Efficacy and Mechanisms of Transcranial Ultrasound Stimulation (TUS) on Cognitive Deficits in Schizophrenia：Based on the Hippocampal-Prefrontal Circuit
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Change from baseline in associative memory test score
研究概览
简要总结
Cognitive deficit is a core symptom of schizophrenia related to poorer functional outcome. Prior studies indicated that abnormalities in the hippocampus-prefrontal circuit and glutamate/GABA imbalances may lead to cognitive deficits. Based on the current background and our previous studies, it has been proved that TUS can modulate neural excitability and plasticity in the hippocampus. In this double-blind, randomized study, the efficacy of different treatment options and mechanisms of TUS on cognitive deficits will be investigated.
详细描述
Cognitive deficit is a core symptom of schizophrenia related to poorer functional outcome which remains largely treatment refractory. Prior studies indicated that abnormalities in the hippocampus-prefrontal circuit and glutamate/GABA imbalances may be the root causes of cognitive deficits. Transcranial ultrasound stimulation (TUS), an emerging non-invasive neuromodulation technique with deep penetration ability, can modulate neural excitability and plasticity in the hippocampus. This is a 4-week double-blind randomized trial of TUS for cognitive deficits in schizophrenia, with either left hippocampus or left dorsolateral prefrontal cortex (DLPFC) or both targeted. This study aims to determine the efficacy of TUS and to reveal its underlying neural mechanism, especially with the hippocampus-prefrontal circuit, by means of TUS, as to assess cortical inhibition and excitability, EEG source imaging, and multi-model MRI. Neuropsychological assessments will also be conducted to develop the optimized treatment strategy. The study points to a novel and promising therapeutic neuromodulation approach that may improve the functional outcome of schizophrenia, which has been the main cause of mental disability.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the DSM-5 diagnostic criteria for schizophrenia ;
- •Age18-50, right-handed, Han nationality;
- •Presence of cognitive deficit: defined as d' value <0.5 in associative memory test;
- •Be in a stable condition, received second-generation antipsychotics for at least 4 weeks or more;
- •Written informed consent;
排除标准
- •Current or past neurological illness, severe physical diseases, substance abuse or alcohol dependence, mental retardation, pregnancy or lactation;
- •Uncooperative or risky patients with high excitement, stupor, disorder of words and deeds, negative suicide, etc.;
- •History of MECT or other physical therapy within 6 months;
- •History of epilepsy, or epileptic waves on the baseline EEG;
- •Ruled out share antiepileptic drugs (carbamazepine, valproic acid salt) or larger doses of benzodiazepine drugs (diazepam > 10mg/day, clonazepam > 2mg/day etc.), if necessary, remain unchanged during the course of treatment;
- •Contraindications to TUS and MRI are present.
研究组 & 干预措施
single target group : left DLPFC
35 eligible patients will be treated with active TUS on the left DLPFC and sham TUS on the left hippocampus for 4 weeks
干预措施: Transcranial ultrasound stimulation (Device)
single target group : left hippocampus
35 eligible patients will be treated with active TUS on the left hippocampus and sham TUS on the left DLPFC for 4 weeks
干预措施: Transcranial ultrasound stimulation (Device)
both-target group : left DLPFC and left hippocampus
35 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC and left hippocampus
干预措施: Transcranial ultrasound stimulation (Device)
sham TUS group
35 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and left hippocampus
干预措施: Transcranial ultrasound stimulation (Device)
结局指标
主要结局
Change from baseline in associative memory test score
时间窗: baseline, 4 weeks and 8 weeks
Change from baseline in the associative memory test score at 4 weeks and 8 weeks.
次要结局
- Change of 64 channels EEG(baseline and 4 weeks)
- Change of information processing speed and attention/vigilance(baseline, 4 weeks and 8 weeks)
- Change of working memory(baseline, 4 weeks and 8 weeks)
- Change from baseline in Positive and Negative Syndrome Scale(PANSS)(baseline, 4 weeks and 8 weeks)
- Change of CGI score(baseline, 4 weeks and 8 weeks)
- Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B)(baseline, 4 weeks and 8 weeks)
- Change of Multi-modal Brain Neuroimaging in structure(baseline and 4 weeks)
- Change of Multi-modal Brain Neuroimaging in resting- state fMRI(baseline and 4 weeks)
- Change of Multi-modal Brain Neuroimaging in 1H-MRS(baseline and 4 weeks)
- Change of TEPs(baseline and 4 weeks)