Lifespan differences in visual short-term memory load-modulated functional connectivity.

Working memory is critical to higher-order executive processes and declines throughout the adult lifespan. However, our understanding of the neural mechanisms underlying this decline is limited. Recent work suggests that functional connectivity between frontal control and posterior visual regions may be critical, but examinations of age differences therein have been limited to a small set of brain regions and extreme group designs (i.e., comparing young and older adults). In this study, we build on previous research by using a lifespan cohort and a whole-brain approach to investigate working memory load-modulated functional connectivity in relation to age and performance. The article reports on analysis of the Cambridge center for Ageing and Neuroscience (Cam-CAN) data. Participants from a population-based lifespan cohort (N = 101, age 23-86) performed a visual short-term memory task during functional magnetic resonance imaging. Visual short-term memory was measured with a delayed recall task for visual motion with three different loads. Whole-brain load-modulated functional connectivity was estimated using psychophysiological interactions in a hundred regions of interest, sorted into seven networks (Schaefer et al., 2018, Yeo et al., 2011). Results showed that load-modulated functional connectivity was strongest within the dorsal attention and visual networks during encoding and maintenance. With increasing age, load-modulated functional connectivity strength decreased throughout the cortex. Whole-brain analyses for the relation between connectivity and behavior were non-significant. Our results give additional support to the sensory recruitment model of working memory. We also demonstrate the widespread negative impact of age on the modulation of functional connectivity by working memory load. Older adults might already be close to ceiling in terms of their neural resources at the lowest load and therefore less able to further increase connectivity with increasing task demands.

Trichophyton mentagrophytes complex: A retrospective study of 64 dogs from the Central United States (1997-2020).

BACKGROUND: There are limited clinical studies evaluating the Trichophyton mentagrophytes complex, with most reports confined to small case studies. Additionally, the studies are dated and provide limited information on response to newer or currently available therapies. HYPOTHESIS/OBJECTIVES: The aim of the study was to determine if there is a breed prevalence, lesion distribution and seasonality associated with the T. mentagrophytes complex for dogs evaluated in the central United States. An additional aim of the study was to evaluate response to therapies because there are minimal data available on clinical response with newer systemic antifungal drugs. ANIMALS: A total of 64 canine medical records were evaluated that had a previous diagnosis of T. mentagrophytes complex infection. MATERIALS AND METHODS: A retrospective study of medical records to evaluate signalment, time of onset of clinical signs, clinical presentation and therapeutic management. RESULTS: A higher incidence of T. mentagrophytes complex infection was observed in the American Kennel Club (AKC) Sporting group (43%) and Terrier group (20%). A seasonal influence was noted, with the onset of clinical signs being highest in October. Lesions most often affected the muzzle (48%), followed by the head excluding the pinnae (21%). Ketoconazole, itraconazole and terbinafine appeared equivalent as systemic therapeutic options to treat T. mentagrophytes complex infections. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified patterns in breeds, seasonality and lesion distribution for the T. mentagrophytes complex in dogs from the central United States. Additionally, the study found several reasonable and reliable treatment options for systemic therapy.

The role of the arousal system in age-related differences in cortical functional network architecture.

A common finding in the aging literature is that of the brain's decreased within- and increased between-network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS functioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam-CAN) population-based cohort. Our results show that ARAS-cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age-related differences in connectivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connectivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS-cortical connectivity relates to cognitive performance with age.

Associations Between Atopic Dermatitis and Anxiety, Aggression, and Fear-Based Behaviors in Dogs.

The goal of this study was to determine if anxiety, aggression, and fear-related behaviors are more common in pruritic dogs with atopic dermatitis than nonpruritic, healthy dogs. One hundred forty-one pruritic dogs >1 yr of age with a clinical diagnosis of atopic dermatitis and a >3 mo history of pruritus were recruited. Dog owners completed a behavioral survey (canine behavioral assessment and research questionnaire) and a pruritus scale (pruritus visual analog scale). Pruritic, atopic dogs showed significant increases in fear- and anxiety-related behaviors as well as aggression compared with a large control group of healthy dogs. Stranger-directed aggression, owner-directed aggression, familiar-dog aggression, dog-directed fear, nonsocial fear, touch sensitivity, excitability, and attention-seeking behaviors were all increased in the study group. Trainability was decreased in the study group. Chronically pruritic dogs experience fear and anxiety and are more likely to display aggression. This is an important welfare issue for these animals. Early recognition of the behavioral derangements that can be associated with chronic pruritic skin disease could allow early intervention with a multidisciplinary approach for these patients, thus improving patient and owner quality of life and long-term treatment outcomes.

