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Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

Social interactions have large effects on individual physiology and fitness. In the immediate sense, social stimuli are often highly salient and engaging. Over longer time scales, competitive interactions often lead to distinct social ranks and differences in physiology and behavior. Understanding how initial responses lead to longer-term effects of social interactions requires examining the changes in responses over time. Here we examined the effects of social interactions on transcriptomic signatures at two times, at the end of a 45-minute interaction and 4 hours later, in female Polistes fuscatus paper wasp foundresses. Female P. fuscatus have variable facial patterns that are used for visual individual recognition, so we separately examined the transcriptional dynamics in the optic lobe and the non-visual brain. Results demonstrate much stronger transcriptional responses to social interactions in the non-visual brain compared to the optic lobe. Differentially regulated genes in response to social interactions are enriched for memory-related transcripts. Comparisons between winners and losers of the encounters revealed similar overall transcriptional profiles at the end of an interaction, which significantly diverged over the course of 4 hours, with losers showing changes in expression levels of genes associated with aggression and reproduction in paper wasps. On nests, subordinate foundresses are less aggressive, do more foraging and lay fewer eggs compared to dominant foundresses and we find losers shift expression of many genes in the non-visual brain, including vitellogenin, related to aggression, worker behavior, and reproduction within hours of losing an encounter. These results highlight the early neurogenomic changes that likely contribute to behavioral and physiological effects of social status changes in a social insect., Author summary Aggressive interactions often create inequalities–some individuals win while others lose. Winning versus losing can lead to large physiological differences between individuals, including different neurogenomic profiles between winners and losers. How this information about contest outcome leads to distinct neurogenomic profiles is poorly understood. Here we examine gene expression in response to aggressive social encounters in paper wasps, which naturally form dominance hierarchies on their nests in the wild. Shortly following encounters winners and losers have similar expression profiles, likely because similar mechanisms are engaged by social experiences. Four hours later, we find divergent neurogenomic profiles between winners and losers, with losers showing larger shifts in expression compared to winners. Many of the most dynamically expressed genes have been previously associated with dominance and caste differences in paper wasps showing how a single interaction can engage many of the same genomic networks that are involved in mediating more dramatic differences in queen-worker behavioral differences are also involved in responses shortly following social interactions.

Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.

Three-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer’s disease and glioma.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221119760 for Transfer function analysis of dynamic cerebral autoregulation: a CARNet white paper 2022 update by Ronney B Panerai, Patrice Brassard, Joel S Burma, Pedro Castro, Jurgen AHR Claassen, Johannes J van Lieshout, Jia Liu, Samuel JE Lucas, Jatinder S Minhas, Georgios D Mitsis, Ricardo C Nogueira, Shigehiko Ogoh, Stephen J Payne, Caroline A Rickards, Andrew D Robertson, Gabriel D Rodrigues, Jonathan D Smirl David M Simpson in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221119760 for Transfer function analysis of dynamic cerebral autoregulation: a CARNet white paper 2022 update by Ronney B Panerai, Patrice Brassard, Joel S Burma, Pedro Castro, Jurgen AHR Claassen, Johannes J van Lieshout, Jia Liu, Samuel JE Lucas, Jatinder S Minhas, Georgios D Mitsis, Ricardo C Nogueira, Shigehiko Ogoh, Stephen J Payne, Caroline A Rickards, Andrew D Robertson, Gabriel D Rodrigues, Jonathan D Smirl David M Simpson in Journal of Cerebral Blood Flow & Metabolism

The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.

