Targeting Network Imbalance in Schizophrenia: The Application of Temporal Interference Stimulation

Schizophrenia is a highly heterogeneous psychiatric disorder. Antipsychotics have limited efficacy on negative and cognitive symptoms, and are associated with side effects and high relapse rates. The core pathophysiology remains unclear, with most existing studies providing correlational neuroimaging descriptions lacking causal validation and precise intervention methods. The triple network model proposes that dynamic imbalance among the default mode network (DMN), salience network (SN), and central executive network (CEN) is a key feature of the disorder, underpinned by thalamocortical circuit disruption. Specifically, DMN hyperactivation, reduced SN connectivity, weakened CEN activation, and failure of SN-mediated network switching are observed. In schizophrenia, DMN hyperactivation initially serves as a compensatory response but eventually progresses to pathological decompensation. Conventional noninvasive stimulation techniques cannot effectively target deep brain nodes, limiting causal validation and precise intervention. As a novel noninvasive technique, temporal interference (TI) stimulation uses high-frequency alternating current interference to target deep brain regions, enabling both causal testing of network interactions and personalized modeling-based precise intervention. In summary, dynamic imbalance of the DMN-SN-CEN network is central to schizophrenia pathophysiology, with SN dysfunction as a potential causal factor. Targeting SN function using TI stimulation could directly test its causal role in network dynamics and symptoms, offering a route toward precision network intervention in this disorder.