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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
105
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).
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, China
Change from baseline in associative memory test score
Change from baseline in the associative memory test score at 4 weeks and 8 weeks.
Time frame: baseline, 4 weeks and 8 weeks
Change of information processing speed and attention/vigilance
Change from baseline in 4 MCCB subtests score at 4 weeks and 8 weeks.
Time frame: 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.
Time frame: 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.
Time frame: baseline, 4 weeks and 8 weeks
Change of CGI score
Change from baseline in Clinical Global Impression (CGI) at 4 weeks and 8 weeks.
Time frame: baseline, 4 weeks and 8 weeks
Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B)
Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B) at 4 weeks and 8 weeks.
Time frame: baseline, 4 weeks and 8 weeks
Change of Multi-modal Brain Neuroimaging in structure
Brain structure data will be acquired.
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI
Resting-state fMRI data will be acquired.
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS
1H-MRS data will be acquired.
Time frame: baseline and 4 weeks
Change of TEPs
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.
Time frame: baseline and 4 weeks
Change of 64 channels EEG
64 channels EEG data will be acquired.
Time frame: baseline and 4 weeks
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