Neural reinstatement of context memory in adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is associated with episodic memory impairment. However, episodic memories include a variety of contextual details, and it is difficult to solely rely on behavioral data to assess how specifically (i.e. event-specific reinstatement) an event is remembered. We applied encoding-retrieval representational similarity (ERS) analysis to EEG data to assess event-specific ERS for object-context associations in a sample of 34 adults (17 with, 17 without ASD). Participants studied objects presented alongside 2 contextual features: scene/color, and attention was directed toward one object-context relationship. At retrieval, memory was assessed for the object and both contexts. Behavioral results revealed no group differences in item or context memory performance. ERS results revealed group temporal differences in reinstatement. Results may indicate differences in both encoding (i.e. fewer perceptual details) and retrieval (i.e. ineffectively skipping through memory fragments) in ASD and should be further investigated in studies modulating the perceptual detail required for memory decisions. Results highlight the utility of ERS as a methodology used to evaluate episodic reinstatement even in the absence of behavioral differences in memory performance.

Empirically derived psychosocial-behavioral phenotypes in Black/African American and Hispanic/Latino older adults enrolled in HABS-HD: Associations with AD biomarkers and cognitive outcomes.

INTRODUCTION: Identification of psychosocial-behavioral phenotypes to understand within-group heterogeneity in risk and resiliency to Alzheimer's disease (AD) within Black/African American and Hispanic/Latino older adults is essential for the implementation of precision health approaches. METHODS: A cluster analysis was performed on baseline measures of socioeconomic resources (annual income, social support, occupational complexity) and psychiatric distress (chronic stress, depression, anxiety) for 1220 racially/ethnically minoritized adults enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). Analyses of covariance adjusting for sociodemographic factors examined phenotype differences in cognition and plasma AD biomarkers. RESULTS: The cluster analysis identified (1) Low Resource/High Distress (n = 256); (2) High Resource/Low Distress (n = 485); and (3) Low Resource/Low Distress (n = 479) phenotypes. The Low Resource/High Distress phenotype displayed poorer cognition and higher plasma neurofilament light chain; differences between the High Resource/Low Distress and Low Resource/Low Distress phenotypes were minimal. DISCUSSION: The identification of psychosocial-behavioral phenotypes within racially/ethnically minoritized older adults is crucial to the development of targeted AD prevention and intervention efforts.

Lower Body Mass Index at Baseline Is Related to Steeper Cognitive Decline in the Alzheimer's Disease Neuroimaging Initiative Cohort.

OBJECTIVE: Midlife obesity is a risk factor for dementia, whereas obesity in older age may be protective of cognition, a phenomenon known as the "obesity paradox." The mechanisms underlying this phenomenon and the relationship between body mass index (BMI) and cognitive function over time remain unclear. METHODS: In 1399 adults with and without mild cognitive impairment (median age 73.6 years) from the Alzheimer's Disease Neuroimaging Initiative, we modeled the effects of baseline BMI on within-person trajectories of cognitive decline using Latent Growth Curve Modeling. We also tested if the effects of BMI on cognitive decline are global or specific to memory, executive function, or language. RESULTS: Higher baseline BMI was associated with better memory ( ßBMI = 0.06, p < .05) and worse executive function ( ßBMI = -0.05, p < .05) and not associated with language. Independent of baseline diagnosis, higher baseline BMI was associated with slower rate of decline in executive function, memory, and language ( ßBMI = 0.13, 0.12, and 0.12, respectively; p < .01). Higher BMI was not associated with the intercept ( ßBMI = 0.04, p = .059) or change ( ßBMI = 0.04, p = .415) in a global cognitive factor. CONCLUSIONS: We found that higher baseline BMI was associated with slower cognitive decline in participants with and without mild cognitive impairment diagnosis. Higher BMI in this context seems to be protective of cognitive function for people at risk for dementia. Our findings also support domain-specific effects of obesity on various cognitive functions rather than a final common pathway.

Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing.

Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed 'optimally ageing'. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular - compensation, maintenance and reserve - have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

Author Correction: Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing.

In the originally published version of article, there were two errors in the references. The reference "Nilsson, J. & Lövdén, M. Naming is not explaining: future directions for the "cognitive reserve" and "brain maintenance" theories. Alzheimer's Res. Ther. 10, 34 (2018)" was missing. This reference has been added as REF. 14 in the HTML and PDF versions of the article and cited at the end of the sentence "However, over the years, these terms have been used inconsistently, creating confusion and slowing progress." on page 701 and at the end of the sentence "If reserve is defined merely as the factor that individuals with greater reserve have and then this factor is used to explain why some individuals have greater reserve, the argument is clearly circular." on page 704. The reference list has been renumbered accordingly. In addition, in the original reference list, REF. 91 was incorrect. The reference should have read "Cabeza, R. Hemispheric asymmetry reduction in older adults. The HAROLD model. Psychol. Aging 17, 85-100 (2002)". This reference, which is REF. 92 in the corrected reference list, has been corrected in the HTML and PDF versions of the article.

