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'Groundbreaking … [provides] a deep history of the invention of the \"normal\" mind as one of the most damaging and oppressive tools of capitalism. To read it is to see the world more clearly' Steve Silberman, author of NeuroTribes 'Argues that a radical politics of neurodiversity is necessary, not only for neurodivergent folk, but for our collective liberation' Professor Hel Spandler, editor, Asylum magazine 'A vital book that kindles the flames of a neurodivergent revolution' Beatrice Adler-Bolton, co-author of Health Communism Neurodiversity is on the rise. Awareness and diagnoses have exploded in recent years, but we are still missing a wider understanding of how we got here and why. Beyond simplistic narratives of normativity and difference, this groundbreaking book exposes the very myth of the 'normal' brain as a product of intensified capitalism. Exploring the rich histories of the neurodiversity and disability movements, Robert Chapman shows how the rise of capitalism created an 'empire of normality' that transformed our understanding of the body into that of a productivity machine. Neurodivergent liberation is possible – but only by challenging the deepest logics of capitalism. Empire of Normality is an essential guide to understanding the systems that shape our bodies, minds and deepest selves – and how we can undo them. Robert Chapman is a neurodivergent philosopher who has taught at King's College London and Bristol University. They are currently Assistant Professor in Critical Neurodiversity Studies at Durham University. They blog at Psychology Today and at Critical Neurodiversity.

Elizabeth Barnes argues compellingly that disability is primarily a social phenomenon- a way of being a minority, a way of facing social oppression, but not a way of being inherently or intrinsically worse off. This is how disability is understood in the Disability Rights and Disability Pride movements; but there is a massive disconnect with the way disability is typically viewed within analytic philosophy. The idea that disability is not inherently bad or sub-optimal is one that many philosophers treat with open skepticism, and sometimes even with scorn. The goal of this book is to articulate and defend a version of the view of disability that is common in the Disability Rights movement.

We examine the mechanisms explaining the dropout intentions of students with disabilities by integrating Tinto's model of student integration, the student attrition model, the composite persistence model, and insights from social stratification research. The resulting theoretical model posits that not only students' academic and social integration, but also their private resources (financial, home learning, and personal resources) are crucial for academic success. Analysing data from a 2020 Germany-wide student survey, we find that students with disabilities are substantially more likely to intend to drop out of higher education than students without disabilities. Linear regressions and Kitagawa-Oaxaca-Blinder decompositions show that their lower academic integration and fewer personal resources are most relevant for explaining this difference, while their lower social integration, home learning, and financial resources play subordinate roles. Further analyses reveal that dropout intent is highest among students with psychic disabilities, followed by students with learning disabilities and students with physical disabilities. Regarding all three disability groups, less academic integration and fewer personal resources are most relevant for explaining their higher dropout intent (compared to students without disabilities). However, the disability groups differ regarding the importance of the different explanatory factors. Overall, our results highlight the importance of considering both students' integration into higher education and their private resources for understanding student-group-specific dropout intent.

Alzheimer’s disease (AD) is the most common type of dementia. Its diagnosis and progression detection have been intensively studied. Nevertheless, research studies often have little effect on clinical practice mainly due to the following reasons: (1) Most studies depend mainly on a single modality, especially neuroimaging; (2) diagnosis and progression detection are usually studied separately as two independent problems; and (3) current studies concentrate mainly on optimizing the performance of complex machine learning models, while disregarding their explainability. As a result, physicians struggle to interpret these models, and feel it is hard to trust them. In this paper, we carefully develop an accurate and interpretable AD diagnosis and progression detection model. This model provides physicians with accurate decisions along with a set of explanations for every decision. Specifically, the model integrates 11 modalities of 1048 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) real-world dataset: 294 cognitively normal, 254 stable mild cognitive impairment (MCI), 232 progressive MCI, and 268 AD. It is actually a two-layer model with random forest (RF) as classifier algorithm. In the first layer, the model carries out a multi-class classification for the early diagnosis of AD patients. In the second layer, the model applies binary classification to detect possible MCI-to-AD progression within three years from a baseline diagnosis. The performance of the model is optimized with key markers selected from a large set of biological and clinical measures. Regarding explainability, we provide, for each layer, global and instance-based explanations of the RF classifier by using the SHapley Additive exPlanations (SHAP) feature attribution framework. In addition, we implement 22 explainers based on decision trees and fuzzy rule-based systems to provide complementary justifications for every RF decision in each layer. Furthermore, these explanations are represented in natural language form to help physicians understand the predictions. The designed model achieves a cross-validation accuracy of 93.95% and an F1-score of 93.94% in the first layer, while it achieves a cross-validation accuracy of 87.08% and an F1-Score of 87.09% in the second layer. The resulting system is not only accurate, but also trustworthy, accountable, and medically applicable, thanks to the provided explanations which are broadly consistent with each other and with the AD medical literature. The proposed system can help to enhance the clinical understanding of AD diagnosis and progression processes by providing detailed insights into the effect of different modalities on the disease risk.