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients.

OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system. METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model. RESULTS: The final sample included 108 patients (chronic migraine = 64; non-chronic migraine = 44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio = 5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio = 2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio = 9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio = 4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%. CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events.

Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. However, the precise role played by each of these structures and, indeed, the direction of information flow between them during episodic simulation, is still not well understood. In this study, we scanned participants using functional magnetic resonance imaging while they imagined future events in response to object cues. We then used dynamic causal modeling to examine effective connectivity between the left anterior hippocampus and vmPFC during the initial mental construction of the events. Our results show that while there is strong bidirectional intrinsic connectivity between these regions (i.e., irrespective of task conditions), only the hippocampus to vmPFC connection increases during the construction of episodic future events, suggesting that the hippocampus initiates event simulation in response to retrieval cues, driving activation in the vmPFC where episodic details may be further integrated.

Robust Resilience of the Frontotemporal Syntax System to Aging.

UNLABELLED: Brain function is thought to become less specialized with age. However, this view is largely based on findings of increased activation during tasks that fail to separate task-related processes (e.g., attention, decision making) from the cognitive process under examination. Here we take a systems-level approach to separate processes specific to language comprehension from those related to general task demands and to examine age differences in functional connectivity both within and between those systems. A large population-based sample (N = 111; 22-87 years) from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) was scanned using functional MRI during two versions of an experiment: a natural listening version in which participants simply listened to spoken sentences and an explicit task version in which they rated the acceptability of the same sentences. Independent components analysis across the combined data from both versions showed that although task-free language comprehension activates only the auditory and frontotemporal (FTN) syntax networks, performing a simple task with the same sentences recruits several additional networks. Remarkably, functionality of the critical FTN is maintained across age groups, showing no difference in within-network connectivity or responsivity to syntactic processing demands despite gray matter loss and reduced connectivity to task-related networks. We found no evidence for reduced specialization or compensation with age. Overt task performance was maintained across the lifespan and performance in older, but not younger, adults related to crystallized knowledge, suggesting that decreased between-network connectivity may be compensated for by older adults' richer knowledge base. SIGNIFICANCE STATEMENT: Understanding spoken language requires the rapid integration of information at many different levels of analysis. Given the complexity and speed of this process, it is remarkably well preserved with age. Although previous work claims that this preserved functionality is due to compensatory activation of regions outside the frontotemporal language network, we use a novel systems-level approach to show that these "compensatory" activations simply reflect age differences in response to experimental task demands. Natural, task-free language comprehension solely recruits auditory and frontotemporal networks, the latter of which is similarly responsive to language-processing demands across the lifespan. These findings challenge the conventional approach to neurocognitive aging by showing that the neural underpinnings of a given cognitive function depend on how you test it.

Task-linked Diurnal Brain Network Reorganization in Older Adults: A Graph Theoretical Approach.

Testing older adults in the morning generally improves behavioral performance relative to afternoon testing. Morning testing is also associated with brain activity similar to that of young adults. Here, we used graph theory to explore how time of day (TOD) affects the organization of brain networks in older adults across rest and task states. We used nodes from the automated anatomical labeling atlas to construct participant-specific correlation matrices of fMRI data obtained during 1-back tasks with interference and rest. We computed pairwise group differences for key graph metrics, including small-worldness and modularity. We found that older adults tested in the morning and young adults did not differ on any graph metric. Both of these groups differed from older adults tested in the afternoon during the tasks-but not rest. Specifically, the latter group had lower modularity and small-worldness (indices of more efficient network organization). Across all groups, higher modularity and small-worldness strongly correlated with reduced distractibility on an implicit priming task. Increasingly, TOD is seen as important for interpreting and reproducing neuroimaging results. Our study emphasizes how TOD affects brain network organization and executive control in older adults.

Priming, not inhibition, of related concepts during future imagining.

Remembering the past and imagining the future both involve the retrieval of details stored in episodic memory and rely on the same core network of brain regions. Given these parallels, one might expect similar component processes to be involved in remembering and imagining. While a strong case can be made for the role of inhibition in memory retrieval, few studies have examined whether inhibition is also necessary for future imagining and results to-date have been mixed. In the current study, we test whether related concepts are inhibited during future imagining using a modified priming approach. Participants first generated a list of familiar places and for each place, the people they most strongly associate with it. A week later, participants imagined future events involving recombinations of people and places, immediately followed by a speeded response task in which participants made familiarity decisions about people's names. Across two experiments, our results suggest that related concepts are not inhibited during future imagining, but rather are automatically primed. These results fit with recent work showing that autobiographically significant concepts (e.g., friends' names) are more episodic than semantic in nature, automatically activating related details in memory and potentially fuelling the flexible simulation of future events.

