Noninvasive Manipulation of Hippocampal-Cortical Brain Networks and Memory

 描述（由申请人提供）：记忆障碍发生在各种神经精神疾病中（例如，抑郁症和精神分裂症）和许多神经系统疾病（例如，神经变性疾病和脑损伤）。不幸的是，记忆障碍对生活质量有毁灭性的后果，目前还没有可靠的治疗方法来改善记忆功能。该项目的目标是更好地了解一种新的程序，用于非侵入性地增强人类大脑皮层网络，这些网络被认为是关键的支持记忆。这种非侵入性脑刺激程序可以产生强大和持久（至少~24小时）的大脑皮层网络的增强和长期联想记忆的伴随改善。然而，相关的大脑机制必须更充分地说明之前，这个程序可以更广泛地应用于更好地理解和治疗记忆障碍。因此，我们提出了一系列实验，旨在回答三个长期存在的机械问题。首先，我们的目标是测试是否可以选择性地增强不同的大脑皮层网络，这将决定刺激是否作用于离散的目标记忆网络。其次，我们的目标是确定这些增强的时间过程和持续时间，这对于评估假定的神经机制和临床实用性的潜力是必不可少的。最后，我们的目的是测试海马是否是刺激诱导增强海马-皮质网络的关键部位，通过靶向单侧内侧颞叶切除术治疗难治性癫痫患者的完整与手术切除的海马组织。当缺失的海马组织被靶向时，刺激诱导的海马-皮层网络和记忆增强的损伤将证实海马在刺激效应中的必要/因果作用。所有提出的实验都涉及对大脑皮层依赖的记忆功能和大脑皮层-大脑皮层网络的复杂评估。因此，研究结果将深入了解刺激效应，同时产生关于大脑皮层网络在记忆中的作用的重要信息。这项研究的见解可以促进对记忆障碍的理解，并通过非侵入性刺激进行治疗。

 DESCRIPTION (provided by applicant): Memory impairment occurs in a variety of neuropsychiatric conditions (e.g., depression and schizophrenia) and in many neurologic disorders (e.g., neurodegenerative disease and brain injury). Unfortunately, memory impairments have devastating consequences for life quality and there are no current treatments that reliably improve memory function. The goal of this project is to better understand a new procedure for the noninvasive enhancement of human hippocampal-cortical brain networks that are thought to critically support memory. This noninvasive brain-stimulation procedure can produce robust and lasting (at least ~24 hours) enhancement of hippocampal-cortical networks and concomitant improvement in long-term associative memory. However, relevant brain mechanisms must be more fully specified before this procedure can be more broadly applied to better understand and treat memory impairments. We therefore propose a collection of experiments that aim to answer three standing mechanistic questions. First, we aim to test whether distinct hippocampal-cortical brain networks can be selectively enhanced, which would determine whether stimulation acts on discrete targeted memory networks. Second, we aim to determine the timecourse and duration of these enhancements, which is essential for evaluation of putative neural mechanisms and of potential for clinical utility. Finally, we aim to test whethe the hippocampus is the key site of stimulation-induced enhancement of hippocampal-cortical networks by targeting intact versus surgically removed hippocampal tissue in individuals with unilateral medial temporalobectomy performed for treatment of refractory epilepsy. Impairments in stimulation-induced enhancement of hippocampal-cortical networks and memory when missing hippocampal tissue is targeted would confirm the necessary/causal role of hippocampus in the effects of stimulation. All proposed experiments involve sophisticated assessments of hippocampal-dependent memory function and of hippocampal-cortical brain networks. Findings will thus deeply inform understanding of stimulation effects while at the same time producing important information on the role of hippocampal-cortical networks in memory. Insights from this research could propel understanding of memory impairment and its treatment by noninvasive stimulation.