Rationale & Objective: Spousal caregivers participate extensively in the care of patients with kidney failure. Although previous studies suggested that these caregivers experience a high burden, a comprehensive understanding of the determinants of this burden and strategies to alleviate it are needed. Therefore, this study sought to explore the contributing and alleviating determinants of burden in spousal caregivers of patients with kidney failure.
View Article and Find Full Text PDFBackground: Informal caregivers play a crucial role in dialysis care but may experience significant burden, potentially affecting both caregiver and patient outcomes. Research on caregiver burden and health-related quality of life (HRQoL) and the relation to patient-reported outcomes (PROs) is lacking. Therefore, we aimed to (i) describe informal caregivers' experienced burden and HRQoL and (ii) investigate how these are related to dialysis patients' HRQoL and symptoms.
View Article and Find Full Text PDFThe brain's functionality is developed and maintained through synaptic plasticity. As synapses undergo plasticity, they also affect each other. The nature of such 'co-dependency' is difficult to disentangle experimentally, because multiple synapses must be monitored simultaneously.
View Article and Find Full Text PDFDe novo heterozygous variants in encoding the voltage-gated potassium (K) channel subunit Kv3.2 are a recently described cause of developmental and epileptic encephalopathy (DEE). A de novo variant in c.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2023
So-called spontaneous activity is a central hallmark of most nervous systems. Such non-causal firing is contrary to the tenet of spikes as a means of communication, and its purpose remains unclear. We propose that self-initiated firing can serve as a release valve to protect neurons from the toxic conditions arising in mitochondria from lower-than-baseline energy consumption.
View Article and Find Full Text PDFClinical Decision Support Systems (CDSS) have the potential to improve and standardise care with probabilistic guidance. However, many CDSS deploy static, generic rule-based logic, resulting in inequitably distributed accuracy and inconsistent performance in evolving clinical environments. Data-driven models could resolve this issue by updating predictions according to the data collected.
View Article and Find Full Text PDFIntroduction: Starting dialysis not only has a major impact on the life of patients but also on their informal caregivers. Previous research shows greater burden and lower quality of life among caregivers of dialysis patients compared with the general population. Unfortunately, the evidence on the course of both positive and negative experience in caregivers of incident dialysis patients is scarce.
View Article and Find Full Text PDFChanges in the short-term dynamics of excitatory synapses over development have been observed throughout cortex, but their purpose and consequences remain unclear. Here, we propose that developmental changes in synaptic dynamics buffer the effect of slow inhibitory long-term plasticity, allowing for continuously stable neural activity. Using computational modeling we demonstrate that early in development excitatory short-term depression quickly stabilises neural activity, even in the face of strong, unbalanced excitation.
View Article and Find Full Text PDFNeuronal networks encode information through patterns of activity that define the networks' function. The neurons' activity relies on specific connectivity structures, yet the link between structure and function is not fully understood. Here, we tackle this structure-function problem with a new conceptual approach.
View Article and Find Full Text PDFDravet syndrome is a neurodevelopmental disorder characterized by epilepsy, intellectual disability, and sudden death due to pathogenic variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.
View Article and Find Full Text PDFIn this issue of Neuron, Tyulmankov et al., 2022 propose a model for familiarity detection whose parameters-including those guiding plasticity-are fully machine-tuned.
View Article and Find Full Text PDFTauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology.
View Article and Find Full Text PDFLegacy conferences are costly and time consuming, and exclude scientists lacking various resources or abilities. During the 2020 pandemic, we created an online conference platform, Neuromatch Conferences (NMC), aimed at developing technological and cultural changes to make conferences more democratic, scalable, and accessible. We discuss the lessons we learned.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies.
View Article and Find Full Text PDFBrains process information in spiking neural networks. Their intricate connections shape the diverse functions these networks perform. Yet how network connectivity relates to function is poorly understood, and the functional capabilities of models of spiking networks are still rudimentary.
View Article and Find Full Text PDFTraditional scientific conferences and seminar events have been hugely disrupted by the COVID-19 pandemic, paving the way for virtual forms of scientific communication to take hold and be put to the test.
View Article and Find Full Text PDFCortical areas comprise multiple types of inhibitory interneurons, with stereotypical connectivity motifs that may follow specific plasticity rules. Yet, their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyze the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations.
View Article and Find Full Text PDFMechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators-trained using model simulations-to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features.
View Article and Find Full Text PDFBackground: Neuronal accumulation of hyperphosphorylated and truncated tau aggregates is one of the major defining factors and key drivers of neurodegeneration in Alzheimer's disease and other tauopathies.
Objective: We developed an AAV-induced model of tauopathy mediated by human truncated tau protein without familial frontotemporal dementia-related mutations to study tau propagation and the functional consequences of tau pathology.
Methods: We performed targeted transductions of the hippocampus or entorhinal cortex in adult mice followed by histological analysis to study the progression of hippocampal tau pathology and tau spreading.
Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies, biochemical composition, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential vulnerability of brain areas to tau pathology, its cell-to-cell transmission, and characteristics of the different strains that tau aggregates can adopt.
View Article and Find Full Text PDFTauopathies are a heterogenous class of diseases characterized by cellular accumulation of aggregated tau and include diseases such as Alzheimer's disease (AD), progressive supranuclear palsy and chronic traumatic encephalopathy. Tau pathology is strongly linked to neurodegeneration and clinical symptoms in tauopathy patients. Furthermore, synapse loss is an early pathological event in tauopathies and is the strongest correlate of cognitive decline.
View Article and Find Full Text PDFWorking memory, the ability to keep recently accessed information available for immediate manipulation, has been proposed to rely on two mechanisms that appear difficult to reconcile: self-sustained neural firing, or the opposite-activity-silent synaptic traces. Here we review and contrast models of these two mechanisms, and then show that both phenomena can co-exist within a unified system in which neurons hold information in both activity and synapses. Rapid plasticity in flexibly-coding neurons allows features to be bound together into objects, with an important emergent property being the focus of attention.
View Article and Find Full Text PDFIn the version of this article initially published, in the PDF, equations (2) and (4) erroneously displayed a curly bracket on the right hand side of the equation. This should not be there. The errors have been corrected in the PDF version of the article.
View Article and Find Full Text PDFMotor cortex (M1) exhibits a rich repertoire of neuronal activities to support the generation of complex movements. Although recent neuronal-network models capture many qualitative aspects of M1 dynamics, they can generate only a few distinct movements. Additionally, it is unclear how M1 efficiently controls movements over a wide range of shapes and speeds.
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