Age differences in the neural correlates of distraction regulation: A network interaction approach.

Older adults show decrements in the ability to ignore or suppress distraction relative to younger adults. However, age differences in the neural correlates of distraction control and the role of large-scale network interaction in regulating distractors are scarcely examined. In the current study, we investigated age differences in how the anticorrelation between an externally oriented dorsal attention network (DAN) and an internally focused default mode network (DMN) is related to inhibiting distractors presented during a 1-back working memory task. For both young and older adults, the extent of DAN-DMN anticorrelation predicted reduced distractibility. Activation in a common set of frontal and insular control regions during the task was, however, associated with opposite patterns of network interaction and distractibility in the age groups. For older adults, recruitment of these regions was associated with greater DAN-DMN anticorrelation and less distractibility (better performance). For younger adults, it was associated with decreased DAN-DMN anticorrelation and more distractibility (worse performance). Our findings demonstrate the age-dependent relationship between DAN-DMN interaction patterns and engagement of control regions during an externally oriented distraction control task. This suggests that engagement of those regions may play a compensatory role for older adults but may be indicative of less efficient neural control mechanisms in younger adults.

Contact dermatitis: a comparative and translational review of the literature.

BACKGROUND: Contact dermatitis (CD) is an inflammatory skin condition induced by direct contact with a specific chemical. Irritant CD (ICD) is a nonspecific inflammatory cutaneous reaction to an irritating agent. Allergic CD (ACD) is an immune-mediated antigen-specific skin reaction to an allergenic chemical. OBJECTIVES AND METHODS: The biomedical literature (human, basic science, veterinary) was reviewed to evaluate the current state of knowledge regarding CD. RESULTS: The incidence of human CD remains unclear, but represents up to 90-95% of all occupational skin diseases. The prevalence of CD has not been established in veterinary medicine. The pathogenesis of CD is not fully understood, but involves a complex cascade of events between resident skin cells, relocated immune cells, pro-inflammatory cytokines and chemokines. The main difference between ICD and ACD is that ACD is an antigen-specific reaction to an allergenic irritating agent whereas ICD is not antigen-specific. To date, there is no fully validated diagnostic test available for CD. Thus, its clinical diagnosis relies on the patient's history, clinical examination, dermatological tests and, in some cases, research-based assays. The most important factor in CD management is the identification and avoidance of the culprit irritant or allergen. In addition, various topical and systemic therapies can be considered. CONCLUSION AND CLINICAL RELEVANCE: CD is a relatively common occupational skin disease in human beings, but the prevalence in veterinary medicine is undefined. It can lead to debilitating clinical signs. Further research in human medicine and even more so in veterinary patients, will be required in order to allow for an evidence-based approach in its diagnosis and management.

Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin-8 and CD40, which are affected by certain antibiotics.

BACKGROUND: Bacterial skin infections are common in dogs and humans. Keratinocytes have phenotypic features of nonprofessional antigen-presenting cells and express various cytokines. However, little is known about the effects of antibiotics on inflammatory markers in canine keratinocytes. HYPOTHESIS/OBJECTIVES: To investigate inflammatory markers in canine progenitor epidermal keratinocytes (CPEKs) and to determine the effects of selected antibiotics on these markers. METHODS: The CPEKs were exposed for 2-24 h to three concentrations of amoxicillin, cefalexin, sulfadimethoxine, sulfamethoxazole (or its nitroso metabolite), amikacin or enrofloxacin. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect major histocompatibility complex (MHC) II. CD40 and CXCR1 [interleukin (IL)-8 receptor] were detected using ELISA. Secreted cytokines/chemokines were quantified using a multiplex kit. RESULTS: No MHC II protein was detected. CD40 protein was found at 24 h, with levels being significantly increased by enrofloxacin. The CPEKs secreted no detectable monocyte chemotactic protein-1; undetectable to low (picogram per millilitre range) concentrations of IL-6, IL-7, IL-10, IL-15, tumour necrosis factor-α, interferon-γ and granulocyte-macrophage colony-stimulating factor; and high (nanogram per millilitre range) concentrations of IL-8. Levels of IL-8 increased over 24 h following cell proliferation. They were significantly increased by enrofloxacin after 8 h, and by cefalexin, sulfadimethoxine, sulfamethoxazole, its nitroso metabolite and enrofloxacin after 24 h. The CPEKs expressed CXCR1. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine progenitor epidermal keratinocytes express various inflammatory proteins, with expression profiles being affected by certain antibiotics. This supports previous work showing keratinocytes to be mediators of inflammation and demonstrates the potential pro-inflammatory effects of certain antibiotics in the skin.

