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Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular, and neuroimaging evidence. As a consequence, predicting clinical features requires a description of large-scale neuronal dynamics. Normally, brain activity dynamically recon...

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Autores principales: Polverino, Arianna, Troisi Lopez, Emahnuel, Minino, Roberta, Liparoti, Marianna, Romano, Antonella, Trojsi, Francesca, Lucidi, Fabio, Gollo, Leonardo, Jirsa, Viktor, Sorrentino, Giuseppe, Sorrentino, Pierpaolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687404/
https://www.ncbi.nlm.nih.gov/pubmed/36180240
http://dx.doi.org/10.1212/WNL.0000000000201200
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author Polverino, Arianna
Troisi Lopez, Emahnuel
Minino, Roberta
Liparoti, Marianna
Romano, Antonella
Trojsi, Francesca
Lucidi, Fabio
Gollo, Leonardo
Jirsa, Viktor
Sorrentino, Giuseppe
Sorrentino, Pierpaolo
author_facet Polverino, Arianna
Troisi Lopez, Emahnuel
Minino, Roberta
Liparoti, Marianna
Romano, Antonella
Trojsi, Francesca
Lucidi, Fabio
Gollo, Leonardo
Jirsa, Viktor
Sorrentino, Giuseppe
Sorrentino, Pierpaolo
author_sort Polverino, Arianna
collection PubMed
description BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular, and neuroimaging evidence. As a consequence, predicting clinical features requires a description of large-scale neuronal dynamics. Normally, brain activity dynamically reconfigures over time, recruiting different brain areas. Brain pathologies induce stereotyped dynamics which, in turn, are linked to clinical impairment. Hence, based on recent evidence showing that brain functional networks become hyperconnected as ALS progresses, we hypothesized that the loss of flexible dynamics in ALS would predict the symptoms severity. METHODS: To test this hypothesis, we quantified flexibility using the “functional repertoire” (i.e., the number of configurations of active brain areas) as measured from source-reconstructed magnetoencephalography (MEG) in patients with ALS and healthy controls. The activity of brain areas was reconstructed in the classic frequency bands, and the functional repertoire was estimated to quantify spatiotemporal fluctuations of brain activity. Finally, we built a k-fold cross-validated multilinear model to predict the individual clinical impairment from the size of the functional repertoire. RESULTS: Comparing 42 patients with ALS and 42 healthy controls, we found a more stereotyped brain dynamics in patients with ALS (p < 0.05), as conveyed by the smaller functional repertoire. The relationship between the size of the functional repertoire and the clinical scores in the ALS group showed significant correlations in both the delta and the theta frequency bands. Furthermore, through a k-fold cross-validated multilinear regression model, we found that the functional repertoire predicted both clinical staging (p < 0.001 and p < 0.01, in the delta and theta bands, respectively) and symptoms severity (p < 0.001, in both the delta and theta bands). DISCUSSION: Our work shows that (1) ALS pathology reduces the flexibility of large-scale brain dynamics, (2) subcortical regions play a key role in determining brain dynamics, and (3) reduced brain flexibility predicts disease stage and symptoms severity. Our approach provides a noninvasive tool to quantify alterations in brain dynamics in ALS (and, possibly, other neurodegenerative diseases), thus opening new opportunities in disease management and a framework to test, in the near future, the effects of disease-modifying interventions at the whole-brain level.
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spelling pubmed-96874042022-11-25 Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis Polverino, Arianna Troisi Lopez, Emahnuel Minino, Roberta Liparoti, Marianna Romano, Antonella Trojsi, Francesca Lucidi, Fabio Gollo, Leonardo Jirsa, Viktor Sorrentino, Giuseppe Sorrentino, Pierpaolo Neurology Research Article BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular, and neuroimaging evidence. As a consequence, predicting clinical features requires a description of large-scale neuronal dynamics. Normally, brain activity dynamically reconfigures over time, recruiting different brain areas. Brain pathologies induce stereotyped dynamics which, in turn, are linked to clinical impairment. Hence, based on recent evidence showing that brain functional networks become hyperconnected as ALS progresses, we hypothesized that the loss of flexible dynamics in ALS would predict the symptoms severity. METHODS: To test this hypothesis, we quantified flexibility using the “functional repertoire” (i.e., the number of configurations of active brain areas) as measured from source-reconstructed magnetoencephalography (MEG) in patients with ALS and healthy controls. The activity of brain areas was reconstructed in the classic frequency bands, and the functional repertoire was estimated to quantify spatiotemporal fluctuations of brain activity. Finally, we built a k-fold cross-validated multilinear model to predict the individual clinical impairment from the size of the functional repertoire. RESULTS: Comparing 42 patients with ALS and 42 healthy controls, we found a more stereotyped brain dynamics in patients with ALS (p < 0.05), as conveyed by the smaller functional repertoire. The relationship between the size of the functional repertoire and the clinical scores in the ALS group showed significant correlations in both the delta and the theta frequency bands. Furthermore, through a k-fold cross-validated multilinear regression model, we found that the functional repertoire predicted both clinical staging (p < 0.001 and p < 0.01, in the delta and theta bands, respectively) and symptoms severity (p < 0.001, in both the delta and theta bands). DISCUSSION: Our work shows that (1) ALS pathology reduces the flexibility of large-scale brain dynamics, (2) subcortical regions play a key role in determining brain dynamics, and (3) reduced brain flexibility predicts disease stage and symptoms severity. Our approach provides a noninvasive tool to quantify alterations in brain dynamics in ALS (and, possibly, other neurodegenerative diseases), thus opening new opportunities in disease management and a framework to test, in the near future, the effects of disease-modifying interventions at the whole-brain level. Lippincott Williams & Wilkins 2022-11-22 /pmc/articles/PMC9687404/ /pubmed/36180240 http://dx.doi.org/10.1212/WNL.0000000000201200 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Article
Polverino, Arianna
Troisi Lopez, Emahnuel
Minino, Roberta
Liparoti, Marianna
Romano, Antonella
Trojsi, Francesca
Lucidi, Fabio
Gollo, Leonardo
Jirsa, Viktor
Sorrentino, Giuseppe
Sorrentino, Pierpaolo
Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title_full Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title_fullStr Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title_full_unstemmed Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title_short Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis
title_sort flexibility of fast brain dynamics and disease severity in amyotrophic lateral sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687404/
https://www.ncbi.nlm.nih.gov/pubmed/36180240
http://dx.doi.org/10.1212/WNL.0000000000201200
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