Assessment of the capacity to modulate brain signals in a home-based SMR neurofeedback training setting

Electroencephalogram (EEG)-based neurofeedback (NF) is mainly used in clinical settings as a therapeutic intervention or to optimize performance in healthy individuals. Home-based NF systems are available and might facilitate general access to NF training, especially when repeated training sessions are necessary. However, it remains an open question whether NF training at home is possible without remote monitoring. In the present study, we assessed the capacity of healthy individuals to modulate their own EEG activity when using a home-based NF training system in a comparable manner as if participants had purchased a commercially available NF system. Participants’ face-to-face contact with experimenters was reduced to a minimum, and instructions were provided only in the form of written information or videos. Initially, 38 participants performed 9 sessions of sensorimotor rhythm (SMR) (12–15 Hz) based NF training (three generalization sessions, six training sessions). An active control group (n = 19) received feedback on random EEG frequencies. Because of technical problems, bad EEG data quality, or non-compliance, 21 participants had to be excluded from the final data analysis, providing first evidence for the difficulties of non-supervised home-based NF training. In this study, participants were not able to modulate their own brain activity in a desired direction during NF training. Our results indicate that personal interaction with a NF expert might be of relevance and that remote supervision of the training data and more direct communication with the NF users are necessary to enable successful NF training performance. We provide suggestions for the development and implementation of home-based NF systems

Virtual reality in neurologic rehabilitation of spatial disorientation

BACKGROUND: Topographical disorientation (TD) is a severe and persistent impairment of spatial orientation and navigation in familiar as well as new environments and a common consequence of brain damage. Virtual reality (VR) provides a new tool for the assessment and rehabilitation of TD. In VR training programs different degrees of active motor control over navigation may be implemented (i.e. more passive spatial navigation vs. more active). Increasing demands of active motor control may overload those visuo-spatial resources necessary for learning spatial orientation and navigation. In the present study we used a VR-based verbally-guided passive navigation training program to improve general spatial abilities in neurologic patients with spatial disorientation. METHODS: Eleven neurologic patients with focal brain lesions, which showed deficits in spatial orientation, as well as 11 neurologic healthy controls performed a route finding training in a virtual environment. Participants learned and recalled different routes for navigation in a virtual city over five training sessions. Before and after VR training, general spatial abilities were assessed with standardized neuropsychological tests. RESULTS: Route finding ability in the VR task increased over the five training sessions. Moreover, both groups improved different aspects of spatial abilities after VR training in comparison to the spatial performance before VR training. CONCLUSIONS: Verbally-guided passive navigation training in VR enhances general spatial cognition in neurologic patients with spatial disorientation as well as in healthy controls and can therefore be useful in the rehabilitation of spatial deficits associated with TD

Does Feedback Design Matter? A Neurofeedback Study Comparing Immersive Virtual Reality and Traditional Training Screens in Elderly

Neurofeedback (NF) is a Brain-Computer Interface (BCI) application, in which the brain activity is fed back to the user in real-time enabling voluntary brain control. In this context, the significance of the feedback design is mainly unexplored. Highly immersive feedback scenarios using virtual reality (VR) technique are available. However, their effects on subjective user experience as well as on objective outcome measures remain open. In the present article, we discuss the general pros and cons of using VR as feedback modality in BCI applications. Furthermore, we report on the results of an empirical study, in which the effects of traditional two-dimensional and three-dimensional VR based feedback scenarios on NF training performance and user experience in healthy older individuals and neurologic patients were compared. In conclusion, we suggest indications and contraindications of immersive VR feedback designs in BCI applications. Our results show that findings in healthy individuals are not always transferable to patient populations having an impact on serious game and feedback design

Ability to Gain Control Over One’s Own Brain Activity and its Relation to Spiritual Practice: A Multimodal Imaging Study

Spiritual practice, such as prayer or meditation, is associated with focusing attention on internal states and self-awareness processes. As these cognitive control mechanisms presumably are also important for neurofeedback (NF), we investigated whether people who pray frequently (N = 20) show a higher ability of self-control over their own brain activity compared to a control group of individuals who rarely pray (N = 20). All participants underwent structural magnetic resonance imaging (MRI) and one session of sensorimotor rhythm (SMR, 12–15 Hz) based NF training. Individuals who reported a high frequency of prayer showed improved NF performance compared to individuals who reported a low frequency of prayer. The individual ability to control one’s own brain activity was related to volumetric aspects of the brain. In the low frequency of prayer group, gray matter volumes in the right insula and inferior frontal gyrus were positively associated with NF performance, supporting prior findings that more general self-control networks are involved in successful NF learning. In contrast, participants who prayed regularly showed a negative association between gray matter volume in the left medial orbitofrontal cortex (Brodmann’s area (BA) 10) and NF performance. Due to their regular spiritual practice, they might have been more skillful in gating incoming information provided by the NF system and avoiding task-irrelevant thoughts

Engaging learners with games–Insights from functional near-infrared spectroscopy

The use of game elements in learning tasks is thought to facilitate emotional and behavioral responses as well as learner engagement. So far, however, little is known about the underlying neural mechanisms of game-based learning. In the current study, we added game elements to a number line estimation task assessing fraction understanding and compared brain activation patterns to a non-game-based task version. Forty-one participants performed both task versions in counterbalanced order while frontal brain activation patterns were assessed using near-infrared spectroscopy (within-subject, cross-sectional study design). Additionally, heart rate, subjective user experience, and task performance were recorded. Task performance, mood, flow experience, as well as heart rate did not differ between task versions. However, the game-based task-version was rated as more attractive, stimulating and novel compared to the non-game-based task version. Additionally, completing the game-based task version was associated with stronger activation in frontal brain areas generally involved in emotional and reward processing as well as attentional processes. These results provide new neurofunctional evidence substantiating that game elements in learning tasks seem to facilitate learning through emotional and cognitive engagement.Peer reviewe

