Brain Model Based on the Canonical Ensemble with Functional MRI: A Thermodynamic Exploration of the Neural System

Objective. System modeling is an important method to study the working mechanisms of the brain. This study attempted to build a model of the brain from the perspective of thermodynamics at the system level, which brought a new perspective to brain modeling. Approach. Regarding brain regions as systems, voxels as particles, and intensity of signals as energy of particles, the thermodynamic model of the brain was built based on the canonical ensemble theory. Two pairs of activated regions and two pairs of inactivated brain regions were selected for comparison in this study, and the thermodynamic properties based on the proposed model were analyzed. In addition, the thermodynamic properties were extracted as input features for the detection of Alzheimer’s disease. Main Results. The experimental results verified the assumption that the brain follows thermodynamic laws. This demonstrated the feasibility and rationality of the proposed brain thermodynamic modeling method, indicating that thermodynamic parameters drawn from our model can be applied to describe the state of the neural system. Meanwhile, the brain thermodynamic model achieved good accuracy in the detection of Alzheimer’s disease, suggesting the potential application of thermodynamic models in auxiliary diagnosis. Significance. (1) In the previous studies, only some thermodynamic parameters in physics were analogized and applied to brain image analysis, while, in this study, a complete system model of the brain was proposed through the principles of thermodynamics. And, based on the neural system models proposed, thermodynamic parameters were obtained to describe the observation and evolution of the neural system. (2) Based on the proposed thermodynamic models, we found and confirmed that the neural system also follows the laws of thermodynamics: the activation of system always leads to increased internal energy, increased free energy, and decreased entropy as what is discovered in many other systems besides classic thermodynamic system. (3) The detection of neural disease was demonstrated to benefit from the thermodynamic model, which confirmed that the thermodynamic model proposed can indeed describe the evolution of the neural system diseases. And it further implied the immense potential of thermodynamics in auxiliary diagnosis.

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Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

Neural Computing and Applications ◽

10.1007/s00521-021-06105-4 ◽

2021 ◽

Author(s):

Antonio Giovannetti ◽

Gianluca Susi ◽

Paola Casti ◽

Arianna Mencattini ◽

Sandra Pusil ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Regions ◽

Ensemble Classification ◽

The Novel ◽

Ensemble Classifiers ◽

Deep Convolutional Neural Networks ◽

Early Signs ◽

Data Representations ◽

The Brain

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer’s disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships.

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Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

Nature Communications ◽

10.1038/s41467-021-22399-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Angela M. Crist ◽

Kelly M. Hinkle ◽

Xue Wang ◽

Christina M. Moloney ◽

Billie J. Matchett ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Digital Pathology ◽

Selective Vulnerability ◽

Brain Regions ◽

Biochemical Analyses ◽

The Brain ◽

Relevant Gene ◽

Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

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Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice

Experimental Biology and Medicine ◽

10.1177/15353702211056866 ◽

2021 ◽

pp. 153537022110568

Author(s):

Natalia V Bobkova ◽

Daria Y Zhdanova ◽

Natalia V Belosludtseva ◽

Nikita V Penkov ◽

Galina D Mironova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Spatial Memory ◽

Intranasal Administration ◽

Brain Structures ◽

Brain Regions ◽

Dependent Manner ◽

Behavioral Experiments ◽

Hippocampal Cell Culture ◽

The Brain

Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer’s type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.

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Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APPSLand APPSL/PS1M146LMouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?

International Journal of Alzheimer s Disease ◽

10.4061/2011/920958 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Laurence Barrier ◽

Bernard Fauconneau ◽

Anastasia Noël ◽

Sabrina Ingrand

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Models ◽

Neuronal Death ◽

Time Course ◽

Neuronal Loss ◽

Brain Regions ◽

App Processing ◽

Ceramide Accumulation ◽

The Brain

There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels in the brain of the APPSL/PS1Ki mouse model of AD, preceding the neuronal death. To extend these findings, we analyzed ceramide and related-sphingolipid contents in brain from two other mouse models (i.e., APPSLand APPSL/PS1M146L) in which the time-course of pathology is closer to that seen in most currently available models. Conversely to our previous work, ceramides did not accumulate in disease-associated brain regions (cortex and hippocampus) from both models. However, the APPSL/PS1Ki model is unique for its drastic neuronal loss coinciding with strong accumulation of neurotoxic Aβisoforms, not observed in other animal models of AD. Since there are neither neuronal loss nor toxic Aβspecies accumulation in APPSLmice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.

