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TIS for Improving Cognitive Impairment in Schizophrenia

2026年7月15日 更新者：Renrong Wu、Central South University

Efficacy and Safety of Time Interference Stimulation on Cognitive Impairment in Patients With Schizophrenia

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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

The investigators will conduct a randomized controlled clinical trial. 50 participants with schizophrenia (25 in each group) will be recruited and randomly assigned to an active treatment group or a sham treatment group. The intervention will be given twice a day for 2 weeks. The changes in clinical symptoms, cognitive function, E/I imbalance, and brain structure and function will be collected at baseline, at the end of the 2-week intervention, and 4 weeks after the intervention to explore the short-term efficacy, safety, and neurobiological mechanism of TIS in improving cognitive function in schizophrenia.

研究类型

介入性

注册 (估计的)

50

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 中国
    • Hunan
      • Changsha、Hunan、中国、410011
        • 招聘中
        • Second Xiangya Hospital, Central South University
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人

接受健康志愿者

不

描述

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：三倍

武器和干预

参与者组/臂
干预/治疗
实验性的：Active TIS
Active TIS group will be administered active temporal interference stimulation
设备：temporal interference stimulation
TIS will use 2 pairs of electrodes placed according to a 10-10 EEG system and fixed with conductive paste to produce a theta burst stimulation pattern. Electric field modeling will be performed utilizing MRI T1 images to optimize the individualized electrode configuration to generate electric field intensities above 0.6 V/m in the hippocampus of each patient. Each session of stimulation lasts 30 minutes.
假比较器：sham TIS
Sham TIS group will be administered sham temporal interference stimulation
设备：Sham stimulation
The sham stimulation only includes a 15-second ramp-up at the start and ramp-down at the beginning of each stimulus, which could simulate the scalp pulsing sensation caused by the change of current at the beginning and end of the stimulus.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
changes on the MATRICS Consensus Cognitive Battery (MCCB) scores
大体时间：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.
Baseline, after 2-week intervention, 4 weeks post-treatment

次要结果测量

结果测量
措施说明
大体时间
脑功能变化
大体时间：基线，2周干预后
功能磁共振成像（fMRI）基于血氧水平依赖（BOLD）对比度，能够检测血氧变化，从而分析干预后脑功能的变化。
基线，2周干预后
Changes in Positive and Negative Symptom Scale (PANSS) scores
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Range from 30 to 210, higher score indicates more severe positive and negative symptoms.
Baseline, after 2-week intervention, 4 weeks post-treatment
Change in Scale for Assessment of Negative Symptoms (SANS) score
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The score range is 0-120; the higher the score, the more severe the negative symptoms are.
Baseline, after 2-week intervention, 4 weeks post-treatment
Changes in Calgary Depression Scale for Schizophrenia (CDSS) score
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Ranges from 0 to 27; a higher score indicates more severe affective symptoms.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on neuroelectrophysiological signals
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The changes of neuroelectrophysiological signals were collected under the task-based electroencephalogram.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on global function
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Global function will be measured by the Global Assessment of Functioning (GAF). GAF is a 0-100 numerical scale used by clinicians to subjectively rate a person's overall psychological, social, and occupational functioning. Higher scores (91-100) indicate superior functioning, while lower scores (1-10) indicate severe danger or impairment.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes in social function.
大体时间：Baseline, 4 weeks post-treatment
Social function will be assessed by the Global Functioning: Social (GF:Social) and Role (GF:Role) scales (GFS) and the Social Functioning Scale (SFS). The GFS is a clinician-rated, 1-10 point tool designed to measure social and occupational functioning. They focus on development, allowing for the assessment of change over time, and avoid confounding functioning with psychiatric symptoms. The SFS is a 79-item self-report measure designed to assess social functioning in schizophrenia. Items assess ability and performance related to social engagement, interpersonal contact, recreation, independence and competence in activities, activities of daily living, and employment.
Baseline, 4 weeks post-treatment
changes on aperiodic 1/f-like signal exponent
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The aperiodic component of the neural power spectrum, quantified as the slope of the 1/f-like signal recorded by electroencephalogram, will be used as an index of excitation/inhibition balance. The unit of measure is the exponent (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on long-range temporal correlations (LRTCs)
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Long-range temporal correlations of neural oscillations recorded by electroencephalogram will be measured as an index of the temporal stability of excitation/inhibition balance. The unit of measure is the Hurst exponent (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on functional E/I ratio
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The ratio of excitatory to inhibitory neural activity derived from electroencephalogram signals will be calculated as a functional excitation/inhibition balance index. The unit of measure is a ratio (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on oscillation power across all frequency bands
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The power of neural oscillations across all frequency bands (e.g., delta, theta, alpha, beta, gamma) recorded by electroencephalogram will be measured. The power values from all bands will be averaged to produce a single composite oscillation power index. The unit of measure is microvolts squared (μV²).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on 40 Hz auditory steady-state responses (40Hz-ASSRs)
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The 40 Hz auditory steady-state responses recorded by electroencephalogram will be measured, including both evoked power and inter-trial phase coherence. The unit of measure for evoked power is μV², and the unit of measure for phase coherence is unitless.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on mismatch negativity (MMN)
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The mismatch negativity amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on P300 event-related potential
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
The P300 amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on behavioral performance - Sternberg Item-Recognition Paradigm
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Behavioral performance will be evaluated using the Sternberg Item-Recognition Paradigm, a memory task that measures reaction time and accuracy. The unit of measure for reaction time is milliseconds (ms), and the unit of measure for accuracy is percentage correct (%).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on behavioral performance - Mnemonic Similarity Task
大体时间：Baseline, after 2-week intervention, 4 weeks post-treatment
Behavioral performance will be evaluated using the Mnemonic Similarity Task, a memory task that measures pattern separation and recognition memory. Three indices will be derived and reported separately: the Lure Discrimination Index (LDI), the similarity object recognition index, and the old object recognition index. All three indices are measured in d-prime (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on peripheral blood allostatic load index
大体时间：Baseline, 4 weeks post-treatment
Approximately 10 mL of blood will be collected intravenously to measure peripheral blood biomarkers: brain-derived neurotrophic factor (BDNF) in ng/mL, C-reactive protein (CRP) in mg/L, interleukin-6 (IL-6) in pg/mL, Kynurenic acid in nM, high-density lipoprotein (HDL) in mg/dL, low-density lipoprotein (LDL) in mg/dL, and triglycerides (TG) in mg/dL. These biomarkers will be combined into a single allostatic load index using a standardized high-risk count algorithm. For each biomarker, a cutoff score based on population norms or clinical thresholds (e.g., highest-risk quartile) will be applied to determine high-risk status (1 = high-risk, 0 = not high-risk). The allostatic load score is the sum of high-risk indicators across all biomarkers. The unit of measure is the allostatic load score (unitless, integer count).
Baseline, 4 weeks post-treatment

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Central South University

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年6月24日

初级完成 (估计的)

2027年3月1日

研究完成 (估计的)

2027年3月30日

研究注册日期

首次提交

2026年2月27日

首先提交符合 QC 标准的

2026年6月9日

首次发布 (实际的)

2026年6月15日

研究记录更新

最后更新发布 (实际的)

2026年7月17日

上次提交的符合 QC 标准的更新

2026年7月15日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • TIS20250606
  • 82325020 (其他赠款/资助编号：National Natural Science Foundation of China)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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