Long term study of motivational and cognitive effects of low-intensity focused ultrasound neuromodulation in the dorsal striatum of nonhuman primates.
Long term study of motivational and cognitive effects of low-intensity focused ultrasound neuromodulation in the dorsal striatum of nonhuman primates.
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DOI：
10.1016/j.brs.2022.01.014
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发表时间：
2022-03
影响因子：
7.7
通讯作者：
Ferrera, V. P.
中科院分区：
文献类型：
--
作者：
Munoz, F.;Meaney, A.;Gross, A.;Liu, K.;Pouliopoulos, A. N.;Liu, D.;Konofagou, E. E.;Ferrera, V. P.
关键词：
使用经颅聚焦超声（FUS）的非侵入性脑刺激作为研究和临床工具具有许多潜在的应用，包括纳入神经修复术用于认知康复。为了开发这项技术，有必要评估FUS神经调节对特定脑靶点和认知功能的安全性和有效性。同样重要的是要测试是否重复长期应用FUS脑深部靶改善或降低行为和认知功能。为此，我们研究了FUS在非人灵长类动物（NHP）背侧纹状体中的作用，这些灵长类动物执行视觉运动决策任务，获得小或大的奖励。在2年的过程中，我们进行了129和147 FUS应用程序，分别在两个NHP。将FUS（0.5 MHz@0.2 - 0.8 MPa）应用于两个半球的壳核和尾状核，以评估对运动准确性、动机、决策准确性和反应时间的影响。单方面对尾状核或壳核进行超声处理，在动机和决策准确性方面产生了适度但具有统计学意义的改善，但代价是反应时间较慢。影响是剂量（即，FUS压力）和奖励依赖。对达到准确性没有影响，在T1加权、T2加权或磁共振成像扫描上也没有明显的长期行为障碍或神经创伤。超声处理还导致尾状核和多个皮质区域之间的静息状态功能连接的显着变化。结果表明，应用FUS背侧纹状体可以积极影响决策的动机和认知方面。FUS改善NHP动机和认知的能力表明其在治疗各种人类神经疾病方面的治疗潜力，并值得进一步发展为非侵入性脑深部电刺激的新技术。
Noninvasive brain stimulation using transcranial focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2 – 0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.
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