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Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s

BACKGROUND: Spatial cognition deteriorates in Parkinson’s disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction. OB...

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Autores principales: Harrington, Deborah L., Shen, Qian, Wei, Xiangyu, Litvan, Irene, Huang, Mingxiong, Lee, Roland R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589098/
https://www.ncbi.nlm.nih.gov/pubmed/36299614
http://dx.doi.org/10.3389/fnagi.2022.987225
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author Harrington, Deborah L.
Shen, Qian
Wei, Xiangyu
Litvan, Irene
Huang, Mingxiong
Lee, Roland R.
author_facet Harrington, Deborah L.
Shen, Qian
Wei, Xiangyu
Litvan, Irene
Huang, Mingxiong
Lee, Roland R.
author_sort Harrington, Deborah L.
collection PubMed
description BACKGROUND: Spatial cognition deteriorates in Parkinson’s disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction. OBJECTIVE: This study aimed to identify functional connectivity abnormalities in cognitively normal PD (PDCN) in regions that support spatial cognition to determine their relationship to interfacing cognitive functions and motor disability, and to determine if they predict cognitive and motor progression 2 years later in a PDCN subsample. METHODS: Sixty-three PDCN and 43 controls underwent functional MRI while judging whether pictures, rotated at various angles, depicted the left or right hand. The task activates systems that respond to increases in rotation angle, a proxy for visuospatial difficulty. Angle-modulated functional connectivity was analyzed for frontal cortex, posterior cortex, and basal ganglia regions. RESULTS: Two aberrant connectivity patterns were found in PDCN, which were condensed into principal components that characterized the strength and topology of angle-modulated connectivity. One topology related to a marked failure to amplify frontal, posterior, and basal ganglia connectivity with other brain areas as visuospatial demands increased, unlike the control group (control features). Another topology related to functional reorganization whereby regional connectivity was strengthened with brain areas not recruited by the control group (PDCN features). Functional topologies correlated with diverse cognitive domains at baseline, underscoring their influences on spatial cognition. In PDCN, expression of topologies that were control features predicted greater cognitive progression longitudinally, suggesting inefficient communications within circuitry normally recruited to handle spatial demands. Conversely, stronger expression of topologies that were PDCN features predicted less longitudinal cognitive decline, suggesting functional reorganization was compensatory. Parieto-occipital topologies (control features) had different prognostic implications for longitudinal changes in motor disability. Expression of one topology predicted less motor decline, whereas expression of another predicted increased postural instability and gait disturbance (PIGD) feature severity. Concurrently, greater longitudinal decline in spatial cognition predicted greater motor and PIGD feature progression, suggesting deterioration in shared substrates. CONCLUSION: These novel discoveries elucidate functional mechanisms of visuospatial cognition in PDCN, which foreshadow future cognitive and motor disability.
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spelling pubmed-95890982022-10-25 Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s Harrington, Deborah L. Shen, Qian Wei, Xiangyu Litvan, Irene Huang, Mingxiong Lee, Roland R. Front Aging Neurosci Neuroscience BACKGROUND: Spatial cognition deteriorates in Parkinson’s disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction. OBJECTIVE: This study aimed to identify functional connectivity abnormalities in cognitively normal PD (PDCN) in regions that support spatial cognition to determine their relationship to interfacing cognitive functions and motor disability, and to determine if they predict cognitive and motor progression 2 years later in a PDCN subsample. METHODS: Sixty-three PDCN and 43 controls underwent functional MRI while judging whether pictures, rotated at various angles, depicted the left or right hand. The task activates systems that respond to increases in rotation angle, a proxy for visuospatial difficulty. Angle-modulated functional connectivity was analyzed for frontal cortex, posterior cortex, and basal ganglia regions. RESULTS: Two aberrant connectivity patterns were found in PDCN, which were condensed into principal components that characterized the strength and topology of angle-modulated connectivity. One topology related to a marked failure to amplify frontal, posterior, and basal ganglia connectivity with other brain areas as visuospatial demands increased, unlike the control group (control features). Another topology related to functional reorganization whereby regional connectivity was strengthened with brain areas not recruited by the control group (PDCN features). Functional topologies correlated with diverse cognitive domains at baseline, underscoring their influences on spatial cognition. In PDCN, expression of topologies that were control features predicted greater cognitive progression longitudinally, suggesting inefficient communications within circuitry normally recruited to handle spatial demands. Conversely, stronger expression of topologies that were PDCN features predicted less longitudinal cognitive decline, suggesting functional reorganization was compensatory. Parieto-occipital topologies (control features) had different prognostic implications for longitudinal changes in motor disability. Expression of one topology predicted less motor decline, whereas expression of another predicted increased postural instability and gait disturbance (PIGD) feature severity. Concurrently, greater longitudinal decline in spatial cognition predicted greater motor and PIGD feature progression, suggesting deterioration in shared substrates. CONCLUSION: These novel discoveries elucidate functional mechanisms of visuospatial cognition in PDCN, which foreshadow future cognitive and motor disability. Frontiers Media S.A. 2022-10-10 /pmc/articles/PMC9589098/ /pubmed/36299614 http://dx.doi.org/10.3389/fnagi.2022.987225 Text en Copyright © 2022 Harrington, Shen, Wei, Litvan, Huang and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Harrington, Deborah L.
Shen, Qian
Wei, Xiangyu
Litvan, Irene
Huang, Mingxiong
Lee, Roland R.
Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title_full Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title_fullStr Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title_full_unstemmed Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title_short Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson’s
title_sort functional topologies of spatial cognition predict cognitive and motor progression in parkinson’s
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589098/
https://www.ncbi.nlm.nih.gov/pubmed/36299614
http://dx.doi.org/10.3389/fnagi.2022.987225
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