Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aß-positive and Aß-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Direct brain recordings suggest a causal subsequent-memory effect.

Endogenous variation in brain state and stimulus-specific evoked activity can both contribute to successful encoding. Previous studies, however, have not clearly distinguished among these components. We address this question by analysing intracranial EEG recorded from epilepsy patients as they studied and subsequently recalled lists of words. We first trained classifiers to predict recall of either single items or entire lists and found that both classifiers exhibited similar performance. We found that list-level classifier output-a biomarker of successful encoding-tracked item presentation and recall events, despite having no information about the trial structure. Across widespread brain regions, decreased low- and increased high-frequency activity (HFA) marked successful encoding of both items and lists. We found regional differences in the hippocampus and prefrontal cortex, where in the hippocampus HFA correlated more strongly with item recall, whereas, in the prefrontal cortex, HFA correlated more strongly with list performance. Despite subtle differences in item- and list-level features, the similarity in overall classification performance, spectral signatures of successful recall and fluctuations of spectral activity across the encoding period argue for a shared endogenous process that causally impacts the brain's ability to learn new information.

Single-value scores of memory-related brain activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging.

Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy middle-aged and older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and other neuropsychological measures including flexibility. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in other aging-related functions. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.

The relationship between resting-state amplitude fluctuations and memory-related deactivations of the default mode network in young and older adults.

The default mode network (DMN) typically exhibits deactivations during demanding tasks compared to periods of relative rest. In functional magnetic resonance imaging (fMRI) studies of episodic memory encoding, increased activity in DMN regions even predicts later forgetting in young healthy adults. This association is attenuated in older adults and, in some instances, increased DMN activity even predicts remembering rather than forgetting. It is yet unclear whether this phenomenon is due to a compensatory mechanism, such as self-referential or schema-dependent encoding, or whether it reflects overall reduced DMN activity modulation in older age. We approached this question by systematically comparing DMN activity during successful encoding and tonic, task-independent, DMN activity at rest in a sample of 106 young (18-35 years) and 111 older (60-80 years) healthy participants. Using voxel-wise multimodal analyses, we assessed the age-dependent relationship between DMN resting-state amplitude (mean percent amplitude of fluctuation, mPerAF) and DMN fMRI signals related to successful memory encoding, as well as their modulation by age-related hippocampal volume loss, while controlling for regional grey matter volume. Older adults showed lower resting-state DMN amplitudes and lower task-related deactivations. However, a negative relationship between resting-state mPerAF and subsequent memory effect within the precuneus was observed only in young, but not older adults. Hippocampal volumes showed no relationship with the DMN subsequent memory effect or mPerAF. Lastly, older adults with higher mPerAF in the DMN at rest tend to show higher memory performance, pointing towards the importance of a maintained ability to modulate DMN activity in old age.

Pre-associative item encoding influences associative memory: Behavioral and ERP evidence.

It is unknown whether the manner with which an item is encoded in isolation, immediately before it is encoded into an inter-inter association, influences associative memory. We therefore presented the items of to-be-encoded associative pairings sequentially and manipulated how each first item of a pair was encoded (before associative encoding could begin). Furthermore, we recorded ERPs during memory encoding to investigate the neurocognitive processes that might relate pre-associative item encoding to subsequent associative memory performance. Behaviorally, we found that pre-associative item elaboration (vs. no elaboration) led to a memory tradeoff-enhanced item memory relative to impaired associative memory. This tradeoff likely reflected that item elaboration reduced cognitive resources for ensuing associative encoding, indexed by a reduced P300 and frontal slow wave at the time of associative encoding. However, frontal slow wave subsequent memory effects measured during pre-associative item encoding revealed that, for a given item, greater semantic elaboration was related to better item and associative memory while greater visual elaboration was related to better item and worse associative memory. Thus, there are likely two opposing ways in which pre-associative item encoding can influence associative memory: (1) by depleting encoding resources to impair associative memory and (2) by scaffolding inter-item associations to enhance associative memory. When item encoding occurs immediately before associative encoding, it appears that the temporary depletion of encoding resources is more important in determining later memory performance. Future research should compare the independent effects of resource depletion and encoding strategy during pre-associative item encoding.

Hippocampal-Medial Prefrontal Event Segmentation and Integration Contribute to Episodic Memory Formation.

How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., "activation pattern" similarity and within-region voxel-based "connectivity pattern" similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared with forgotten events, successfully remembered events were associated with distinct "activation patterns" in the hippocampus and medial prefrontal cortex. In contrast, similar "connectivity pattern" between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events, while similar connectivity patterns encode context information and, therefore, integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.

Informative and uninformative prestimulus cues at encoding benefit familiarity and source memory.

