Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are well-recognised as an extended disease spectrum. This study hypothesised that cortical hyperexcitability, an early pathophysiological abnormality in ALS, would distinguish cognitive phenotypes, as a surrogate marker o...

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Autores principales:	Smriti Agarwal, Elizabeth Highton-Williamson, Jashelle Caga, James Howells, Thanuja Dharmadasa, José M. Matamala, Yan Ma, Kazumoto Shibuya, John R. Hodges, Rebekah M. Ahmed, Steve Vucic, Matthew C. Kiernan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f078d7f7bedc4ed1b7dc8b9ca05c2cf6
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spelling	oai:doaj.org-article:f078d7f7bedc4ed1b7dc8b9ca05c2cf62021-12-02T10:47:54ZMotor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis10.1038/s41598-021-81612-x2045-2322https://doaj.org/article/f078d7f7bedc4ed1b7dc8b9ca05c2cf62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81612-xhttps://doaj.org/toc/2045-2322Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are well-recognised as an extended disease spectrum. This study hypothesised that cortical hyperexcitability, an early pathophysiological abnormality in ALS, would distinguish cognitive phenotypes, as a surrogate marker of pathological disease burden. 61 patients with ALS, matched for disease duration (pure motor ALS, n = 39; ALS with coexistent FTD, ALS-FTD, n = 12; ALS with cognitive/behavioural abnormalities not meeting FTD criteria, ALS-Cog, n = 10) and 30 age-matched healthy controls. Cognitive function on the Addenbrooke’s cognitive examination (ACE) scale, behavioural function on the motor neuron disease behavior scale (MiND-B) and cortical excitability using transcranial magnetic stimulation (TMS) were documented. Cortical resting motor threshold (RMT), lower threshold indicating hyperexcitability, was lower in ALS-FTD (50.2 ± 6.9) compared to controls (64.3 ± 12.6, p < 0.005), while ALS-Cog (63.3 ± 12.7) and ALS (60.8 ± 13.9, not significant) were similar to controls. Short interval intracortical inhibition (SICI) was reduced across all ALS groups compared to controls, indicating hyperexcitability. On receiver operating characteristic curve analysis, RMT differentiated ALS-FTD from ALS (area under the curve AUC = 0.745, p = 0.011). The present study has identified a distinct pattern of cortical excitability across cognitive phenotypes in ALS. As such, assessment of cortical physiology may provide more precise clinical prognostication in ALS.Smriti AgarwalElizabeth Highton-WilliamsonJashelle CagaJames HowellsThanuja DharmadasaJosé M. MatamalaYan MaKazumoto ShibuyaJohn R. HodgesRebekah M. AhmedSteve VucicMatthew C. KiernanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Smriti Agarwal Elizabeth Highton-Williamson Jashelle Caga James Howells Thanuja Dharmadasa José M. Matamala Yan Ma Kazumoto Shibuya John R. Hodges Rebekah M. Ahmed Steve Vucic Matthew C. Kiernan Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
description	Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are well-recognised as an extended disease spectrum. This study hypothesised that cortical hyperexcitability, an early pathophysiological abnormality in ALS, would distinguish cognitive phenotypes, as a surrogate marker of pathological disease burden. 61 patients with ALS, matched for disease duration (pure motor ALS, n = 39; ALS with coexistent FTD, ALS-FTD, n = 12; ALS with cognitive/behavioural abnormalities not meeting FTD criteria, ALS-Cog, n = 10) and 30 age-matched healthy controls. Cognitive function on the Addenbrooke’s cognitive examination (ACE) scale, behavioural function on the motor neuron disease behavior scale (MiND-B) and cortical excitability using transcranial magnetic stimulation (TMS) were documented. Cortical resting motor threshold (RMT), lower threshold indicating hyperexcitability, was lower in ALS-FTD (50.2 ± 6.9) compared to controls (64.3 ± 12.6, p < 0.005), while ALS-Cog (63.3 ± 12.7) and ALS (60.8 ± 13.9, not significant) were similar to controls. Short interval intracortical inhibition (SICI) was reduced across all ALS groups compared to controls, indicating hyperexcitability. On receiver operating characteristic curve analysis, RMT differentiated ALS-FTD from ALS (area under the curve AUC = 0.745, p = 0.011). The present study has identified a distinct pattern of cortical excitability across cognitive phenotypes in ALS. As such, assessment of cortical physiology may provide more precise clinical prognostication in ALS.
format	article
author	Smriti Agarwal Elizabeth Highton-Williamson Jashelle Caga James Howells Thanuja Dharmadasa José M. Matamala Yan Ma Kazumoto Shibuya John R. Hodges Rebekah M. Ahmed Steve Vucic Matthew C. Kiernan
author_facet	Smriti Agarwal Elizabeth Highton-Williamson Jashelle Caga James Howells Thanuja Dharmadasa José M. Matamala Yan Ma Kazumoto Shibuya John R. Hodges Rebekah M. Ahmed Steve Vucic Matthew C. Kiernan
author_sort	Smriti Agarwal
title	Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
title_short	Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
title_full	Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
title_fullStr	Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
title_full_unstemmed	Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
title_sort	motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f078d7f7bedc4ed1b7dc8b9ca05c2cf6
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Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis

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