Vascular contributions to dementia and Alzheimer’s disease are increasingly recognized 1 – 6 . Recent studies have suggested that breakdown of the blood–brain barrier (BBB) is an early biomarker of human cognitive dysfunction 7 , including the early clinical stages of Alzheimer’s disease 5 , 8 – 10 . The E4 variant of apolipoprotein E ( APOE4 ), the main susceptibility gene for Alzheimer’s disease 11 – 14 , leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes 15 – 19 , which maintain BBB integrity 20 – 22 . It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the ε3/ε4 or ε4/ε4 alleles) are distinguished from those without APOE4 (ε3/ε3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography 23 . High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ 7 , 8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway 19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4 -associated cognitive decline independently of Alzheimer’s disease pathology, and might be a therapeutic target in APOE4 carriers. Breakdown of the blood–brain barrier in individuals carrying the ε4 allele of the APOE gene, but not the ε3 allele, increases with and predicts cognitive impairment and is independent of amyloid β or tau pathology.

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer’s disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer’s disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases. Meningeal lymphatic dysfunction promotes amyloid-β deposition in the meninges and worsens brain amyloid-β pathology, acting as an aggravating factor in Alzheimer’s disease and in age-associated cognitive decline; improving meningeal lymphatic function could help to prevent or delay age-associated neurological diseases.

Key Points Brain–computer interfaces (BCIs) are starting to prove their efficacy as assistive and rehabilitative technologies in patients with severe motor impairments BCIs can be invasive or noninvasive, and designed to detect and decode a variety of brain signals Assistive BCIs are intended to enable paralyzed patients to communicate or control external robotic devices; rehabilitative BCIs are intended to facilitate neural recovery EEG-based BCIs have enabled some paralyzed patients to communicate, but near-infrared spectroscopy combined with a classical conditioning paradigm is the only successful approach for complete locked-in syndrome The combination of EEG-based BCIs with behavioural physiotherapy is a feasible option for rehabilitation in stroke; the approach is to induce neuroplasticity and restore lost function after stroke There is an urgent need for more large randomized controlled clinical trials using invasive and noninvasive BCIs with long-term follow-ups in patients rather than healthy populations Brain–computer interfaces (BCIs) enable severely disabled patients to interact with the environment. In this Review, Chaudhary et al . provide an overview on current use of BCIs for communication, movement and rehabilitation in patients who are paralyzed as a result of amyotrophic lateral sclerosis, stroke or spinal cord injury. Brain–computer interfaces (BCIs) use brain activity to control external devices, thereby enabling severely disabled patients to interact with the environment. A variety of invasive and noninvasive techniques for controlling BCIs have been explored, most notably EEG, and more recently, near-infrared spectroscopy. Assistive BCIs are designed to enable paralyzed patients to communicate or control external robotic devices, such as prosthetics; rehabilitative BCIs are designed to facilitate recovery of neural function. In this Review, we provide an overview of the development of BCIs and the current technology available before discussing experimental and clinical studies of BCIs. We first consider the use of BCIs for communication in patients who are paralyzed, particularly those with locked-in syndrome or complete locked-in syndrome as a result of amyotrophic lateral sclerosis. We then discuss the use of BCIs for motor rehabilitation after severe stroke and spinal cord injury. We also describe the possible neurophysiological and learning mechanisms that underlie the clinical efficacy of BCIs.

In this study, we investigated lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6J mice by using behavioral tests, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Western blot. We found that LPS treatment leads to sickness behavior and cognitive impairment in mice as shown in the Morris water maze and passive avoidance test, and these effects were accompanied by microglia activation (labeled by ionized calcium binding adaptor molecule-1, IBA-1) and neuronal cell loss (labeled by microtubule-associated protein 2, MAP-2) in the hippocampus. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the serum and brain homogenates were reduced by the LPS treatment, while the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE 2 ) and nitric oxide (NO) were increased. In addition, LPS promoted the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the brain homogenates. The Western blot analysis showed that the nuclear factor kappa B (NF-κB) signaling pathway was activated in the LPS groups. Furthermore, VIPER, which is a TLR-4-specific inhibitory peptide, prevented the LPS-induced neuroinflammation and cognitive impairment. These data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, we compared the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections of LPS in LPS-induced neuroinflammation and cognitive impairment, and these data may provide additional insight for researchers performing neuroinflammation research.

Dietary habits and vascular risk factors promote both Alzheimer’s disease and cognitive impairment caused by vascular factors 1 – 3 . Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer’s pathology 4 , is also linked to vascular cognitive impairment 5 , 6 . In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion 7 . Here we report that dietary salt induces hyperphosphorylation of tau followed by cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly. A high-salt diet in mice induces cognitive impairment through a signalling cascade that culminates in increased phosphorylation of tau.