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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.

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field. ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsråd, Kreftforeningen and Helse Sør-Øst RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05.

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.

In the recent years, discoveries in neuroscience have greatly impacted upon the need to modify therapeutic practice starting from the evidence showing some cerebral mechanisms capable of coping with mental health crisis and traumatic events of the individual's life history by redesigning the narrative plot and the person's sense of the Self. The emerging dialogue between neuroscience and psychotherapy is increasingly intense and modern psychotherapy cannot ignore the heritage deriving from studies about neuropsychological modification of memory traces, neurobiology of attachment theory, cognitive mechanisms involved in psychopathology, neurophysiology of human empathy, neuroimaging evidence about psychotherapeutic treatment, and somatoform disorders connecting the brain and the body. In the present article, we critically examined sectorial literature and claimed that psychotherapy has to referred to a neuroscience-based approach in order to adopt the most tailored interventions for specific groups of patients or therapy settings. We also provided recommendations for care implementation in clinical practice and illustrated challenges of future research.

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.

The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson’s disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward., SCOPUS: re.j, info:eu-repo/semantics/published

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

The cerebellum is involved in multiple closed-loops circuitry which connect the cerebellar modules with the motor cortex, prefrontal, temporal, and parietal cortical areas, and contribute to motor control, cognitive processes, emotional processing, and behavior. Among them, the cerebello-thalamo-cortical pathway represents the anatomical substratum of cerebellum-motor cortex inhibition (CBI). However, the cerebellum is also connected with basal ganglia by disynaptic pathways, and cerebellar involvement in disorders commonly associated with basal ganglia dysfunction (e.g., Parkinson’s disease and dystonia) has been suggested. Lately, cerebellar activity has been targeted by non-invasive brain stimulation (NIBS) techniques including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to indirectly affect and tune dysfunctional circuitry in the brain. Although the results are promising, several questions remain still unsolved. Here, a panel of experts from different specialties (neurophysiology, neurology, neurosurgery, neuropsychology) reviews the current results on cerebellar NIBS with the aim to derive the future steps and directions needed. We discuss the effects of TMS in the field of cerebellar neurophysiology, the potentials of cerebellar tDCS, the role of animal models in cerebellar NIBS applications, and the possible application of cerebellar NIBS in motor learning, stroke recovery, speech and language functions, neuropsychiatric and movement disorders.

Objective : To elaborate normative values for a clinical psychophysical taste test ("Taste Strips”). Background : The "Taste Strips” are a psychophysical chemical taste test. So far, no definitive normative data had been published and only a fairly small sample size has been investigated. In light of this shortcoming for this easy, reliable and quick taste testing device, we attempted to provide normative values suitable for the clinical use. Setting : Normative value acquisition study, multicenter study. Methods : The investigation involved 537 participants reporting a normal sense of smell and taste (318 female, 219 male, mean age 44 years, age range 18-87 years). The taste test was based on spoonshaped filter paper strips ("Taste Strips”) impregnated with the four (sweet, sour, salty, and bitter) taste qualities in four different concentrations. The strips were placed on the left or right side of the anterior third of the extended tongue, resulting in a total of 32 trials. With their tongue still extended, patients had to identify the taste from a list of four descriptors, i. e., sweet, sour, salty, and bitter (multiple forcedchoice). To obtain an impression of overall gustatory function, the number of correctly identified tastes was summed up for a "taste score”. Results : Taste function decreased significantly with age. Women exhibited significantly higher taste scores than men which was true for all age groups. The taste score at the 10th percentile was selected as a cut-off value to distinguish normogeusia from hypogeusia. Results from a small series of patients with ageusia confirmed the clinical usefulness of the proposed normative values. Conclusion : The present data provide normative values for the "Taste Strips” based on over 500 subjects tested

Bottom-up neuroscience aims to engineer well-defined networks of neurons to investigate the functions of the brain. By reducing the complexity of the brain to achievable target questions, such in vitro bioassays better control experimental variables and can serve as a versatile tool for fundamental and pharmacological research. Astrocytes are a cell type critical to neuronal function, and the addition of astrocytes to neuron cultures can improve the quality of in vitro assays. Here, we present cellulose as an astrocyte culture substrate. Astrocytes cultured on the cellulose fiber matrix thrived and formed a dense 3D network. We devised a novel co-culture platform by suspending the easy-to-handle astrocytic paper cultures above neuronal networks of low densities typically needed for bottom-up neuroscience. There was significant improvement in neuronal viability after 5 days in vitro at densities ranging from 50,000 cells/cm2 down to isolated cells at 1,000 cells/cm2. Cultures exhibited spontaneous spiking even at the very low densities, with a significantly greater spike frequency per cell compared to control mono-cultures. Applying the co-culture platform to an engineered network of neurons on a patterned substrate resulted in significantly improved viability and almost doubled the density of live cells. Lastly, the shape of the cellulose substrate can easily be customized to a wide range of culture vessels, making the platform versatile for different applications that will further enable research in bottom-up neuroscience and drug development., Frontiers in Neuroscience, 12, ISSN:1662-453X, ISSN:1662-4548

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.

The success of a scientist depends on their production of scientific papers and the impact factor of the journal in which they publish. Because most major scientific journals are published in English, success is related to publishing in this language. Currently, 98% of publications in science are written in English, including researchers from English as a Foreign Language (EFL) countries. Colombia is among the countries with the lowest English proficiency in the world. Thus, understanding the disadvantages that Colombians face in publishing is crucial to reducing global inequality in science. This paper quantifies the disadvantages that result from the language hegemony in scientific publishing by examining the additional costs that communicating in English creates in the production of articles. It was identified that more than 90% of the scientific articles published by Colombian researchers are in English, and that publishing in a second language creates additional financial costs to Colombian doctoral students and results in problems with reading comprehension, writing ease and time, and anxiety. Rejection or revision of their articles because of the English grammar was reported by 43.5% of the doctoral students, and 33% elected not to attend international conferences and meetings due to the mandatory use of English in oral presentations. Finally, among the translation/editing services reviewed, the cost per article is between one-quarter and one-half of a doctoral monthly salary in Colombia. Of particular note, we identified a positive correlation between English proficiency and higher socioeconomic origin of the researcher. Overall, this study exhibits the negative consequences of hegemony of English that preserves the global gap in science. Although having a common language is important for science communication, generating multilinguistic alternatives would promote diversity while conserving a communication channel. Such an effort should come from different actors and should not fall solely on EFL researchers.