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

Not Applicable

Not yet recruiting

• Conditions: Cognitive Deficit in Schizophrenia

• Registration Number: NCT06904092
• Lead Sponsor: Shanghai Mental Health Center

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.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-25
• Study First Submitted QC: 2025-03-25
• Last Update Submitted: 2025-03-25
• Study Start: 2025-04-01
• Study First Posted: 2025-04-01
• Last Update Posted: 2025-04-01
• Primary Completion: 2027-07-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 105

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change from baseline in associative memory test score	baseline, 4 weeks and 8 weeks	Change from baseline in the associative memory test score at 4 weeks and 8 weeks.

Secondary Outcome Measures

Name	Time	Method
Change of information processing speed and attention/vigilance	baseline, 4 weeks and 8 weeks	Change from baseline in 4 MCCB subtests score at 4 weeks and 8 weeks.
Change of working memory	baseline, 4 weeks and 8 weeks	Change from baseline in N-back task at 4 weeks and 8 weeks. The outcome measures include accuracy, D-prime value, and reaction time.
Change from baseline in Positive and Negative Syndrome Scale(PANSS)	baseline, 4 weeks and 8 weeks	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.
Change of CGI score	baseline, 4 weeks and 8 weeks	Change from baseline in Clinical Global Impression (CGI) at 4 weeks and 8 weeks.
Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B)	baseline, 4 weeks and 8 weeks	Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B) at 4 weeks and 8 weeks.
Change of Multi-modal Brain Neuroimaging in structure	baseline and 4 weeks	Brain structure data will be acquired.
Change of Multi-modal Brain Neuroimaging in resting- state fMRI	baseline and 4 weeks	Resting-state fMRI data will be acquired.
Change of Multi-modal Brain Neuroimaging in 1H-MRS	baseline and 4 weeks	1H-MRS data will be acquired.
Change of TEPs	baseline and 4 weeks	TMS-evoked potentials (TEPs) from target regions will be measured in participants at baseline, after a single TUS intervention, and at 4 weeks. The study aimed to clarify the effects of TUS treatment on the components of TEPs in individuals with schizophrenia, as well as the association between changes in TEP components and cognitive deficits.
Change of 64 channels EEG	baseline and 4 weeks	64 channels EEG data will be acquired.

Trial Locations

Locations (1)

Shanghai Mental Health Center; 🇨🇳 Shanghai, Shanghai, China