Transcranial focused ultrasound stimulation enhances semantic memory by modulating brain morphology, neurochemistry and neural dynamics

Abstract

Abstract The ventromedial anterior temporal lobe (ATL) is a core transmodal hub for semantic memory, yet non-invasive modulation of this region has remained challenging. Transcranial ultrasound stimulation (TUS) offers high spatial precision suitable for deep brain targets. In this study, we investigated whether theta-burst TUS (tbTUS) to the ventromedial ATL enhances semantic memory, using a multimodal neuroimaging approach—magnetic resonance spectroscopy (MRS), functional MRI (fMRI), and voxel-based morphometry (VBM). Compared to control stimulation, tbTUS improved semantic task performance. MRS showed decreased GABA and increased Glx, reflecting shifts in excitation-inhibition balance, alongside increases in NAA, creatine and choline, suggesting enhanced neuronal metabolism. fMRI demonstrated reduced ATL activity during semantic processing and strengthened effective connectivity across the semantic network. VBM revealed increased ATL grey matter volume. These findings provide convergent evidence that tbTUS modulates neurochemistry, functional dynamics, and brain morphology to enhance semantic memory, highlighting its neurorehabilitation potential.