scholarly journals Signature laminar distributions of pathology in frontotemporal lobar degeneration

2022 ◽  
Author(s):  
Daniel T. Ohm ◽  
Katheryn A. Q. Cousins ◽  
Sharon X. Xie ◽  
Claire Peterson ◽  
Corey T. McMillan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Frontotemporal Lobar Degeneration ◽  
Large Scale ◽  
Lower Layer ◽  
Clinical Syndrome ◽  
Tau Pathology ◽  
Clinical Syndromes ◽  
Severe Pathology ◽  
Large Scale Networks ◽  
Percent Area

AbstractFrontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.

scholarly journals Post-Stroke Cognitive Impairment: Pathophysiological Insights into Brain Disconnectome from Advanced Neuroimaging Analysis Techniques

2021 ◽  
Vol 23 (3) ◽  
pp. 297-311
Author(s):  
Jae-Sung Lim ◽  
Jae-Joong Lee ◽  
Choong-Wan Woo
Keyword(s):  
Cognitive Impairment ◽  
Large Scale ◽  
Imaging Techniques ◽  
Brain Network ◽  
Clinical Neurology ◽  
Post Stroke ◽  
Large Scale Networks ◽  
High Level ◽  
New Treatments ◽  
The Brain

The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.

Falling All the Time

2016 ◽  
Author(s):  
Richard A. Walsh
Keyword(s):  
Cognitive Impairment ◽  
Progressive Supranuclear Palsy ◽  
Postmortem Examination ◽  
Tau Pathology ◽  
Disease Modifying Therapies ◽  
Clinical Syndromes ◽  
Advanced Stages ◽  
Disease Modifying ◽  
Richardson’S Syndrome ◽  
Gaze Palsy

Progressive supranuclear palsy is a four-repeat tauopathy that is confirmed, like all neurodegenerative disease, at postmortem examination. An expanding group of clinical syndromes are now linked with this pathology in its early stages, although with disease progression there tends to be greater clinical similarity with the classical Richardson’s syndrome, an akinetic rigid form of parkinsonism with a progressive supranuclear gaze palsy and prominent frontal cognitive impairment. Currently, there are no disease-modifying therapies for progressive supranuclear palsy; however, there continues to be interest in immunotherapies targeted at tau pathology. Liaison with colleagues with an interest in palliative neurology is appropriate for patients in the advanced stages of the disease.

scholarly journals Mild cognitive impairment: the Manchester consensus

2020 ◽  
Author(s):  
Ross A Dunne ◽  
Dag Aarsland ◽  
John T O’Brien ◽  
Clive Ballard ◽  
Sube Banerjee ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sensitivity And Specificity ◽  
Large Scale ◽  
Ecological Validity ◽  
Neuropsychological Testing ◽  
Functional Decline ◽  
Research Participation ◽  
Clinical Syndrome ◽  
Cognitive Testing

Abstract Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.

scholarly journals Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

2021 ◽  
Author(s):  
Miguel Dasilva ◽  
Christian Brandt ◽  
Marc Alwin Gieselmann ◽  
Claudia Distler ◽  
Alexander Thiele
Keyword(s):  
Attentional Control ◽  
Large Scale ◽  
Neuronal Excitability ◽  
Cell Types ◽  
Receptor Activation ◽  
Frontal Eye Field ◽  
Control Signals ◽  
Cognitive Operations ◽  
Eye Field ◽  
Large Scale Networks

Abstract Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

scholarly journals How does the position of firms in the supply chain affect their performance? An empirical study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Siddharth Arora ◽  
Alexandra Brintrup
Keyword(s):  
Supply Chain ◽  
Empirical Data ◽  
Large Scale ◽  
Individual Performance ◽  
Supply Network ◽  
Supply Chain Networks ◽  
Focal Firm ◽  
Cooperative Competition ◽  
Large Scale Networks ◽  
The Relationship

AbstractThe relationship between a firm and its supply chain has been well studied, however, the association between the position of firms in complex supply chain networks and their performance has not been adequately investigated. This is primarily due to insufficient availability of empirical data on large-scale networks. To addresses this gap in the literature, we investigate the relationship between embeddedness patterns of individual firms in a supply network and their performance using empirical data from the automotive industry. In this study, we devise three measures that characterize the embeddedness of individual firms in a supply network. These are namely: centrality, tier position, and triads. Our findings caution us that centrality impacts individual performance through a diminishing returns relationship. The second measure, tier position, allows us to investigate the concept of tiers in supply networks because we find that as networks emerge, the boundaries between tiers become unclear. Performance of suppliers degrade as they move away from the focal firm (i.e., Toyota). The final measure, triads, investigates the effect of buying and selling to firms that supply the same customer, portraying the level of competition and cooperation in a supplier’s network. We find that increased coopetition (i.e., cooperative competition) is a performance enhancer, however, excessive complexity resulting from being involved in both upstream and downstream coopetition results in diminishing performance. These original insights help understand the drivers of firm performance from a network perspective and provide a basis for further research.

scholarly journals BFL: a node and edge betweenness based fast layout algorithm for large scale networks

2009 ◽  
Vol 10 (1) ◽  
pp. 19 ◽  
Author(s):  
Tatsunori B Hashimoto ◽  
Masao Nagasaki ◽  
Kaname Kojima ◽  
Satoru Miyano
Keyword(s):  
Large Scale ◽  
Layout Algorithm ◽  
Edge Betweenness ◽  
Large Scale Networks
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