Publisher Correction: Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing.

In Figure 3b of the originally published article, the colours of the bars were incorrectly reversed. The bars shown in green should have been shown in blue to represent the findings from older adults, whereas the bars shown in blue should have been shown in green to represent the findings from young adults. This has been corrected in the HTML and PDF versions of the article. Images of the original figure are shown in the correction notice.

Neural Reinstatement of Overlapping Memories in Young and Older Adults.

When we update our episodic memories with new information, mnemonic competition between old and new memories may result because of the presence of shared features. Behavioral studies suggest that this competition can lead to proactive interference, resulting in unsuccessful memory updating, particularly for older adults. It is difficult with behavioral data alone to measure the reactivation of old, overlapping memories during retrieval and its impact on memory for new memories. Here, we applied encoding-retrieval representational similarity (ERS) analysis to EEG data to estimate event-specific encoding-related neural reinstatement of old associations during the retrieval of new ones and its impact on memory for new associations in young and older adults. Our results showed that older adults' new associative memory performance was more negatively impacted by proactive interference from old memories than that of young adults. In both age groups, ERS for old associative memories was greater for trials for which new associative memories were forgotten than remembered. In contrast, ERS for new associative memories was greater when they were remembered than forgotten. In addition, older adults showed relatively attenuated target (i.e., new associates) and lure (i.e., old associates) ERS effects compared to younger adults. Collectively, these results suggest that the neural reinstatement of interfering memories during retrieval contributes to proactive interference across age, whereas overall attenuated ERS effect in older adults might reflect their reduced memory fidelity.

Evaluation of classification approaches for distinguishing brain states predictive of episodic memory performance from electroencephalography: Abbreviated Title: Evaluating methods of classifying memory states from EEG.

Previous studies have attempted to separate single trial neural responses for events a person is likely to remember from those they are likely to forget using machine learning classification methods. Successful single trial classification holds potential for translation into the clinical realm for real-time detection of memory and other cognitive states to provide real-time interventions (i.e., brain-computer interfaces). However, most of these studies-and classification analyses in general- do not make clear if the chosen methodology is optimally suited for the classification of memory-related brain states. To address this problem, we systematically compared different methods for every step of classification (i.e., feature extraction, feature selection, classifier selection) to investigate which methods work best for decoding episodic memory brain states-the first analysis of its kind. Using an adult lifespan sample EEG dataset collected during performance of an episodic context encoding and retrieval task, we found that no specific feature type (including Common Spatial Pattern (CSP)-based features, mean, variance, correlation, features based on AR model, entropy, phase, and phase synchronization) outperformed others consistently in distinguishing different memory classes. However, extracting all of these feature types consistently outperformed extracting only one type of feature. Additionally, the combination of filtering and sequential forward selection was the optimal method to select the effective features compared to filtering alone or performing no feature selection at all. Moreover, although all classifiers performed at a fairly similar level, LASSO was consistently the highest performing classifier compared to other commonly used options (i.e., naïve Bayes, SVM, and logistic regression) while naïve Bayes was the fastest classifier. Lastly, for multiclass classification (i.e., levels of context memory confidence and context feature perception), generalizing the binary classification using the binary decision tree performed better than the voting or one versus rest method. These methods were shown to outperform alternative approaches for three orthogonal datasets (i.e., EEG working memory, EEG motor imagery, and MEG working memory), supporting their generalizability. Our results provide an optimized methodological process for classifying single-trial neural data and provide important insight and recommendations for a cognitive neuroscientist's ability to make informed choices at all stages of the classification process for predicting memory and other cognitive states.

Preparing for the Worst: Evidence that Older Adults Proactively Downregulate Negative Affect.

Previous studies have only investigated age-related differences in emotional processing and encoding in response to, not in anticipation of, emotional stimuli. In the current study, we investigated age-related differences in the impact of emotional anticipation on affective responses and episodic memory for emotional images. Young and older adults were scanned while encoding negative and neutral images preceded by cues that were either valid or invalid predictors of image valence. Participants were asked to rate the emotional intensity of the images and to complete a recognition task. Using multivariate behavioral partial least squares (PLS) analysis, we found that greater anticipatory recruitment of the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus in older adults predicted reduced memory for negative than neutral images and the opposite for young adults. Seed PLS analysis further showed that following negative cues older adults, but not young adults, exhibited greater activation of vmPFC, reduced activation of amygdala, and worse memory for negative compared with neutral images. To the best of our knowledge, this is the first study to provide evidence that the "positivity effect" seen in older adults' memory performance may be related to the spontaneous emotional suppression of negative affect in anticipation of, not just in response to, negative stimuli.

