The Cognitive Control of Memory: Age Differences in the Neural Correlates of Successful Remembering and Intentional Forgetting

Successful memory encoding depends on the ability to intentionally encode relevant information (via differential encoding) and intentionally forget that which is irrelevant (via inhibition). Both cognitive processes have been shown to decline in aging and are theorized to underlie age-related deficits in the cognitive control of memory. The current study uses the Directed Forgetting paradigm in conjunction with fMRI to investigate age-related differences in both cognitive processes, with the specific aim of elucidating neural evidence supporting these theorized deficits. Results indicate relatively preserved differential encoding, with age differences consistent with previous models of age-related compensation (i.e., increased frontal and bilateral recruitment). Older adults did display noticeable differences in the recruitment of brain regions related to intentional forgetting, specifically exhibiting reduced activity in the right superior prefrontal cortex, a region shown to be critical to inhibitory processing. However, older adults exhibited increased reliance on processing in right inferior parietal lobe associated with successful forgetting. Activity in this region was negatively correlated with activity in the medial temporal lobe, suggesting a shift in the locus of inhibition compared to the frontally mediated inhibition observed in younger adults. Finally, while previous studies found intentional and incidental forgetting to be dissociable in younger adults, this differentiation appears to be reduced in older adults. The current results are the first to provide neural evidence for an age-related reduction in processes that support intentional forgetting.     

Age-Related Changes in Task Related Functional Network Connectivity

Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.     

Characteristics of learning in ontogeny

The rate of learning in young animals and in adults is different, it is higher in ontogenesis. The mechanism of learning in young animals is also different. In the ontogenesis it is similar to imprinting. Probably the mechanisms of the infantile amnesia develops according to the model of dissociated when the association is a certain chemical composition of brain which is typical of this age level. The information more important from the biological point of view is less dissipated and better restored that testifies the low effectiveness of reproductive system and not low memory trace consolidation. The difficulties in extinction and differentiation in experiments with rats are connected with reflex automatisation but not with the deficit in inhibition.     

What can functional brain imaging studies tell us about typical and atypical cognitive development in children?

Functional brain imaging has been largely reserved for adults. However, in recent years there have been increasing attempts to use functional brain imaging to inform our understanding of child development. These have taken three main forms: (1) Children with known or suspected neurological disorders may undergo brain imaging for medical diagnostic purposes and/or for the purpose of research into the nature of the disorders. (2) There have been a few studies where children, usually over the age of 8, have undergone functional brain imaging. (3) Results from brain imaging studies of adults have influenced theories about children's development. This chapter discusses the impact of brain imaging studies on our understanding of working memory; reading; and arithmetic. The different forms of brain imaging converge in demonstrating that different brain regions show differential activation for different domains and for different components within the domains: e.g. different reading strategies and different components of arithmetic. They show important similarities between children and adults, though it must be remembered that very few studies have involved young children. They also indicate that experience influences brain function, as well as the other way around.     

Effect of juvenile hormone on short-term olfactory memory in young honeybees (Apis mellifera).

Reliable retention of olfactory learning following a 1-trial classical conditioning of the proboscis extension reflex (PER) is not achieved in honeybees until they are 6-7 days old. Here we show that treatment of newly emerged honeybees with juvenile hormone (JH) has a profound effect on the maturation of short-term olfactory memory. JH-treated individuals display excellent short-term (1 h) memory of associative learning at times as early as 3 days of age and perform consistently better than untreated bees for at least the first week of their lives. By contrast, the retention of long-term (24 h) memory following a 3-trial conditioning of the PER is not significantly improved in JH-treated bees. Our study also shows that experience and (or) chemosensory activation are not essential to improve learning performance in olfactory tasks. The lack of accelerated development of long-term retention of olfactory memories in JH-treated honeybees is discussed in the context of neural circuits suspected to mediate memory formation and retrieval in the honeybee brain.     

时间认知的年老化及其神经机制

时间认知功能的增龄性衰退表现得较晚,主要在高龄老年人中表现出时间认知功能的衰退.随着年龄的增长,老年人内部时钟的速率变慢,变异增大.注意及记忆功能随年龄增长而衰退,这些一般认知功能的改变影响老年人的时间认知功能.正常的时间认知功能依赖于"核心-背景"时间加工脑网络结构和功能的完好,这些脑区或功能通路的障碍会导致时间认知功能的损伤.老年人在一定的年龄范围内,可以通过认知补偿策略保持相对完好的时间认知功能.     

