Efficacy and Mechanisms of TUS on Cognitive Deficits in Schizophrenia: Based on the Hippocampal-Prefrontal Circuit

NCT ID: NCT06904092

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2027-12-31

Brief 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. 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.

Conditions

Cognitive Deficit in Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

single target group : left DLPFC

35 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC

Group Type: ACTIVE_COMPARATOR

Transcranial ultrasound stimulation

Intervention Type: DEVICE

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).

single target group : left hippocampus

35 eligible patients will be treated with active TUS for 4 weeks on the left hippocampus

Group Type: ACTIVE_COMPARATOR

Transcranial ultrasound stimulation

Intervention Type: DEVICE

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).

both-target group : left DLPFC and left hippocampus

35 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC and left hippocampus

Group Type: ACTIVE_COMPARATOR

Transcranial ultrasound stimulation

Intervention Type: DEVICE

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).

Interventions

Transcranial ultrasound stimulation

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).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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;

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Mental Health Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Dengtang LIU

Role: CONTACT

liudengtang@smhc.org.cn

021-34773434

Facility Contacts

Dengtang LIU

Role: primary

liudengtang@smhc.org.cn

021-34773434

Other Identifiers

82371504

Identifier Type: -

Identifier Source: org_study_id