging (fMRI) analysis showed that the functional connectivity between anterior cingulate gyrus (ACC) and medial temporal gyrus (MTG) was related to insight. Studies have shown that ACC theta oscillation is the key to self monitoring, and theta-alpha phase synchronization between frontotemporal is closely related to cognition. Therefore, this project hypothesized that targeted regulation of ACC theta oscillations could promote theta-alpha phase synchronization and functional connectivity between ACC and MTG, thereby improving patients' insight. The first-episode and high-risk subjects were recruited to detect the theta oscillation of ACC, theta-Alpha phase synchronization and functional connectivity between ACC and MTG using EEG-fMRI. Deep transcranial magnetic stimulation was introduced to regulate ACC theta oscillations. The high-risk subjects were followed up for two years. It was estimated that the theta-alpha phase synchronization of ACC-MTG and insight in the active-dTMS group were significantly improved. And the outcome of the high-risk subjects is better. The project develops neuroregulatory techniques for impaired insight of schizophrenia and is expected to provide a solution for this clinical pain point.
详细描述
The study will conduct randomized and controlled experimental design, including deep transcranial magnetic stimulation (dTMS) and sham stimulation (SH-dTMS). Each included participant will be given informed consent and then randomly assigned to different montage of stimulation. Participants are blind to the dTMS montage. Researchers in this study will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysts. Before unblinding, each group of researchers will have no access to the information collected by the other groups. For example, except the dTMS operators, no one knows which stimulus montage any of the participants receive. The sessions of dTMS will be conducted twice daily for 5 consecutive days, and twice sessions of a day will be separated by 3 hours at least. Clinical assessments and laboratory tests will be administered at baseline and at the end of the last session. After the post-intervention tests, first stage unblinding will be conducted. At this moment, dTMS operators will provide the groups of A and B, but no corresponding montage, to the statistical analysts. After analyzing the differences between the two groups, second stage unblinding will be performed and the results of the clinical trial will be further analyzed by revealing the corresponding stimulus montage of each group. This study will be implemented at a single center, the Shanghai Mental Health Center (SMHC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants are blind to the dTMS montage. Researchers in this study will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysis. Before unblinding, each group of researchers will have no access to the information collected by the other groups.
入排标准
- 年龄范围
- 15 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •14~35 years old;
- •Meet the criteria of clinical high risk for psychosis or meet the DSM-V diagnostic criteria for schizophrenia;
- •Meeting the following definition of impaired insight;
- •Having completed at least six years of primary education;
- •Being able to give informed consent, oral or written. Patients under 18 years old give oral consent and their next of kin or legal guardians give written consent.
排除标准
- •Participating in any other clinical intervention research;
- •Meeting the diagnostic criteria of psychotic disorders (including affective disorders);
- •Threshold symptoms are induced by other mental disorders or psychoactive substances;
- •Undergoing anti-psychotic medication for more than 2 weeks;
- •Being diagnosed as organic brain diseases, or severe somatic diseases;
- •Had Experienced traumatic brain injury, and got scores of 7;
- •Dementia, or mental retardation (IQ<70);
- •Being a condition of scalp infection;
- •A pacemaker or other metal implants in the body, pregnancy, or claustrophobia.
结局指标
主要结局
Change in Resting-state functional brain connectivity between anterior cingulate cortex (ACC) and middle temporal gyrus (MTG)
时间窗: Baseline and immediately after the intervention
Imaging data will be collected on a 3-T Siemens Magnetom Verio syngo MR B17 scanner and a 32-channel head coil, including structural phase and resting stage detection, which will be used to analyze the functional connection between ACC and MTG.
Change in error-related negativity
时间窗: Baseline and immediately after the intervention
The error-related negativity (ERN) is observed over frontocentral sites within 100 ms following an error response in behavioral tasks, reflecting error-detecting activity, and a reduced ERN indicates reduced error monitoring. EEG epochs were marked with artifacts and excluded from the following ERN analysis if on any electrode, (i) the maximal peak-to-peak amplitude exceeded 100 μV within any moving window (width: 200 ms; step: 50 ms) or (ii) the absolute amplitude exceeded 100 μV at any time point. The calculation for the ERN was based on no fewer than five available epochs with erroneous responses.
Change in clinical insight
时间窗: Baseline and immediately after the intervention
Clinical insight will be assessed using SAI. SAI is a semi-structured interview tools including seven items, with a total score of 14, 0-6 for recognition of illness, 0-4 for relabeling of psychotic phenomena, and 0-4 for treatment compliance. Patients, with less than 3 scores on recognition of illness, 2 on relabeling of psychotic phenomena, and 2 on treatment compliance, are considered to be improved on insight.
次要结局
- Convertion rate of transition into psychosis(2 year)
- Change in theta oscillation in ACC and theta-alpha phase synchronization between ACC and MTG(Baseline and immediately after the intervention)
- Covariant change of clinical insight and psychopathological symptoms(Baseline and immediately after the intervention)
- Change in psychopathological symptoms(Baseline and immediately after the intervention)
- Change in reality monitoring ability(Baseline and immediately after the intervention)