How Proactive Interference during New Associative Learning Impacts General and Specific Memory in Young and Old.

Some prior research has found that older adults are more susceptible to proactive interference than young adults. The current study investigated whether age-related deficits in pFC-mediated cognitive control processes that act to detect and resolve interference underlie increased susceptibility to proactive interference in an associative memory task. Young and older adults were scanned while tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high, low, or no proactive interference. After scanning, participants' memory was tested for varying levels of episodic detail about the pairings (i.e., target category vs. specific target category vs. specific target associate). Young and older adults were similarly susceptible to proactive interference. Memory for both the general target category and the specific target associate worsened as the level of proactive interference increased, with no robust age differences. For both young and older adults, the left ventrolateral pFC, which has been indicated in controlled retrieval of goal-relevant conceptual representations, was sensitive to increasing levels of interference during encoding but was insensitive to associative memory accuracy. Consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis model of cognitive aging, the ventromedial pFC, which is involved in the monitoring of internally generated information, was recruited more by older than young adults to support the successful retrieval of target-object pairs at lower levels of proactive interference. Collectively, these results suggest that some older adults are able to engage in the cognitive control processes necessary to resolve proactive interference to the same extent as young adults.

Multielement Episodic Encoding in Young and Older Adults.

Previous research on age-related associative memory deficits has generally focused on memory for single associations. However, our real-world experiences contain a multitude of details that must be effectively integrated and encoded into coherent representations to facilitate subsequent retrieval of the event as a whole. How aging interferes with the processes necessary for multielement encoding is still unknown. We investigated this issue in the current fMRI study. While undergoing scanning, young and older adults were presented with an occupation and an object and were asked to judge how likely the two were to interact, either in general or within the context of a given scene. After scanning, participants completed recognition tasks for the occupation-object pairs and the sources/contexts with which the pairs were studied. Using multivariate behavioral partial least squares analyses, we identified a set of regions including anterior pFC and medial-temporal lobes whose activity was beneficial to subsequent memory for the pairs and sources in young adults but detrimental in older adults. An additional behavioral partial least squares analysis found that, although both groups recruited anterior pFC areas to support context memory performance, only in the young did this activity appear to reflect integration of the occupation, object, and scene features. This was also consistent with behavioral results, which found that young adults showed greater conditional dependence between pair and context memory compared with older adults. Together, these findings suggest that binding and/or retrieving multiple details as an integrated whole becomes increasingly difficult with age.

Decoding selective attention to context memory: An aging study.

Emerging evidence has suggested that the tendency for older adults to bind too much contextual information during encoding (i.e., hyper-binding) may contribute to poorer memory for relevant contextual information during retrieval. While these findings are consistent with theories of age-related declines in selective attention and inhibitory control, the degree to which older adults are able to selectively attend to relevant contextual information during encoding is unknown. To better understand the neural dynamics associated with selective attention during encoding, the current study applied multivariate pattern analyses (MVPA) to oscillatory EEG in order to track moment-to-moment shifts of attention between relevant and irrelevant contextual information during encoding. Young and older adults studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object's relationship with one of those contexts (i.e., target context). Results showed that patterns of oscillatory power successfully predicted whether selective attention was directed to a scene or color, across age groups. Individual differences in overall classification performance were associated with individual differences in target context memory accuracy during retrieval. However, changes in classification performance within a trial, suggestive of fluctuations in selective attention, predicted individual differences in hyper-binding. To the best of our knowledge, this is the first study to use MPVA techniques to decode attention during episodic encoding and the impact of attentional shifts toward distracting information on age-related context memory impairments and hyper-binding. These results are consistent with the as-of-yet unsubstantiated theory that age-related declines in context memory may be attributable to poorer selective attention and/or greater inhibitory deficits in older adults.

The effect of mild acute stress during memory consolidation on emotional recognition memory.

Stress during consolidation improves recognition memory performance. Generally, this memory benefit is greater for emotionally arousing stimuli than neutral stimuli. The strength of the stressor also plays a role in memory performance, with memory performance improving up to a moderate level of stress and thereafter worsening. As our daily stressors are generally minimal in strength, we chose to induce mild acute stress to determine its effect on memory performance. In the current study, we investigated if mild acute stress during consolidation improves memory performance for emotionally arousing images. To investigate this, we had participants encode highly arousing negative, minimally arousing negative, and neutral images. We induced stress using the Montreal Imaging Stress Task (MIST) in half of the participants and a control task to the other half of the participants directly after encoding (i.e. during consolidation) and tested recognition 48h later. We found no difference in memory performance between the stress and control group. We found a graded pattern among confidence, with responders in the stress group having the least amount of confidence in their hits and controls having the most. Across groups, we found highly arousing negative images were better remembered than minimally arousing negative or neutral images. Although stress did not affect memory accuracy, responders, as defined by cortisol reactivity, were less confident in their decisions. Our results suggest that the daily stressors humans experience, regardless of their emotional affect, do not have adverse effects on memory.

Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference.

Aging affects the interaction between attentional control and source memory: an fMRI study.

Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.

Medial prefrontal cortex supports source memory for self-referenced materials in young and older adults.

Behavioral evidence suggests that young and older adults show a benefit in source memory accuracy when processing materials in reference to the self. In the young, activity within the medial prefrontal cortex supports this source memory benefit at study. In this investigation, we examined whether the same neural regions support this memory benefit in both age groups. Using fMRI, we scanned participants while they studied and retrieved pictures of objects paired with one of three scenes (source) under self-reference and other-reference conditions. At the time of study, half of the items were presented once and half twice, allowing us to match behavioral performance between the groups. Both groups showed equivalent source accuracy benefits for objects encoded self-referentially. Activity in the left dorsal medial prefrontal cortex supported subsequent source memory in both age groups for the self-referenced relative to the other-referenced items. At the time of test, source accuracy for both the self- and other-referenced items was supported by a network of regions including the precuneus in both age groups. At both study and test, little in the way of age differences emerged, suggesting that when they are matched on behavioral performance, young and older adults engage similar regions in support of source memory when processing materials in reference to the self; however, when we did not match performance, age differences in functional recruitment were prevalent. These results suggest that by capitalizing on preserved processes (self-referential encoding), older adults can show improvement in memory for source details that they would typically not remember well, relative to the young.

More than the sum of its parts: investigating episodic memory as a multidimensional cognitive process.

Why do we remember some events but forget others? Previous studies attempting to decode successful vs. unsuccessful brain states to investigate this question have met with limited success, potentially due, in part, to assessing episodic memory as a unidimensional process, despite evidence that multiple domains contribute to episodic encoding. Using a novel machine learning algorithm known as "transfer learning", we leveraged visual perception, sustained attention, and selective attention brain states to better predict episodic memory performance from trial-to-trial encoding electroencephalography (EEG) activity. We found that this multidimensional treatment of memory decoding improved prediction performance compared to traditional, unidimensional, methods, with each cognitive domain explaining unique variance in decoding of successful encoding-related neural activity. Importantly, this approach could be applied to cognitive domains outside of memory. Overall, this study provides critical insight into the underlying reasons why some events are remembered while others are not.

Age exacerbates the negative effect of depression on executive functioning in racial and ethnic minorities.

Age and depression may interact to produce a "double jeopardy" for cognitive impairment, and executive functioning, in cognitively unimpaired aging. Few studies have considered middle age or the ethnoracial diversity of subjects, despite evidence of more severe cognitive outcomes in historically minoritized people. In this pilot study, we investigated the impact of age on depression-related cognitive impairment and the underlying brain volumes in middle-aged non-Hispanic White adults (116), and Hispanic and Black adults (60), with a total number of 176 adults. The result shows a significant interaction between age and depression for executive functioning, specifically for middle-aged Hispanic and Black adults, but not non-Hispanic White adults. Prefrontal cortex volumes, which were reduced in the Black and Hispanic compared to the non-Hispanic White adults, partially mediated the relationship between depression level and executive functioning, across age and ethnoracial group. Collectively, these results suggest that the negative impact of depression on executive functioning and Prefrontal cortex volumes integrity may be exacerbated by age and that historically minoritized people may be particularly sensitive to this double jeopardy.

The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval.

Age-related declines in source memory have been observed for various stimuli and associated details. These impairments may be related to alterations in brain regions contributing to source memory via material-independent processes and/or regions specialized for processing specific materials. Using event-related functional magnetic resonance imaging, we investigate the effects of aging on source memory and associated neural activity for words and objects. Source accuracy was equally impaired in older adults for both materials. Imaging data revealed both groups recruited similar networks of regions to support source memory accuracy irrespective of material, including parietal and prefrontal cortices (PFC) and the hippocampus. Age-related decreases in material-independent activity linked to postretrieval monitoring were observed in right lateral PFC. Additionally, age-related increases in source accuracy effects were shown in perirhinal cortex, which were positively correlated with performance in older adults, potentially reflecting functional compensation. In addition to group differences in material-independent regions, age-related crossover interactions for material-dependent source memory effects were observed in regions selectively engaged by objects. These results suggest that older adults' source memory impairments reflect alterations in regions making material-independent contributions to source memory retrieval, primarily the lateral PFC, but may be further impacted by changes in regions sensitive to particular materials.