Disruptions in effective connectivity within and between default mode network and anterior forebrain mesocircuit in prolonged disorders of consciousness

Sean Coulborn, Chris Taylor, Lorina Naci, Adrian M. Owen, Davinia Fernández-Espejo*

*Corresponding author for this work

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Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterizes PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum, paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.
Original languageEnglish
Article number749
Number of pages16
JournalBrain Sciences
Issue number6
Publication statusPublished - 4 Jun 2021

Bibliographical note

Funding Information:
This work was supported by the Medical Research Council (MRC) via studentship to S.C., Data collection for this study was supported by funding for a postdoctoral fellowship (D.F.-E.) and operating grant 0000032597 (A.M.O.) from the Canadian Institutes of Health Research, grant 220020156.01 from the James S. McDonnell Foundation (A.M.O.), and chair 0000025914 from the Canada Excellence Research Chairs Program (A.M.O. and D.F.-E.). D.F.-E. is further supported by an MRC-NIRG (MR/P02596X/1).


  • Anterior forebrain mesocircuit
  • Coma recovery scale-revised
  • Default mode network
  • Disorders of consciousness
  • Dynamic causal modelling
  • Effective connectivity
  • FMRI
  • Minimally conscious state
  • Parametric empirical Bayes
  • Vegetative state

ASJC Scopus subject areas

  • Neuroscience(all)


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