David A. Gallo - US grants

[unreadable] DESCRIPTION (provided by applicant): Metamemory, or knowledge of one's own memory abilities and corresponding strategies, is essential for regulating the accuracy of memory retrieval. Metamemory is needed to select appropriate retrieval strategies, to accurately assess confidence in one's memories, and to avoid memory distortions. In both healthy aging and the early stages of Alzheimer's disease (AD), impaired metamemory can limit one's ability to effectively use memory in everyday situations, causing psychological and behavioral difficulties. Despite the significance of this problem, few studies have separated the contributions of metamemory from memory availability in aging and AD. Further, the degree that metamemory is affected by different types of memories is poorly understood, limiting our understanding of how metamemory abilities generalize across various situations. The current research addresses several fundamental questions about metamemory in aging and AD. Aim 1 is to identify the extent that aging and AD differentially affect metamemory at retrieval. To achieve this aim, Experiments 1 and 2 compare metamemory accuracy across groups, using a novel procedure that equates the groups on memory availability (recollection). Metamemory ability will be measured as the correspondence between subjective confidence judgments and objective memory accuracy. Aim 2 is to determine how emotional memories, which are differentially affected by aging and AD, influence metamemory. To achieve this aim, Experiments 3 and 4 investigate the effects of emotional valence and arousal on memory distortion. These experiments will extend the results of the first two experiments to a false recognition task, investigating accuracy and confidence for both neutral and emotional memories. Aim 3 is to understand the nature of individual differences in metamemory in aging and AD. This aim will be addressed by investigating the relationship between metamemory accuracy, frontal functioning, and personal beliefs in memory ability (including anosognosia, or impaired awareness of cognitive declines in AD). In addition to exploring the potential anatomical correlates of metamemory, these analyses will test the hypothesis that personal beliefs about memory are a critical ingredient to metamemory accuracy, thereby advancing our understanding of individual differences in metamemory in aging and AD. Metamemory is a key aspect of cognitive functioning, especially when more basic memory functions are compromised. A better understanding of metamemory is critical for addressing many of the psychological problems that older adults confront, such as an elevated susceptibility to memory distortion. Further, the ability to detect changes in metamemory that may occur in the early stages of AD might help to distinguish between healthy and diseased states, potentially leading to earlier and more effective clinical interventions. This project focuses on separating the effects of normal aging and the early stages of Alzheimer's disease on memory abilities. Understanding the cognitive changes associated with these populations is critical for distinguishing between healthy and diseased states, and for evaluating treatments that might help to improve quality of life. PUBLIC HEALTH RELEVANCE: This project focuses on separating the effects of normal aging and the early stages of Alzheimer's disease on memory abilities. Understanding the cognitive changes associated with these populations is critical for distinguishing between healthy and diseased states, and for evaluating treatments that might help to improve quality of life. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Normal aging can reduce memory resolution, or the degree of clarity and sensory detail in subjectively experienced recollections. However, we do not know the degree that these reductions are due to a primary loss of resolution abilities, diminished strategic or cognitively controlled processes, or both. The interaction of these factors at the behavioral level has limited understanding of aging effects on memory. Recent developments in fMRI research, along with well-characterized cognitive tasks, can lead to unique insights into the memory resolution problem. The recollection of previously studied pictures has been found to reliably activate specific object processing regions, reflecting the reactivation of high-level visual content in memory. Under appropriate task conditions this activity can serve as a neural signature for perceptually detailed recollections, providing a new way to test theories of memory resolution. The proposed research has two aims. Aim 1 is to understand how visually distinctive memories influence neural activity in aging. Recent research shows that aging can spare the recollection of pictures compared to words, owing to the enhanced perceptual distinctiveness and subsequent memory resolution of pictures. The degree that these distinctiveness effects influence control processes in aging is unclear. Experiment 1 tests the hypothesis that picture memories minimize the need to recruit prefrontally mediated control processes in both age groups, relying more on posterior object-processing regions that are less affected by aging. This hypothesis contrasts with a prevailing theory of aging and memory, which is that older adults recruit prefrontal control processes whenever they need to recollect specific information. Aim 2 is to investigate aging effects on memory resolution, independent from control processes. To this end, Experiment 2 uses a parametric manipulation of the resolution of presented pictures, and also manipulates the required level of cognitive control across groups. To avoid problems with direct comparisons of fMRI activity across age groups, these experiments will test for age x task interactions across comparable conditions and regions. These experiments will advance our understanding of aging effects on memory resolution and frontally mediated control processes, a topic with important health implications. Aside from control processes, memory resolution depends on the integrity of medial temporal and posterior cortical areas, regions that are most likely to be impaired in the preclinical stages of Alzheimer's disease. By characterizing normal age-related effects on memory resolution and control processes, this research will lay the foundation for future fMRI studies of memory resolution as a potential marker of the transition between healthy aging and age-related disease. PUBLIC HEALTH RELEVANCE: This project uses fMRI and cognitive tasks to investigate healthy aging effects on memory. Understanding how aging affects different memory processes is critical for developing fMRI tools to help diagnose healthy and diseased states, and for evaluating interventions that might help to improve quality of life.

