Cognitive neuroscience of aging: contributions of functional neuroimaging

By revealing how brain activity during cognitive performance changes as a function of aging, studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are contributing to the development of a new discipline of Cognitive Neuroscience of Aging. This article reviews functional neuroimaging studies of cognitive aging in the domains of visual perception, episodic memory encoding and semantic memory retrieval, episodic memory retrieval, implicit memory, and working memory. The most consistent finding of these studies was that brain activity tends to be less lateralized in older adults than in younger adults. This finding is conceptualized in terms of a model called Hemispheric Asymmetry Reduction in Old Adults (HAROLD). According to a compensation hypothesis, bihemispheric involvement could help counteract age-related neurocognitive decline, whereas, according to a dedifferentiation hypothesis, it reflects a difficulty in recruiting specialized neural mechanisms.     

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: what’s memory got to do with it?

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability.     

情景记忆成功年老化的神经机制

随着年龄的增长, 大部分老年人的情景记忆会出现衰退, 但也会有一部分老年人的情景记忆表现出成功的年老化, 即记忆成绩较好或随增龄的衰退程度较小。脑保持理论、神经去分化理论、认知储备理论以及神经补偿理论分别从不同角度解释了情景记忆成功年老化的神经机制。基于选择性优化与补偿模型对现有理论进行整合, 发现情景记忆成功年老化可能与个体的认知储备水平直接相关：高认知储备的老年人能够对情景记忆相关的脑区和脑网络进行优化且具备更强的神经补偿能力, 因而其脑功能(比如, 神经表征和神经加工通路的特异性)可能会保持地更好。未来研究需要更多地采用纵向设计来考察各理论之间的关系及其影响因素, 从而更好地解释记忆成功年老化的神经机制并为提升老年人的脑与认知健康提供支持。     

认知功能的性别差异

我们了概述认知功能的性别差异, 尤其是情节记忆功能的性别差异。已有的研究结果表明女性在言语生成、情节记忆、面孔识别任务中比男性存在明显的优势, 而男性的优势则表现在视空间任务中, 如视空间情节记忆任务。本文批判性地讨论了一个流行的假设: 类固醇激素影响认知功能的性别差异, 得出的结论是内源性睾丸激素或雌二醇均未显著影响认知功能的性别差异。     

Visual associations cued recall A Paradigm for Measuring Episodic Memory Decline in Alzheimer’s Disease

Repeated measurements of episodic memory are needed for monitoring amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD). Most episodic memory tests may pose a challenge to patients, even when they are in the milder stages of the disease. This cross-sectional study compared floor effects of the Visual Association Test (VAT) and the Rey Auditory Verbal Learning Test (RAVLT) in healthy elderly controls and in patients with aMCI or AD (N = 125). A hierarchical multiple regression analysis was used to examine whether linear or quadratic trends best fitted the data of cognitive test performance across global cognitive impairment. Results showed that VAT total scores decreased linearly across the range of global cognitive impairment, whereas RAVLT total scores showed a quadratic trend, with total scores levelling off for 90% of aMCI patients and 94% of AD patients. We conclude that the VAT shows few if any floor effects in patients with aMCI and mild AD and is therefore a potentially promising cognitive test for monitoring episodic memory impairment.     

Visual associations to retrieve episodic memory across healthy elderly,mild cognitive impairment,and patients with Alzheimer’s disease

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer’s disease (AD), this may support health care to be more closely aligned with patients’ memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects. The VAT-E consists of 24 pairs of black-and-white line drawings. In a within-group design, we compared score distributions of VAT-E subtests in healthy elderly controls, mild cognitive impairment (MCI), and AD (n = 144), as well as in relation to global cognitive impairment. Paired associate recall showed a floor effect in 41% of MCI patients and 62% of AD patients. Free recall showed a floor effect in 73% of MCI patients and 84% of AD patients. Multiple-choice cued recognition did not show a floor effect in either of the patient groups. We conclude that the VAT-E covers a broad range of episodic memory decline in patients. As expected, paired associate recall was of intermediate difficulty, free recall was most difficult, and multiple-choice cued recognition was least difficult for patients. These varying levels of difficulty enable a more accurate determination of the level of retrieval support that can still benefit patients across a broad range of cognitive decline.     