Background: Utilizing information technology (IT) systems, for example in form of computerized cognitive screening or exergame-based (also called active videogames) training, has gained growing interest for supporting healthy aging and to detect, prevent and treat neurocognitive disorders (NCD). To ameliorate the effectiveness of exergaming, the neurobiological mechanisms as well as the most effective components for exergame-based training remain to be established. At the same time, it is important to account for the end-users’ capabilities, preferences, and therapeutic needs during the design and development process to foster the usability and acceptance of the resulting program in clinical practice. This will positively influence adherence to the resulting exergame-based training program, which, in turn, favors more distinct training-related neurobiological effects. Objectives and Methods: This methodological paper describes the design and development process of novel exergame-based training concepts guided by a recently proposed methodological framework: The ‘Multidisciplinary Iterative Design of Exergames (MIDE): A Framework for Supporting the Design, Development, and Evaluation of Exergames for Health’ (Li et al., 2020). Case Study: A step-by-step application of the MIDE-framework as a specific guidance in an ongoing project aiming to design, develop, and evaluate an exergame-based training concept with the aim to halt and/or reduce cognitive decline and improve quality of life in older adults with mild neurocognitive disorder (mNCD) is illustrated. Discussion and Conclusion: The development of novel exergame-based training concepts is greatly facilitated when it is based on a theoretical framework (e.g., the MIDE-framework). Applying this framework resulted in a structured, iterative, and evidence-based approach that led to the identification of multiple key requirements for the exergame design as well as the training components that otherwise may have been overlooked or neglected. This is expected to foster the usability and acceptance of the resulting exergame intervention in “real life” settings. Therefore, it is strongly recommended to implement a theoretical framework (e.g., the MIDE-framework) for future research projects in line with well-known checklists to improve completeness of reporting and replicability when serious games for motor-cognitive rehabilitation purposes are to be developed. ISSN:1663-4365

Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the quality of life of affected patients. Neurons are able to regenerate their injured axons in the peripheral nerves; however, the endogenous repair mechanisms usually do not allow for a satisfactory functional recovery, especially after severe nerve injuries. The interest on regeneration after peripheral nerve injuries has increased in the recent years due to the numerous advances derived from studies of neurobiology, cell therapy, and tissue engineering. This Thematic Papers Issue brings together a number of papers, authored by researchers in the field, which cover a wide spectrum of topics related to regeneration and repair of peripheral nerve injuries. The Issue proposal originated from the recent 4th International Symposium on Peripheral Nerve Regeneration (ISPNR2017) which was hosted by Xavier Navarro and the European Society for the Study of Peripheral Nerve Repair and Regeneration in Barcelona, Spain. Anat Rec, 301:1614-1617, 2018. © 2018 Wiley Periodicals, Inc.

Science is increasingly done in large teams, making it more likely that papers will be written by several authors from different institutes, disciplines, and cultural backgrounds. A small number of “Ten simple rules” papers have been written on collaboration and on writing but not on combining the two. Collaborative writing with multiple authors has additional challenges, including varied levels of engagement of coauthors, provision of fair credit through authorship or acknowledgements, acceptance of a diversity of work styles, and the need for clear communication. Miscommunication, a lack of leadership, and inappropriate tools or writing approaches can lead to frustration, delay of publication, or even the termination of a project. To provide insight into collaborative writing, we use our experience from the Global Lake Ecological Observatory Network (GLEON) to frame 10 simple rules for collaboratively writing a multi-authored paper. We consider a collaborative multi-authored paper to have three or more people from at least two different institutions. A multi-authored paper can be a result of a single discrete research project or the outcome of a larger research program that includes other papers based on common data or methods. The writing of a multi-authored paper is embedded within a broader context of planning and collaboration among team members. Our recommended rules include elements of both the planning and writing of a paper, and they can be iterative, although we have listed them in numerical order. It will help to revisit the rules frequently throughout the writing process. With the 10 rules outlined below, we aim to provide a foundation for writing multi-authored papers and conducting exciting and influential science.

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges.

Sleep deprivation is a common complaint in modern societies. Insufficient sleep has increased the risk of catching neurodegenerative diseases such as Alzheimer Several studies have indicated that restricted sleep increases the level of deposition of β-amyloid and formation of neurofibrillary tangles, the major brain microstructural hallmarks for Alzheimer disease. The mechanisms by which sleep deprivation affects the pathology of Alzheimer disease has not yet been fully and definitively identified. However, risk factors like apolipoprotein E risk alleles, kinases and phosphatases dysregulation, reactive oxygen species, endoplasmic reticulum damages, glymphatic system dysfunctions and orexinergic system inefficacy have been identified as the most important factors which mediates between the two conditions. In this review, these factors are briefly discussed.

