scholarly journals Spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain and its connectome

2019 ◽  
Author(s):  
Sveva Fornari ◽  
Amelie Schäfer ◽  
Ellen Kuhl ◽  
Alain Goriely
Keyword(s):  
Anisotropic Diffusion ◽  
Transport Processes ◽  
Misfolded Proteins ◽  
Size Distributions ◽  
Discrete Laplacian ◽  
Brain Connectome ◽  
Spatially Extended ◽  
Smoluchowski Theory ◽  
The Brain ◽  
Disease Specific

AbstractThe prion-like hypothesis of neurodegenerative diseases states that the accumulation of misfolded proteins in the form of aggregates is responsible for tissue death and its associated neurodegenerative pathology and cognitive decline. Some disease-specific misfolded proteins can interact with healthy proteins to form long chains that are transported through the brain along axonal pathways. Since aggregates of different sizes have different transport properties and toxicity, it is important to follow independently their evolution in space and time. Here, we model the spreading and propagation of aggregates of misfolded proteins in the brain using the general Smoluchowski theory of nucleation, aggregation, and fragmentation. The transport processes considered here are either anisotropic diffusion along axonal bundles or discrete Laplacian transport along a network. In particular, we model the spreading and aggregation of both amyloid-β and τ molecules in the brain connectome. We show that these two models lead to different size distributions and different propagation along the network. A detailed analysis of these two models reveals the existence of four different stages with different dynamics and invasive properties.

scholarly journals The Modular Organization of Pain Brain Networks: An fMRI Graph Analysis Informed by Intracranial EEG

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Camille Fauchon ◽  
David Meunier ◽  
Isabelle Faillenot ◽  
Florence B Pomares ◽  
Hélène Bastuji ◽  
...  
Keyword(s):  
Information Integration ◽  
Functional Organization ◽  
Brain Connectivity ◽  
Brain Networks ◽  
Modular Organization ◽  
Noxious Heat ◽  
Intracranial Eeg ◽  
Brain Connectome ◽  
Posterior Parietal ◽  
The Brain

Abstract Intracranial EEG (iEEG) studies have suggested that the conscious perception of pain builds up from successive contributions of brain networks in less than 1 s. However, the functional organization of cortico-subcortical connections at the multisecond time scale, and its accordance with iEEG models, remains unknown. Here, we used graph theory with modular analysis of fMRI data from 60 healthy participants experiencing noxious heat stimuli, of whom 36 also received audio stimulation. Brain connectivity during pain was organized in four modules matching those identified through iEEG, namely: 1) sensorimotor (SM), 2) medial fronto-cingulo-parietal (default mode-like), 3) posterior parietal-latero-frontal (central executive-like), and 4) amygdalo-hippocampal (limbic). Intrinsic overlaps existed between the pain and audio conditions in high-order areas, but also pain-specific higher small-worldness and connectivity within the sensorimotor module. Neocortical modules were interrelated via “connector hubs” in dorsolateral frontal, posterior parietal, and anterior insular cortices, the antero-insular connector being most predominant during pain. These findings provide a mechanistic picture of the brain networks architecture and support fractal-like similarities between the micro-and macrotemporal dynamics associated with pain. The anterior insula appears to play an essential role in information integration, possibly by determining priorities for the processing of information and subsequent entrance into other points of the brain connectome.

scholarly journals Co-factor-free aggregation of tau into seeding-competent RNA-sequestering amyloid fibrils

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pijush Chakraborty ◽  
Gwladys Rivière ◽  
Shu Liu ◽  
Alain Ibáñez de Opakua ◽  
Rıza Dervişoğlu ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Corticobasal Degeneration ◽  
Binding Studies ◽  
Rigid Core ◽  
Tau Aggregation ◽  
The Brain ◽  
Tau Aggregate ◽  
Disease Specific ◽  
Tau Fibrils

AbstractPathological aggregation of the protein tau into insoluble aggregates is a hallmark of neurodegenerative diseases. The emergence of disease-specific tau aggregate structures termed tau strains, however, remains elusive. Here we show that full-length tau protein can be aggregated in the absence of co-factors into seeding-competent amyloid fibrils that sequester RNA. Using a combination of solid-state NMR spectroscopy and biochemical experiments we demonstrate that the co-factor-free amyloid fibrils of tau have a rigid core that is similar in size and location to the rigid core of tau fibrils purified from the brain of patients with corticobasal degeneration. In addition, we demonstrate that the N-terminal 30 residues of tau are immobilized during fibril formation, in agreement with the presence of an N-terminal epitope that is specifically detected by antibodies in pathological tau. Experiments in vitro and in biosensor cells further established that co-factor-free tau fibrils efficiently seed tau aggregation, while binding studies with different RNAs show that the co-factor-free tau fibrils strongly sequester RNA. Taken together the study provides a critical advance to reveal the molecular factors that guide aggregation towards disease-specific tau strains.