Cognitive processes supporting episodic memory formation in childhood: The role of source memory,binding, and executive functioning

Episodic memories contain various forms of contextual detail (e.g., perceptual, emotional, cognitive details) that need to become integrated. Each of these contextual features can be used to attribute a memory episode to its source, or origin of information. Memory for source information is one critical component in the formation of episodic memories. Likewise, the establishment of episodic memories also requires binding, which reflects the process of encoding the relations among stimuli and provides the experience that certain features of a memory episode belong together. The aims of the present review are to explore the roles of (1) cognitive and neural mechanisms involved in source memory and binding and how the development of these cognitive processes relates to episodic memory formation in childhood and (2) other higher-order cognitive processes, namely executive functioning, in early episodic memory development. We conclude by examining the challenges within this field of research, highlighting the role of other cognitive processes (e.g., sense of self, language, use of strategies) that may contribute to episodic memory formation, addressing areas that can be improved with additional research, and exploring directions for future work.     

Contextual inference in learning and memory

Context is widely regarded as a major determinant of learning and memory across numerous domains, including classical and instrumental conditioning, episodic memory, economic decision-making, and motor learning. However, studies across these domains remain disconnected due to the lack of a unifying framework formalizing the concept of context and its role in learning. Here, we develop a unified vernacular allowing direct comparisons between different domains of contextual learning. This leads to a Bayesian model positing that context is unobserved and needs to be inferred. Contextual inference then controls the creation, expression, and updating of memories. This theoretical approach reveals two distinct components that underlie adaptation, proper and apparent learning, respectively referring to the creation and updating of memories versus time-varying adjustments in their expression. We review a number of extensions of the basic Bayesian model that allow it to account for increasingly complex forms of contextual learning.     

The effect of education on the onset and rate of terminal decline

Differences in the time of onset and magnitude of terminal decline were examined in three cognitive domains: processing speed, episodic memory, and global function. In addition, cognitive reserve was investigated by testing whether education affected the onset or rate of decline across these domains. Eight hundred ninety-six community-dwelling Australian adults aged ≥ 70 years were assessed up to four times over 12 years, with vital status followed for 17 years. For each of the cognitive measures, a series of change point models were fitted across the 20 years before death to find the optimal point at which terminal decline was distinguished from preterminal decline. Change points were then assessed separately for high- and low-education groups. The change points were 8.5 years for processing speed (95% CI: 6.0-11.2 years), 7.1 years for global function (6.2-9.3), and 6.6 years for episodic memory (5.3-7.1). The rate of decline was two to four times greater in the terminal phase relative to the preterminal phase, depending on the domain. Increased education changed the terminal decline effect differently for each of the three tests, either by significantly hastening the onset of terminal decline and decreasing the rate of decline, or by increasing the rate of either preterminal or terminal decline. Analyses were repeated excluding participants diagnosed with dementia, with no substantive change to the outcomes. In conclusion, the rate and onset of terminal decline varied somewhat across cognitive domains. Education affected terminal decline differently across the domains, but this modification was not consistent with the predictions of cognitive reserve theory.     

Brain activations associated with shifts in response criterion on a recognition test.

Sensitivity and bias can be manipulated independently on a recognition test. The goal of this fMRI study was to determine whether neural activations associated with manipulations of a decision criterion would be anatomically distinct from neural activations associated with manipulations of memory strength and episodic retrieval. The results indicated that activations associated with shifting criteria (a manipulation of bias) were located in bilateral regions of the lateral cerebellum, lateral parietal lobe, and the dorsolateral prefrontal cortex extending from the supplementary motor area. These regions were anatomically distinct from activations in the prefrontal cortex produced during memory-based retrieval processes (manipulations of sensitivity), which tended to be more medial and anterior. These later activations are consistent with previous studies of episodic retrieval. Determining patterns of neural activations associated with decision-making processes relative to memory processes has important implications for Cognitive Neuroscience, including the use of these patterns to compare memory models in different paradigms.     

