Integrating Region- and Network-level Contributions to Episodic Recollection Using Multilevel Structural Equation Modeling.

The brain is composed of networks of interacting brain regions that support higher-order cognition. Among these, a core network of regions has been associated with recollection and other forms of episodic construction. Past research has focused largely on the roles of individual brain regions in recollection or on their mutual engagement as part of an integrated network. However, the relationship between these region- and network-level contributions remains poorly understood. Here, we applied multilevel structural equation modeling to examine the functional organization of the posterior medial (PM) network and its relationship to episodic memory outcomes. We evaluated two aspects of functional heterogeneity in the PM network: first, the organization of individual regions into subnetworks, and second, the presence of regionally specific contributions while accounting for network-level effects. Our results suggest that the PM network is composed of ventral and dorsal subnetworks, with the ventral subnetwork making a unique contribution to recollection, especially to recollection of spatial information, and that memory-related activity in individual regions is well accounted for by these network-level effects. These findings highlight the importance of considering the functions of individual brain regions within the context of their affiliated networks.

Patterns of episodic content and specificity predicting subjective memory vividness.

The ability to remember and internally represent events is often accompanied by a subjective sense of "vividness". Vividness measures are frequently used to evaluate the experience of remembering and imagining events, yet little research has considered the objective attributes of event memories that underlie this subjective judgment, and individual differences in this mapping. Here, we tested how the content and specificity of event memories support subjectively vivid recollection. Over three experiments, participants encoded events containing a theme word and three distinct elements - a person, a place, and an object. In a memory test, memory for event elements was assessed at two levels of specificity - semantic gist (names) and perceptual details (lure discrimination). We found a strong correspondence between memory vividness and memory for gist information that did not vary by which elements were contained in memory. There was a smaller, additive benefit of remembering specific perceptual details on vividness, which, in one study, was driven by memory for place details. Moreover, we found individual differences in the relationship between memory vividness and objective memory attributes primarily along the specificity dimension, such that one cluster of participants used perceptual detail to inform memory vividness whereas another cluster was more driven by gist information. Therefore, while gist memory appears to drive vividness on average, there were idiosyncrasies in this pattern across participants. When assessing subjective ratings of memory and imagination, research should consider how these ratings map onto objective memory attributes in the context of their study design and population.

Antimicrobial stewardship of antiseptics that are pertinent to wounds: the need for a united approach.

Long before the nature of infection was recognized, or the significance of biofilms in delayed healing was understood, antimicrobial agents were being used in wound care. In the last 70 years, antibiotics have provided an effective means to control wound infection, but the continued emergence of antibiotic-resistant strains and the documented antibiotic tolerance of biofilms has reduced their effectiveness. A range of wound dressings containing an antimicrobial (antibiotic or non-antibiotic compound) has been developed. Whereas standardized methods for determining the efficacy of non-antibiotic antimicrobials in bacterial suspension tests were developed in the early twentieth century, standardized ways of evaluating the efficacy of antimicrobial dressings against microbial suspensions and biofilms are not available. Resistance to non-antibiotic antimicrobials and cross-resistance with antibiotics has been reported, but consensus on breakpoints is absent and surveillance is impossible. Antimicrobial stewardship is therefore in jeopardy. This review highlights these difficulties and in particular the efficacy of current non-antibiotic antimicrobials used in dressings, their efficacy, and the challenges of translating in vitro efficacy data to the efficacy of dressings in patients. This review calls for a unified approach to developing standardized methods of evaluating antimicrobial dressings that will provide an improved basis for practitioners to make informed choices in wound care.

Mapping the organization and dynamics of the posterior medial network during movie watching.

Brain regions within a posterior medial network (PMN) are characterized by sensitivity to episodic tasks, and they also demonstrate strong functional connectivity as part of the default network. Despite its cohesive structure, delineating the intranetwork organization and functional diversity of the PMN is crucial for understanding its contributions to multidimensional event cognition. Here, we probed functional connectivity of the PMN during movie watching to identify its pattern of connections and subnetwork functions in a split-sample replication of 136 participants. Consistent with prior findings of default network fractionation, we identified distinct PMN subsystems: a Ventral PM subsystem (retrosplenial cortex, parahippocampal cortex, posterior angular gyrus) and a Dorsal PM subsystem (medial prefrontal cortex, hippocampus, precuneus, posterior cingulate cortex, anterior angular gyrus). Ventral and Dorsal PM subsystems were differentiated by functional connectivity with parahippocampal cortex and precuneus and integrated by retrosplenial cortex and posterior cingulate cortex, respectively. Finally, the distinction between PMN subsystems is functionally relevant: whereas both Dorsal and Ventral PM connectivity tracked the movie content, only Ventral PM connections increased in strength at event transitions and appeared sensitive to episodic memory. Overall, these findings reveal PMN functional pathways and the distinct functional roles of intranetwork subsystems during event cognition.

