Modulating Emotional and Cognitive Circuits in Major Depressive Disorder via Temporal Interference Stimulation

Major depressive disorder (MDD) often leads to cognitive impairments such as impaired inhibitory control, involving complex circuits in both cortical and subcortical regions. We applied non-invasive temporal interference (TI) stimulation to specific neural circuits to explore its modulatory effects on the abnormal neural networks in MDD. In a randomized, crossover study, 15 patients received TI stimulation targeting the left DLPFC, left sgACC, right amygdala, left VS and sham stimulation delivered in a random order. Functional connectivity and behavioral changes from before and after stimulation were assessed using rs-fMRI and an emotional Stroop task. TI stimulation of the sgACC reduced the FC between the sgACC and the frontal cortex, while stimulation of the right amygdala enhanced the FC between the amygdala and bilateral hippocampi. These FC changes were accompanied by an improvement in Stroop task reaction time, along with significant clinical symptom improvement. This study is one of the first to demonstrate that TI can effectively modulate MDD-related network activity, providing a new approach to understanding and regulating cognitive-emotional functions at the neural circuit level.