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Graph Theory-Based Brain Network Connectivity Analysis and Classification of Alzheimer’s Disease

International Journal of Image and Graphics ◽

10.1142/s021946782240006x ◽

2021 ◽

Author(s):

A. Thushara ◽

C. Ushadevi Amma ◽

Ansamma John

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Graph Theory ◽

Neurodegenerative Disorder ◽

Brain Networks ◽

Network Connectivity ◽

Brain Regions ◽

Brain Network ◽

Fiber Tracts ◽

The Brain

Alzheimer’s Disease (AD) is basically a progressive neurodegenerative disorder associated with abnormal brain networks that affect millions of elderly people and degrades their quality of life. The abnormalities in brain networks are due to the disruption of White Matter (WM) fiber tracts that connect the brain regions. Diffusion-Weighted Imaging (DWI) captures the brain’s WM integrity. Here, the correlation betwixt the WM degeneration and also AD is investigated by utilizing graph theory as well as Machine Learning (ML) algorithms. By using the DW image obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, the brain graph of each subject is constructed. The features extracted from the brain graph form the basis to differentiate between Mild Cognitive Impairment (MCI), Control Normal (CN) and AD subjects. Performance evaluation is done using binary and multiclass classification algorithms and obtained an accuracy that outperforms the current top-notch DWI-based studies.

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The Presence of Human Herpesvirus 6 in the Brain in Health and Disease

Biomolecules ◽

10.3390/biom10111520 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1520

Author(s):

Gabriel Santpere ◽

Marco Telford ◽

Pol Andrés-Benito ◽

Arcadi Navarro ◽

Isidre Ferrer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Current Knowledge ◽

Human Herpesvirus ◽

Brain Regions ◽

Specific Cell ◽

Human Herpesvirus 6 ◽

Detection Techniques ◽

Herpesvirus 6 ◽

The Brain

The human herpesvirus 6 (HHV‐6) ‐A and ‐B are two dsDNA beta‐herpesviruses infectingalmost the entire worldwide population. These viruses have been implicated in multipleneurological conditions in individuals of various ages and immunological status, includingencephalitis, epilepsy, and febrile seizures. HHV‐6s have also been suggested as playing a role inthe etiology of neurodegenerative diseases such as multiple sclerosis and Alzheimer’s disease. Theapparent robustness of these suggested associations is contingent on the accuracy of HHV‐6detection in the nervous system. The effort of more than three decades of researching HHV‐6 in thebrain has yielded numerous observations, albeit using variable technical approaches in terms oftissue preservation, detection techniques, sample sizes, brain regions, and comorbidities. In thisreview, we aimed to summarize current knowledge about the entry routes and direct presence ofHHV‐6 in the brain parenchyma at the level of DNA, RNA, proteins, and specific cell types, inhealthy subjects and in those with neurological conditions. We also discuss recent findings relatedto the presence of HHV‐6 in the brains of patients with Alzheimer’s disease in light of availableevidence.

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Alzheimer’s disease under the purview of Graph Theory Centric Genetic Networks

BRAIN. BROAD RESEARCH IN ARTIFICIAL INTELLIGENCE AND NEUROSCIENCE ◽

10.18662/brain/12.2/199 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Yegnanarayanan Venkatraman ◽

◽

Narayanaa Y Krithicaa ◽

Valentina E. Balas ◽

Marius M. Balas ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Graph Theory ◽

Network Theory ◽

Memory Loss ◽

Amyloid Plaque ◽

Brain Regions ◽

Protein Protein Interaction ◽

Communication Demands ◽

The Brain

Notice that the synapsis of brain is a form of communication. As communication demands connectivity, it is not a surprise that "graph theory" is a fastest growing area of research in the life sciences. It attempts to explain the connections and communication between networks of neurons. Alzheimer’s disease (AD) progression in brain is due to a deposition and development of amyloid plaque and the loss of communication between nerve cells. Graph/network theory can provide incredible insights into the incorrect wiring leading to memory loss in a progressive manner. Network in AD is slanted towards investigating the intricate patterns of interconnections found in the pathogenesis of brain. Here, we see how the notions of graph/network theory can be prudently exploited to comprehend the Alzheimer’s disease. We begin with introducing concepts of graph/network theory as a model for specific genetic hubs of the brain regions and cellular signalling. We begin with a brief introduction of prevalence and causes of AD followed by outlining its genetic and signalling pathogenesis. We then present some of the network-applied outcome in assessing the disease-signalling interactions, signal transduction of protein-protein interaction, disturbed genetics and signalling pathways as compelling targets of pathogenesis of the disease.

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Comparison of machine learning approaches for enhancing Alzheimer’s disease classification

PeerJ ◽

10.7717/peerj.10549 ◽

2021 ◽

Vol 9 ◽

pp. e10549

Author(s):

Qi Li ◽

Mary Qu Yang

Keyword(s):

Machine Learning ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Structural Changes ◽