Understanding memory impairment with memory models and hierarchical Bayesian analysis

The study of human episodic memory is a topic that interests cognitive and mathematical psychologists as well as clinicians interested in the diagnosis and assessment of Alzheimer’s disease and related disorders (ADRD). In this paper, we use simple cognitive models for the recognition and recall tasks typically applied in clinical assessments of ADRD to study memory performance in ADRD patients. Our models make use of hierarchical Bayesian methods as a way to model individual differences in patient performance and to facilitate the modeling of performance changes that occur during multiple recall tasks. We show how the models are able to account for different aspects of patient performance, and also discuss some of the predictive capabilities of the model. We conclude with a discussion on the scope to improve on our results by discussing the link between memory theory in psychology and clinical practice.     

The posterior parietal paradox: Why do functional magnetic resonance imaging and lesion studies on episodic memory produce conflicting results?

Recent functional magnetic resonance imaging (fMRI) studies addressing healthy subjects point towards posterior parietal cortex (PPC) involvement in episodic memory tasks. This is noteworthy, since neuropsychological studies usually do not connect parietal lesions to episodic memory impairments. Therefore an inventory of the possible factors behind this apparent paradox is warranted. This review compared fMRI studies which demonstrated PPC activity in episodic memory tasks, with findings with studies of patients with PPC lesions. A systematic evaluation of possible explanations for the posterior parietal paradox indicates that PPC activation in fMRI studies does not appear to be attributable to confounding cognitive/psychomotor processes, such as button pressing or stimulus processing. What may be of more importance is the extent to which an episodic memory task loads on three closely related cognitive processes: effort and attention, self‐related activity, and scene and image construction. We discuss to what extent these cognitive processes can account for the paradox between lesion and fMRI results. They are strongly intertwined with the episodic memory and may critically determine in how far the PPC plays a role in a given memory task. Future patient studies might profit from specifically taking these cognitive factors into consideration in the task design.     

Type 2 Diabetes Mellitus and Cognitive Performance in a Population-Based Sample of the Oldest Old: Impact of Comorbid Dementia

We examined the relationship between type 2 diabetes mellitus and cognitive function in a population-based sample of very old people. The sample comprised 338 persons, aged 80-93 years (mean age 83.5 years), of whom 70 persons had type 2 diabetes mellitus. Measures of cognitive functioning included tests of perceptual speed, visuo-spatial ability, inductive reasoning, short-term memory, semantic memory, episodic memory, and the Mini-Mental State Examination. Regression analyses showed that type 2 diabetes mellitus duration was related to test performance across all cognitive domains, with the exception of short-term memory, such that longer duration was associated with lower test performance. When cases with dementia were excluded from the sample, further analyses showed that diabetes duration was not associated with cognitive test performance. This indicates that diabetes is not related to lower cognitive function in the general population of non-demented old people. Diabetes, however, increases the risk for cerebrovascular incidents, like stroke, that may contribute to vascular dementia.     

提取练习效应的产生机制:编码、提取的整合演变

提取练习效应指相比同等时间的重复学习,对所学材料进行提取练习(即使无反馈)可使被试在之后的回忆测验中表现更好。早期研究从编码或提取单维度地对提取练习效应进行了描述性解释,新近以来,研究者整合了编码和提取在提取练习效应中的作用,从记忆加工全过程的角度考察了提取练习效应的产生机制,并得到诸多研究证据的支持。论文梳理了提取练习效应产生机制的各类假说,并重点分析比较了精细提取假说和情景背景假说,指出后者在解释提取练习效应上的优势。未来研究可结合认知神经科学的研究技术为情景背景假说提供更直接的证据,有关提取练习对于短期和长期记忆促进效果的争议也有待进一步解释厘清,同时如何在揭示其原理的基础上将其更高效地加以应用亦有待实践探索。     

Terminal decline and cognitive performance in very old age: does cause of death matter?

