Journal Article


Damien Coyle
Declan Lyons
Brian Lawlor
Dervla Farrell
Liam Maguire
Rose Kenny
Elizabeth Kehoe
Arun Bokde
Thomas Alderson



independent component analysis alzheimer disease older adults default mode diffusion tensor imaging third age ageing mild cognitive impairment white matter functional and effective connectivity high resolution neuroscience cognitive network ageing brain injury tractography

Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment. (2017)

Abstract 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 adults with 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, impaired thalamo-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 cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.
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Full list of authors on original publication

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

Experts in our system

Declan Lyons
University of Limerick
Total Publications: 16
Brian A. Lawlor
National College Ireland
Total Publications: 125
Dervla Farrell
Trinity College Dublin
Total Publications: 4
Rose Anne Kenny
Trinity College Dublin
Total Publications: 252
Elizabeth G Kehoe
Trinity College Dublin
Total Publications: 13
Arun L W Bokde
Trinity College Dublin
Total Publications: 144