Spatial Information ◽

Neurodegenerative Disorder ◽

Brain Regions ◽

Disease Classification ◽

Support Vector ◽

The Brain

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, accounting for nearly 60% of all dementia cases. The occurrence of the disease has been increasing rapidly in recent years. Presently about 46.8 million individuals suffer from AD worldwide. The current absence of effective treatment to reverse or stop AD progression highlights the importance of disease prevention and early diagnosis. Brain structural Magnetic Resonance Imaging (MRI) has been widely used for AD detection as it can display morphometric differences and cerebral structural changes. In this study, we built three machine learning-based MRI data classifiers to predict AD and infer the brain regions that contribute to disease development and progression. We then systematically compared the three distinct classifiers, which were constructed based on Support Vector Machine (SVM), 3D Very Deep Convolutional Network (VGGNet) and 3D Deep Residual Network (ResNet), respectively. To improve the performance of the deep learning classifiers, we applied a transfer learning strategy. The weights of a pre-trained model were transferred and adopted as the initial weights of our models. Transferring the learned features significantly reduced training time and increased network efficiency. The classification accuracy for AD subjects from elderly control subjects was 90%, 95%, and 95% for the SVM, VGGNet and ResNet classifiers, respectively. Gradient-weighted Class Activation Mapping (Grad-CAM) was employed to show discriminative regions that contributed most to the AD classification by utilizing the learned spatial information of the 3D-VGGNet and 3D-ResNet models. The resulted maps consistently highlighted several disease-associated brain regions, particularly the cerebellum which is a relatively neglected brain region in the present AD study. Overall, our comparisons suggested that the ResNet model provided the best classification performance as well as more accurate localization of disease-associated regions in the brain compared to the other two approaches.

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Predicting Brain Regions Related to Alzheimer’s Disease Based on Global Feature

10.1101/2020.11.27.401950 ◽

2020 ◽

Author(s):

Qi Wang ◽

Siwei Chen ◽

He Wang ◽

Luzeng Chen ◽

Yongan Sun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Network Analysis ◽

Diffusion Tensor ◽

The Elderly ◽

Brain Regions ◽

Imaging Method ◽

Global Feature ◽

Objective Monitoring ◽

The Brain

AbstractAlzheimer’s disease (AD) is a common neurodegenerative disease in the elderly, early diagnosis and timely treatment are very important to delay the course of the disease. In the past, most of the brain regions related to AD were identified based on the imaging method, which can only identify some atrophic brain regions. In this work, we used mathematical models to find out the potential brain regions related to AD. First, diffusion tensor imaging (DTI) was used to construct the brain structural network. Next, we set a new local feature index 2hop-connectivity to measure the correlation among different areas. And for this, we proposed a novel algorithm named 2hopRWR to measure 2hop-connectivity. At last, we proposed a new index GFS (Global Feature Score) based on global feature by combing 5 local features: degree centrality, betweenness centrality, closeness centrality, the number of maximal cliques, and 2hop-connectivity, to judge which brain regions are likely related to Alzheimer’s Disease. As a result, all the top ten brain regions in GFS scoring difference between the AD group and the non-AD group were related to AD by literature verification. Finally, the results of the canonical correlation analysis showed that the GFS was significantly correlated with the scores of the mini-mental state examination (MMSE) scale and montreal cognitive assessment (MoCA) scale. So, we believe the GFS can also be used as a new index to assist in diagnosis and objective monitoring of disease progression. Besides, the method proposed in this paper can be used as a differential network analysis method in other areas of network analysis.

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3265 Analysis of High-Dimensional Patient Data in Characterizing Alzheimer’s Disease Progression

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.10 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 3-3

Author(s):

Daniel Baer ◽

Andrew B. Lawson ◽

Brandon Vaughan ◽

Jane E. Joseph

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Graph Theory ◽

Cognitive Decline ◽

Brain Regions ◽

Clustering Coefficient ◽

Eigenvector Centrality ◽

Research Hypothesis ◽

The Brain ◽

Over Time

OBJECTIVES/SPECIFIC AIMS: Our research hypothesis is that resting state fMRI (rsfMRI) data can be used to identify regions of the brain which are associated with cognitive decline in patients – thereby providing a tool by which to characterize AD progression in patients. METHODS/STUDY POPULATION: We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to analyze Mini-Mental State Examination (MMSE) questionnaire scores from 14 patients diagnosed with AD at two measurement occasions. RsfMRI data was available at the first of these occasions for these patients. These rsfMRI data were summarized into 264 node-based graph theory measures of clustering coefficient and eigenvector centrality. To address our research hypothesis, we modeled changes in patient MMSE scores over time as a function of these rsfMRI data, controlling for relevant confounding factors. This model accounted for the high-dimensionality of our predictor data, the longitudinal nature of the outcome, and our desire to identify a subset of regions in the brain most associated with the MMSE outcome. RESULTS/ANTICIPATED RESULTS: The use of either the clustering coefficient or eigenvector centrality rsfMRI predictors in modeling MMSE scores for patients over time resulted in the identification of different subsets of brain regions associated with cognitive decline. This suggests that these predictors capture different information on patient propensity for cognitive decline. Further work is warranted to validate these results on a larger sample of ADNI patients. DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that different rsfMRI graph theory measures capture different aspects of cognitive function and decline in patients, which could be a future consideration in clinical practice.

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