Altered topology of the functional speech production network in non-fluent/agrammatic variant of PPA

Maria Luisa Mandelli, Ariane E. Welch, Eduard Vilaplana, Christa Watson, Giovanni Battistella, Jesse A. Brown, Katherine L. Possin, Honey I. Hubbard, Zachary A. Miller, Maya L. Henry, Gabe A. Marx, Miguel A. Santos-Santos, Lynn P. Bajorek, Juan Fortea, Adam Boxer, Gil Rabinovici, Suzee Lee, Jessica Deleon, Howard J. Rosen, Bruce L. MillerWilliam W. Seeley, Maria Luisa Gorno-Tempini

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Non-fluent/agrammatic primary progressive aphasia (nfvPPA) is caused by neurodegeneration within the left fronto-insular speech and language production network (SPN). Graph theory is a branch of mathematics that studies network architecture (topology) by quantifying features based on its elements (nodes and connections). This approach has been recently applied to neuroimaging data to explore the complex architecture of the brain connectome, though few studies have exploited this technique in PPA. Here, we used graph theory on functional MRI resting state data from a group of 20 nfvPPA patients and 20 matched controls to investigate topological changes in response to focal neurodegeneration. We hypothesized that changes in the network architecture would be specific to the affected SPN in nfvPPA, while preserved in the spared default mode network (DMN). Topological configuration was quantified by hub location and global network metrics. Our findings showed a less efficiently wired and less optimally clustered SPN, while no changes were detected in the DMN. The SPN in the nfvPPA group showed a loss of hubs in the left fronto-parietal-temporal area and new critical nodes in the anterior left inferior-frontal and right frontal regions. Behaviorally, speech production score and rule violation errors correlated with the strength of functional connectivity of the left (lost) and right (new) regions respectively. This study shows that focal neurodegeneration within the SPN in nfvPPA is associated with network-specific topological alterations, with the loss and gain of crucial hubs and decreased global efficiency that were better accounted for through functional rather than structural changes. These findings support the hypothesis of selective network vulnerability in nfvPPA and may offer biomarkers for future behavioral intervention.

Original languageEnglish
Pages (from-to)252-264
Number of pages13
JournalCortex
Volume108
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
The study was supported by grants from the National Institutes of Health (NINDS R01NS050915, NIDCD K24DC015544, NIDCD R01DC016291, NIA U01AG052943, NIA P50AG023501, NIA P01AG019724, R01AG038791, U01AG045390, U54NS092089) Alzheimer's Disease Research Center of California (03-75271 DHS/ADP/ARCC); Larry L. Hillblom Foundation (2013-A-029-SUP and 2005/2T); John Douglas French Alzheimer's Foundation; Koret Family Foundation; Consortium for Frontotemporal Dementia Research; and McBean Family Foundation.

Funding Information:
The study was supported by grants from the National Institutes of Health ( NINDS R01NS050915 , NIDCD K24DC015544 , NIDCD R01DC016291 , NIA U01AG052943 , NIA P50AG023501 , NIA P01AG019724 , R01AG038791 , U01AG045390 , U54NS092089 ) Alzheimer's Disease Research Center of California ( 03-75271 DHS/ADP/ARCC ); Larry L. Hillblom Foundation ( 2013-A-029-SUP and 2005/2T ); John Douglas French Alzheimer's Foundation ; Koret Family Foundation ; Consortium for Frontotemporal Dementia Research ; and McBean Family Foundation .

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

  • Functional connectivity
  • Graph theory
  • Primary progressive aphasia
  • Speech production network
  • Topological configuration

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience

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