Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease

Abstract The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the...

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Autores principales:	Nicholas D’Cruz, Griet Vervoort, Sima Chalavi, Bauke W. Dijkstra, Moran Gilat, Alice Nieuwboer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d52f9f02aae340318b6977fbaf6ee4d3
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spelling	oai:doaj.org-article:d52f9f02aae340318b6977fbaf6ee4d32021-12-02T13:20:16ZThalamic morphology predicts the onset of freezing of gait in Parkinson’s disease10.1038/s41531-021-00163-02373-8057https://doaj.org/article/d52f9f02aae340318b6977fbaf6ee4d32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00163-0https://doaj.org/toc/2373-8057Abstract The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.Nicholas D’CruzGriet VervoortSima ChalaviBauke W. DijkstraMoran GilatAlice NieuwboerNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Nicholas D’Cruz Griet Vervoort Sima Chalavi Bauke W. Dijkstra Moran Gilat Alice Nieuwboer Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
description	Abstract The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.
format	article
author	Nicholas D’Cruz Griet Vervoort Sima Chalavi Bauke W. Dijkstra Moran Gilat Alice Nieuwboer
author_facet	Nicholas D’Cruz Griet Vervoort Sima Chalavi Bauke W. Dijkstra Moran Gilat Alice Nieuwboer
author_sort	Nicholas D’Cruz
title	Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
title_short	Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
title_full	Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
title_fullStr	Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
title_full_unstemmed	Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
title_sort	thalamic morphology predicts the onset of freezing of gait in parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d52f9f02aae340318b6977fbaf6ee4d3
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Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease

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