In our planned study, we shall empirically study the assessment of cited papers within the framework of the anchoring-and-adjustment heuristic. We are interested in the question whether citation decisions are (mainly) driven by the quality of cited references. The design of our study is oriented towards the study by Teplitskiy, Duede [10]. We shall undertake a survey of corresponding authors with an available email address in the Web of Science database. The authors are asked to assess the quality of papers that they cited in previous papers. Some authors will be assigned to three treatment groups that receive further information alongside the cited paper: citation information, information on the publishing journal (journal impact factor), or a numerical access code to enter the survey. The control group will not receive any further numerical information. In the statistical analyses, we estimate how (strongly) the quality assessments of the cited papers are adjusted by the respondents to the anchor value (citation, journal, or access code). Thus, we are interested in whether possible adjustments in the assessments can not only be produced by quality-related information (citation or journal), but also by numbers that are not related to quality, i.e. the access code. The results of the study may have important implications for quality assessments of papers by researchers and the role of numbers, citations, and journal metrics in assessment processes.

“There is no problem that a library card can't solve” according to author Eleanor Brown [1]. This advice is sound, probably for both life and science, but even the best tool (like the library) is most effective when accompanied by instructions and a basic understanding of how and when to use it. For many budding scientists, the first day in a new lab setting often involves a stack of papers, an email full of links to pertinent articles, or some promise of a richer understanding so long as one reads enough of the scientific literature. However, the purpose and approach to reading a scientific article is unlike that of reading a news story, novel, or even a textbook and can initially seem unapproachable. Having good habits for reading scientific literature is key to setting oneself up for success, identifying new research questions, and filling in the gaps in one’s current understanding; developing these good habits is the first crucial step. Advice typically centers around two main tips: read actively and read often. However, active reading, or reading with an intent to understand, is both a learned skill and a level of effort. Although there is no one best way to do this, we present 10 simple rules, relevant to novices and seasoned scientists alike, to teach our strategy for active reading based on our experience as readers and as mentors of undergraduate and graduate researchers, medical students, fellows, and early career faculty. Rules 1–5 are big picture recommendations. Rules 6–8 relate to philosophy of reading. Rules 9–10 guide the “now what?” questions one should ask after reading and how to integrate what was learned into one’s own science.

The paper entitled "Regulation of DARPP-32 dephosphorylation at PKA and Cdk5-sites by NMDA and AMPA receptors", authored by Nishi, A., Bibb, J.A., Matsuyama, S., Hamada, M., Higushi, H., Nairn, A.C. and Greengard. P., and published in the Journal of Neurochemistry. [J. Neurochem. (2002) Vol. 5, pp832-841] describes the study the effects of ionotropic glutamate NMDA and AMPA receptors on DARPP-32 phosphorylation in neostriatal slices and purported to show that activation of NMDA and AMPA receptors caused the decrease of phosphorylations of threonone 34 and threonine 75 DARPP-32 mediated by Ca 2+-dependent activation of calcineurin and protein phosphatase-2A respectively. However, no supporting scientific results were provided. Figures 1A, 1B, 1C and 1D are duplicates of each other. With exactly the same figures depicting exactly the same immunublots, the authors somehow came up with different bar charts that supposedly quantify the extent of DARPP-32 phosphorylation levels under different conditions. Figures 3A and 3C are also duplicates of each other. It is not clear how the reviewer(s) and the Editor of the Journal of Neurochemistry could have missed the glaring evidence of Data Fabrication and and Data Falsification.

