Multifocal transcranial current stimulation for cognitive and motor dysfunction in dementia

项目概要： 在患有轻度痴呆的老年人中，完成日常生活工具性活动的能力中断 这不仅源于记忆缺陷，还源于执行功能障碍，这也影响步态和平衡。 因此，迫切需要开发安全的多组分干预措施，以最大限度地发挥功能性 通过同时针对记忆，执行功能和复杂的功能， 控制步态和平衡。现在已经确定记忆和执行运动缺陷是由 在特定的和空间上不同的大脑网络内改变功能，而且，不同形式的经颅神经网络， 电流刺激可以针对这些网络来为该人群提供症状缓解。平行线 初步证据明确表明，1）经颅交流电刺激针对左侧 γ频率下的角回（tACS）可以改善情景记忆和自传体记忆;以及2） 针对左背外侧前额叶皮层的经颅直流电刺激（tDCS）可以改善 执行功能和步态表现，特别是当老年人在进行额外的步行时， 认知任务（即，双重任务）。与此同时，重要的技术进步最近使 研究人员：研究和优化多通道刺激剪辑（即，电极位置和电流 参数）;目标多于一个 大脑网络在同一时间在同一蒙太奇;实施积极的假协议，促进 双盲和控制外周刺激的潜在影响;并安全地提供干预措施， 参与者在他们自己的家中通过远程监督，刺激的管理。 在这些初步研究和进展的基础上，我们建议进行一项II期、随机、假- 一项对照、双盲、平行组试验，旨在评估tACS靶向 γ频率下的左角回和针对左背外侧前额叶皮层的tDCS对记忆的影响， 轻度脑梗死患者的执行功能、双任务步态和工具性日常生活活动 痴呆症（具体目标1）。在这项试验中，我们还将确定 一方面干预记忆，另一方面干预执行功能和双任务步态表现 一方面，取决于分别在左侧角回和左侧角回中感生的电场的大小。 背外侧前额叶皮层，如通过个体化电场高分辨率建模（特定目标2）评估的。 该项目预计将证明tACS和tDCS可以组合成一个单一的干预措施， 优化对患有轻度痴呆症的老年人的家庭干预的功能影响。它将 还提供了对大脑网络和症状之间映射的特异性的见解，并提供了关键的 为在未来试验中实现刺激干预的个性化优化奠定了基础。

PROJECT SUMMARY: In older adults with mild dementia, disruption in the ability to complete instrumental activities of daily living stems not only from memory deficits, but also from executive dysfunction which also impacts gait and balance. There is thus an urgent need to develop safe, multi-component interventions designed to maximize functional capacity in this vulnerable population by simultaneously targeting memory, executive function, and the complex control of gait and balance. It is now well-established that memory and executive-motor deficits arise from altered function within specific and spatially distinct brain networks, and, that different forms of transcranial current stimulation can target these networks to provide symptomatic relief to this population. Parallel lines of preliminary evidence specifically suggest that 1) transcranial alternating current stimulation targeting the left angular gyrus (tACS) at gamma frequency can improve episodic and autobiographical memory; and 2) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex can improve executive function and gait performance, especially when older adults are walking while performing additional cognitive tasks (i.e., dual tasking). At the same time, important technological advances have recently enabled researchers to: study and optimize multi-channel stimulation montages (i.e., electrode placement and current parameters) based upon individualized modeling of generated cortical electric fields; target more than one brain network at the same time within the same montage; implement active-sham protocols that facilitate double-blinding and control of the potential effects of peripheral stimulation; and safely deliver interventions to participants within their own homes via remotely-supervised, caregiver-led administration of stimulation. Building upon these preliminary studies and advances, we propose to conduct a phase II, randomized, sham- controlled, double-blinded, parallel-arm trial to assess the separate and combined effects of tACS targeting the left angular gyrus at gamma frequency and tDCS targeting the left dorsolateral prefrontal cortex on memory, executive function, dual task gait, and instrumental activities of daily living in ambulatory older adults with mild dementia (Specific Aim 1). Within this trial, we will also determine how much of the clinical effects of intervention on memory on the one hand, and executive function and dual task gait performance on the other hand, depend upon the amount of the electric field induced respectively in the left angular gyrus and the left dorsolateral prefrontal cortex, as assessed by individualized e-field high-resolution modelling (Specific Aim 2). This project is expected to demonstrate that tACS and tDCS can be combined into one single intervention to optimize the functional impact of a home-based intervention for older adults suffering from mild dementia. It will also provide insights into the specificity of mapping between brain networks and symptoms, and offer critical foundation to enable personalized optimization of stimulation interventions within future trials.