Cross-sectional differences and longitudinal changes in cognitive functioning in relation to mortality across a 7-year follow-up period, with 3 times of measurement, were examined in a population-based sample of very old adults. The authors also sought to determine whether cause of death (cerebro/cardiovascular disease [CVD]; non-CVD) modified the magnitude of mortality-related cognitive deficits. Cognitive performance was indexed by tests of general cognitive ability, episodic memory, primary memory, verbal fluency, and visuospatial ability. Results indicated cross-sectional differences on all domains of functioning, with persons who would die within 3 years after baseline testing performing more poorly. Longitudinally, greater decrements were observed on all domains for persons who would die after the first follow-up period, as compared with survivors. Cause of death failed to modify the magnitude of the cross-sectional and longitudinal deficits. The pattern of results point to the general nature of this phenomenon.     

Cognition in schizophrenia: core psychological and neural mechanisms

The challenge in understanding cognitive impairment in schizophrenia is that people with this illness have deficits in an array of domains. Here, we briefly review evidence regarding the pattern of deficits within three domains: context processing, working memory and episodic memory. We suggest that there may be a common mechanism driving deficits in these domains - an impairment in the ability to actively represent goal information in working memory to guide behavior, a function we refer to as proactive control. We suggest that such deficits in proactive control reflect impairments in dorsolateral prefrontal cortex, its interactions with other brain regions, such as parietal cortex, thalamus and striatum, and the influence of neurotransmitter systems, such as dopamine, GABA and glutamate.     

Cognitive neuroscience of episodic memory encoding

This paper presents a cognitive neuroscientific perspective on how human episodic memories are formed. Convergent evidence from multiple brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggests a role for frontal cortex in episodic memory encoding. Activity levels within frontal cortex can predict episodic memory encoding across a wide range of behavioral manipulations known to influence memory performance, such as those present during levels of processing and divided attention manipulations. Activity levels within specific frontal and medial temporal regions can even predict, on an item by item basis, whether an episodic memory is likely to form. Furthermore, separate frontal regions appear to participate in supplying code-specific information, including distinct regions which process semantic attributes of verbal information as well as right-lateralized regions which process nonverbal information. We hypothesize that activity within these multiple frontal regions provides a functional influence (input) to medical temporal regions that bind the information together into a lasting episodic memory trace.     

A simple neural network model of the hippocampus suggesting its pathfinding role in episodic memory retrieval

The goal of this work is to extend the theoretical understanding of the relationship between hippocampal spatial and memory functions to the level of neurophysiological mechanisms underlying spatial navigation and episodic memory retrieval. The proposed unifying theory describes both phenomena within a unique framework, as based on one and the same pathfinding function of the hippocampus. We propose a mechanism of reconstruction of the context of experience involving a search for a nearly shortest path in the space of remembered contexts. To analyze this concept in detail, we define a simple connectionist model consistent with available rodent and human neurophysiological data. Numerical study of the model begins with the spatial domain as a simple analogy for more complex phenomena. It is demonstrated how a nearly shortest path is quickly found in a familiar environment. We prove numerically that associative learning during sharp waves can account for the necessary properties of hippocampal place cells. Computational study of the model is extended to other cognitive paradigms, with the main focus on episodic memory retrieval. We show that the ability to find a correct path may be vital for successful retrieval. The model robustly exhibits the pathfinding capacity within a wide range of several factors, including its memory load (up to 30,000 abstract contexts), the number of episodes that become associated with potential target contexts, and the level of dynamical noise. We offer several testable critical predictions in both spatial and memory domains to validate the theory. Our results suggest that (1) the pathfinding function of the hippocampus, in addition to its associative and memory indexing functions, may be vital for retrieval of certain episodic memories, and (2) the hippocampal spatial navigation function could be a precursor of its memory function.     

Which processes are involved in cognitive procedural learning?

Procedural memory is characterised by a relative resistance to pathology, making its assessment of the utmost importance. However, few studies have looked at the cognitive processes involved in cognitive procedural learning. In an initial experiment, we studied the role of different cognitive functions in massed cognitive procedural learning. Our results confirmed the existence of three separate learning phases and, for the first time, demonstrated the involvement of episodic memory and executive functions in the first learning phase. In a second experiment, we studied the effect of distributed learning conditions on the dynamics of procedural learning. This second study confirmed our results but showed that these conditions slow down the process of cognitive procedural learning. Our overall findings call into question the status of functionally autonomous memory system that is currently allotted to procedural memory, and suggest that the role of nonprocedural cognitive components should be taken into account in patient rehabilitation.