Deconstructing the Posterior Medial Episodic Network.

Our ability to remember or imagine specific events involves the construction of complex mental representations, a process that engages cortical and hippocampal regions in a core posterior medial (PM) brain network. Existing theoretical approaches have described the overarching contributions of the PM network, but less is known about how episodic content is represented and transformed throughout this system. Here, we review evidence of key functional interactions among PM regions and their relation to the core cognitive operations and representations supporting episodic construction. Recent demonstrations of intranetwork functional diversity are integrated with existing accounts to inform a network-based model of episodic construction, in which PM regions flexibly share and manipulate event information to support the variable phenomenology of episodic memory and simulation.

A database of news videos for investigating the dynamics of emotion and memory.

Emotional experiences are known to be both perceived and remembered differently from nonemotional experiences, often leading to heightened encoding of salient visual details and subjectively vivid recollection. The vast majority of previous studies have used static images to investigate how emotional event content modulates cognition, yet natural events unfold over time. Therefore, little is known about how emotion dynamically modulates continuous experience. Here we report a norming study wherein we developed a new stimulus set of 126 emotionally negative, positive, and neutral videos depicting real-life news events. Participants continuously rated the valence of each video during its presentation and judged the overall emotional intensity and valence at the end of each video. In a subsequent memory test, participants reported how vividly they could recall the video details and estimated each video's duration. We report data on the affective qualities and subjective memorability of each video. The results replicate the well-established effect that emotional experiences are remembered more vividly than nonemotional experiences. Importantly, this novel stimulus set will facilitate research into the temporal dynamics of emotional processing and memory.

Progression from Feature-Specific Brain Activity to Hippocampal Binding during Episodic Encoding.

The hallmark of episodic memory is recollecting multiple perceptual details tied to a specific spatial-temporal context. To remember an event, it is therefore necessary to integrate such details into a coherent representation during initial encoding. Here we tested how the brain encodes and binds multiple, distinct kinds of features in parallel, and how this process evolves over time during the event itself. We analyzed data from 27 human subjects (16 females, 11 males) who learned a series of objects uniquely associated with a color, a panoramic scene location, and an emotional sound while fMRI data were collected. By modeling how brain activity relates to memory for upcoming or just-viewed information, we were able to test how the neural signatures of individual features as well as the integrated event changed over the course of encoding. We observed a striking dissociation between early and late encoding processes: left inferior frontal and visuo-perceptual signals at the onset of an event tracked the amount of detail subsequently recalled and were dissociable based on distinct remembered features. In contrast, memory-related brain activity shifted to the left hippocampus toward the end of an event, which was particularly sensitive to binding item color and sound associations with spatial information. These results provide evidence of early, simultaneous feature-specific neural responses during episodic encoding that predict later remembering and suggest that the hippocampus integrates these features into a coherent experience at an event transition.SIGNIFICANCE STATEMENT Understanding and remembering complex experiences are crucial for many socio-cognitive abilities, including being able to navigate our environment, predict the future, and share experiences with others. Probing the neural mechanisms by which features become bound into meaningful episodes is a vital part of understanding how we view and reconstruct the rich detail of our environment. By testing memory for multimodal events, our findings show a functional dissociation between early encoding processes that engage lateral frontal and sensory regions to successfully encode event features, and later encoding processes that recruit hippocampus to bind these features together. These results highlight the importance of considering the temporal dynamics of encoding processes supporting multimodal event representations.

Memories Fade: The Relationship Between Memory Vividness and Remembered Visual Salience.

Past events, particularly emotional experiences, are often vividly recollected. However, it remains unclear how qualitative information, such as low-level visual salience, is reconstructed and how the precision and bias of this information relate to subjective memory vividness. Here, we tested whether remembered visual salience contributes to vivid recollection. In three experiments, participants studied emotionally negative and neutral images that varied in luminance and color saturation, and they reconstructed the visual salience of each image in a subsequent test. Results revealed, unexpectedly, that memories were recollected as less visually salient than they were encoded, demonstrating a novel memory-fading effect, whereas negative emotion increased subjective memory vividness and the precision with which visual features were encoded. Finally, memory vividness tracked both the precision and remembered salience (bias) of visual information. These findings provide evidence that low-level visual information fades in memory and contributes to the experience of vivid recollection.

