Noninvasive Manipulation of Hippocampal-Cortical Brain Networks and Memory

 描述(申请人提供)：记忆障碍发生在各种神经精神疾病(例如，抑郁症和精神分裂症)和许多神经疾病(例如，神经退行性疾病和脑损伤)中。不幸的是，记忆损伤会对生活质量造成毁灭性的后果，目前还没有可靠地改善记忆功能的治疗方法。这个项目的目标是更好地理解一种新的程序，以非侵入性地增强被认为对记忆起关键支持作用的人类海马体-皮质脑网络。这种非侵入性的脑刺激程序可以产生强大而持久的(至少~24小时)海马皮层网络的增强，并伴随着长期联想记忆的改善。然而，在更广泛地应用这一程序以更好地理解和治疗记忆损伤之前，相关的大脑机制必须得到更充分的说明。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性问题。首先，我们的目标是测试是否可以选择性地增强不同的海马-皮质脑网络，这将决定刺激是否作用于离散的靶向记忆网络。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潜在的临床应用是必不可少的。最后，我们的目标是测试海马区是否是刺激诱导增强海马皮层网络的关键部位，通过靶向完整的和手术切除的海马区组织来治疗难治性癫痫。当缺失的海马组织作为靶点时，刺激诱导的海马皮层网络和记忆增强的损害将证实海马体在刺激效果中的必要/因果作用。所有被提议的实验都涉及对海马体依赖的记忆功能和海马体-皮质脑网络的复杂评估。因此，这些发现将深入了解刺激效应，同时产生关于海马皮层网络在记忆中的作用的重要信息。这项研究的见解可能会推动人们对记忆障碍及其非侵入性刺激治疗的理解。

 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.