? DESCRIPTION (provided by applicant): This project uses neuroimaging to enrich our understanding of the impact of negative aging stereotypes on cognitive performance in older adults - a phenomenon known as stereotype threat. We will identify task-related brain activity associated with stereotype threat, and the extent to which individual beliefs in memory ability, stereotype self-relevance, and anxiety mediate these neural effects. We also will test two hypothesized mechanisms of threat, using traditional fMRI methods and novel pattern classifier techniques. This project will inform theories of ageist stereotype threat at the psychological and neural level, which is critical for disentangling the effects of aging-related neural decline and social factors on brain activity. The impact of stereotype threat on cognitive tests has significan public health implications, not only for cognitive functioning in daily life, but because cognitive tests are used to diagnose the earliest stages of Alzheimer's disease. To the extent that threat impairs performance on these tests, an individual's true cognitive ability would be underestimated. In our study, cognitively normal older adults will be explicitly exposed to negative stereotypes about aging memory (threat condition) or a positive, age-fair framing of the task (control condition). Next, during fMRI, they will take a recollection task known to be sensitive to aging stereotype threat effects. The neural mechanisms of stereotype threat will be determined by directly comparing brain activity between the threat and control groups, as well as comparisons to brain activity in younger adult groups that are tested in conditions that simulate the cognitive processes thought to drive stereotype threat. In determining which neural mechanisms drive stereotype threat in aging populations, we hope to minimize the negative impact of ageist stereotypes on older adults, in daily cognitive routines and in medical settings where cognitive tests are used for diagnosis.

This project uses two rigorous and well-powered behavioral experiments to identify the necessary conditions for obtaining robust and reliable effects of transcranial direct current stimulation (tDCS) on human cognition. We recently discovered that time-of-day is a critical factor when stimulating dorsolateral prefrontal cortex (dlPFC), a factor that has been overlooked and may be responsible for some of the mixed results in the prior tDCS literature. The current experiments are aimed at understanding these time-of-day effects and the extent that they differ in younger and older adults, where time-of-day effects on cognition are known to reverse. To the extent that tDCS is most likely to impact cognition during suboptimal times of day, due to circadian rhythms that naturally lead to suboptimal recruitment of prefrontal cortex, we expect tDCS to dlPFC will have its largest benefit on cognition in younger adults in the morning, whereas tDCS should benefit older adults more in the afternoon. By attending to time of day and using relatively large samples, our study also will provide a stronger test of the idea that tDCS is more likely to improve cognition in older adults, as normal age-related declines in the recruitment of prefrontal processes may cause older adults to be more sensitive to prefrontal stimulation. We also will determine the extent that these benefits of tDCS generalize across episodic and working memory tasks for different kinds of information, thereby informing our understanding of the basic mechanisms through which tDCS to dlPFC can improve cognitive performance in younger and older adults. Finally, we will assess the spatial resolution of the standard tDCS technique by comparing two stimulation sites (left dlPFC vs. left parietal cortex) to sham, and we will determine the extent that a pre-post between-subjects tDCS design minimizes the unwanted effects of individual variability, thereby improving experimental sensitivity to tDCS effects while preserving the validity of the tDCS sham condition. Health Relevance: Because tDCS is the safest and most accessible non-invasive brain stimulation technique available, the identification of experimental factors that can optimize the use of the technique for experimentally manipulating brain function should lead to widespread adoption in future scientific and clinical applications. This research also will illuminate the causal role of dlPFC on the processing of different kinds of information in episodic and working memory, thereby informing our theoretical understanding of these fundamental cognitive mechanisms and how they might be impacted by the aging brain. With this knowledge in hand, future work using tDCS to manipulate brain function will be better poised to make scientific advances, and future work combining tDCS with cognitive training to induce more lasting benefits to cognitive performance will be better poised to test the effectiveness of the training techniques.