Efficacy and Safety of Time Interference Stimulation on Cognitive Impairment in Patients With Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- changes on the MATRICS Consensus Cognitive Battery (MCCB) scores
研究概览
简要总结
This study aims to evaluate the efficacy, safety, and underlying neural mechanisms of TIS targeting the hippocampus in ameliorating cognitive impairment associated with schizophrenia (CIAS). Researchers will compare active TIS to a sham control to see if TIS works to treat CIAS. Participants will receive TIS twice a day for 2 weeks. Their clinical data, including the baseline clinical symptom scale score, cognitive function, E/I imbalance index recorded by EEG, and MRI data, will be collected at baseline, at the end of the 2-week intervention, and 4 weeks after the intervention.
详细描述
Schizophrenia is a chronic psychiatric disorder that imposes a substantial and increasing global disease burden. Cognitive impairment associated with schizophrenia (CIAS) is a core deficit that strongly predicts global function and quality of life. While effective for positive symptoms, antipsychotics cannot meet treatment requirements on CIAS and are limited by severe metabolic and extrapyramidal side effects. Consequently, there is an urgent need to explore effective treatments for CIAS.
Non-invasive brain stimulation (NIBS), including TMS and TES, has emerged as a promising adjunctive therapy for CIAS by modulating cortical excitability and neuroplasticity. However, conventional NIBS is constrained by limited focal depth, indirectly influencing subcortical circuits. Temporal Interference Stimulation (TIS) overcomes these limitations by utilizing intersecting high-frequency electric fields to generate a low-frequency envelope, enabling the selective modulation of deep neural targets while sparing the superficial cortex. TIS offers superior spatial precision and tolerability for treating neuropsychiatric disorders involving deep-circuit dysfunction.
Neurophysiological evidence implicates glutamatergic dysregulation and excitatory-inhibitory (E/I) imbalance as key mechanisms in schizophrenia. Hippocampal hyperactivity enhances excitatory drive to the prefrontal cortex, disrupting cortico-hippocampal communication, attenuating γ-band oscillations, and impairing network synchrony that supports working memory and executive processes.
Recent studies in healthy individuals demonstrate that 5 Hz TIS targeting the left anterior hippocampus enhances episodic memory and hippocampal-prefrontal connectivity. Intermittent theta-burst stimulation (iTBS) of the right hippocampus improves spatial memory. Only one pilot study in schizophrenia has examined high-frequency (130 Hz) TIS targeting the right nucleus accumbens, showing improvements in negative and cognitive symptoms.
This study aims to evaluate the efficacy and underlying neural mechanisms of TIS targeting the hippocampus in ameliorating CIAS.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The treatment operator will maintain a randomization form containing the specific randomization identification number and the treatment assignment code of each participant. The treatment operator is not involved in other processes of this study. After the participants complete the screening and baseline assessment, they will be assigned a randomization identification number, and the treatment operator will check the corresponding treatment assignment code and provide the appropriate treatment. Neither the investigators who assessed the efficacy nor the participants will be aware of the treatment assignments. Meanwhile, participants will be instructed by the investigator not to discuss their treatment assignment with study staff members or other participants.
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
- •Age 18-50 years old;
- •meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-5) diagnostic criteria;
- •the diagnosis of schizophrenia is confirmed by the Structured Clinical Interview for DSM-5 (SCID-5);
- •the disease duration does not exceed 8 years;
- •1-2 antipsychotic drugs are taken, and the treatment dose of antipsychotic drugs was stable for at least 1 week before enrollment. Mood stabilizers, antidepressants, and excessive benzodiazepines (lorazepam when 2 doses exceeded 2 mg/d) are not allowed;
- •The type of antipsychotic drugs remains unchanged during treatment, and the dose is adjusted by no more than 25%;
- •Impaired functioning in daily activities;
- •The Global Deficit Score (GDS) for the MATRICS Consensus Cognitive Battery (MCCB) reaches 0.5 or above;
- •Agree to participate in this study and provide written informed consent
排除标准
- •Presence of other psychiatric comorbidities, intellectual disability, obvious mood symptoms, or substance use disorders (other than caffeine and/or tobacco);
- •with clear drug-induced extrapyramidal reaction;
- •A history of seizures, meningitis, or encephalitis;
- •with contraindications to transcranial electrical stimulation;
- •History of intracranial tumors or surgery;
- •history of severe head trauma;
- •have received other regimens of electrical or magnetic therapy in 1 month before enrollment.
结局指标
主要结局
changes on the MATRICS Consensus Cognitive Battery (MCCB) scores
时间窗: Baseline, after 2-week intervention, 4 weeks post-treatment
The MATRICS Consensus Cognitive Battery (MCCB) can be used for cognitive assessment of schizophrenia, bipolar disorder, and other neuropsychiatric diseases. The MCCB covers nine cognitive domains, including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function, and fine motor skills. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.
次要结局
- Changes in Positive and Negative Symptom Scale (PANSS) scores(Baseline, after 2-week intervention, 4 weeks post-treatment)
- Change in Scale for Assessment of Negative Symptoms (SANS) score(Baseline, after 2-week intervention, 4 weeks post-treatment)
- Changes in Calgary Depression Scale for Schizophrenia (CDSS) score(Baseline, after 2-week intervention, 4 weeks post-treatment)
- Changes in brain function(Baseline, after 2-week intervention)
- changes on neuroelectrophysiological signals(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on global function(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes in social function.(Baseline, 4 weeks post-treatment)
- changes on aperiodic 1/f-like signal exponent(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on P300 event-related potential(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on long-range temporal correlations (LRTCs)(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on functional E/I ratio(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on oscillation power across all frequency bands(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on 40 Hz auditory steady-state responses (40Hz-ASSRs)(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on mismatch negativity (MMN)(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on behavioral performance - Sternberg Item-Recognition Paradigm(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on behavioral performance - Mnemonic Similarity Task(Baseline, after 2-week intervention, 4 weeks post-treatment)
- changes on peripheral blood allostatic load index(Baseline, 4 weeks post-treatment)
研究者
Renrong Wu
Professor
Second Xiangya Hospital of Central South University