Cortico-hippocampal network connections support the multidimensional quality of episodic memory.

Episodic memories reflect a bound representation of multimodal features that can be reinstated with varying precision. Yet little is known about how brain networks involved in memory, including the hippocampus and posterior-medial (PM) and anterior-temporal (AT) systems, interact to support the quality and content of recollection. Participants learned color, spatial, and emotion associations of objects, later reconstructing the visual features using a continuous color spectrum and 360-degree panorama scenes. Behaviorally, dependencies in memory were observed for the gist but not precision of event associations. Supporting this integration, hippocampus, AT, and PM regions showed increased connectivity and reduced modularity during retrieval compared to encoding. These inter-network connections tracked a multidimensional, objective measure of memory quality. Moreover, distinct patterns of connectivity tracked item color and spatial memory precision. These findings demonstrate how hippocampal-cortical connections reconfigure during episodic retrieval, and how such dynamic interactions might flexibly support the multidimensional quality of remembered events.

Exploring the neurocognitive basis of episodic recollection in autism.

Increasing evidence indicates that the subjective experience of recollection is diminished in autism spectrum disorder (ASD) compared to neurotypical individuals. The neurocognitive basis of this difference in how past events are re-experienced has been debated and various theoretical accounts have been proposed to date. Although each existing theory may capture particular features of memory in ASD, recent research questions whether any of these explanations are alone sufficient or indeed fully supported. This review first briefly considers the cognitive neuroscience of how episodic recollection operates in the neurotypical population, informing predictions about the encoding and retrieval mechanisms that might function atypically in ASD. We then review existing research on recollection in ASD, which has often not distinguished between different theoretical explanations. Recent evidence suggests a distinct difficulty engaging recollective retrieval processes, specifically the ability to consciously reconstruct and monitor a past experience, which is likely underpinned by altered functional interactions between neurocognitive systems rather than brain region-specific or process-specific dysfunction. This integrative approach serves to highlight how memory research in ASD may enhance our understanding of memory processes and networks in the typical brain. We make suggestions for future research that are important for further specifying the neurocognitive basis of episodic recollection in ASD and linking such difficulties to social developmental and educational outcomes.

Social Conformity in Autism.

Humans are extremely susceptible to social influence. Here, we examine whether this susceptibility is altered in autism, a condition characterized by social difficulties. Autistic participants (N = 22) and neurotypical controls (N = 22) completed a memory test of previously seen words and were then exposed to answers supposedly given by four other individuals. Autistic individuals and controls were as likely to alter their judgements to align with inaccurate responses of group members. These changes reflected both temporary judgement changes (public conformity) and long-lasting memory changes (private conformity). Both groups were more susceptible to answers believed to be from other humans than from computer algorithms. Our results suggest that autistic individuals and controls are equally susceptible to social influence when reporting their memories.

Catalyst free, C-3 functionalization of imidazo[1,2-a]pyridines to rapidly access new chemical space for drug discovery efforts.

Multicomponent reactions (MCRs) are robust tools for the rapid synthesis of complex, small molecule libraries for use in drug discovery and development. By utilizing MCR chemistry, we developed a protocol to functionalize the C-3 position of imidazo[1,2-a]pyridine through a three component, decarboxylation reaction involving imidazo[1,2-a]pyridine, glyoxalic acid, and boronic acid.

Non-antibiotic antimicrobial interventions and antimicrobial stewardship in wound care.

Control of wound infection today relies largely on antibiotics, but the continual emergence of antibiotic-resistant microorganisms threatens a return to the pre-antibiotic era when physicians used antiseptics to prevent and manage infection. Some of those antiseptics are still used today, and others have become available. A diverse variety of non-antibiotic antimicrobial interventions are found on modern formularies. Unlike the mode of action of antibiotics, which affect specific cellular target sites of pathogens, many non-antibiotic antimicrobials affect multiple cellular target sites in a non-specific way. Although this reduces the likelihood of selecting for resistant strains of microorganisms, some have emerged and cross-resistance between antibiotics and antiseptics has been detected. With the prospect of a post-antibiotic era looming, ways to maintain and extend our antimicrobial armamentarium must be found. In this narrative review, current and emerging non-antibiotic antimicrobial strategies will be considered and the need for antimicrobial stewardship in wound care will be explained.

Presenting a food in multiple smaller units increases expected satiety.