Supplemental material, JCB905433 Supplemental Material2 for Guidelines for the content and format of PET brain data in publications and archives: A consensus paper by Gitte M Knudsen, Melanie Ganz, Stefan Appelhoff, Ronald Boellaard, Guy Bormans, Richard E Carson, Ciprian Catana, Doris Doudet, Antony D Gee, Douglas N Greve, Roger N Gunn, Christer Halldin, Peter Herscovitch, Henry Huang, Sune H Keller, Adriaan A Lammertsma, Rupert Lanzenberger, Jeih-San Liow, Talakad G Lohith, Mark Lubberink, Chul H Lyoo, J John Mann, Granville J Matheson, Thomas E Nichols, Martin Nørgaard, Todd Ogden, Ramin Parsey, Victor W Pike, Julie Price, Gaia Rizzo, Pedro Rosa-Neto, Martin Schain, Peter JH Scott, Graham Searle, Mark Slifstein, Tetsuya Suhara, Peter S Talbot, Adam Thomas, Mattia Veronese, Dean F Wong, Maqsood Yaqub, Francesca Zanderigo, Sami Zoghbi and Robert B Innis in Journal of Cerebral Blood Flow & Metabolism

To commemorate the 100th anniversary of the creation of the Instituto Cajal, we bring this thematic issue to honor Spanish neuroscience. The issue includes several papers written by scientists, most of them being direct descendants of those who lived on the front lines of the dawn of Spanish neuroscience. These pages reflect a summary of the main achievements of this unique group of neuroscientists, all of them belonging to the Cajal School. Finally, this school of scientists became the forerunner of the modern worldwide neuroscience. Anat Rec, 303:1179–1180, 2020. © 2020 American Association for Anatomy.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field. The present research was supported by the European Commission 7th Framework Programme (FP7/2007-2013), “Challenge 2—Cognitive Systems, Interaction, Robotics,” grant agreement No. ICT IP-231722, project “IM-CLeVeR—Intrinsically Motivated Cumulative Learning Versatile Robots” to D. Caligiore; by the Human Frontier Science Program (HFSP), award number RGY0088/2014 to G. Pezzulo; in parts by funds from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs and National Institutes of Health Grants R01 NS24328, R01 MH56661, P40 OD010996, and P30 NS076405 to P. L. Strick; by the European Research Council project MotMotLearn (637488) to J. Galea; by the MRC (grant R/J012610/1) to R.C. Miall and Wellcome Trust, grant WT087554 to R.C. Miall and A. Lago-Rodriguez; by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 341196 to P. F. M. J. Verschure; and by the European Commission’s Horizon 2020 socSMC (under agreement number socSMC-641321H2020-FETPROACT-2014) to I. Herreros. We thank the two anonymous reviewers and Professor Michael A. Arbib who have contributed to enhance the quality of this consensus paper with precious comments.

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Item does not contain fulltext Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org).

A game of rock-paper-scissors is an interesting example of an interaction where none of the pure strategies strictly dominates all others, leading to a cyclic pattern. In this work, we consider an unstable version of rock-paper-scissors dynamics and allow individuals to make behavioural mistakes during the strategy execution. We show that such an assumption can break a cyclic relationship leading to a stable equilibrium emerging with only one strategy surviving. We consider two cases: completely random mistakes when individuals have no bias towards any strategy and a general form of mistakes. Then, we determine conditions for a strategy to dominate all other strategies. However, given that individuals who adopt a dominating strategy are still prone to behavioural mistakes in the observed behaviour, we may still observe extinct strategies. That is, behavioural mistakes in strategy execution stabilise evolutionary dynamics leading to an evolutionary stable and, potentially, mixed co-existence equilibrium., Author summary A game of rock-paper-scissors is more than just a children’s game. This type of interactions is often used to describe competition among animals or humans. A special feature of such an interaction is that none of the pure strategies dominates, resulting in a cyclic pattern. However, in wild communities such interactions are rarely observed by biologists. Our results suggest that this lack of cyclicity may stem from imperfectness of interacting individuals. In other words, we show analytically that heterogeneity in behavioural patterns may break a cyclic relationship and lead to a stable equilibrium in pure or mixed strategies.