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Maroua Jalouli ◽  
Md. Ataur Rahman ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Misfolded Proteins ◽  
Inflammatory Signaling ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Immunological Mechanisms ◽  
The Brain

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

A finite element model for predicting the distribution of drugs delivered intracranially to the brain

1997 ◽  
Vol 273 (5) ◽  
pp. R1810-R1821 ◽  
Author(s):  
S. Kalyanasundaram ◽  
V. D. Calhoun ◽  
K. W. Leong
Keyword(s):  
Drug Delivery ◽  
Finite Element ◽  
Spin Echo ◽  
Interleukin 2 ◽  
Chemical Species ◽  
Transport Processes ◽  
Proton Density ◽  
Clear Understanding ◽  
Tissue Properties ◽  
The Brain

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.

scholarly journals From static to temporal network theory: Applications to functional brain connectivity

2017 ◽  
Vol 1 (2) ◽  
pp. 69-99 ◽  
Author(s):  
William Hedley Thompson ◽  
Per Brantefors ◽  
Peter Fransson
Keyword(s):  
Network Theory ◽  
Temporal Dynamics ◽  
Brain Connectivity ◽  
Resting State Fmri ◽  
Network Activity ◽  
Temporal Network ◽  
Functional Brain ◽  
Brain Connectome ◽  
The Brain ◽  
Network Neuroscience

Network neuroscience has become an established paradigm to tackle questions related to the functional and structural connectome of the brain. Recently, interest has been growing in examining the temporal dynamics of the brain’s network activity. Although different approaches to capturing fluctuations in brain connectivity have been proposed, there have been few attempts to quantify these fluctuations using temporal network theory. This theory is an extension of network theory that has been successfully applied to the modeling of dynamic processes in economics, social sciences, and engineering article but it has not been adopted to a great extent within network neuroscience. The objective of this article is twofold: (i) to present a detailed description of the central tenets of temporal network theory and describe its measures, and; (ii) to apply these measures to a resting-state fMRI dataset to illustrate their utility. Furthermore, we discuss the interpretation of temporal network theory in the context of the dynamic functional brain connectome. All the temporal network measures and plotting functions described in this article are freely available as the Python package Teneto.

Dyslexia as the most prevalent form of specific learning disabilities

2021 ◽  
Vol 2 (3) ◽  
pp. 146-158
Author(s):  
Nikolay N. Zavadenko
Keyword(s):  
Learning Disabilities ◽  
Executive Functions ◽  
Emotional Disorders ◽  
Functional Neuroimaging ◽  
Specific Learning Disabilities ◽  
Speech Development ◽  
Language Development Disorders ◽  
Brain Connectome ◽  
The Brain ◽  
Specific Learning

Dyslexia is the most common form of specific learning disabilities. Dyslexia is observed in 5-17.5 % of schoolchildren, and among children with specific learning disabilities, it accounts for about 70-80 %. Usually, dyslexia manifests itself as the inability to achieve an appropriate level of reading skills development that would be proportional to their intellectual abilities and writing and spelling skills. Secondary consequences of dyslexia may include problems in reading comprehension and reduced reading experience that can impede the growth of vocabulary and background skills. The review discusses neurological management of reading and writing as complex higher mental functions, including many components that are provided by various brain areas. The principles of dyslexia classification, the main characteristics of its traditionally defined forms are given: phonemic, optical, mnestic, semantic, agrammatic. The article analyzes the cerebral mechanisms of dyslexia development, the results of studies using neuropsychological methods, functional neuroimaging, and the study of the brain connectome. The contribution to dyslexia development of disturbances in phonological awareness, rapid automated naming (RAN), the volume of visual attention (VAS), components of the brain executive functions is discussed. The origin of emotional disorders in children with dyslexia, risk factors for dyslexia development (including genetic predisposition) are considered. Dyslexia manifestations in children are listed, about which their parents seek the advice of a specialist for the first time. In the process of diagnosing dyslexia, attention should be paid to the delay in the child’s speech development, cases of speech and language development disorders and specific learning disabilities among family members. It is necessary to consider possible comorbidity of dyslexia in a child with attention deficit hyperactivity disorder, dyscalculia, developmental dyspraxia, disorders of emotional control and brain executive functions. Timely diagnosis determines the effectiveness of early intervention programs based on an integrated multimodal approach.

Creutzfeldt-Jakob Disease

2021 ◽  
pp. 42-58
Author(s):  
Sadeeq Muhammad Sheshe
Keyword(s):  
Nervous System ◽  
Rare Disease ◽  
Prion Proteins ◽  
Diagnosis And Treatment ◽  
Misfolded Proteins ◽  
Jakob Disease ◽  
Complex Mechanisms ◽  
The Brain

Creutzfeldt-Jakob disease (CJD) is a rare disease associated with neurodegeneration mostly characterized by damage to the neurons. CJD is caused by aggregation of misfolded proteins known as prions; thus, CJD is said to be a prion-related illness. CJD and other prion-related illnesses such as Kuru and Gerstmann-Sträussler-Scheinker disease (GSS) have been reported to have complex mechanisms due to their association with the brain and the nervous system in general. A lot of questions have been raised about the mechanism, diagnosis, and pathogenesis of this disease. The complexity of prion proteins themselves have contributed to more questions about the complications of CJD, whether misfolding of the prions are responsible for neurodegeneration or the misfolding are mere symptoms of the disease. This chapter attempts to explore some details about CJD and answers most related questions about the disease's mechanism. The author finally attempts to explore recent development in pathogenesis, diagnosis, and treatment of CJD.

scholarly journals Delayed correlations improve the reconstruction of the brain connectome

PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0228334 ◽  
Author(s):  
Mite Mijalkov ◽  
Joana B. Pereira ◽  
Giovanni Volpe
Keyword(s):  
Brain Connectome ◽  
The Brain

The effects of a mid-task break on the brain connectome in healthy participants: A resting-state functional MRI study

NeuroImage ◽  
2017 ◽  
Vol 152 ◽  
pp. 19-30 ◽  
Author(s):  
Yu Sun ◽  
Julian Lim ◽  
Zhongxiang Dai ◽  
KianFoong Wong ◽  
Fumihiko Taya ◽  
...  
Keyword(s):  
Functional Mri ◽  
Resting State ◽  
Brain Connectome ◽  
Mri Study ◽  
The Brain ◽  
Healthy Participants
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