Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment
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 su...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00370/full |
| _version_ | 1819232296446722048 |
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| author | Thomas Alderson Elizabeth Kehoe Liam Maguire Dervla Farrell Brian Lawlor Rose A. Kenny Declan Lyons Arun L. W. Bokde Damien Coyle |
| author_facet | