直接电刺激人类记忆:经验教训与未来展望。

Direct electrical brain stimulation of human memory: lessons learnt and future perspectives.

机构信息

BioTechMed Center, Brain & Mind Electrophysiology Lab, Multimedia Systems Department, Faculty of Electronics, Telecommunication and Informatics, Gdansk University of Technology, 80-233 Gdansk, Poland.

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Brain. 2023 Jun 1;146(6):2214-2226. doi: 10.1093/brain/awac435.

Abstract

Modulation of cognitive functions supporting human declarative memory is one of the grand challenges of neuroscience, and of vast importance for a variety of neuropsychiatric, neurodegenerative and neurodevelopmental diseases. Despite a recent surge of successful attempts at improving performance in a range of memory tasks, the optimal approaches and parameters for memory enhancement have yet to be determined. On a more fundamental level, it remains elusive as to how delivering electrical current in a given brain area leads to enhanced memory processing. Starting from the local and distal physiological effects on neural populations, the mechanisms of enhanced memory encoding, maintenance, consolidation or recall in response to direct electrical stimulation are only now being unravelled. With the advent of innovative neurotechnologies for concurrent recording and stimulation intracranially in the human brain, it becomes possible to study both acute and chronic effects of stimulation on memory performance and the underlying neural activities. In this review, we summarize the effects of various invasive stimulation approaches for modulating memory functions. We first outline the challenges that were faced in the initial studies of memory enhancement and the lessons learnt. Electrophysiological biomarkers are then reviewed as more objective measures of the stimulation effects than behavioural outcomes. Finally, we classify the various stimulation approaches into continuous and phasic modulation with an open or closed loop for responsive stimulation based on analysis of the recorded neural activities. Although the potential advantage of closed-loop responsive stimulation over the classic open-loop approaches is inconclusive, we foresee the emerging results from ongoing longitudinal studies and clinical trials will shed light on both the mechanisms and optimal strategies for improving declarative memory. Adaptive stimulation based on the biomarker analysis over extended periods of time is proposed as a future direction for obtaining lasting effects on memory functions. Chronic tracking and modulation of neural activities intracranially through adaptive stimulation opens tantalizing new avenues to continually monitor and treat memory and cognitive deficits in a range of brain disorders. Brain co-processors created with machine-learning tools and wireless bi-directional connectivity to seamlessly integrate implanted devices with smartphones and cloud computing are poised to enable real-time automated analysis of large data volumes and adaptively tune electrical stimulation based on electrophysiological biomarkers of behavioural states. Next-generation implantable devices for high-density recording and stimulation of electrophysiological activities, and technologies for distributed brain-computer interfaces are presented as selected future perspectives for modulating human memory and associated mental processes.

摘要

调节支持人类陈述性记忆的认知功能是神经科学的重大挑战之一,对于各种神经精神疾病、神经退行性疾病和神经发育障碍具有重要意义。尽管最近在一系列记忆任务的表现改善方面取得了成功,但最佳的增强记忆方法和参数仍有待确定。在更基本的层面上,如何在特定脑区施加电流以增强记忆处理仍然难以捉摸。从对神经群体的局部和远程生理效应开始,人们才刚刚开始揭示直接电刺激如何增强记忆编码、维持、巩固或回忆的机制。随着创新的神经技术的出现,这些技术可以在人类大脑中进行颅内同时记录和刺激,人们有可能研究刺激对记忆表现和潜在神经活动的急性和慢性影响。在这篇综述中,我们总结了各种侵入性刺激方法调节记忆功能的效果。我们首先概述了记忆增强初始研究中面临的挑战和吸取的经验教训。然后,电生理生物标志物被视为比行为结果更客观的刺激效果测量指标。最后,我们根据记录的神经活动分析,将各种刺激方法分为连续和相位调制,分为开环或闭环,用于响应性刺激。虽然基于记录的神经活动分析,闭环响应性刺激相对于经典的开环方法具有潜在的优势,但尚无定论,我们预计正在进行的纵向研究和临床试验的结果将阐明改善陈述性记忆的机制和最佳策略。提出基于生物标志物分析的自适应刺激作为获得对记忆功能持久影响的未来方向。通过自适应刺激对颅内神经活动进行慢性跟踪和调节,为持续监测和治疗一系列大脑疾病中的记忆和认知缺陷开辟了诱人的新途径。使用机器学习工具和无线双向连接创建的脑协处理器,将植入设备与智能手机和云计算无缝集成,有望实现对大量数据的实时自动分析,并根据行为状态的电生理生物标志物自适应调整电刺激。用于高密度记录和刺激电生理活动的下一代植入式设备以及分布式脑机接口技术被提出来作为调节人类记忆和相关心理过程的未来展望。

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