Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory is selectively impaired following the expression of a genetically encoded Rac1-inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Item-specific and relational encoding are effective at reducing the illusion of competence.

Metamemory, or the ability to understand the capacities of one's own memory, is important for learning. To investigate questions surrounding metamemory, researchers commonly have participants make judgments of learning (JOLs) at encoding, in which participants rate their likelihood of recalling the target in a cue-target word pair when shown only the cue at test. However, the associative direction of cue-target pairs can affect the calibration of JOLs. Unlike forward associates (e.g., credit-card), in which JOLs often accurately predict recall, an illusion of competence has been reported for backward associates (e.g., card-credit), symmetrical associates (e.g., salt-pepper), and unrelated cue-target pairs (e.g., artery-bronze) such that JOLs overestimate later recall. The present study evaluates whether the illusion of competence can be reduced when participants apply deep item-specific or relational encoding tasks relative to silent reading. Across two experiments, we show that both item-specific and relational encoding strategies reduce the illusion of competence for backward associates and unrelated pairs while improving the calibration between JOLs and recall. Our findings suggest that these encoding strategies are effective at reducing the illusion of competence, with increased calibration primarily reflecting improved recall. Thus, item-specific and relational encoding strategies primarily affect retrieval processes rather than metacognitive processes that participants engage in at encoding.

Is discriminability a requirement for reactivity? Comparing the effects of mixed vs. pure list presentations on judgment of learning reactivity.

Providing judgments of learning (JOLs) at study tends to produce reactive effects on recall of cue-target word pairs. This reactivity generally produces memory improvements (i.e., positive reactivity) but only for related word pairs. For unrelated pairs, reactivity is typically not observed. Researchers have primarily investigated reactivity using study lists that contain at least two distinct pair types (i.e., related vs. unrelated pairs). Using these mixed lists, reactivity may occur because participants use distinguishing pair characteristics to inform their study goals (i.e., prioritizing related vs. unrelated pairs). The present study examined whether detection of separate pair types within mixed lists is a requisite for reactivity to occur. Experiment 1 replicated previous work showing that in mixed lists, JOLs produced positive reactivity on related pairs but are nonreactive on unrelated pairs. Importantly, Experiment 1 also found that these patterns extended to pure lists, in which only one pair type is presented. Experiments 2 and 3 then extended these patterns to backward and symmetrical paired associates. Finally, across experiments, reactivity patterns reported for JOLs extended to frequency of co-occurrence judgments across pair and list types. Our findings that reactivity patterns consistently emerge using pure lists supports a cue-strengthening account of reactivity.

Distinctive Sans Forgetica font does not benefit memory accuracy in the DRM paradigm.

A common method used by memory scholars to enhance retention is to make materials more challenging to learn-a benefit termed desirable difficulties. Recently, researchers have investigated the efficacy of Sans Forgetica, a perceptually disfluent/distinctive font which may increase processing effort required at study and enhance memory as a result. We examined the effects of Sans Forgetica relative to a standard control font (Arial) on both correct memory and associative memory errors using the Deese/Roediger-McDermott (DRM) false memory paradigm, to evaluate Sans Forgetica effects on overall memory accuracy. Across four experiments, which included nearly 300 participants, Sans Forgetica was found to have no impact on correct or false memory of DRM lists relative to a standard Arial control font, regardless of whether font type was manipulated within or between subjects or whether memory was assessed via free recall or recognition testing. Our results indicate that Sans Forgetica is ineffective for improving memory accuracy even when accounting for associative memory errors.

Virtual Adaptation of an International Exchange Program in Medical Education.

Medical education has drastically transformed during the COVID-19 pandemic. Measures such as adopting telemedicine visits, minimizing the number of trainees on service, discontinuing external rotations, and converting in-person to online didactics have been broadly and swiftly implemented. While these innovations have promoted greater interconnectivity amongst institutions and made continuing medical education possible, international exchange programs in medical education are still largely disrupted. In response to the changing guidelines and restrictions necessitated by the COVID-19 pandemic, the authors used Kern's six-step approach to design and implement a virtual curriculum to replace the in-person activities of the 2020-2021 Neurology Peru-Rochester exchange program (NeuroPro). Twenty-seven trainees participated in this virtual adaptation. The average daily attendance was ≥85% and the program was rated 9/10 on average in a feedback survey (63% response rate). The median percentage of correct answers during the pre-test was 64% and it increased to 79% during the post-test (P = 0.003). Virtual adaptation of international exchange programs in medical education is feasible to safely continue international collaborative efforts to promote symbiotic building of local expertise and cross-cultural exchange during the ongoing COVID-19 pandemic and beyond.