Memory tests in healthy elderly: age factors and norms

The study aimed to assess the strength of age effects on both standard laboratory and ecological memory tests and the psychometric qualities of these tests. Furthermore, norm data are constructed. Memory performance was assessed in a random group of older adults (mean age 62 years, range 46-89) and a group of older adults having memory complaints who applied for memory training (mean age 63 years, range 45-85). Age effects were found on almost all memory tests, whether artificial laboratory or more ecological tests were used. Age effects remained generally present after correction for educational level. Retest reliabilities of the ecological memory tests did not differ systematically from those of standard laboratory tests. However, not all tests showed satisfactory retest reliabilities, this was even true for tests often used in clinical settings. For tests with retest reliabilities above r = .65 norms corrected for age and educational level were provided. The group of older adults having memory complaints performed on average better than the random group of older adults from the population. In the first group, higher performance thresholds should be employed in assessing whether memory performance is deviant.     

Changes in Brain Network Efficiency and Working Memory Performance in Aging

Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.     

日龄雏鸡的学习记忆模型及其分子机制和药理学研究进展

日龄雏鸡一次性被动回避学习和厌恶性条件化学习模型被广泛用于学习记忆机制的研究,并取得了很大的进展. 上纹体和旁嗅核是参与雏鸡学习记忆的主要脑区. 结合相关的分子机制研究,药理学实验发现了多种能影响不同记忆阶段的药物,如去甲肾上腺素对长时记忆有增强和调控作用. 由于鸟类和哺乳动物与记忆相关的脑结构和功能具有一定可比性,上述工作可为了解大脑的学习记忆功能提供重要参考.     

Leisure Activity,Brain β‐amyloid,and Episodic Memory in Adults with Down Syndrome

The present study provided an investigation of associations between leisure activity and early Alzheimer’s disease neuropathology (i.e., brain β‐amyloid) and episodic memory in a sample of 65 adults with Down syndrome (aged 30–53 years), at baseline and follow‐up, approximately three years apart. Findings indicated that leisure activity at baseline was not associated with brain β‐amyloid at baseline or change in brain β‐amyloid from baseline to follow‐up. Greater cognitively stimulating leisure activity at baseline was associated with better episodic memory at baseline, and greater social leisure activity at baseline was associated with less decline in episodic memory from baseline to follow‐up. High (as opposed to low) levels of social and overall leisure activity at baseline moderated the association between increase in brain β‐amyloid and decline in episodic memory, from baseline to follow‐up. Findings suggest that cognitively stimulating and social leisure activity could protect against the effect of Alzheimer’s disease neuropathology on episodic memory in adults with Down syndrome.     

Sensory mechanisms of natal stream imprinting and homing in Oncorhynchus spp.

Juvenile Oncorhynchus spp. can memorise their natal stream during downstream migration; juveniles migrate to feed during their growth phase and then they migrate long distances from their feeding habitat to their natal stream to reproduce as adults. Two different sensory mechanisms, olfaction and navigation, are involved in the imprinting and homing processes during short-distance migration within the natal stream and long-distance migration in open water, respectively. Here, olfactory functions are reviewed from both neurophysiological studies on the olfactory discrimination ability of natal stream odours and neuroendocrinological studies on the hormonal controlling mechanisms of olfactory memory formation and retrieval in the brain. These studies revealed that the long-term stability of dissolved free amino-acid composition in the natal stream is crucial for olfactory imprinting and homing. Additionally, the brain–pituitary–thyroid and brain–pituitary–gonadal hormones play important roles in olfactory memory formation and retrieval, respectively. Navigation functions were reviewed from physiological biotelemetry techniques with sensory interference experiments during the homing migration of anadromous and lacustrine Oncorhynchus spp. The experiments demonstrated that Oncorhynchus spp. used compass navigation mechanisms in the open water. These findings are discussed in relation to the sensory mechanisms involved in natal stream imprinting and homing in Oncorhynchus spp.     

Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats

The current experiments examined the impact of early‐life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal‐dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal‐dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal‐dependent context pre‐exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL‐1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL‐1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL‐1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL‐6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal‐dependent learning deficits at this young age. These findings underscore the need to consider age and associated on‐going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early‐life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221–1236, 2017     

Odor identification, consistency of label use, olfactory threshold and their relationships to odor memory over the human lifespan.

The purpose of this study was to investigate olfactory threshold, odor identification, consistency of label use and their relationships to odor memory in the context of semantic/episodic memory across the human lifespan. A total of 137 subjects aged 4-90 years were tested with several olfactory test procedures. We found that olfactory sensitivity was well developed in children despite the finding that their odor naming and odor memory were inferior to that of adults. In the elderly population, olfactory functions gradually declined, with odor memory and odor identification demonstrating the most significant decline. Semantic encoding was differentially related to odor memory over the human age span. Whereas consistency of label use was the main predictor for odor memory in children and young adults, olfactory identification ability was the main predictor in the elderly study group. We also calculated response bias for the separate age groups and found no differences between children, young adults and elderly. However, with age false alarm rates increased. We conclude that children possess equal olfactory sensitivity compared with adults; however, due to limitations in linguistic capabilities and familiarity to odorants, odor memory and odor identification performance was limited. Additionally, our data indicate major alterations of olfactory processing in advanced age with substantial losses in odor memory and odor identification performance.     

Identification of a Functional Connectome for Long-Term Fear Memory in Mice

Long-term memories are thought to depend upon the coordinated activation of a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated a much more global network. Here we used a global mapping approach to identify networks of brain regions activated following recall of long-term fear memories in mice. Analysis of Fos expression across 84 brain regions allowed us to identify regions that were co-active following memory recall. These analyses revealed that the functional organization of long-term fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. Most importantly, these analyses indicate that long-term memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties, and contains hub-like regions in the prefrontal cortex and thalamus that may play privileged roles in memory expression.     

Increased brain signal variability accompanies lower behavioral variability in development

As the brain matures, its responses become optimized. Behavioral measures show this through improved accuracy and decreased trial-to-trial variability. The question remains whether the supporting brain dynamics show a similar decrease in variability. We examined the relation between variability in single trial evoked electrical activity of the brain (measured with EEG) and performance of a face memory task in children (8–15 y) and young adults (20–33 y). Behaviorally, children showed slower, more variable response times (RT), and less accurate recognition than adults. However, brain signal variability increased with age, and showed strong negative correlations with intrasubject RT variability and positive correlations with accuracy. Thus, maturation appears to lead to a brain with greater functional variability, which is indicative of enhanced neural complexity. This variability may reflect a broader repertoire of metastable brain states and more fluid transitions among them that enable optimum responses. Our results suggest that the moment-to-moment variability in brain activity may be a critical index of the cognitive capacity of the brain.     

Docosahexaenoic Acid and Adult Memory: A Systematic Review and Meta-Analysis

Introduction

Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function.

Objectives

The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature.

Methods

A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge’s g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested.

Results

Episodic memory outcomes of adults with MMC were significantly (P<.004) improved with DHA/EPA supplementation. Regardless of cognitive status at baseline, > 1 g/day DHA/EPA improved episodic memory (P<.04). Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults.

Conclusion

DHA, alone or combined with EPA, contributes to improved memory function in older adults with mild memory complaints.     

Age-Related Decline in Associative Learning in Healthy Chinese Adults

Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.     

Is the alpha rhythm a control parameter for brain responses?

 The main goal of the present study is to develop a conceptual analysis of alpha response in the brain based on single sweep evaluation. A new method was employed to estimate a set of single-sweep parameters and quantify the oscillatory behaviour of single, electroencephalograph (EEG) sweeps. It was aimed to demonstrate that brain alpha responses are governed by spontaneous alpha activity and to validate the principle of brain response excitability. Because the spontaneous alpha activity depends on both the topology of recording and the subject’s age, topology and age models were used. Spontaneous and evoked alpha activity were recorded at frontal and occipital sites in three groups of subjects: 3-year-old children, young adults and middle-aged subjects. Amplitude, enhancement and phase-locking of single alpha responses to visual stimuli were analysed. Major results showed that: (1) visual alpha responses could be recorded only if the alpha rhythm was developed in the spontaneous EEG independent of electrode location; (2) middle-aged adults showed more expressed frontal spontaneous alpha activity in comparison with young adults; (3) accordingly, alpha responses with higher amplitude and stronger phase-locking were produced over the frontal brain area in middleaged than young adults. These results validate the principle of brain response excitability and demonstrate that a shift towards frontal brain areas for both the spontaneous and evoked alpha activity occurs with increasing age in adults. The results are discussed in the context of the diffuse and distributed alpha system of the brain. Age-dependent changes in frontal alpha activity are suggested to be related to frontal brain functioning during aging. Received: 6 November 1995 / Accepted in revised form: 13 March 1997     

Role of RNA and protein synthesis in memory formation

A brief review is given of experiments which are concerned with the hypothesis that brain RNA and protein synthesis are directly involved in the establishment of long-term memory. It is concluded that these experiments neither support or refute this hypothesis. A convincing demonstration is lacking of interanimal memory transfer by injection of macromolecular extracts. The majority of experiments which attempt to correlate increased macromolecular synthesis with learning use radioactive precursor methods and these studies do not exclude possible changes in precursor specific activity as the cause of the increased labeling. Although some studies find directly observable changes in brain macromolecules in response to training, their relationship to memory formation is unclear. It is possible that these changes represent only an enhanced production of constitutive macromolecules in response to an increase in cerebral metabolism during training, rather than molecular changes that are directly involved with modifying synaptic connectivity. Inhibitors of cerebral protein synthesis block memory formation, but these drugs are not pharmacologically specific and this complicates the interpretation of these studies.