Time spent imagining does not influence younger and older adults' episodic simulation of helping behavior.

Shared cognitive processes underlie our ability to remember the past (i.e., episodic memory) and imagine the future (i.e., episodic simulation) and age-related declines in episodic memory are also noted when simulating future scenarios. Given older adults' reduced cognitive control and protracted memory retrieval time, we examined whether imposing time limits on episodic simulation of future helping scenarios affects younger and older adults' willingness to help, phenomenological experience, and the type of details produced. Relative to a control task, episodic simulation increased younger and older participants' willingness to help, scene vividness, and perspective-taking regardless of the time spent imagining future helping scenarios. Notably, time spent imagining influenced the number, but not proportion of internal details produced, suggesting that participants' use of episodic-like information remained consistent regardless of the time they spent imagining. The present findings highlight the importance of collecting phenomenological experience when assessing episodic simulation abilities across the lifespan.

Some young adults hyper-bind too: Attentional control relates to individual differences in hyper-binding.

Hyper-binding - the erroneous encoding of target and distractor information into associative pairs in memory - has been described as a unique age effect caused by declines in attentional control. Previous work has found that, on average, young adults do not hyper-bind. However, if hyper-binding is caused by reduced attentional control, then young adults with poor attention regulation should also show evidence of hyper-binding. We tested this question with an individual differences approach, using a battery of attentional control tasks and relating this to individual differences in hyper-binding. Participants (N = 121) completed an implicit associative memory test measuring memory for both target-distractor (i.e., hyper-binding) and target-target pairs, followed by a series of tasks measuring attentional control. Our results show that on average, young adults do not hyper-bind, but as predicted, those with poor attentional control show a larger hyper-binding effect than those with good attentional control. Exploratory analyses also suggest that individual differences in attentional control relate to susceptibility to interference at retrieval. These results support the hypothesis that hyper-binding in older adults is due to age-related declines in attentional control, and demonstrate that hyper-binding may be an issue for any individual with poor attentional control, regardless of age.

Shift happens: aging alters the content but not the organization of memory for complex events.

While cognitive aging research has compared episodic memory accuracy between younger and older adults, less work has described differences in how memories are encoded and recalled. This is important for memories of real-world experiences, since there is immense variability in which details can be accessed and organized into narratives. We investigated age effects on the organization and content of memory for complex events. In two independent samples (N = 45; 60), young and older adults encoded and recalled the same short-movie. We applied a novel scoring on the recollections to quantify recall accuracy, temporal organization (temporal contiguity, forward asymmetry), and content (perceptual, conceptual). No age-effects on recall accuracy nor on metrics of temporal organization emerged. Older adults provided more conceptual and non-episodic content, whereas younger adults reported a higher proportion of event-specific information. Our results indicate that age-related differences in episodic recall reflect distinctions in what details are assembled from the past.

Distraction can reduce age-related forgetting.

In three experiments, we assessed whether older adults' generally greater tendency to process distracting information can be used to minimize widely reported age-related differences in forgetting. Younger and older adults studied and recalled a list of words on an initial test and again on a surprise test after a 15-min delay. In the middle (Experiments 1a and 2) or at the end (Experiment 3) of the delay, participants completed a 1-back task in which half of the studied words appeared as distractors. Across all experiments, older adults reliably forgot unrepeated words; however, older adults rarely or never forgot the words that had appeared as distractors, whereas younger adults forgot words in both categories. Exposure to distraction may serve as a rehearsal episode for older adults, and thus as a method by which general distractibility may be co-opted to boost memory.

The effect of 'allergenic' and 'nonallergenic' antibiotics on dog keratinocyte viability in vitro.