Presentation of the same amount of a food in multiple smaller units ('segmentation') has been shown to reduce food intake and increase estimates of the amount of food consumed. However, this effect has been demonstrated for ad libitum food intake only. In the majority of cases, meals are not consumed ad libitum, but are pre-selected and consumed in their entirety, Expected satiety (ES; the anticipated capacity of a portion of food to relieve hunger between meals) is an excellent predictor of portion size selection. This study tested the hypothesis that segmentation increases ES. It was also hypothesised that perceived volume (PV) may account for the relationship between segmentation and ES. Sixty-eight participants made computer-based ES and PV judgments for equicaloric portions of three test foods (salted peanuts, spaghetti Bolognese, and chicken tikka masala), which were presented in either a single unit or as multiple smaller units (three or six units). Results revealed a consistent effect of segmentation on ES - foods presented in multiple smaller units were expected to deliver significantly greater satiety than when presented in a single unit (p < 0.005). Furthermore, results indicated that the effect of segmentation on ES was attributable to an increase in PV. ES plays an important role in determining the portion sizes that people select. Therefore, awareness of the effect of segmentation on ES may help to inform the design of foods that confer benefits for healthy weight maintenance.

Disorder-specific versus generic cognitive-behavioral treatment of anxiety disorders in children and young people: a systematic narrative review of evidence for the effectiveness of disorder-specific CBT compared with the disorder-generic treatment, Coping Cat.

BACKGROUND: Coping Cat (CC), a generic cognitive-behavioral intervention for anxiety disorders in children and young people, is recommended in the United Kingdom for social anxiety disorder (SAD), generalized anxiety disorder, separation anxiety (SA), and specific phobias (SP), with disorder-specific approaches generally favored in treatment of anxiety disorders in adults. OBJECTIVES: To compare CC with disorder-specific cognitive-behavioral therapy (CBT) interventions based on anxiety-related treatment outcomes. STUDY SELECTION: Primary research articles describing treatment of children and young people aged 7-17 for SAD, generalized anxiety disorder, SA, and SP, using CC or disorder-specific CBT. RESULTS: Ten studies implemented CC and four implemented disorder-specific CBT. One study compared CC with a disorder-specific approach. There was a lack of data to support use of CC in treatment of SPs. However, CC was equally effective as disorder-specific treatments for SA and SAD. CONCLUSIONS: A lack of data exists for disorder-specific CBT interventions compared to CC.

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies.

INTRODUCTION: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD). METHODS: Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response. Skin swabs were obtained from both sites before and after treatment to investigate the presence of staphylococci and enterotoxin production. In addition, the ability of MH and its methanolic and hexane extracts to down regulate IL4-induced CCL26 protein release from HaCaT cells was evaluated by enzyme linked immunosorbent assay. Also, the ability of MH to modulate calcium ionophore-induced mast cell degranulation was assessed by enzyme immunoassay. RESULTS: In 14 patients, AD lesions significantly improved post MH treatment versus pre-treatment as compared to control lesions. No significant changes in the skin staphylococci were observed after day 7, irrespective of honey treatment. Consistent with the clinical observation, MH significantly down regulated IL4-induced CCL26 release from HaCaT cells in a dose-dependent manner. This effect was partially lost, though remained significant, when methanolic and hexane extracts of MH were utilized. In addition, mast cell degranulation was significantly inhibited following treatment with MH. CONCLUSIONS: MH is potentially effective in the treatment of AD lesions based on both clinical and cellular studies through different mechanisms. This needs to be confirmed by randomized and controlled clinical trials.

Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism.

Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.

Eye movements reveal a dissociation between memory encoding and retrieval in adults with autism.

People with Autism Spectrum Disorder (ASD) exhibit subtle deficits in recollection, which have been proposed to arise from encoding impairments, though a direct link has yet to be demonstrated. In the current study, we used eye-tracking to obtain trial-specific measures of encoding (eye movement patterns) during incidental (natural viewing) and intentional (strategic) encoding conditions in adults with ASD and typical controls. Using this approach, we tested the degree to which differences in encoding might contribute to recollection impairments, or whether group differences in memory primarily emerge at retrieval. Following encoding of scenes, participants were asked to distinguish between old and similar lure scenes and provide 'remember'/'familiar' responses. Intentional encoding increased eye movements and subsequent recollection in both groups to a similar degree, but the ASD group were impaired overall at the memory task and used recollection less frequently. In controls, eye movements at encoding predicted subsequent correct responses and subsequent recollection on a trial-by-trial basis, as expected. In contrast, despite a similar pattern of eye movements during encoding in the two groups, eye movements did not predict trial-by-trial subsequent memory in ASD. Furthermore, recollection was associated with lower similarity between encoding- and retrieval-related eye movements in the ASD group compared to the control group. The eye-tracking results therefore provide novel evidence for a dissociation between encoding and recollection-based retrieval in ASD.