In an ever-changing and often ambiguous environment, organisms must use previously learned associations between antecedents and outcomes to predict future associations and make optimal choices. Chronic stress can impair one's ability to flexibly adjust behaviors when environmental contingencies change, particularly in cases of early-life stress. In mice, exposure to elevated levels of the primary stress hormone, corticosterone (CORT), during early adolescence is sufficient to impair response-outcome decision making later in life, biasing response strategies towards inflexible habits. Nevertheless, neurobiological mechanisms are still being defined. Here, we report that exposure to excess CORT in adolescence causes a loss of dendritic spines on excitatory pyramidal neurons in the lateral, but not medial, orbital prefrontal cortex (loPFC) of mice, and spine loss correlates with the severity of habit biases in adulthood. Excess CORT also reduces the presence of ventral hippocampal (vHC) axon terminals in the loPFC. To identify functional consequences, we inactivated vHC→loPFC projections in typical healthy mice during a period when mice must update response-outcome expectations to optimally acquire food reinforcers. Inactivation impaired the animals' subsequent ability to sustainably choose actions based on likely outcomes, causing them to defer to habit-based response strategies. Thus, vHC→loPFC projections are necessary for response-outcome expectancy updating and a target of excess glucocorticoids during early-life development. Their degradation is likely involved in long-term biases towards habit-based behaviors following glucocorticoid excess in adolescence.

Peripheral nervous system (PNS) toxicity is surveyed inconsistently in nonclinical general toxicity studies. These Society of Toxicologic Pathology “best practice” recommendations are designed to ensure consistent, efficient, and effective sampling, processing, and evaluation of PNS tissues for four different situations encountered during nonclinical general toxicity (screening) and dedicated neurotoxicity studies. For toxicity studies where neurotoxicity is unknown or not anticipated (situation 1), PNS evaluation may be limited to one sensorimotor spinal nerve. If somatic PNS neurotoxicity is suspected (situation 2), analysis minimally should include three spinal nerves, multiple dorsal root ganglia, and a trigeminal ganglion. If autonomic PNS neuropathy is suspected (situation 3), parasympathetic and sympathetic ganglia should be assessed. For dedicated neurotoxicity studies where a neurotoxic effect is expected (situation 4), PNS sampling follows the strategy for situations 2 and/or 3, as dictated by functional or other compound/target-specific data. For all situations, bilateral sampling with unilateral processing is acceptable. For situations 1–3, PNS is processed conventionally (immersion in buffered formalin, paraffin embedding, and hematoxylin and eosin staining). For situation 4 (and situations 2 and 3 if resources and timing permit), perfusion fixation with methanol-free fixative is recommended. Where PNS neurotoxicity is suspected or likely, at least one (situations 2 and 3) or two (situation 4) nerve cross sections should be postfixed with glutaraldehyde and osmium before hard plastic resin embedding; soft plastic embedding is not a suitable substitute for hard plastic. Special methods may be used if warranted to further characterize PNS findings. Initial PNS analysis should be informed, not masked (“blinded”). Institutions may adapt these recommendations to fit their specific programmatic requirements but may need to explain in project documentation the rationale for their chosen PNS sampling, processing, and evaluation strategy.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders.

Light is the major synchronizer of circadian rhythms to local time on earth. Light can also elicit an acute alerting effect on humans. This paper discusses lighting characteristics that affect the circadian system and how self-luminous displays can be used to promote entrainment and alertness.

The word "glia" was coined in the mid-19th century and defined as "the nerve glue". For decades, it was assumed to be a uniform matrix, until cell theorists raised the "neuron doctrine" which stipulated that nervous tissue was composed of individual cells. The term "astrocytes" was introduced in the late 19th century as a synonym for glial cells, but it was Santiago Ramon y Cajal who defined a "third element" distinct from glial cells (astrocytes) and neurons. It was not until 1919 when Pio del Rio-Hortega, an alumnus of the Cajal School, introduced the modern terms we use today, and thoroughly described both "oligodendrocytes" and "microglia" to clearly distinguish them from astrocytes. In a series of four papers published that year in Spanish, Rio-Hortega described the distribution and morphological phenotype of microglia. He also noted that these cells were the origin of the rod cells described earlier in pathologic tissue, and recognized that resting microglia transformed into an ameboid phenotype in different types of brain diseases and pathologies. He also noted the mesodermal origin of these cells and recognized their phagocytic capacity. We here provide the first English translation of these landmark series of papers, which paved the way for modern glial research. To heighten the value and accessibility of these classic papers and their original figures, an introduction to this critical period of neuroscience is provided, along with unpublished photographs. By adding comments to the translated text, we provide sufficient context so that contemporary scientists may fully appreciate it. GLIA 2016;64:1801-1840.