Previous research has shown that neural activity elicited by informative prestimulus cues during encoding differ with respect to subsequent memory outcomes. These findings indicate prestimulus cues create a "brain state" associated with subsequent memory that, potentially, also has downstream effects benefitting processes associated with successful encoding and subsequent memory performance. However, previous studies have not included the conditions necessary to appropriately test this latter assumption. The present study examines how informative and uninformative prestimulus encoding cues affect memory accuracy for upcoming stimuli compared to a no cue condition. At encoding, participants made one of two semantic judgments on words preceded by an informative prestimulus cue that identified the upcoming semantic judgment, an uninformative prestimulus cue that signalled an upcoming trial but no information about the semantic judgment, or no cue. Dual process estimates of familiarity, but not recollection, demonstrated a graded pattern with the informativeness of the prestimulus cues (i.e., informative > uninformative > no cues). Moreover, both informative and uninformative prestimulus cues enhanced subsequent source memory accuracy for the encoding task compared to the no cue condition. These findings suggest that prestimulus cues can strengthen the processes that support successful memory encoding and benefit subsequent familiarity and source memory.

Spiking activity in the human hippocampus prior to encoding predicts subsequent memory.

Encoding activity in the medial temporal lobe, presumably evoked by the presentation of stimuli (postonset activity), is known to predict subsequent memory. However, several independent lines of research suggest that preonset activity also affects subsequent memory. We investigated the role of preonset and postonset single-unit and multiunit activity recorded from epilepsy patients as they completed a continuous recognition task. In this task, words were presented in a continuous series and eventually began to repeat. For each word, the patient's task was to decide whether it was novel or repeated. We found that preonset spiking activity in the hippocampus (when the word was novel) predicted subsequent memory (when the word was later repeated). Postonset activity during encoding also predicted subsequent memory, but was simply a continuation of preonset activity. The predictive effect of preonset spiking activity was much stronger in the hippocampus than in three other brain regions (amygdala, anterior cingulate, and prefrontal cortex). In addition, preonset and postonset activity around the encoding of novel words did not predict memory performance for novel words (i.e., correctly classifying the word as novel), and preonset and postonset activity around the time of retrieval did not predict memory performance for repeated words (i.e., correctly classifying the word as repeated). Thus, the only predictive effect was between preonset activity (along with its postonset continuation) at the time of encoding and subsequent memory. Taken together, these findings indicate that preonset hippocampal activity does not reflect general arousal/attention but instead reflects what we term "attention to encoding."

Functional activation features of memory in successful agers across the adult lifespan.

Much neuroimaging research has explored the neural mechanisms underlying successful cognitive aging. Two different patterns of functional activation, maintenance of youth-like activity and compensatory novel recruitment, have been proposed to represent different brain functional features underlying individual differences in cognitive aging. In this study, we investigated the functional features in individuals across the adult lifespan who appeared to resist age-related cognitive decline, in comparison to those with typical age-related declines, over the course of four years. We first implemented latent mixture modeling, a data-driven approach, to classify participants as successful and average agers in middle-aged, young-old, and very old groups, based on their baseline and longitudinal cognitive performance. Then, using fMRI with a subsequent memory paradigm at the follow-up visit, brain activation specifically related to successful encoding (i.e., subsequent memory effect: subsequently remembered with high confidence > subsequently forgotten) was compared between people who established successful cognitive aging versus average aging in the three age groups. Several differences in the subsequent memory effect were revealed. First, across core task-related regions commonly used during successful encoding, successful agers exhibited high subsequent memory effect, at a level comparable to the young control group, until very old age; in contrast, average agers showed reduced subsequent memory effect, compared to successful agers, beginning in young-old age when memory performance also reduced in average agers, compared to successful agers. Second, additional recruitment in prefrontal clusters, distant from the core task-related regions, were identified in the left superior frontal and right orbitofrontal cortices in successful agers of young-old age, possibly reflecting functional compensation in successful aging. In summary, successful agers demonstrate a pattern of youth-like activation spanning from middle age to young-old age, as well as novel frontal recruitment in young-old age. Overall, our study demonstrated evidence of two neural patterns related to successful cognitive aging, offering an integrated view of functional features underlying successful aging, and suggests the importance of studying individuals across the lifespan to understand brain changes occurring in mid and early-late life.

On the role of item encoding mechanisms in associative memory in young and older adults: A mass univariate ERP study.

