Frontal theta as a mechanism of aging-related differences in cognitive control

项目总结/摘要 衰老与认知控制的下降有关，认知控制是促进目标实现的心理过程， 导向行为。认知控制能力下降影响老年人健康和富有成效的能力 个人和专业的互动，这降低了生活质量，增加了住院治疗， 死亡率。目前几乎没有有效的治疗方法来治疗与年龄相关的认知能力下降。 控制因此，存在开发用于衰老相关的认知衰退的新治疗的未满足的需求。 然而，我们对衰老相关认知功能的潜在机制的理解存在差距， 下降 认知控制与大脑活动的协调模式有关， 包括额叶皮质在内的大脑区域。特别是θ波的低频振荡 额叶皮层中的频带（4-7 Hz）已被证明对于认知控制是重要的。的 拟议研究的总体目标是确定老化如何影响这些电路机制。我 总的假设是，额叶皮层的内侧区域以θ波段频率振荡， 支持认知控制，而老年人中额叶中皮层θ波的衰减解释了 认知控制的年龄相关差异。 我将使用两个不同的实验设计来测试这个整体假设。首先，我将测试 假设额叶皮层内侧区域的θ振荡与任务相关， 在很大程度上theta功率比额叶皮层的侧区。我将用以下方法来检验这个假设： 认知功能完好的帕金森病患者颅内手术期间的人类术中记录 和特发性震颤患者。其次，我将检查年轻人和老年人的大脑活动， 完成两项旨在参与认知控制的任务。在这里，我将测试老化的假设- 认知控制的相关差异对应于额叶皮层中θ振荡的减少。这 假设预测老年人的θ波段振荡将低于年轻人， 并且减少的θ振荡将与更差的认知控制相关联。 总之，拟议的实验将有助于建立一个模型，建立如何在大的变化- 额叶皮层精确区域的尺度振荡动力学对应于年龄相关的下降， 认知控制该提案的数据结果预计将是候选人的知识 治疗认知障碍的靶点。这与衰老和与衰老相关的 疾病如阿尔茨海默病和其它阿尔茨海默病相关痴呆， 帕金森氏症。

Project Summary/Abstract Aging is associated with declines in cognitive control, the mental process that facilitates goal- oriented behaviors. Declining cognitive control affects older adults' ability to have healthy and productive personal and professional interactions, which decreases quality of life and increases hospitalization and mortality rates. There are currently few effective therapies to treat age-related declines in cognitive control. Thus, there is an unmet need to develop new treatments for aging-related cognitive decline. However, there is a gap in our understanding of the underlying mechanisms of aging-related cognitive decline. Cognitive control is associated with coordinated patterns of brain activity across a network of brain regions that includes the frontal cortex. In particular, low-frequency oscillations in the theta frequency band (4-7 hz) in the frontal cortex have been shown to be important for cognitive control. The overall goal of the proposed research is to identify how aging affects these circuit mechanisms. My overall hypothesis is that the medial region of the frontal cortex oscillates at theta-band frequency to support cognitive control, and attenuated midfrontal cortex theta oscillations in older adults accounts for aging-related differences in cognitive control. I will employ two distinct experimental designs to test this overall hypothesis. First, I will test the hypothesis that theta oscillations in the medial regions of the frontal cortex demonstrate task-relevant theta power to a great extent than lateral regions in the frontal cortex. I will test this hypothesis using human intraoperative recordings during intracranial surgeries in cognitively-intact Parkinson's disease and essential tremor patients. Second, I will examine brain activity of both young and older adults as they complete two tasks designed to engage cognitive control. Here I will test the hypothesis that aging- related differences in cognitive control correspond to reduced theta oscillations in the frontal cortex. This hypothesis predicts that theta-band oscillations will be lower in older adults compared to young adults, and reduced theta oscillations will be associated with worse cognitive control. Together, the proposed experiments will contribute to a model establishing how changes in large- scale oscillatory dynamics in precise regions of the frontal cortex correspond to aging-related declines in cognitive control. An outcome of the data from this proposal is expected to be knowledge of candidate targets for therapies for cognitive impairment. This is highly relevant for aging and for aging-related disorders such as Alzheimer's Disease and other Alzheimer's disease-related dementias and Parkinson's disease.