Eleven strategies for making reproducible research and open science training the norm at research institutions.

Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers - in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees - to think creatively about the many ways they can promote reproducible research and open science practices in their institutions.

Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

Finding the best fit for improving reproducibility: reflections from the QUEST Center for Responsible Research.

Increasing the reproducibility and trustworthiness of biomedical research requires engaging stakeholders from all levels in an institutional setting. The QUEST Center for Responsible Research aims to develop and implement new approaches to improve the culture and practice of research, tailored to the needs of these stakeholders. Members of the QUEST Center organised a brainstorm to reflect on the challenges and new opportunities encountered in implementing different projects through QUEST and share the lessons that working groups have learned over the first five years. The authors informally surveyed and interviewed working groups where relevant and highlight common themes that have influenced the success of many projects, including top-down and bottom-up engagement, managing expectations, the availability of expertise, ensuring sustainability, and considering incentives. The commentary authors conclude by encouraging the research community to view initiatives that promote reproducibility not as a one-size-fits-all undertaking, but rather as an opportunity to unite stakeholders and customise drivers of cultural change.

Recommendations for empowering early career researchers to improve research culture and practice.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

How to connect academics around the globe by organizing an asynchronous virtual unconference.

Many conferences and in-person meetings have transitioned to virtual platforms in response to the COVID-19 pandemic. Here, we share strategies and lessons learned from organizing an international virtual unconventional conference, or 'unconference'. The event focused on how early career researchers can advocate for systemic improvements in scientific publishing and research culture. The virtual unconference had three main components: (1) a virtual networking event, (2) asynchronous virtual brainstorming, and (3) a virtual open space, where participants could join or lead in-depth discussions. The unconference format was participant-driven and encouraged dialogue and collaboration between 54 attendees from 20 countries on six continents. Virtual brainstorming allowed participants to contribute to discussions at times that were convenient for them. Activity was consistently high throughout the 48 hours of virtual brainstorming and continued into the next day. The results of these discussions are collaboratively summarized in a paper entitled Empowering Early Career Researchers to Improve Science, co-authored by the unconference participants . We hope that this method report will help others to organize asynchronous virtual unconferences, while also providing new strategies for participant-driven activities that could be integrated into conventional virtual conferences.

Layer 3 Pyramidal Cells in the Medial Entorhinal Cortex Orchestrate Up-Down States and Entrain the Deep Layers Differentially.

Up-down states (UDS) are synchronous cortical events of neuronal activity during non-REM sleep. The medial entorhinal cortex (MEC) exhibits robust UDS during natural sleep and under anesthesia. However, little is known about the generation and propagation of UDS-related activity in the MEC. Here, we dissect the circuitry underlying UDS generation and propagation across layers in the MEC using both in vivo and in vitro approaches. We provide evidence that layer 3 (L3) MEC is crucial in the generation and maintenance of UDS in the MEC. Furthermore, we find that the two sublayers of the L5 MEC participate differentially during UDS. Our findings show that L5b, which receives hippocampal output, is strongly innervated by UDS activity originating in L3 MEC. Our data suggest that L5b acts as a coincidence detector during information transfer between the hippocampus and the cortex and thereby plays an important role in memory encoding and consolidation.

Aberrant alpha and gamma oscillations ex vivo after single application of the NMDA receptor antagonist MK-801.

Clinical symptoms of schizophrenia are associated with altered cortical neuronal oscillations in multiple frequency bands such as alpha (7-13Hz) and gamma (30-90Hz) rhythms. NMDA receptor antagonists induce psychotic symptoms in humans and a schizophrenia-like phenotype in animals, suggesting NMDA receptor dysfunction is involved in the generation of many symptoms of the disorder. We investigated the effects of a single intraperitoneal injection of the NMDA receptor antagonist MK-801 in rats, a model of first-episode schizophrenia, on network oscillations recorded ex vivo in the hippocampus and prefrontal cortex. We found that spontaneous gamma oscillations in hippocampal slices of MK-801-treated animals had a higher peak frequency, but that their rate of occurrence, peak power and Q factor (ratio of peak frequency to half bandwidth) were not affected. Hippocampal gamma oscillations induced by application of acetylcholine displayed a higher peak power, a reduced peak frequency and a shortened induction latency, whereas the Q factor did not change. In the prefrontal cortex, co-application of carbachol and kainate induced two types of network activity in sham animals: continuous gamma oscillations and alternating alpha/gamma oscillations. In MK-801-treated animals, the alternating pattern completely disappeared, and only continuous gamma oscillations could be detected, possessing an increased peak power, decreased peak frequency and decreased Q factor. Alpha oscillations recorded in MK-801-treated animals also had a significantly lower Q factor. In conclusion, our data suggest that NMDA receptor antagonists fundamentally alter the power, peak frequency, dynamics and periodicity of neuronal oscillations in the alpha and gamma frequency band.

Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke.

Given small sample sizes, loss of animals in preclinical experiments can dramatically alter results. However, effects of attrition on distortion of results are unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated.

Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway.

Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.

Indestructible plastic: the neuroscience of the new aging brain.

In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

Shaping the aging brain: role of auditory input patterns in the emergence of auditory cortical impairments.

Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.