Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

Authors Organisations
  • Nicolai Franzmeier(Author)
  • Jens Göttler(Author)
    Technical University of Munich
  • Timo Grimmer(Author)
    Technical University of Munich
  • Alexander Drzezga(Author)
    University of Cologne
    German Center for Neurodegenerative Diseases (DZNE, Bonn)
  • Miguel A. Araque Caballero(Author)
  • Lee Simon-Vermot(Author)
  • Alexander Taylor(Author)
  • Katharina Beurger(Author)
    German Center for Neurodegenerative Diseases (DZNE Munich)
  • Cihan Catak(Author)
  • Daniel Janowitz(Author)
  • Claudia Mueller(Author)
  • Marco Duering(Author)
  • Christian Sorg(Author)
    Technical University of Munich
  • Michael Ewers(Author)
Type Article
Original languageEnglish
Pages (from-to)264
JournalFrontiers in Aging Neuroscience
Publication statusPublished - 07 Aug 2017
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Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFCconnectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the frontoparietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic,
dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anticorrelation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFCconnectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.


  • Cognitive reserve, mild cognitive impairment, frontoparietal control network, memory, Functional connectivity