Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment

Thomas Alderson, Elizabeth Kehoe, Liam Maguire, Dervla Farrell, Brian Lawlor, Rose A. Kenny, Declan Lyons, Arun L. W. Bokde, Damien Coyle

Research output: Contribution to journalArticlepeer-review

16 Citations (SciVal)


Alzheimer’s disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adultswith aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impairedthalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted corticothalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.
Original languageEnglish
Number of pages15
JournalFrontiers in Aging Neuroscience
Publication statusPublished - 8 Nov 2017


  • diffusion MRI
  • tractography
  • effective connectivity
  • Alzheimer’s disease
  • mild cognitive impairment
  • default mode network
  • thalamus
  • resting state


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