Baseline projections for Latin America: base-year assumptions, key drivers and greenhouse emissions

This paper provides an overview of the base-year assumptions and baseline projections for the set of models participating in the LAMP and CLIMACAP projects. We present the range in baseline projections for Latin America, and identify key differences between model projections including how these projections compare to historic trends. We find relatively large differences across models in base year assumptions related to population, GDP, energy and CO2 emissions due to the use of different data sources, but also conclude that this does not influence the range of projections. We find that population and GDP projections across models span a broad range, comparable to the range represented by the set of Shared Socioeconomic Pathways (SSPs). Kaya-factor decomposition indicates that the set of baseline scenarios mirrors trends experienced over the past decades. Emissions in Latin America are projected to rise as a result of GDP and population growth and a minor shift in the energy mix toward fossil fuels. Most scenarios assume a somewhat higher GDP growth than historically observed and continued decline of population growth. Minor changes in energy intensity or energy mix are projected over the next few decades

A user-centred approach to unlock the potential of non-invasive BCIs: an unprecedented international translational effort

Non-invasive Mental Task-based Brain-Computer Interfaces (MT-BCIs) enable their users to interact with the environment through their brain activity alone (measured using electroencephalography for example), by performing mental tasks such as mental calculation or motor imagery. Current developments in technology hint at a wide range of possible applications, both in the clinical and non-clinical domains. MT-BCIs can be used to control (neuro)prostheses or interact with video games, among many other applications. They can also be used to restore cognitive and motor abilities for stroke rehabilitation, or even improve athletic performance.Nonetheless, the expected transfer of MT-BCIs from the lab to the marketplace will be greatly impeded if all resources are allocated to technological aspects alone. We cannot neglect the Human End-User that sits in the centre of the loop. Indeed, self-regulating one’s brain activity through mental tasks to interact is an acquired skill that requires appropriate training. Yet several studies have shown that current training procedures do not enable MT-BCI users to reach adequate levels of performance. Therefore, one significant challenge for the community is that of improving end-user training.To do so, another fundamental challenge must be taken into account: we need to understand the processes that underlie MT-BCI performance and user learning. It is currently estimated that 10 to 30% of people cannot control an MT-BCI. These people are often referred to as “BCI inefficient”. But the concept of “BCI inefficiency” is debated. Does it really exist? Or, are low performances due to insufficient training, training procedures that are unsuited to these users or is the BCI data processing not sensitive enough? The currently available literature does not allow for a definitive answer to these questions as most published studies either include a limited number of participants (i.e., 10 to 20 participants) and/or training sessions (i.e., 1 or 2). We still have very little insight into what the MT-BCI learning curve looks like, and into which factors (including both user-related and machine-related factors) influence this learning curve. Finding answers will require a large number of experiments, involving a large number of participants taking part in multiple training sessions. It is not feasible for one research lab or even a small consortium to undertake such experiments alone. Therefore, an unprecedented coordinated effort from the research community is necessary.We are convinced that combining forces will allow us to characterise in detail MT-BCI user learning, and thereby provide a mandatory step toward transferring BCIs “out of the lab”. This is why we gathered an international, interdisciplinary consortium of BCI researchers from more than 20 different labs across Europe and Japan, including pioneers in the field. This collaboration will enable us to collect considerable amounts of data (at least 100 participants for 20 training sessions each) and establish a large open database. Based on this precious resource, we could then lead sound analyses to answer the previously mentioned questions. Using this data, our consortium could offer solutions on how to improve MT-BCI training procedures using innovative approaches (e.g., personalisation using intelligent tutoring systems) and technologies (e.g., virtual reality). The CHIST-ERA programme represents a unique opportunity to conduct this ambitious project, which will foster innovation in our field and strengthen our community

Understanding the degradation of methylenediammonium and its role in phase-stabilizing formamidinium lead triiodide

Formamidinium lead triiodide (FAPbI3) is the leading candidate for single-junction metal–halide perovskite photovoltaics, despite the metastability of this phase. To enhance its ambient-phase stability and produce world-record photovoltaic efficiencies, methylenediammonium dichloride (MDACl2) has been used as an additive in FAPbI3. MDA2+ has been reported as incorporated into the perovskite lattice alongside Cl–. However, the precise function and role of MDA2+ remain uncertain. Here, we grow FAPbI3 single crystals from a solution containing MDACl2 (FAPbI3-M). We demonstrate that FAPbI3-M crystals are stable against transformation to the photoinactive δ-phase for more than one year under ambient conditions. Critically, we reveal that MDA2+ is not the direct cause of the enhanced material stability. Instead, MDA2+ degrades rapidly to produce ammonium and methaniminium, which subsequently oligomerizes to yield hexamethylenetetramine (HMTA). FAPbI3 crystals grown from a solution containing HMTA (FAPbI3-H) replicate the enhanced α-phase stability of FAPbI3-M. However, we further determine that HMTA is unstable in the perovskite precursor solution, where reaction with FA+ is possible, leading instead to the formation of tetrahydrotriazinium (THTZ-H+). By a combination of liquid- and solid-state NMR techniques, we show that THTZ-H+ is selectively incorporated into the bulk of both FAPbI3-M and FAPbI3-H at ∼0.5 mol % and infer that this addition is responsible for the improved α-phase stability

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly