Brain Connectivity and Network Analysis in Amyotrophic Lateral Sclerosis

Renga, Vijay

doi:10.1155/2022/1838682

Cited by 12 publications

(7 citation statements)

References 90 publications

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“…Other studies that examine the cell-autonomous effect of FUS variants show that restricted expression of FUS in the brain and spinal cord of mice is sufficient to promote dendritic attrition of UMN and LMN, alterations of dendritic spines and NMJs as well as behavior impairments (Qiu et al, 2014;Ho et al, 2021). Consistent with a loss of corticospinal connectivity observed in ALS and FTD-MND patients (Whitwell et al, 2011;Renga, 2022), Prp-FUSR521C mice had loss of dendritic branching and mature spines in UMN and a corresponding reduction in the number and size of presynaptic terminals in spinal motor neurons (Qiu et al, 2014). Brain atrophy and age-dependent cognitive defects in Prp-FUSR514G transgenic mice were also found to cause decreased dendritic spine density and LTP in the hippocampus of these mice (Ho et al, 2021).…”

Section: Fus: Synaptic Dysfunction In Als/ftd Models Of Diseasementioning

confidence: 76%

Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease

Gelon

Dutchak

Sephton

2022

Front. Mol. Neurosci.

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Synaptic loss is a pathological feature of all neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS is a disease of the cortical and spinal motor neurons resulting in fatal paralysis due to denervation of muscles. FTD is a form of dementia that primarily affects brain regions controlling cognition, language and behavior. Once classified as two distinct diseases, ALS and FTD are now considered as part of a common disease spectrum based on overlapping clinical, pathological and genetic evidence. At the cellular level, aggregation of common proteins and overlapping gene susceptibilities are shared in both ALS and FTD. Despite the convergence of these two fields of research, the underlying disease mechanisms remain elusive. However, recent discovers from ALS and FTD patient studies and models of ALS/FTD strongly suggests that synaptic dysfunction is an early event in the disease process and a unifying hallmark of these diseases. This review provides a summary of the reported anatomical and cellular changes that occur in cortical and spinal motor neurons in ALS and FTD tissues and models of disease. We also highlight studies that identify changes in the proteome and transcriptome of ALS and FTD models and provide a conceptual overview of the processes that contribute to synaptic dysfunction in these diseases. Due to space limitations and the vast number of publications in the ALS and FTD fields, many articles have not been discussed in this review. As such, this review focuses on the three most common shared mutations in ALS and FTD, the hexanucleuotide repeat expansion within intron 1 of chromosome 9 open reading frame 72 (C9ORF72), transactive response DNA binding protein 43 (TARDBP or TDP-43) and fused in sarcoma (FUS), with the intention of highlighting common pathways that promote synaptic dysfunction in the ALS-FTD disease spectrum.

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Section: Fus: Synaptic Dysfunction In Als/ftd Models Of Diseasementioning

confidence: 76%

Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease

Gelon

Dutchak

Sephton

2022

Front. Mol. Neurosci.

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“…We started from the substantial observations that ALS is characterized by alterations in the structural and functional brain connectivity, both at the global and at the nodal level [6, 7,42,43], in line with hypothesized spread-out involvement of the brain. In a large ALS cohort study, we have previously shown that functional brain networks are more integrated and vulnerable in patients, and this hyper-connectivity progresses with the clinical evolution of the disease [12].…”

Section: Discussionmentioning

confidence: 99%

Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis

Polverino,

Lopez,

Liparoti

et al. 2023

Preprint

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Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular and neuroimaging evidence. Functional connectivity (FC) studies show alterations in the topological organization of brain network in ALS patients, demonstrating a hyper-connectedness as the disease progresses. This functionally hyper-connected network can be linked to altered brain dynamics, since the brain activity is characterized by large-scale bursts of activations, defined as neuronal avalanches. The number of unique avalanche patterns (i.e., the size of the functional repertoire) might be used as a readout of brain flexibility. In fact, we have previously shown that the size of the functional repertoire is reduced in ALS and predicts clinical disability. However, this approach did not provide information on the spatio-temporal spreading of neuronal avalanches in the brain. In this work, we hypothesized that ALS patients would show an altered spreading of neuronal avalanches. To test our hypothesis, we obtained the source-reconstructed MEG signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM), which represents the probability that two brain regions are consecutively recruited in an avalanche, and used the corresponding network parameter nodal strength to quantify the changes in each region. In fact, this parameter provides key information about which brain regions are mostly involved in the spreading avalanches. Our work demonstrated that ALS patients present higher values of the nodal strength in both cortical and sub-cortical brain areas. Furthermore, the nodal strength correlates directly with disease duration.

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“…Amyotrophic lateral sclerosis disease occurs due to the gradual defcit of motor neurons either in the brain or the spinal cord [1][2][3][4]. Te development of unknown genes or pathophysiological processes is considered the main cause of the disease [3,5,6]. ALS is a complex disorder since it afects the whole body and causes paralysis.…”

Section: Introductionmentioning

confidence: 99%

“…Physicians rely on various syndromes to identify the disease in its early stages, such as behavioral defcits or cognitive dysfunctions [1,[7][8][9][10]. If the disease is diagnosed behind time, then it could afect the treatment plan negatively [2,5]. Te efcient ways to predict and diagnose ALS disease are to look for related biomarkers and perform robust clinical evaluations using biological data [1,11,12].…”

Section: Introductionmentioning

confidence: 99%

A New Artificial Intelligence-Based Model for Amyotrophic Lateral Sclerosis Prediction

Alzahrani,

Alsheikhy,

Shawly

et al. 2023

International Journal of Intelligent Systems

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Currently, amyotrophic lateral sclerosis (ALS) disease is considered fatal since it affects the central nervous system with no cure or clear treatments. This disease affects the spinal cord, more specifically, the lower motor neurons (LMNs) and the upper motor neurons (UMNs) inside the brain along with their networks. Various solutions have been developed to predict ALS. Some of these solutions were implemented using different deep-learning methods (DLMs). Nevertheless, this disease is considered a tough task and a huge challenge. This article proposes a reliable model to predict ALS disease based on a deep-learning tool (DLT). The developed DLT is designed using a UNET architecture. The proposed approach is evaluated for different performance quantities on a dataset and provides promising results. An average obtained accuracy ranged between 82% and 87% with around 86% of the F-score. The obtained outcomes can open the door to applying DLMs to predict and identify ALS disease.

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Brain Connectivity and Network Analysis in Amyotrophic Lateral Sclerosis

Cited by 12 publications

References 90 publications

Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease

Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease

Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis

A New Artificial Intelligence-Based Model for Amyotrophic Lateral Sclerosis Prediction

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