Reactivity from judgments of learning is not only due to memory forecasting: evidence from associative memory and frequency judgments.

Research has shown that judgments of learning (JOLs) often produce a reactive effect on the learning of cue-target pairs in which target recall differs between participants who provide item-based JOLs at study versus those who do not. Positive reactivity, or the memory improvement found when JOLs are provided, is typically observed on related pairs, while no reactivity is commonly found on unrelated pairs. In four experiments, we examined JOL reactivity effects by comparing JOL and no-JOL groups to other groups who engaged in relational-type encoding/judgment tasks. Experiment 1 replicated positive JOL reactivity effects with related pairs with an extension to symmetrically related pairs. Next, Experiment 2 found that providing judgments of associative memory-a task that does not involve memory predictions-yielded equivalent reactivity patterns as JOLs. Experiment 3 replicated this reactivity pattern using a frequency of co-occurrence judgment task. Finally, In Experiment 4, a similar positive reactivity pattern was found using a relational encoding task when compared to a standard JOL. Collectively, our results suggest that previous JOL reactivity patterns are not solely due to memory forecasting processes via JOLs and likely reflect relational encoding that is strategically applied towards related, but not unrelated pairs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11409-022-09301-2.

The lrd package: An R package and Shiny application for processing lexical data.

Recall testing is a common assessment to gauge memory retrieval. Responses from these tests can be analyzed in several ways; however, the output generated from a recall study typically requires manual coding that can be time intensive and error-prone before analyses can be conducted. To address this issue, this article introduces lrd (Lexical Response Data), a set of open-source tools for quickly and accurately processing lexical response data that can be used either from the R command line or through an R Shiny graphical user interface. First, we provide an overview of this package and include a step-by-step user guide for processing both cued- and free-recall responses. For validation of lrd, we used lrd to recode output from cued, free, and sentence-recall studies with large samples and examined whether the results replicated using lrd-scored data. We then assessed the inter-rater reliability and sensitivity and specificity of the scoring algorithm relative to human-coded data. Overall, lrd is highly reliable and shows excellent sensitivity and specificity, indicating that recall data processed using this package are remarkably consistent with data processed by a human coder.

Drawing individual images benefits recognition accuracy in the Deese-Roediger-McDermott paradigm.

We examined the effects of drawing on correct and false recognition within the Deese-Roediger-McDermott (DRM) false memory paradigm. In Experiment 1, we compared drawing of a word's referent using either a standard black pencil or coloured pencils relative to a read-only control group. Relative to reading, drawing in either black or coloured pencil similarly boosted correct recognition and reduced false recognition. Signal-detection analyses indicated that drawing reduced the amount of encoded memory information for critical lures and increased monitoring, indicating that both processes contributed to the false recognition reduction. Experiment 2 compared drawing of individual images of DRM list items relative to drawing integrated images using sets of DRM list items. False recognition was lower for drawing of individual images relative to integrated images-a pattern that reflected a decrease in encoded memory information but not monitoring. Therefore, drawing individual images improves memory accuracy in the DRM paradigm relative to a standard read-control task and an integrated-drawing task, which we argue is due to the recruitment of item-specific processing.

Private sector initiatives to tackle the burden of COVID-19: experiences from the Nigerian frontline.

Across Africa, there is some evidence of COVID-19 private sector activities to tackle COVID-19 which include the development of rapid diagnostic kits, deployment of e-health platforms for bespoke health workforce training, disease surveillance, reporting, auto-screening and advisories. Inequities in living and access to care by disadvantaged populations in the rural areas have been ameliorated by multi-pronged responses such as that mounted by the Joseph Ukpo Hospitals and Research Institute (JUHRI) in Nigeria. The provision, production and donation of personal protective equipment (PPE), the production of hand sanitizers and the engagement of the local community in the process represents an effective strategy to contain COVID-19, protect health workers and provide pathways for economic support for people whose sources of income have been upended during the pandemic. The JUHRI experience underpinned by Catholic medical ethics provides concrete evidence of the value of private sector participation in dealing with public health emergencies.