Adult workers of some social insect species show dramatic behavioral changes as they pass through a sequence of task specializations. In the paper wasp, Polybia aequatorialis, female workers begin adult life within the nest tending brood, progress to maintaining and defending the nest exterior, and ultimately leave the nest to forage. The mushroom body (MB) calyx neuropil increases in volume as workers progress from in-nest to foraging tasks. In other social Hymenoptera (bees and ants), MB Kenyon cell dendrites, axons and synapses change with the transition to foraging, but these neuronal effects had not been studied in wasps. Furthermore, the on-nest worker of Polybia wasps, an intermediate task specialization not identified in bees or ants, provides the opportunity to study pre-foraging worker class transitions. We asked whether Kenyon cell dendritic arborization varies with the task specialization of Polybia workers observed in the field near Monteverde, Costa Rica. Golgi-impregnated arbors in the lip and collar calyces, which receive a predominance of olfactory and visual input, respectively, were quantified using Sholl's concentric circles and a novel application of virtual spherical probes. Arbors of the lip varied in a manner reminiscent of honeybees, with foragers having the largest and in-nest workers having the smallest arbors. In contrast, arbors of the collar were largest in foragers but smallest in on-nest workers. Thus, progression through task specializations in P. aequatorialis involves subregion specific dendritic growth and regression in the MB neuropil. These results may reflect the sensitivity of Kenyon cell dendritic structure to specialization dependent social and sensory experience.

Oxygen concentration is one of the critical factors tightly controlled in each part of an organism to regulate the cells’ role and function. Yet, changes in tissue oxygenation often occur in small focal areas with aging or as a result of an injury. Despite the serious health implications of focal hypoxia, no methodologies exist that can model oxygen supply system accordingly in animal models or in vitro models. Therefore, we designed a novel local hypoxia system as a sensing interface for in vitro cell culture. The oxygen removal efficiencies measured by Clark electrodes showed that O2 concentration can be reduced from 20.9% / 140mmHg or 5% / 35mmHg and maintained at hypoxia (< 1.5% / 10mmHg) in 15 or 8 minutes respectively, compared with 3 hours needed by conventional incubator and hypoxic chambers. The induced hypoxia stimulated localized time-dependent HIF-1α transcription factor nuclear accumulation at the region of interest on human neural progenitor cells. This new culture system can robustly generate a hypoxia gradient in the same culture dish for the first time and provides the opportunity to decipher the impact of focal hypoxia, the function of localised oxygen homeostasis and the pathophysiology of multiple diseases.

The need to complete multiple tasks concurrently is a common occurrence both daily life and in occupational activities, which can often include simultaneous cognitive and physical demands. As one example, there is increasing availability of head-worn display technologies that can be employed when a user is mobile (e.g., while walking). This new method of information presentation may, however, introduce risks of adverse outcomes such as a decrement to gait performance. The goal of this study was thus to quantify the effects of a head-worn display (i.e., smart glasses) on motor variability during gait and to compare these effects with those of other common information displays (i.e., smartphone and paper-based system). Twenty participants completed four walking conditions, as a single task and in three dual-task conditions (three information displays). In the dual-task conditions, the information display was used to present several cognitive tasks. Three different measures were used to quantify variability in gait parameters for each walking condition (using the cycle-to-cycle standard deviation, sample entropy, and the “goal-equivalent manifold” approach). Our results indicated that participants used less adaptable gait strategies in dual-task walking using the paper-based system and smartphone conditions compared with single-task walking. Gait performance, however, was less affected during dual-task walking with the smart glasses. We conclude that the risk of an adverse gait event (e.g., a fall) in head-down walking conditions (i.e., the paper-based system and smartphone conditions) were higher than in single-task walking, and that head-worn displays might help reduce the risk of such events during dual-task gait conditions.

Reading primary research literature is an essential skill for all scientists and students on science degree programmes, however little is known about how researchers at different career stages interact with and interpret scientific papers. To explore this, we conducted a survey of 260 undergraduate students and researchers in Biological Sciences at a research intensive UK university. Responses to Likert scale questions demonstrated increases in confidence and skill with reading the literature between individuals at each career stage, including between postdoctoral researchers and faculty academics. The survey indicated that individuals at different career stages valued different sections of scientific papers, and skill in reading the results section develops slowly over the course of an academic career. Inexperienced readers found the methods and results sections of research papers the most difficult to read, and undervalued the importance of the results section and critical interpretation of data. These data highlight a need for structured support with reading scientific literature at multiple career stages, and for senior academics to be aware that junior colleagues may prioritise their reading differently. We propose a model for the development of literature processing skills, and consider the need for training strategies to help inexperienced readers engage with primary literature, and therefore develop important skills that underpin scientific careers. We also encourage researchers to be mindful of language used when writing papers, and to be more inclusive of diverse audiences when disseminating their work.

Spinal cord repair research appeared to have run out of new ideas in the 1970s. In a 1981 paper, the Aguayo Laboratory revisited an experiment by Tello and Cajal that suggested that central nervous system (CNS) axons could regenerate into peripheral nerve grafts. Using modern axon tracing methods, David and Aguayo showed that axons from neurons in the spinal cord could regenerate for long distances within peripheral nervous system (PNS) grafts, but not back into the CNS. This proved that damaged CNS tissue is inhibitory to axon regeneration while PNS tissue is permissive. The experiment sparked a research revival, leading to the identification of many inhibitory molecules that block axon growth in the mature CNS.

Schizophrenia is a group of severe psychiatric disorders with high heritability but only low odds ratios of risk genes. Despite progress in the identification of pathophysiological processes, valid biomarkers of the disease are still lacking.This comprehensive review summarises recent efforts to identify genetic underpinnings, clinical and cognitive endophenotypes and symptom dimensions of schizophrenia and presents findings from neuroimaging studies with structural, functional and spectroscopy magnetic resonance imaging and positron emission tomography. The potential of findings to be biomarkers of schizophrenia is discussed.Recent findings have not resulted in clear biomarkers for schizophrenia. However, we identified several biomarkers that are potential candidates for future research. Among them, copy number variations and links between genetic polymorphisms derived from genome-wide analysis studies, clinical or cognitive phenotypes, multimodal neuroimaging findings including positron emission tomography and magnetic resonance imaging, and the application of multivariate pattern analyses are promising.Future studies should address the effects of treatment and stage of the disease more precisely and apply combinations of biomarker candidates. Although biomarkers for schizophrenia await validation, knowledge on candidate genomic and neuroimaging biomarkers is growing rapidly and research on this topic has the potential to identify psychiatric endophenotypes and in the future increase insight on individual treatment response in schizophrenia.

It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R2) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies.

Applying steady-state visual evoked potentials (SSVEPs) on a display system, a novel brain-display interaction (BDI) system was presented. This study further proposed an imperceptible flickering visual stimulus to make a SSVEP-based BDI more practical and promising for biomedical applications, such us glaucoma visual field loss diagnosis.

We reviewed the role of melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) in light-dependent functions, including circadian rhythm that is important for health, pupil responses and visual perception. We then discussed the implications for lighting design. Finally we described a five-primary photostimulating method that can independently control melanopsin activation in humans.

This week’s articles identify a mechanism that establishes the senescence-associated secretory phenotype and reveal details about the gating of TRPML channels.

This week’s articles highlight retrograde semaphorin signaling at synapses; a driver of age-related decreases in lipolysis; and a mechanism by which melanoma cells become resistant to combined therapies.

This week’s article shows that the release of oxytocin in the ventral tegmental area influences sociability in mice by stimulating dopaminergic neurons that project to the brain’s reward center.