Optimized dosing of repetitive transcranial magnetic stimulation for enhancement of hippocampal-cortical networks

项目总结/摘要 记忆障碍发生在各种神经精神病症中（例如，抑郁症和精神分裂症）， 在许多神经系统疾病（例如，神经退行性疾病和脑损伤），通常具有破坏性 生活质量的后果。该项目的目标是确定一个新的最佳剂量参数 一种涉及非侵入性增强人类大脑皮层网络的程序， 支持内存。这种非侵入性的脑刺激程序，“HFN刺激”，可以产生强大和持久的， 增强大脑皮层网络，并伴随长期记忆的改善， 刺激后15天。然而，刺激参数尚未优化。目前尚不清楚， HFN-刺激可以被定制为对大脑皮层网络和记忆产生更大的影响。我们 因此，提出了一系列实验，将确定最佳的持续时间，频率和上下文， 通过为这三个参数中的每一个建立剂量-反应关系来刺激。一是 确定增加连续的每日HFN刺激会话（5、10和20天）是否产生更大的 和/或对大脑皮层网络和记忆的更持久的影响。第二，我们将确定 刺激频率是否与大脑皮层网络的内源性振荡活动相匹配 (i.e.,θ节律）对大脑皮层网络产生更大和/或更持久的影响， 内存，相对于HFN-刺激使用的现有频率。最后，我们将确定 当受试者执行一项要求很高的记忆任务时， 皮层网络对大脑皮层网络和记忆产生更大和/或更持久的影响， 相对于不稳健地参与大脑皮层网络的控制任务的性能。 这些研究目标与RFA-MH-16-815的重点是建立 现有神经调节装置的剂量/反应关系，以促进神经科学应用， 临床干预，特别是RFA主题1、3和4，关于持续时间、频率和背景方面， 刺激.所有提出的实验都涉及对依赖于大脑的记忆的复杂评估 以及通过同时进行功能性磁共振成像/脑电图和详细记忆获得的大脑皮层网络 试验.研究结果将为优化非侵入性刺激以增强 大脑皮层网络与记忆这项研究可以推动对记忆障碍的理解 以及通过非侵入性刺激进行治疗。

Project Summary/Abstract 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), often with devastating consequences for life quality. The goal of this project is to determine optimal dosing parameters for a new procedure involving the noninvasive enhancement of human hippocampal-cortical brain networks that critically support memory. This noninvasive brain-stimulation procedure, “HFN-Stim”, can produce robust and lasting enhancement of hippocampal-cortical networks and concomitant improvement in long-term memory for up to 15 days after stimulation. However, stimulation parameters have not been optimized. It is yet unknown whether HFN-Stim could be tailored to have greater effects on hippocampal-cortical networks and memory. We therefore propose a collection of experiments that will determine optimal duration, frequency, and context of stimulation by establishing dose-response relationships for each of these three parameters. First, we will determine whether increasing consecutive, daily HFN-Stim sessions (5, 10, and 20 days) produces greater and/or longer- lasting effects on hippocampal-cortical networks and memory. Second, we will determine whether stimulation frequencies matching endogenous oscillatory activity of the hippocampal-cortical network (i.e., theta rhythm) produce greater and/or longer-lasting effects on hippocampal-cortical networks and memory, relative to existing frequencies that have been used for HFN-Stim. Finally, we will determine whether delivery of HFN-Stim while subjects perform a demanding memory task designed to engage the hippocampal- cortical network produces greater and/or longer-lasting effects on hippocampal-cortical networks and memory, relative to performance of a control task that does not robustly engage the hippocampal-cortical network. These research objectives are in close alignment with the focus of RFA-MH-16-815 on establishing dose/response relationships for existing neuromodulation devices to promote neuroscience applications and clinical interventions, specifically RFA Topics 1, 3, and 4 on the duration, frequency, and contextual aspects of stimulation. All proposed experiments involve sophisticated assessments of hippocampal-dependent memory and of hippocampal-cortical brain networks, obtained through simultaneous fMRI/EEG and detailed memory testing. Findings will deeply inform efforts to optimize noninvasive stimulation for the enhancement of hippocampal-cortical networks and memory. This research could propel understanding of memory impairment and its treatment by noninvasive stimulation.