Looking for the optimal pathway to stimulate the hippocampus in human participants using transcranial ultrasound stimulation: a simulation study

JOURNAL/atin/04.03/02274269-202509000-00001/figure1/v/2025-05-23T114004Z/r/image-tiff Currently, very few methods can directly modulate neural activity in deep brain structures in human participants. Low-intensity transcranial ultrasound stimulation, an emerging and advanced modality of non-invasive brain stimulation, shows great potential for precisely stimulating subcortical structures associated with sleep, emotion, cognition, and motor function. Due to its focal nature, integrating various methods, including magnetic resonance imaging and potential pathways, is essential for performing transcranial ultrasound stimulation interventions that ensure precise targeting and dosing. The aim of this study was to create simulation models for low-intensity transcranial ultrasound stimulation targeting the human hippocampus through the lateral, anterior, and posterior pathways. We compared the effects of these models to identify the optimal pathway for transcranial ultrasound stimulation of the hippocampus. Eight healthy young adults underwent structural transcranial ultrasound stimulation scans as part of the study. Utilizing their structural neuroimaging data, we developed a protocol for low-intensity hippocampal transcranial ultrasound stimulation targeting the three pathways using the K-Plan platform, followed by acoustic and thermal simulations. The simulation results indicated that acoustic stimulation via the lateral pathway was the most effective, delivering the highest acoustic power through this route. Additionally, the geometric characteristics and thickness of the skull, along with the distance from the scalp to the cortex, significantly influenced the transcranial ultrasound stimulation dosage. These findings are a crucial step toward developing personalized treatment protocols, with lateral pathway stimulation of the hippocampus identified as the optimal option. The characteristics of the skull and the scalp-to-cortex distance are essential for accurately determining treatment targets and calculating transcranial ultrasound stimulation doses.