BACKGROUND: Immune-mediated adverse drug reactions (drug hypersensitivity) are relatively common in veterinary medicine, but their pathogenesis is not well understood. For an unknown reason, delayed drug hypersensitivity often targets the skin. Antibiotics, especially ß-lactams and sulfonamides, are commonly associated with these adverse events. The 'danger theory' hypothesizes that 'danger' signals, such as drug-induced cell death, might be part of the pathogenesis of drug hypersensitivity reactions. HYPOTHESIS/OBJECTIVES: The goal of this study was to determine whether antibiotics that are commonly associated with cutaneous drug hypersensitivity (allergenic) decrease canine keratinocyte viability in vitro more than antibiotics that rarely cause such reactions (nonallergenic). METHODS: Immortalized canine keratinocytes (CPEK cells) were exposed to a therapeutic range of drug concentrations of four 'allergenic' antibiotics (two ß-lactams, i.e. amoxicillin and cefalexin, and two sulfonamides, i.e. sulfamethoxazole and sulfadimethoxine) or two 'nonallergenic' antibiotics (enrofloxacin and amikacin) over 48 h (2, 4, 8, 24 and 48 h). The reactive nitroso metabolite of sulfamethoxazole was also tested. RESULTS: Cefalexin (2 mmol/L) significantly decreased cell viability after 48 h (28 ± 7%; P = 0.035). The nitroso metabolite of sulfamethoxazole (100 µmol/L) decreased cell viability after 2 h (21 ± 7%; P = 0.049), but cell numbers were increased after 8 h (22 ± 6%; P = 0.018). In addition, enrofloxacin (500 µmol/L) also significantly decreased cell viability by 37% (±6%; P = 0.0035) at 24 h and by 70% (±8%; P < 0.001) at 48 h. CONCLUSION: It appears that the effect of drugs on the in vitro viability of dog keratinocytes is not a good predictor of the 'allergenic' potential of an antibiotic. Further work is required to investigate other drug-induced 'danger' signals in dog keratinocytes exposed to 'allergenic' antibiotics in vitro.

Reduced distinctiveness of event boundaries in older adults with poor memory performance.

We experience the world as a continuous flow of information but segment it into discrete events in long-term memory. As a result, younger adults are more likely to recall details of an event when cued with information from the same event (within-event cues) than from the prior event (between-event cues), suggesting that stronger associations are formed within events than across event boundaries. The present study aimed to investigate the effects of age and working memory updating on this within > between cued-recall effect and the consequences for subsequent memory. Across two studies, participants viewed two different films (Hitchcock's Bang You're Dead and BBC's Sherlock). They were later shown clips taken from either the beginning/middle (within-event cues) or end (between-event cues) of a scene and asked to recall what happened next in the film. While the main effect of age was not significant in either experiment, overall memory performance related to the within > between effect in older, but not younger, adults. Low-performing older adults showed less of a difference in cued recall for within- and between-event cues than high performers. In Study 2, better two-back task performance also related to a greater within > between effect in older, but not younger, adults, suggesting that working memory updating relates to the distinctiveness of events stored in long-term memory, at least in older adults. Taken together, these findings suggest that age differences in event memory are not inevitable and may critically depend on one's ability update working memory at event boundaries. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Rating the Honesty of White and Black Children via Implicit and Explicit Measures: Implications for Child Victims in the Criminal Justice System.

The present study explored implicit and explicit honesty perceptions of White and Black children and whether these perceptions predicted legal decisions in a child abuse case. Participants consisted of 186 younger and 189 older adults from the online Prolific participant pool. Implicit racial bias was measured via a modified Implicit Association Test and explicit perceptions through self-reports. Participants read a simulated legal case where either a Black or White child alleged physical abuse against their sports coach, and they rated the honesty of the child's testimony and rendered a verdict. Participants were implicitly biased to associate honesty with White children over Black children, and this bias was stronger among older adults. In the legal vignette, for participants who read about a Black child victim, greater implicit racial bias predicted less trust in the child's testimony and a lower likelihood of convicting the coach of abusing the child. In contrast to their implicit bias, participants self-reported Black children as being more honest than White children, suggesting a divergence in racial attitudes across implicit and explicit measures. Implications for child abuse victims are discussed.

Effect of situation similarity on younger and older adults' episodic simulation of helping behaviours.

Similar cognitive processes enable us to remember the past (i.e., episodic memory) and simulate future events (i.e., episodic simulation). In the current study, we demonstrate an important role for previous experience when younger and older adults simulate future behaviours. Participants read short descriptions of a person in need of help in scenarios that were more familiar to either younger or older adults (e.g., dealing with dating apps vs writing a cheque). Participants either imagined helping the person or thought about the style of the story (control task), and then rated their willingness to help, scene vividness, emotional concern, and subjective use of theory of mind. Hierarchical mixed effect modelling revealed that both episodic simulation and one's previous experience increased willingness to help, in that participants were more willing to help if they imagined helping and the situation was more familiar to them. Further, in simulated scenarios the relationship between previous experience and willingness to help was mediated by scene vividness and perspective-taking in younger adults, but only by perspective-taking in older adults. Taken together, these findings suggest that situation similarity and episodic simulation increase willingness to help, possibly via different mechanisms in younger and older adults.