The effects of noradrenergic activity on age-related distractibility

尸检和神经成像数据表明，完整的蓝斑有助于维持认知能力 在老年人身上。然而，这种关系的基本机制仍不清楚。蓝斑是 大脑中大部分去甲肾上腺素的来源，但目前还不清楚蓝斑是如何与年龄相关的下降的 影响去甲肾上腺素能活动，进而，去甲肾上腺素能活动的这些变化如何调节认知 行为。例如，尚不清楚与年龄相关的神经调节和处理缺陷是否会导致 由于蓝斑活动减少或增加所致。我们的长期目标是确定 去甲肾上腺素能活动在调节认知损害中的作用和确定保持稳定自主神经的方法 具有预防或延缓神经退行性疾病进展的作用。本研究的具体研究目标是 建议确定去甲肾上腺素能活动调节注意力分散的机制 老年人和年轻人中不相关的干扰因素。这两个特定目标都将利用静止状态录音和 眼球运动搜索任务，测量眼球运动的注意抑制，以确定是否有补药 去甲肾上腺素能放电直接调节注意控制的抑制机制。在目标1中，我们将 研究使用不可预测的威胁是否提高老年人和年轻人的紧张性去甲肾上腺素能活动 电击通过斜视测量和电生理措施来诱导唤醒。此外，我们还将研究 这些变化是否会通过调节注意抑制的大小来影响注意控制 眼球运动和去甲肾上腺素能时相反应。我们预测老年人的注意力不会那么分散。 比年轻人更容易受到电击威胁的调节，因为我们假设老年人已经 高水平的紧张性去甲肾上腺素释放和多动症。在目标2中，我们将调查是否减少 慢节奏呼吸和冥想练习后的紧张性去甲肾上腺素能活动改善注意力集中 对于基础交感神经活性较高的老年人和年轻人。此目标的目标是确定 管理去甲肾上腺素能活动对注意力控制和一般测量的功能益处 觉醒和时相去甲肾上腺素能放电。我们预测，对目标2进行干预的好处将是 老年人比年轻人更严重。这项提案的总体结果将解决一个关键差距 在将神经调节机制与年龄相关的行为下降联系起来的知识中， 衰老过程中神经保护和保存的理论意义。此外，培训目标和 目标建立在申请人在心理生理学研究和fMRI研究方面的研究专长基础上 老龄化领域的专门知识，实地使用的脑电方法和分析工具方面的培训，以及 转变为独立的学术研究人员所必需的专业发展。这项研究 由Mara Mather博士、Rael Cahn博士和Markus Werkle-Bergner博士组成的导师团队是理想的人选 培训申请人在整个奖学金期间完成他的研究和培训目标。

Post mortem and neuroimaging data suggest an intact locus coeruleus helps to maintain cognitive performance in older adults. However, the basic mechanisms of this relationship are still unknown. The locus coeruleus is the source of most of the brain's noradrenaline but it is not yet clear how age-related decline in the locus coeruleus affects noradrenergic activity, and in turn, how these changes in noradrenergic activity modulate cognitive behavior. For instance, it is unknown whether age-related deficiencies in neuromodulation and processing result from decreased or increased locus coeruleus activity. Our long-term objectives are to determine the role of noradrenergic activity in modulating cognitive impairments and to identify means of preserving stable autonomic function to prevent or delay the progression of neurodegenerative diseases. The specific research goals of this proposal are to identify the mechanisms by which noradrenergic activity modulates distractibility by salient but irrelevant distractors in older and young adults. Both specific aims will utilize resting state recordings and an oculomotor search task that measures attentional inhibition of eye movements to determine whether tonic noradrenergic discharge directly modulates inhibitory mechanisms of attentional control. In Aim 1, we will investigate whether elevating tonic noradrenergic activity in older and young adults using threat of unpredictable shock induces arousal by pupillometric and electrophysiological measures. Furthermore, we will examine whether these changes will influence attentional control by modulating the magnitude of attentional inhibition of eye movements and phasic noradrenergic responses. We predict that older adults' distractibility will be less modulated by threat of shock than that of younger adults given our hypothesis that older adults already sustain higher levels of tonic noradrenergic release and hyperactivity. In Aim 2, we will investigate whether reducing tonic noradrenergic activity following slow-paced breathing and meditative practices improves attentional focus in older adults and young adults with high basal sympathetic activity. The goal of this aim is to determine the functional benefits of managing noradrenergic activity for attentional control as well as for measures of general arousal and phasic noradrenergic discharge. We predict that the benefits of the intervention in Aim 2 will be greater in older adults than that in young adults. The overall findings from this proposal will address a critical gap in knowledge connecting the mechanisms of neuromodulation on age-related declines to behavior, with theoretical implications in neuroprotection and preservation during aging. In addition, the training goals and objectives builds on the applicant's research expertise in psychophysiological research and fMRI with research expertise in the field of aging, training in EEG methodologies and analyses tools that are used in the field, and the professional development necessary to transition into an independent academic investigator. The research and mentorship team comprised of Drs. Mara Mather, Rael Cahn, and Markus Werkle-Bergner are the ideal fit to train the applicant in accomplishing his research and training goals throughout this fellowship.