Efficacy and Mechanisms of 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.

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.