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

项目摘要/摘要 记忆障碍发生在各种神经精神疾病(如抑郁症和精神分裂症)和 在许多神经疾病(例如，神经退行性疾病和脑损伤)中，往往具有破坏性 对生活质量的影响。该项目的目标是确定新的 涉及非侵入性增强人类海马-皮质脑网络的手术 支持内存。这种非侵入性的脑刺激程序，“HFN-STIM”，可以产生强大和持久的 海马区-皮质网络的增强和伴随的长时记忆的改善 刺激后15天。然而，刺激参数并没有得到优化。目前还不清楚 HFN-STIM可以进行定制，以对海马皮层网络和记忆产生更大的影响。我们 因此，建议进行一系列实验，以确定最佳持续时间、频率和环境 通过为这三个参数中的每一个建立剂量-反应关系来进行刺激。首先，我们将 确定增加连续的每日HFN-STim会话(5天、10天和20天)是否会产生更多 和/或对海马皮层网络和记忆的更持久的影响。第二，我们将确定 刺激频率是否与海马-皮质网络的内源性振荡活动相匹配 (即，theta节律)对海马皮层网络产生更大和/或更持久的影响 相对于已用于HFN-STIM的现有频率的内存。最后，我们将确定是否 当受试者执行旨在参与海马区的苛刻记忆任务时，HFN-STIM的交付- 皮质网络对海马-皮质网络和记忆产生更大和/或更持久的影响， 与不牢固地接触到海马皮层网络的控制任务的执行有关。 这些研究目标与RFA-MH-16-815关于建立 现有神经调节设备的剂量/反应关系，以促进神经科学的应用和 临床干预，特别是关于持续时间、频率和背景方面的RFA主题1、3和4 刺激。所有提出的实验都涉及对海马体依赖记忆的复杂评估 以及通过同步的fMRI/EEG和详细记忆获得的海马区-大脑皮层网络 测试。研究结果将为优化非侵入性刺激以增强 海马区-皮层网络和记忆。这项研究可能会促进对记忆障碍的理解 采用非侵入性刺激治疗。

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.