High-fat diet induces neuroinflammation and reduces the serotonergic response to escitalopram in the hippocampus of obese rats.

Clinical studies indicate that obese individuals have an increased risk of developing co-morbid depressive illness and that these patients have reduced responses to antidepressant therapy, including selective serotonin reuptake inhibitors (SSRIs). Obesity, a condition of chronic mild inflammation including obesity-induced neuroinflammation, is proposed to contribute to decreases in synaptic concentrations of neurotransmitters like serotonin (5HT) by decreasing 5HT synthesis in the dorsal raphe nucleus (DRN) and/or affecting 5HT reuptake in DRN target regions like the hippocampus. In view of these observations, the goal of the current study was to examine inflammatory markers and serotonergic dynamics in co-morbid obesity and depression. Biochemical and behavioral assays revealed that high-fat diet produced an obesity and depressive-like phenotype in one cohort of rats and that these changes were marked by increases in key pro-inflammatory cytokines in the hippocampus. In real time using fast scan cyclic voltammetry (FSCV), we observed no changes in basal levels of hippocampal 5HT; however responses to escitalopram were significantly impaired in the hippocampus of obese rats compared to diet resistant rats and control rats. Further studies revealed that these neurochemical observations could be explained by increases in serotonin transporter (SERT) expression in the hippocampus driven by elevated neuroinflammation. Collectively, these results demonstrate that obesity-induced increases in neuroinflammation adversely affect SERT expression in the hippocampus of obese rats, thereby providing a potential synaptic mechanism for reduced SSRI responsiveness in obese subjects with co-morbid depressive illness.

Advanced care planning during the COVID-19 pandemic: ceiling of care decisions and their implications for observational data.

BACKGROUND: Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. METHODS: Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. RESULTS: A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were 'not for resuscitation'. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86-0·93 p < 0·001), frailty (odds 0·48, 0·38-0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52-1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care. CONCLUSION: Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.

Insight Into Myocardial Microstructure of Athletes and Hypertrophic Cardiomyopathy Patients Using Diffusion Tensor Imaging.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure. PURPOSE: To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI. STUDY TYPE: Prospective cohort. POPULATION: Twenty healthy volunteers, 20 athletes, and 20 HCM patients. FIELD STRENGTH/SEQUENCE: 3T/DTI spin echo. ASSESSMENT: In-house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)-reflecting the orientations of laminar sheetlets. STATISTICAL TESTS: Independent samples t-tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were two-tailed. A result was considered statistically significant at P ≤ 0.05. RESULTS: DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MDHCM = 1.52 ± 0.06 × 10-3 mm2 /s, MDAthletes = 1.49 ± 0.03 × 10-3 mm2 /s, MDvolunteers = 1.47 ± 0.02 × 10-3 mm2 /s, P < 0.05; E2AHCM = 58.8 ± 4°, E2Aathletes = 47 ± 5°, E2Avolunteers = 38.5 ± 7°, P < 0.05; FAHCM = 0.30 ± 0.02, FAAthletes = 0.35 ± 0.02, FAvolunteers = 0.36 ± 0.03, P < 0.05). HCM patients had significantly higher E2A in their thickest segments compared to the remote (E2Athickest = 66.8 ± 7, E2Aremote = 51.2 ± 9, P < 0.05). DATA CONCLUSION: DTI depicts an increase in amplitude and isotropy of diffusion in the myocardium of HCM compared to athletes and volunteers as reflected by increased MD and decreased FA values. While significantly higher E2A values in HCM and athletes reflect steeper configurations of the myocardial sheetlets than in volunteers, HCM patients demonstrated an eccentric rise in E2A in their thickest segments, while athletes demonstrated a concentric rise. Further studies are required to determine the diagnostic capabilities of DTI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

The deceptive nature of associative word pairs: the effects of associative direction on judgments of learning.

