Ventromedial Prefrontal Cortex Does Not Play a Selective Role in Pattern Separation.

Humans have the capacity to form new memories of events that are, at times, highly similar to events experienced in the past, as well as the capacity to integrate and associate new information within existing knowledge structures. The former process relies on mnemonic discrimination and is believed to depend on hippocampal pattern separation, whereas the latter is believed to depend on generalization signals and conceptual categorization supported by the neocortex. Here, we examine whether and how the ventromedial prefrontal cortex (vMPFC) supports discrimination and generalization on a widely used task that was primarily designed to tax hippocampal processes. Ten individuals with lesions to the vMPFC and 46 neurotypical control participants were administered an adapted version of the mnemonic similarity task [Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia, 51, 2442-2449, 2013], which assesses the ability to distinguish previously learned images of everyday objects (targets) from unstudied, highly similar images (lures) and dissimilar images (foils). Relative to controls, vMPFC-lesioned individuals showed intact discrimination of lures from targets but a propensity to mistake studied targets and similar lures for dissimilar foils. This pattern was accompanied by inflated confidence despite low accuracy when responding to similar lures. These findings demonstrate a more general role of the vMPFC in memory retrieval, rather than a specific role in supporting pattern separation.

Dentate Gyrus Integrity Is Necessary for Behavioral Pattern Separation But Not Statistical Learning.

Pattern separation, the creation of distinct representations of similar inputs, and statistical learning, the rapid extraction of regularities across multiple inputs, have both been linked to hippocampal processing. It has been proposed that there may be functional differentiation within the hippocampus, such that the trisynaptic pathway (entorhinal cortex > dentate gyrus > CA3 > CA1) supports pattern separation, whereas the monosynaptic pathway (entorhinal cortex > CA1) supports statistical learning. To test this hypothesis, we investigated the behavioral expression of these two processes in B. L., an individual with highly selective bilateral lesions in the dentate gyrus that presumably disrupt the trisynaptic pathway. We tested pattern separation with two novel auditory versions of the continuous mnemonic similarity task, requiring the discrimination of similar environmental sounds and trisyllabic words. For statistical learning, participants were exposed to a continuous speech stream made up of repeating trisyllabic words. They were then tested implicitly through a RT-based task and explicitly through a rating task and a forced-choice recognition task. B. L. showed significant deficits in pattern separation on the mnemonic similarity tasks and on the explicit rating measure of statistical learning. In contrast, B. L. showed intact statistical learning on the implicit measure and the familiarity-based forced-choice recognition measure. Together, these results suggest that dentate gyrus integrity is critical for high-precision discrimination of similar inputs, but not the implicit expression of statistical regularities in behavior. Our findings offer unique new support for the view that pattern separation and statistical learning rely on distinct neural mechanisms.

Scene memory and hippocampal volume in middle-aged women with early hormone loss.

The present study explored whether early midlife bilateral salpingo-oophorectomy (BSO), a female-specific risk factor for dementia, is associated with reduced medial temporal lobe structure and function. Younger middle-aged women with the BRCA1/2 mutation and a BSO prior to spontaneous menopause (SM) were recruited. We determined the performance of women with BSO not taking estradiol-based hormone therapy (n = 18) on a task measuring object and scene recognition and quantified medial temporal lobe subregion volumes using manually segmented high-resolution T2-weighted MRI scans. Comparisons were made to those with BSO taking estradiol-based hormone therapy (n = 20), age-matched premenopausal controls (n = 28), and older women in SM not taking hormone therapy matched for duration of hormone deprivation (n = 17). Reduced hippocampal integrity specific to the BSO group not taking hormone therapy was observed, reflected by significantly smaller dentate gyrus/CA2/CA3 volumes and lower scene recognition memory performance. These findings show that hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.

Protocol for a scoping review of sepsis epidemiology.

INTRODUCTION: Sepsis is a common, life-threatening syndrome of physiologic, pathologic, and biochemical abnormalities that are caused by infection and propagated by a dysregulated immune response. In 2017, the estimated annual incidence of sepsis around the world was 508 cases per 100,000 (95% confidence interval [CI], 422-612 cases per 100,000), however, reported incidence rates vary significantly by country. A scoping review will identify knowledge gaps by systematically investigating the incidence of sepsis. METHODS AND ANALYSIS: This scoping review will be guided by the updated JBI (formerly Joanna Briggs Institute) methodology. We will search the following electronic databases: MEDLINE, EMBASE, CINAHL, and Cochrane Database of Systematic Reviews/Central Register of Controlled Trials. In addition, we will search websites of trial and study registries. We will review titles and abstracts of potentially eligible studies and then full-texts by two independent reviewers. We will include any study that is focused on the incidence of sepsis or septic shock in any population. Data will be abstracted independently using pre-piloted data extraction forms, and we will present results according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols Extension for Scoping Reviews. ETHICS AND DISSEMINATION: The results of this review will be used to create a publicly available indexed and searchable electronic registry of existing sepsis research relating to incidence in neonates, children, and adults. With input from stakeholders, we will identify the implications of study findings for policy, practice, and research. Ethics approval was not required given this study reports on existing literature.

Long-Term Cognitive Outcomes and Sleep in Adults After Extracorporeal Life Support.

OBJECTIVES: To assess differences in cognitive outcomes and sleep in adult survivors of critical illness, managed with venovenous extracorporeal membrane oxygenation as compared to conventional mechanical ventilation only. DESIGN: Retrospective cohort study linked with data from the COGnitive outcomes and WELLness study. SETTING: A multisite study from five adult medical/surgical ICUs in Toronto. PATIENTS: Thirty-three ICU survivors including adult patients who received venovenous extracorporeal membrane oxygenation (n = 11) matched with patients who received mechanical ventilation only (n = 22) using specified covariates (e.g., age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics and admission diagnoses were collected at enrollment. Cognitive outcome was evaluated using the Repeatable Battery for the Assessment of Neuropsychologic Status (global cognitive function) and Trail Making Test B (executive function), and sleep variables were estimated using actigraphy. Assessments occurred at 7 days post ICU discharge and again at 6- and 12-month follow-up. No statistically significant difference was seen between patients treated with or without venovenous extracorporeal membrane oxygenation in the mean daily Riker Sedation Agitation Score; however, patients in the venovenous extracorporeal membrane oxygenation group received greater amounts of fentanyl over their ICU stay as compared to patients receiving conventional mechanical ventilation only (p < 0.001). No significant differences were found in performance on either of the cognitive assessment tools, between survivors treated or not with venovenous extracorporeal membrane oxygenation at any of the time points assessed. Total sleep time estimated by actigraphy increased from approximately 6.5 hours in hospital to 7.5 hours at 6-month follow-up in all patients, regardless of treatment type. Total sleep time remained consistent in both groups from 6 to 12 months post ICU discharge. CONCLUSIONS: In this small retrospective case series, no significant differences were found in sleep or cognitive outcomes between extracorporeal life support and non-extracorporeal life support survivors. Further, in this hypothesis-generating study, differences in administered sedative doses during the ICU stay seen between the two groups did not impact 6- or 12-month cognitive performance or actigraphy-estimated sleep time.