TIS for Improving Cognitive Impairment in Schizophrenia
2026年6月9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.
調査の概要
詳細な説明
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.
We 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.
研究の種類
介入
入学 (推定)
50
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Renrong Wu
- 電話番号：15874179855
- メール：wurenrong@csu.edu.cn
研究場所
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Hunan
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Changsha、Hunan、中国、410011
- Second Xiangya Hospital, Central South University
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コンタクト：
- Yue Qin
- 電話番号：13051119195
- メール：qinyue@csu.edu.cn
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Active TIS
Active TIS group will be administered active temporal interference stimulation
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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.
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偽コンパレータ：sham TIS
Sham TIS group will be administered sham temporal interference stimulation
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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changes on MCCB scores
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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脳機能の変化
時間枠：ベースライン、2週間の介入後
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機能的磁気共鳴画像法（fMRI）は、血液酸素濃度依存性（BOLD）コントラストに基づいており、介入後の脳機能の変化を分析するために血液酸素化の変化を検出することができます。
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ベースライン、2週間の介入後
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Changes in Positive and Negative Symptom Scale (PANSS) scores
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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Range from 30 to 210, higher score indicates more severe positive and negative symptoms.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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Change in Scale for Assessment of Negative Symptoms (SANS) score
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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The score range is 0-120; the higher the score, the more severe the negative symptoms are.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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Changes in Calgary Depression Scale for Schizophrenia (CDSS) score
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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Ranges from 0 to 27; a higher score indicates more severe affective symptoms.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on neuroelectrophysiological signals
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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The changes of neuroelectrophysiological signals were collected under the task-based electroencephalogram.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on global function
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes in social function.
時間枠：Baseline, 4 weeks post-treatment
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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.
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Baseline, 4 weeks post-treatment
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changes on aperiodic 1/f-like signal exponent
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on long-range temporal correlations (LRTCs)
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on functional E/I ratio
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on oscillation power across all frequency bands
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on 40 Hz auditory steady-state responses (40Hz-ASSRs)
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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.
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on mismatch negativity (MMN)
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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The mismatch negativity amplitude recorded by electroencephalogram using an oddball paradigm will be measured.
The unit of measure is microvolts (μV).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on P300 event-related potential
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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The P300 amplitude recorded by electroencephalogram using an oddball paradigm will be measured.
The unit of measure is microvolts (μV).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on behavioral performance - Sternberg Item-Recognition Paradigm
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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 (%).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on behavioral performance - Mnemonic Similarity Task
時間枠：Baseline, after 2-week intervention, 4 weeks post-treatment
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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).
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Baseline, after 2-week intervention, 4 weeks post-treatment
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changes on peripheral blood allostatic load index
時間枠：Baseline, 4 weeks post-treatment
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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).
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Baseline, 4 weeks post-treatment
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年5月30日
一次修了 (推定)
2026年12月1日
研究の完了 (推定)
2026年12月30日
試験登録日
最初に提出
2026年2月27日
QC基準を満たした最初の提出物
2026年6月9日
最初の投稿 (実際)
2026年6月15日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月15日
QC基準を満たした最後の更新が送信されました
2026年6月9日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- TIS20250606
- 82325020 (その他の助成金/資金番号：National Natural Science Foundation of China)
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いいえ
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temporal interference stimulationの臨床試験
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Biotronik SE & Co. KG完了
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University Hospital, Strasbourg, France完了
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Biotronik SE & Co. KG完了心臓ペーシング、人工ドイツ, イスラエル, 香港, オーストリア, チェコ共和国, オーストラリア, ブラジル, カナダ, スロバキア, スペイン