Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia

Background: The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively. Given that behavioral variant f...

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Main Authors: Melanie A. Matyi, Hamsanandini Radhakrishnan, Christopher A. Olm, Jeffrey S. Phillips, Philip A. Cook, Emma Rhodes, James C. Gee, David J. Irwin, Corey T. McMillan, Lauren Massimo
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225001238
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author Melanie A. Matyi
Hamsanandini Radhakrishnan
Christopher A. Olm
Jeffrey S. Phillips
Philip A. Cook
Emma Rhodes
James C. Gee
David J. Irwin
Corey T. McMillan
Lauren Massimo
author_facet Melanie A. Matyi
Hamsanandini Radhakrishnan
Christopher A. Olm
Jeffrey S. Phillips
Philip A. Cook
Emma Rhodes
James C. Gee
David J. Irwin
Corey T. McMillan
Lauren Massimo
author_sort Melanie A. Matyi
collection DOAJ
description Background: The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively. Given that behavioral variant frontotemporal degeneration (bvFTD) is a neurodegenerative disease associated with executive dysfunction and selective vulnerability of the salience network, we tested the hypotheses that bvFTD structural networks are de-differentiated compared to cognitively normal controls (CNC) and that network de-differentiation relates to worse executive function. Methods: In a sample of 90 patients with bvFTD and 71 age-matched CNC with diffusion MRI data we generated probabilistic tractography maps and calculated system segregation, a metric that compares within-network to between-network connectivity, to reflect the extent to which brain networks were differentiated. Patients with bvFTD also completed tests of executive function (digit span backwards, phonemic fluency, category fluency) and a control task (lexical retrieval). We assessed group differences in system segregation, reflecting network differentiation, and, within bvFTD, associations between system segregation and neuropsychological test performance. Results: Compared to CNC, patients with bvFTD exhibited lower system segregation of the salience (p < 0.001) and global brain network (p = 0.008). In bvFTD, lower salience network system segregation was associated with worse executive function (pcorrected = 0.021) but not lexical retrieval. Conclusions: Results demonstrate associations between executive dysfunction and salience network de-differentiation in patients with bvFTD. Our findings indicate that brain network de-differentiation, reflecting reduced neural capacity for specialized processing, may contribute to the emergence of executive dysfunction in bvFTD.
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spelling doaj-art-ced2d04cdf9a4e93a3a98bd7e2f3b7522025-08-20T03:34:28ZengElsevierNeuroImage: Clinical2213-15822025-01-014810385310.1016/j.nicl.2025.103853Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementiaMelanie A. Matyi0Hamsanandini Radhakrishnan1Christopher A. Olm2Jeffrey S. Phillips3Philip A. Cook4Emma Rhodes5James C. Gee6David J. Irwin7Corey T. McMillan8Lauren Massimo93700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Imaging and Computing Science Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Imaging and Computing Science Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA3700 Hamilton Walk, Richards Medical Laboratories, Penn Frontotemporal Degeneration Center, Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; 418 Curie Boulevard, Fagin Hall, Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author at: 3700 Hamilton Walk, B603 Richards Medical Laboratories, Philadelphia, PA 19104, United States.Background: The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively. Given that behavioral variant frontotemporal degeneration (bvFTD) is a neurodegenerative disease associated with executive dysfunction and selective vulnerability of the salience network, we tested the hypotheses that bvFTD structural networks are de-differentiated compared to cognitively normal controls (CNC) and that network de-differentiation relates to worse executive function. Methods: In a sample of 90 patients with bvFTD and 71 age-matched CNC with diffusion MRI data we generated probabilistic tractography maps and calculated system segregation, a metric that compares within-network to between-network connectivity, to reflect the extent to which brain networks were differentiated. Patients with bvFTD also completed tests of executive function (digit span backwards, phonemic fluency, category fluency) and a control task (lexical retrieval). We assessed group differences in system segregation, reflecting network differentiation, and, within bvFTD, associations between system segregation and neuropsychological test performance. Results: Compared to CNC, patients with bvFTD exhibited lower system segregation of the salience (p < 0.001) and global brain network (p = 0.008). In bvFTD, lower salience network system segregation was associated with worse executive function (pcorrected = 0.021) but not lexical retrieval. Conclusions: Results demonstrate associations between executive dysfunction and salience network de-differentiation in patients with bvFTD. Our findings indicate that brain network de-differentiation, reflecting reduced neural capacity for specialized processing, may contribute to the emergence of executive dysfunction in bvFTD.http://www.sciencedirect.com/science/article/pii/S2213158225001238Network differentiationSystem segregationBehavioural variant frontotemporal degenerationExecutive functionSalience networkFrontoparietal Control Network
spellingShingle Melanie A. Matyi
Hamsanandini Radhakrishnan
Christopher A. Olm
Jeffrey S. Phillips
Philip A. Cook
Emma Rhodes
James C. Gee
David J. Irwin
Corey T. McMillan
Lauren Massimo
Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
NeuroImage: Clinical
Network differentiation
System segregation
Behavioural variant frontotemporal degeneration
Executive function
Salience network
Frontoparietal Control Network
title Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
title_full Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
title_fullStr Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
title_full_unstemmed Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
title_short Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
title_sort executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
topic Network differentiation
System segregation
Behavioural variant frontotemporal degeneration
Executive function
Salience network
Frontoparietal Control Network
url http://www.sciencedirect.com/science/article/pii/S2213158225001238
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