Success requires focus and the ability to screen out distractions. This is especially important in arousing situations: When avoiding imminent danger, tackling a cognitive challenge or trying to achieve a desired goal, focusing on what has highest priority or is most salient is often helpful. We plan to test the hypothesis that when arousing or challenging situations activate the locus coeruleus (LC) in healthy younger adults, it enhances processing high priority or highly salient items but impairs processing of less active competing representations. The framework behind this hypothesis is the first to explain how arousal both enhances and impairs attention and memory and this project will be the first to systematically examine the relationship between LC structural decline and cognitive function in normal aging and in Alzheimer's disease. We predict that, in older adults, the LC has a less targeted effect than it does in younger adults, meaning that arousal still has a significant impact on older adults' cognitive processing but that it is less likely to increase the selectivity of their attention or the specificity of their memories. Furthermore, we predict that in Alzheimer's disease, declines in structural connectivity will be extensive enough to impair both the excitatory and inhibitory effects of LC activity. This work to understand the role of the LC in cognitive function becomes particularly urgent in light of recent striking findings indicating that the LC is the first place in the brain that sporadic (or late-onset) Alzheimer's related tau pathology emerges, and that by young adulthood, most people have at least some tau pathology in the LC. Here we use neuromelanin-weighted structural MRI images and diffusion tensor imaging structural connectivity measures to examine how LC integrity relates to function on a variety of tasks that assess cognitive selectivity. We will test healthy older adults, older adults with late-onset Alzheimer's and younger and middle-aged adults with genetic subtypes of Alzheimer's disease (due to mutations in the PSEN1 and APP genes) that lead to early onset of the disease.
Recent findings indicate that the locus coeruleus is the first place in the brain that Alzheimer?s disease pathology is found and that nearly all adults have at least some disease-related pathology there by age 40. Post-mortem neuron density in the locus coeruleus is also one of the strongest brain predictors of cognitive decline, yet little is known about how function in this region changes with age and disease. In this project, we examine relationships between the locus coeruleus and attention and memory processes in aging and in Alzheimer?s disease.
|Clewett, David V; Huang, Ringo; Velasco, Rico et al. (2018) Locus Coeruleus Activity Strengthens Prioritized Memories Under Arousal. J Neurosci 38:1558-1574|
|Martins, Bruna; Sheppes, Gal; Gross, James J et al. (2018) Age Differences in Emotion Regulation Choice: Older Adults Use Distraction Less Than Younger Adults in High-Intensity Positive Contexts. J Gerontol B Psychol Sci Soc Sci 73:603-611|
|Yoo, Hyun Joo; Thayer, Julian F; Greening, Steven et al. (2018) Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples. Brain Struct Funct 223:727-737|
|Sutherland, Matthew R; Mather, Mara (2018) Arousal (but not valence) amplifies the impact of salience. Cogn Emot 32:616-622|
|Tang, Yuchun; Sun, Wei; Toga, Arthur W et al. (2018) A probabilistic atlas of human brainstem pathways based on connectome imaging data. Neuroimage 169:227-239|
|Aydogan, Dogu Baran; Shi, Yonggang (2018) Tracking and validation techniques for topographically organized tractography. Neuroimage 181:64-84|
|Martins, Bruna; Florjanczyk, Jan; Jackson, Nicholas J et al. (2018) Age differences in emotion regulation effort: Pupil response distinguishes reappraisal and distraction for older but not younger adults. Psychol Aging 33:338-349|
|Durbin, Kelly A; Clewett, David; Huang, Ringo et al. (2018) Age differences in selective memory of goal-relevant stimuli under threat. Emotion 18:906-911|
|Lee, Tae-Ho; Greening, Steven G; Ueno, Taiji et al. (2018) Arousal increases neural gain via the locus coeruleus-norepinephrine system in younger adults but not in older adults. Nat Hum Behav 2:356-366|
|Nashiro, Kaoru; Guevara-Aguirre, Jaime; Braskie, Meredith N et al. (2017) Brain Structure and Function Associated with Younger Adults in Growth Hormone Receptor-Deficient Humans. J Neurosci 37:1696-1707|
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