Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial

Abstract Background Cognitive deficits and negative symptoms are core features of schizophrenia (SCZ) and remain major therapeutic challenges due to their limited responsiveness to antipsychotic medications. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive brain stimula...

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Main Authors: Shuzhe Wang, Junhao Chen, Linxuan Wang, Jingxuan Liu, Lijun Wang, Wenjie Sun, Shen Li, Jie Li
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07158-8
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author Shuzhe Wang
Junhao Chen
Linxuan Wang
Jingxuan Liu
Lijun Wang
Wenjie Sun
Shen Li
Jie Li
author_facet Shuzhe Wang
Junhao Chen
Linxuan Wang
Jingxuan Liu
Lijun Wang
Wenjie Sun
Shen Li
Jie Li
author_sort Shuzhe Wang
collection DOAJ
description Abstract Background Cognitive deficits and negative symptoms are core features of schizophrenia (SCZ) and remain major therapeutic challenges due to their limited responsiveness to antipsychotic medications. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive brain stimulation technique that enables targeted modulation of deep brain structures with high spatial specificity. While tTIS has shown promise in preliminary studies of other neuropsychiatric conditions, its clinical utility in SCZ has not been established. This study aims to evaluate the safety and efficacy of tTIS targeting the right nucleus accumbens (NAc) in ameliorating cognitive deficits and negative symptoms in SCZ individuals. Methods In this randomized, double-blind, controlled trial, 76 SCZ patients with prominent cognitive deficits and negative symptoms will be recruited and randomly assigned to receive either active or sham tTIS. All participants will maintain stable antipsychotic regimens for at least 30 days prior to and throughout the intervention. The tTIS protocol comprises ten 30-min weekday stimulation sessions. Outcome assessments will be conducted at four time points: baseline (T0), post-intervention (T1), two weeks (T2), and four weeks (T3) after the final sesseion. The primary outcome is the change in cognitive performance, measured by the MATRICS Consensus Cognitive Battery (MCCB). Secondary outcomes include changes in positive and negative symptoms, depressive and anxiety symptoms, sleep quality, quality of life, and resting-state functional magnetic resonance imaging (rs-fMRI) parameters. Discussion This trial will provide the first randomized controlled evidence on the clinical efficacy and neural effects of tTIS in SCZ patients. We hypothesize that participants receiving active tTIS will demonstrate significantly greater improvements in cognitive function and negative symptoms compared to those receiving sham stimulation. Trial registration Chinese Clinical Trial Registry (ChiCTR2500102724). Recruitment is scheduled to begin on May 27, 2025.
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spelling doaj-art-2629fcec1a0a4d7e83ff1ae56868ff7e2025-08-20T04:02:55ZengBMCBMC Psychiatry1471-244X2025-07-0125111110.1186/s12888-025-07158-8Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trialShuzhe Wang0Junhao Chen1Linxuan Wang2Jingxuan Liu3Lijun Wang4Wenjie Sun5Shen Li6Jie Li7Mental Health Center of Tianjin University, Tianjin Anding HospitalInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityMental Health Center of Tianjin University, Tianjin Anding HospitalMental Health Center of Tianjin University, Tianjin Anding HospitalMental Health Center of Tianjin University, Tianjin Anding HospitalMental Health Center of Tianjin University, Tianjin Anding HospitalAbstract Background Cognitive deficits and negative symptoms are core features of schizophrenia (SCZ) and remain major therapeutic challenges due to their limited responsiveness to antipsychotic medications. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive brain stimulation technique that enables targeted modulation of deep brain structures with high spatial specificity. While tTIS has shown promise in preliminary studies of other neuropsychiatric conditions, its clinical utility in SCZ has not been established. This study aims to evaluate the safety and efficacy of tTIS targeting the right nucleus accumbens (NAc) in ameliorating cognitive deficits and negative symptoms in SCZ individuals. Methods In this randomized, double-blind, controlled trial, 76 SCZ patients with prominent cognitive deficits and negative symptoms will be recruited and randomly assigned to receive either active or sham tTIS. All participants will maintain stable antipsychotic regimens for at least 30 days prior to and throughout the intervention. The tTIS protocol comprises ten 30-min weekday stimulation sessions. Outcome assessments will be conducted at four time points: baseline (T0), post-intervention (T1), two weeks (T2), and four weeks (T3) after the final sesseion. The primary outcome is the change in cognitive performance, measured by the MATRICS Consensus Cognitive Battery (MCCB). Secondary outcomes include changes in positive and negative symptoms, depressive and anxiety symptoms, sleep quality, quality of life, and resting-state functional magnetic resonance imaging (rs-fMRI) parameters. Discussion This trial will provide the first randomized controlled evidence on the clinical efficacy and neural effects of tTIS in SCZ patients. We hypothesize that participants receiving active tTIS will demonstrate significantly greater improvements in cognitive function and negative symptoms compared to those receiving sham stimulation. Trial registration Chinese Clinical Trial Registry (ChiCTR2500102724). Recruitment is scheduled to begin on May 27, 2025.https://doi.org/10.1186/s12888-025-07158-8SchizophreniaTemporal interference stimulationNon-invasive brain stimulationCognitive impairmentsNegative symptomsNucleus accumbens
spellingShingle Shuzhe Wang
Junhao Chen
Linxuan Wang
Jingxuan Liu
Lijun Wang
Wenjie Sun
Shen Li
Jie Li
Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
BMC Psychiatry
Schizophrenia
Temporal interference stimulation
Non-invasive brain stimulation
Cognitive impairments
Negative symptoms
Nucleus accumbens
title Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
title_full Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
title_fullStr Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
title_full_unstemmed Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
title_short Individualized transcranial temporal interference stimulation (tTIS) for cognitive impairments and negative symptoms in patients with schizophrenia: a study protocol for a randomized controlled trial
title_sort individualized transcranial temporal interference stimulation ttis for cognitive impairments and negative symptoms in patients with schizophrenia a study protocol for a randomized controlled trial
topic Schizophrenia
Temporal interference stimulation
Non-invasive brain stimulation
Cognitive impairments
Negative symptoms
Nucleus accumbens
url https://doi.org/10.1186/s12888-025-07158-8
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