Transcranial focused ultrasound (tFUS) enables non-invasive deep brain neuromodulation with millimeter-scale resolution, but its application in geriatric rehabilitation is hindered by age-related cranial morphological variability and the absence of population-specific dosing protocols. Standard brain templates like MNI152, derived from Caucasian populations, fail to accurately reflect the cranial characteristics of Asian elderly, causing focal deviation and inconsistent clinical efficacy. This study aimed to validate a simulation-to-clinic translational framework for determining optimal acoustic parameters to modulate the DLPFC and enhance executive function in older adults. We used high-fidelity computational simulations based on the Chinese2020 brain template to screen 2,400 parameter combinations, selecting four protocols (per <1.0°C safety threshold) for a clinical trial with 30 healthy older adults (58.47±7.88 years) using a 2×2 factorial design (500/800 kHz; 20%/33% duty cycle), with outcomes assessed via EEG, fNIRS, and cognitive tasks. Acoustic simulations confirmed peak tissue temperature rise <0.31°C for all protocols; Protocol 2 (500 kHz, 20% duty cycle) elicited robust neural responses (increased prefrontal Alpha/Theta power, enhanced left DLPFC-Broca’s area connectivity) and improved high-load visuospatial task performance, while 800 kHz stimulation only modulated simple motor reaction times. This study identifies low-frequency, low-duty-cycle tFUS as optimal for activating the aging brain’s executive control network, establishing a precision dosing framework bridging physical modeling and clinical outcomes

Hujun Wang, a 2020 graduate in Rehabilitation Therapy, skilled in clinical assessment, instrument operation and data analysis. With internship experience in multiple rehabilitation departments, he has participated in academic exchanges and research projects