The accuracy of judgments of learning (JOLs) in forecasting later recall of cue-target pairs is sensitive to associative direction. JOLs are generally well calibrated for forward associative pairs (e.g., credit-card), but recall accuracy is often overestimated for backward pairs (e.g., card-credit). The present study further examines the effect of associative direction on JOL accuracy by comparing forward and backward pairs to unrelated pairs and symmetrical associates (e.g., salt-pepper)-a novel comparison. The correspondence between initial JOLs and recall accuracy was examined when study was either self-paced with concurrent JOLs (Experiment 1), when study/JOL duration was equated across pair types (Experiment 2), when JOLs were made immediately following study (Experiment 3), and when JOLs were made after a delay (Experiment 4). Across experiments, JOLs accurately estimated correct recall for forward pairs, but overestimated recall for symmetrical, backward, and unrelated pairs-an overestimation that was particularly robust for backward pairs. Calibration plots depicting JOL ratings against their corresponding recall accuracy indicated overestimations occurred for all pair types, though overestimations only occurred at high JOL ratings for symmetrical and forward pairs, a qualitative difference that was not captured in standard analyses of mean JOL and recall rates.

Investigating the interaction of direct and indirect relation on memory judgments and retrieval.

This study examined the interactive relationship between two measures of association (direct and indirect associations) when predicting relatedness judgments and cued-recall performance. Participants were recruited from Amazon's Mechanical Turk and were given word pairs of varying relatedness to judge for their semantic, thematic, and associative strength. After completing a distractor task, participants then completed a cued-recall task. First, we sought to expand previous work on judgments of associative memory to include semantic- and thematic-based judgments (judgments of relatedness), while also replicating bias and sensitivity findings. Next, we tested for an interaction between direct and indirect association when predicting participant judgments while also expanding upon previous work by examining that interaction when predicting recall. The interaction between direct and indirect association was significant for both judgments and recall. For low indirect association, direct association was the primary predictor of both judgment strength and recall proportions. However, this trend reversed for high indirect association, as higher levels of indirect relation decreased the effectiveness of direct relation as a predictor. Overall, our findings indicate the degree to which the processing of similarity information impacts cognitive processes such as retrieval and item judgments, while also parsing apart the underlying, interactive relationship that exists between the norms used to represent concept information.

English semantic feature production norms: An extended database of 4436 concepts.

A limiting factor in understanding memory and language is often the availability of large numbers of stimuli to use and explore in experimental studies. In this study, we expand on three previous databases of concepts to over 4000 words including nouns, verbs, adjectives, and other parts of speech. Participants in the study were asked to provide lists of features for each concept presented (a semantic feature production task), which were combined with previous research in this area. These feature lists for each concept were then coded into their root word form and affixes (i.e., cat and s for cats) to explore the impact of word form on semantic similarity measures, which are often calculated by comparing concept feature lists (feature overlap). All concept features, coding, and calculated similarity information is provided in a searchable database for easy access and utilization for future researchers when designing experiments that use word stimuli. The final database of word pairs was combined with the Semantic Priming Project to examine the relation of semantic similarity statistics on semantic priming in tandem with other psycholinguistic variables.

LAB: Linguistic Annotated Bibliography - a searchable portal for normed database information.

This article presents the Linguistic Annotated Bibliography (LAB) as a searchable Web portal to quickly and easily access reliable database norms, related programs, and variable calculations. These publications were coded by language, number of stimuli, stimuli type (i.e., words, pictures, symbols), keywords (i.e., frequency, semantics, valence), and other useful information. This tool not only allows researchers to search for the specific type of stimuli needed for experiments but also permits the exploration of publication trends across 100 years of research. Details about the portal creation and use are outlined, as well as various analyses of change in publication rates and keywords. In general, advances in computational power have allowed for the increase in dataset size in the recent decades, in addition to an increase in the number of linguistic variables provided in each publication.

SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis.

SIRT1 is an NAD+ -dependent deacetylase that functions in a variety of cells and tissues to mitigate age-associated diseases. However, it remains unknown if SIRT1 also acts to prevent pathological changes that accrue in motor neurons during aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1 expression decreases in the spinal cord of wild-type mice during normal aging. Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we found that SIRT1 slows age-related degeneration of motor neurons' presynaptic sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord shows an overlap of greater than 90% when comparing alterations during normal aging with changes during ALS, revealing a substantial upregulation in immune and inflammatory response genes and a downregulation of synaptic transcripts. In addition, overexpressing SIRT1 in motor neurons delays progression to end-stage disease in high copy SOD1G93A mice. Thus, our findings suggest that there are parallels between ALS and aging, and interventions to impede aging may also slow the progression of this devastating disease.