We examined the role of item encoding mechanisms in older adults' disproportionate deficit in memory for associations and individual differences therein. Young and older adults encoded sequentially presented object pairs via interactive imagery while their EEG was recorded. Compared to the young adults, older adults exhibited a reduction in associative, but not in item memory performance. Young adults showed frontal slow wave subsequent memory effects (SME) in both an item encoding contrast and an associative encoding contrast, presumably reflecting elaborative item processing, as well as the elaboration of an internal interactive image. Based on their performance in the subsequent associative memory test, older adults were subdivided into a high and a low performing group. In low performers, instead of a frontal slow wave SME a polarity-reversed, early parietal item SME was prominent, whose magnitude was negatively correlated with associative memory performance, potentially reflecting shallow, perceptual item encoding processes that are not well-suited for the formation of new associations. The present findings suggest that age-related deficits in elaboration of item information and an emphasis on the encoding of perceptual, item-specific details may contribute to reduced associative memory performance in older adults.

Neural Correlates of Successful Memory Encoding in Kindergarten and Early Elementary School Children: Longitudinal Trends and Effects of Schooling.

From age 5 to 7, there are remarkable improvements in children's cognitive abilities ("5-7 shift"). In many countries, including Germany, formal schooling begins in this age range. It is, thus, unclear to what extent exposure to formal schooling contributes to the "5-7 shift." In this longitudinal study, we investigated if schooling acts as a catalyst of maturation. We tested 5-year-old children who were born close to the official cutoff date for school entry and who were still attending a play-oriented kindergarten. One year later, the children were tested again. Some of the children had experienced their first year of schooling whereas the others had remained in kindergarten. Using 2 functional magnetic resonance imaging tasks that assessed episodic memory formation (i.e., subsequent memory effect), we found that children relied strongly on the medial temporal lobe (MTL) at both time points but not on the prefrontal cortex (PFC). In contrast, older children and adults typically show subsequent memory effects in both MTL and PFC. Both children groups improved in their memory performance, but there were no longitudinal changes nor group differences in neural activation. We conclude that successful memory formation in this age group relies more heavily on the MTL than in older age groups.

Effects of Age on Prestimulus Neural Activity Predictive of Successful Memory Encoding: An fMRI Study.

Prestimulus subsequent memory effects (SMEs)-differences in neural activity preceding the onset of study items that are predictive of later memory performance-have consistently been reported in young adults. The present functional magnetic resonance imaging experiment investigated potential age-related differences in prestimulus SMEs. During study, healthy young and older participants made one of two semantic judgments on images, with the judgment signaled by a preceding cue. In test phase, participants first made an item recognition judgment and, for each item judged old, a source memory judgment. Age-invariant prestimulus SMEs were observed in left dorsomedial prefrontal cortex, left hippocampus, and right subgenual cortex. In each case, the effects reflected lower blood oxygen level dependent signal for later recognized items, regardless of source accuracy, than for unrecognized items. A similar age-invariant pattern was observed in left orbitofrontal cortex, but this effect was specific to items attracting a correct source response compared to unrecognized items. In contrast, the left angular gyrus and fusiform cortex demonstrated negative prestimulus SMEs that were exclusive to young participants. The findings indicate that age differences in prestimulus SMEs are regionally specific and suggest that prestimulus SMEs reflect multiple cognitive processes, only some of which are vulnerable to advancing age.

Bayesian model selection favors parametric over categorical fMRI subsequent memory models in young and older adults.

Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18-35 years) and older (51-80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.

Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study.

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial EEG across multiple frequency bands in the supramarginal gyrus (SmG) and angular gyrus (AnG), as twenty-four epilepsy patients with indwelling electrodes performed a free recall task. We found a significant SME of decreased theta power and increased high gamma power in the VPC overall, and specifically in the SmG. Furthermore, SmG exhibited significantly greater spectral tilt SME from 0.5 to 1.6 s post-stimulus, in which power spectra slope differences between recalled and unrecalled words were greater than in the AnG (p = 0.04). These results affirm the contribution of VPC to episodic memory encoding, and suggest an anterior-posterior dissociation within VPC with respect to its electrophysiological underpinnings.

A comprehensive score reflecting memory-related fMRI activations and deactivations as potential biomarker for neurocognitive aging.

Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Düzel et al., Hippocampus, 2011; 21: 803-814). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE-SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults' activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age-group-related differences for the subsequent memory contrast, and the FADE-SAME score additionally exhibited age-group-related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single-value scores of memory-related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.

The more you know: Schema-congruency supports associative encoding of novel compound words. Evidence from event-related potentials.

We aimed to investigate the neurocognitive mechanisms of event congruency with prior (schema) knowledge for the learning of novel compound words. Event-related potentials (ERPs) were recorded during an incidental learning task, in which novel noun-noun compounds were presented in a semantically congruent context, enabling schema-supported processing, or in a neutral context. As expected, associative memory performance was better for compounds preceded by a congruent context. Although the N400 was attenuated in the congruent condition, subsequent memory effects (SMEs) in the N400 time interval did not differ across conditions, suggesting that the processes reflected in the N400 cannot account for the memory advantage in the congruent condition. However, a parietal SME was obtained for compounds preceded by a congruent context, only, which we interpret as reflecting the schema-supported formation of a conceptual compound representation. A late frontal SME was obtained in both conditions, presumably reflecting the more general inter-item associative encoding of compound constituents.

