Department of Biomedical Engineering, University of Utah, 36 South Wasatch Dr, Salt Lake City, UT 84112, United States of America.
Department of Biomedical Engineering, University of Utah, 36 South Wasatch Dr, Salt Lake City, UT 84112, United States of America.
Brain Stimul. 2023 May-Jun;16(3):798-805. doi: 10.1016/j.brs.2023.04.012. Epub 2023 Apr 18.
Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects.
Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates.
Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months.
The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation.
This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset.
经颅聚焦超声具有非侵入性调节深部脑回路并产生持续神经重塑效应的潜力。
通过在执行任务的非人类灵长类动物中证明深部脑回路的持续调节和选择行为，使该方法更接近转化。
在非人类灵长类动物中，以受控的方式将持续 30 秒的低强度经颅超声传递到深部脑目标（左侧或右侧外侧膝状体；LGN），而受试动物决定是先出现左侧还是右侧视觉目标。当动物执行任务时，我们从枕骨螺钉记录颅内脑电图。超声每天传递到深部脑目标超过 6 个月。
短暂的刺激对选择行为产生影响，持续时间长达 15 分钟，且仅针对受激目标。刺激左侧/右侧 LGN 增加了右侧/左侧选择的比例。这些效应伴随着视觉皮层伽马活动的增加。与假刺激相比，对选择行为和伽马的对侧效应表明刺激兴奋了目标神经回路。在长达数月的刺激过程中，动物的辨别性能没有受到损害。
这项研究表明，短暂的 30 秒超声刺激可特异性地诱导目标深部脑回路产生神经重塑效应，且每日应用无不良影响。这些发现鼓励在有功能障碍的深部脑回路的人类中重复应用经颅超声，以期提供持久的治疗重置。
