Cognitive Deficit in SchizophreniaNCT06904092
Efficacy and Mechanisms of TUS on Cognitive Deficits in Schizophrenia: Based on the Hippocampal-Prefrontal Circuit
A study testing Transcranial ultrasound stimulation in people with Cognitive Deficit in Schizophrenia, run by Shanghai Mental Health Center at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Cognitive Deficit in Schizophrenia
- What is being tested?
- Transcranial ultrasound stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2026to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, 200030
Dengtang LIU, 021-34773434, liudengtang@smhc.org.cn
About this study
Official title: Efficacy and Mechanisms of Transcranial Ultrasound Stimulation (TUS) on Cognitive Deficits in Schizophrenia：Based on the Hippocampal-Prefrontal Circuit
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.
Read the detailed description
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.
- Conditions
- Cognitive Deficit in Schizophrenia
- Being tested
- Transcranial ultrasound stimulation
- Keywords
- Schizophrenia; Cognitive Deficit; Transcranial Ultrasound Stimulation; Hippocampus- Prefrontal Circuit
- Medical subject headings
- Schizophrenia, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial ultrasound stimulationDevice
The TUS was administered using Transcranial Ultrasound Stimulator UNS-III (model UNS-III), which has passed the safety test for medical electrical equipment (GB9706.1-2007). Transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).
| Study group | Role | What they receive |
|---|---|---|
| single target group : left DLPFC | Active comparator | 35 eligible patients will be treated with active TUS on the left DLPFC and sham TUS on the left hippocampus for 4 weeks Receives: Device: Transcranial ultrasound stimulation |
| single target group : left hippocampus | Active comparator | 35 eligible patients will be treated with active TUS on the left hippocampus and sham TUS on the left DLPFC for 4 weeks Receives: Device: Transcranial ultrasound stimulation |
| both-target group : left DLPFC and left hippocampus | Active comparator | 35 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC and left hippocampus Receives: Device: Transcranial ultrasound stimulation |
| sham TUS group | Sham comparator | 35 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and left hippocampus Receives: Device: Transcranial ultrasound stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in associative memory test score
Change from baseline in the associative memory test score at 4 weeks and 8 weeks.
Measured: baseline, 4 weeks and 8 weeks
Secondary outcomes (8)
Change of information processing speed and attention/vigilance
Change from baseline in 4 MCCB subtests score at 4 weeks and 8 weeks.
Measured: baseline, 4 weeks and 8 weeks
Change of working memory
Change from baseline in N-back task at 4 weeks and 8 weeks. The outcome measures include accuracy, D-prime value, and reaction time.
Measured: baseline, 4 weeks and 8 weeks
Change from baseline in Positive and Negative Syndrome Scale(PANSS)
Change from baseline in Positive and Negative Syndrome Scale(PANSS) at 4 weeks and 8 weeks. The minimum to maximum value is 30-210. Lower scores mean a better outcome.
Measured: baseline, 4 weeks and 8 weeks
Change of CGI score
Change from baseline in Clinical Global Impression (CGI) at 4 weeks and 8 weeks.
Measured: baseline, 4 weeks and 8 weeks
Change of Multi-modal Brain Neuroimaging in structure
Brain structure data will be acquired.
Measured: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI
Resting-state fMRI data will be acquired.
Measured: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS
1H-MRS data will be acquired.
Measured: baseline and 4 weeks
Change of 64 channels EEG
64 channels EEG data will be acquired.
Measured: baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2025
- Study start1 Jul 2026 (estimated)
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive Deficit in SchizophreniaStudies of the same condition, open and under way.
- More trials run by Shanghai Mental Health CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Mental Health Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06904092
- Sponsor's protocol ID
- 82371504
- Status last verified
- Jun 2026
- First submitted
- 25 Mar 2025
- Last updated
- 12 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Mechanisms of Transcranial Ultrasound Stimulation (TUS) on Cognitive Deficits in Schizophrenia：Based on the Hippocampal-Prefrontal Circuit
- ClinicalTrials.gov ID
- NCT06904092
- Acronym / sponsor ID
- 82371504
- Conditions
- Cognitive Deficit in Schizophrenia
- Keywords
- Schizophrenia; Cognitive Deficit; Transcranial Ultrasound Stimulation; Hippocampus- Prefrontal Circuit
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Shanghai Mental Health CenterUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 1 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| single target group : left DLPFC | Active comparator | Device: Transcranial ultrasound stimulation35 eligible patients will be treated with active TUS on the left DLPFC and sham TUS on the left hippocampus for 4 weeks |
| single target group : left hippocampus | Active comparator | Device: Transcranial ultrasound stimulation35 eligible patients will be treated with active TUS on the left hippocampus and sham TUS on the left DLPFC for 4 weeks |
| both-target group : left DLPFC and left hippocampus | Active comparator | Device: Transcranial ultrasound stimulation35 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC and left hippocampus |
| sham TUS group | Sham comparator | Device: Transcranial ultrasound stimulation35 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and left hippocampus |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial ultrasound stimulationThe TUS was administered using Transcranial Ultrasound Stimulator UNS-III (model UNS-III), which has passed the safety test for medical electrical equipment (GB9706.1-2007). Transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks). | Device | both-target group : left DLPFC and left hippocampus, sham TUS group, single target group : left DLPFC, single target group : left hippocampus |
Primary outcome
Change from baseline in associative memory test score
Time frame: baseline, 4 weeks and 8 weeks
Change from baseline in the associative memory test score at 4 weeks and 8 weeks.
8 secondary outcomes
Change of information processing speed and attention/vigilance
Time frame: baseline, 4 weeks and 8 weeks
Change of working memory
Time frame: baseline, 4 weeks and 8 weeks
Change from baseline in Positive and Negative Syndrome Scale(PANSS)
Time frame: baseline, 4 weeks and 8 weeks
Change of CGI score
Time frame: baseline, 4 weeks and 8 weeks
Change of Multi-modal Brain Neuroimaging in structure
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS
Time frame: baseline and 4 weeks
Change of 64 channels EEG
Time frame: baseline and 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial ultrasound stimulation in people with Cognitive Deficit in Schizophrenia, run by Shanghai Mental Health Center at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dengtang LIU (021-34773434, liudengtang@smhc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in associative memory test score (time frame: baseline, 4 weeks and 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.