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience.

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula [aI] and anterior prefrontal cortex [aPFC]) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

Dissociation of the Perirhinal Cortex and Hippocampus During Discriminative Learning of Similar Objects.

Discriminative learning is a paradigm that has been used in animal studies, in which memory of a stimulus is enhanced when it is presented with a similar stimulus rather than with a different one. Human studies have shown that through discriminative learning of similar objects, both item memory and contextual memories are enhanced. However, the underlying neural mechanisms for it are unclear. The hippocampus and perirhinal cortex (PRC) are two possible regions involved in discriminating similar stimuli and forming distinctive memory representations. In this study, 28 participants (15 males) were scanned using high-resolution fMRI when a picture (e.g., a dog) was paired with the same picture, with a similar picture of the same concept (e.g., another dog), or with a picture of a different concept (e.g., a cat). Then, after intervals of 20 min and 1 week, the participants were asked to perform an old/new recognition task, followed by a contextual judgment. The results showed that during encoding, there was stronger activation in the PRC for the "similar" than for the "same" and "different" conditions and it predicted subsequent item memory for the "similar" condition. The hippocampal activation decreased for the "same" versus the "different" condition and the DG/CA3 activation predicted subsequent contextual memory for the "similar" condition. These results suggested that the PRC and hippocampus are functionally dissociated in encoding simultaneously presented objects and predicting subsequent item and contextual memories after discriminative learning.SIGNIFICANCE STATEMENT How the brain separates similar input into nonoverlapping representations and forms distinct memory for them is a fundamental question for the neuroscience of memory. By discriminative learning of similar (vs different) objects, both item and contextual memories are enhanced. This study found functional dissociations between perirhinal cortex (PRC) and hippocampus in discriminating pairs of similar and different objects and in predicting subsequent memory of similar objects in their item and contextual aspects. The results provided clear evidence on the neural mechanisms of discriminative learning and highlighted the importance of the PRC and hippocampus in processing different types of object information when the objects were simultaneously presented.

Predicting memory from study-related brain activity.

To isolate brain activity that may reflect effective cognitive processes during the study phase of a memory task, cognitive neuroscientists commonly contrast brain activity during study of later-remembered versus later-forgotten items. This "subsequent memory effect" method has been described as identifying brain activity "predictive" of memory outcome. However, the modern field of machine learning distinguishes between descriptive analysis, subject to overfitting, and true prediction, that can classify untrained data. First, we tested whether classic event-related potential signals were, in fact, predictive of later old/new recognition memory (N = 62, 225 items/participant); this produced significant but small predictive success. Next, pattern classification of the multivariate spatiotemporal features of the single-trial EEG waveform also succeeded in predicting memory. However, the prediction was still small in magnitude. In addition, topographic maps suggested individual differences in sources of predictive activity. These findings suggest that, on average, brain activity, measured by EEG, during the study phase is only marginally predictive of subsequent memory. It is possible that this predictive approach will succeed better when other experimental factors known to influence memory outcome are also integrated into the models.NEW & NOTEWORTHY For both basic and applied reasons, an important goal is to identify brain activity present while people study materials that enable us to predict whether they will remember those materials. We show that this is possible with the conventional event-related potential "subsequent-memory-effect" signals as well as with machine learning classifiers, but only to a small degree. This is in line with behavioral research, which supports many determinants of memory apart from the cognitive processes during study.

Survival processing modulates the neurocognitive mechanisms of episodic encoding.

Memories formed in the context of an imagined survival scenario are more easily remembered, but the mechanisms underlying this effect are still under debate. We investigated the neurocognitive processes underlying the survival processing effect by examining event-related potentials (ERPs) during memory encoding. Participants imagined being either stranded in a foreign land and needing to survive, or in an overseas moving (control) scenario, while incidentally encoding a list of words. Words encountered in the survival context were associated with improved recall and reduced false-memory intrusions during a later memory test. Survival processing was associated with an increased frontal slow wave, while there was no effect on the overall P300 amplitude, relative to the control scenario. Furthermore, a subsequent memory effect in the P300 time window was found only in the control scenario. These findings suggest that survival processing leads to a shift away from lower level encoding processes, which are sensitive to motivation and stimulus salience and which were evident in the control scenario, to more active and elaborative forms of encoding. The results are consistent with a richness of encoding account of the survival processing effect and offer novel insights into the encoding processes that lead to enhanced memory for fitness-relevant information.