CAUSAL MECHANISMS OF DISTRIBUTED BRAIN NETWORK FUNCTION DURING EPISODIC MEMORY RETRIEVAL

项目摘要 该提案来自先前批准的K99奖学金，西北大学作为拟议的R 00阶段机构。记忆障碍是许多神经和精神疾病的常见症状，包括阿尔茨海默病和抑郁症，这给社会带来了沉重的负担。脑刺激是一种潜在的强大的治疗策略，有可能引起情节记忆的改善。然而，其功效取决于刺激的精确靶向，以尊重个体功能性大脑解剖结构的特质的方式。功能性磁共振成像（fMRI）的最新进展使大脑网络能够在个体内精确定义。与记忆障碍特别相关的是，最近在个体中发现了一个分布式网络，该网络包括后顶叶和海马旁皮质区域--记忆调制的突出刺激目标--以及分布在额叶、顶叶、颞叶和中线皮质的其他区域。目前尚不清楚刺激这些额外的分布区域是否会导致记忆改善。如果是这样的话，这可以为基于刺激的治疗提供额外的和潜在的更容易获得的靶点。在本项目中，将对计划接受颅内监测的癫痫患者进行个体水平的功能磁共振网络映射。将在个体患者中精确描绘包括海马旁和后顶叶皮质的分布式网络，并将使用所得网络图选择用于刺激的候选植入电极。分布式脑网络参与情景记忆的特点是在高的时间和空间分辨率，通过记录在情景记忆任务。记录将允许探索该网络的电生理特性，以及量化其与相邻网络的分离和相互作用，并将直接皮层刺激应用于各个部位，目的是测试网络对情景记忆的因果影响。为了实现这一项目，PI将在西北大学范伯格医学院建立一个研究项目，建立在K99培训期间在斯坦福大学获得的程序、方案和经验的基础上，并与神经科学家（Joel Voss博士）合作。和癫痫学家（StephanSchuele，Ph.D.）在西北大学。由此产生的数据将完善目前对情景记忆中涉及的神经系统的理解，并且重要的是为使用个体水平的网络映射来指导颅内脑记录和刺激提供原理证明，这可能对一系列精神健康障碍的刺激疗法具有重要意义。

Project Summary This proposal follows from a previously approved K99 fellowship, with Northwestern University as the proposed R00-phase institution. Memory impairments are common to many neurological and psychiatric disorders, including Alzheimer’s disease and depression, which impose a heavy burden on society. Brain stimulation is a potentially powerful therapeutic strategy with the potential to elicit improvements in episodic memory. However, its efficacy depends on precise targeting of stimulation, in a manner that respects the idiosyncrasies of an individual’s functional brain anatomy. Recent advances in functional magnetic resonance imaging (fMRI) have allowed brain networks to be defined with precision within individuals. Of particular relevance to memory disorders, a distributed network was recently identified within individuals that includes regions of posterior parietal and parahippocampal cortices – prominent stimulation targets for modulation of memory – in combination with other regions distributed throughout frontal, parietal, temporal and midline cortices. It is not known whether stimulation of these additional distributed regions can lead to memory improvements. If so, this could provide additional and potentially more accessible targets for stimulation-based therapies. In this project, individual-level network mapping with fMRI will be performed on epilepsy patients who are scheduled to undergo intracranial monitoring. The distributed network which includes parahippocampal and posterior parietal cortex will be delineated with precision in individual patients and the resulting network maps will be used to select candidate implanted electrodes for stimulation. The involvement of the distributed brain network in episodic memory will be characterized at high temporal and spatial resolution through recordings obtained during an episodic memory task. Recordings will allow the exploration of electrophysiological properties of this network, as well as quantify its separation and interactions with neighboring networks, and direct cortical stimulation will be applied to individual sites with the aim of testing the causal influence of the network on episodic memory. To achieve this project, the PI will establish a research program at the Northwestern University Feinberg School of Medicine, building on procedures, protocols and experience gained at Stanford University during the K99 training, and in collaboration with neuroscientists (Joel Voss, Ph.D.) and epileptologists (Stephan Schuele, Ph. D.) at Northwestern University. The resulting data will refine the current understanding of the neural systems involved in episodic memory, and importantly provide a proof-of-principle for the use of individual-level network mapping to guide intracranial brain recording and stimulation, which could have important implications for stimulation therapies for a range of mental health disorders.