Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.

BackgroundWe completed a scoping review on the barriers and facilitators to use of systematic reviews by health care managers and policy makers, including consideration of format and content, to develop recommendations for systematic review authors and to inform research efforts to develop and test formats for systematic reviews that may optimise their uptake.MethodsWe used the Arksey and O’Malley approach for our scoping review. Electronic databases (e.g., MEDLINE, EMBASE, PsycInfo) were searched from inception until September 2014. Any study that identified barriers or facilitators (including format and content features) to uptake of systematic reviews by health care managers and policy makers/analysts was eligible for inclusion. Two reviewers independently screened the literature results and abstracted data from the relevant studies. The identified barriers and facilitators were charted using a barriers and facilitators taxonomy for implementing clinical practice guidelines by clinicians.ResultsWe identified useful information for authors of systematic reviews to inform their preparation of reviews including providing one-page summaries with key messages, tailored to the relevant audience. Moreover, partnerships between researchers and policy makers/managers to facilitate the conduct and use of systematic reviews should be considered to enhance relevance of reviews and thereby influence uptake.ConclusionsSystematic review authors can consider our results when publishing their systematic reviews. These strategies should be rigorously evaluated to determine impact on use of reviews in decision-making.Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-016-0370-1) contains supplementary material, which is available to authorized users.

Objective: To assess the characteristics and core statistical methodology specific to network meta-analyses (NMAs) in clinical research articles. Study Design and What is new?Key findings Although the amount of evidence (the number of treatments and studies) included in published NMAs remains stable, the undertaking and reporting of statistical methods have significantly improved over the years. The assumptions underlying NMA are increasingly discussed and evaluated using appropriate methods. Less than 10% of NMAs published in 2014 and 2015 failed to evaluate the assumptions of the joint synthesis. What this adds to what is knownThis meta-epidemiological study presents the largest collection of published NMAs over the past 16 years. It provides an overview of the structural characteristics and statistical methodology of 456 published networks of interventions. It shows that the statistical methods in NMA have considerably improved in all aspects and some, such as the use of appropriate methods to evaluate the plausibility of the assumptions, are now routinely performed. We conclude that the increasingly populous community of NMA methodologists is quickly advancing through the learning curve of statistical methods employed in NMA. What is the implication, what should change nowThe updated description of the structural characteristics of the published NMAs can be used to inform pragmatic simulations studies and the development of methods that are relevant to the type of networks typically found in the medical literature. Future tutorials and training should be focused on improving the methodology and reporting on items that, although they have improved, their prevalence remains low, such as the formal exploration of heterogeneity and inconsistency and the presentation of all pairwise treatment effects.

BackgroundNetwork meta-analysis (NMA) has become a popular method to compare more than two treatments. This scoping review aimed to explore the characteristics and methodological quality of knowledge synthesis approaches underlying the NMA process. We also aimed to assess the statistical methods applied using the Analysis subdomain of the ISPOR checklist.MethodsComprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 14, 2015. References of relevant reviews were scanned. Eligible studies compared at least four different interventions from randomised controlled trials with an appropriate NMA approach. Two reviewers independently performed study selection and data abstraction of included articles. All discrepancies between reviewers were resolved by a third reviewer. Data analysis involved quantitative (frequencies) and qualitative (content analysis) methods. Quality was evaluated using the AMSTAR tool for the conduct of knowledge synthesis and the ISPOR tool for statistical analysis.ResultsAfter screening 3538 citations and 877 full-text papers, 456 NMAs were included. These were published between 1997 and 2015, with 95% published after 2006. Most were conducted in Europe (51%) or North America (31%), and approximately one-third reported public sources of funding. Overall, 84% searched two or more electronic databases, 62% searched for grey literature, 58% performed duplicate study selection and data abstraction (independently), and 62% assessed risk of bias. Seventy-eight (17%) NMAs relied on previously conducted systematic reviews to obtain studies for inclusion in their NMA. Based on the AMSTAR tool, almost half of the NMAs incorporated quality appraisal results to formulate conclusions, 36% assessed publication bias, and 16% reported the source of funding. Based on the ISPOR tool, half of the NMAs did not report if an assessment for consistency was conducted or whether they accounted for inconsistency when present. Only 13% reported heterogeneity assumptions for the random-effects model.ConclusionsThe knowledge synthesis methods and analytical process for NMAs are poorly reported and need improvement.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0764-6) contains supplementary material, which is available to authorized users.

We present a dataset of 1,576 single neurons recorded from the human amygdala and hippocampus in 65 sessions from 42 patients undergoing intracranial monitoring for localization of epileptic seizures. Subjects performed a recognition memory task with pictures as stimuli. Subjects were asked to identify whether they had seen a particular image the first time (‘new’) or second time (‘old’) on a 1–6 confidence scale. This comprehensive dataset includes the spike times of all neurons and their extracellular waveforms, behavior, electrode locations determined from post-operative MRI scans, demographics, and the stimuli shown. As technical validation, we provide spike sorting quality metrics and assessment of tuning of cells to verify the presence of visually-and memory selective cells. We also provide analysis code that reproduces key scientific findings published previously on a smaller version of this dataset. Together, this large dataset will facilitate the investigation of the neural mechanism of declarative memory by providing a substantial number of hard to obtain human single-neuron recordings during a well characterized behavioral task.