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

Lu, Hanna1,2,*; Li, Zeyan1; Ni, Xi1; Guo, Liwei3; Qiu, Zhihai4; Meng, Lin5; Yuan, Yi6,7

1Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

2The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China

3Department of Mechanical Engineering, University College London, London, UK

4Guangdong Institute of Intelligence Science and Technology, Zhuhai, Guangdong Province, China

5Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China

6School of Electrical Engineering, Yanshan University, Qinhuangdao, Hebei Province, China

7Key Laboratory of Intelligent Rehabilitation and Neuromodulation of Hebei Province, Yanshan University, Qinhuangdao, Hebei Province, China

*Correspondence to: Hanna Lu, PhD., hannalu@cuhk.edu.hk.

Funding:This work was supported by the Research Data Management Development Fund, The Chinese University of Hong Kong, No. 4730324 (to HL) and the Start-Up Fund from the Chinese University of Hong Kong, No. 4937147 (to HL).

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Advanced Technology in Neuroscience 2(3):p 103-108, September 2025. | DOI: 10.4103/ATN.ATN-D-24-00032

Abstract

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.

中文摘要

目前，能直接调节人脑深层结构神经活动的方法非常有限。低强度经颅超声刺激作为一种新兴和先进的非侵入性脑部刺激方式，在局部刺激与睡眠、情绪和认知运动功能相关的皮质下结构方面具有巨大的潜力。由于其定位性，整合各种方法（包括磁共振成像和可能的路径）对于进行经颅超声刺激干预以精确定位和剂量非常重要。此研究的目的是构建3种低强度经颅超声刺激经不同路径(侧方、前方和后方)刺激人类海马体的模拟模型，并比较3种模型的效果，以确定经颅超声刺激法刺激人类海马体的最佳路径。该研究招募8名健康志愿者进行结构性磁共振成像(MRI)扫描，基于其T1加权成像数据，利用K-Plan平台设计3种不同路径的经颅超声刺激刺激方案，并进行声学模拟和热模拟。模拟结果显示，经侧方路径刺激海马体效果最佳，该路径下传递的声学功率最强。此外，颅骨的几何特征和厚度以及头皮到皮质的距离对经颅超声刺激的剂量有重要影响。上述数据证实，研究结果为开发个性化经颅超声刺激治疗方案提供了关键一步，确定了经侧方路径刺激海马体为理想选择。颅骨特征和头皮到皮质距离在精确确定治疗目标和计算经颅超声刺激剂量中至关重要。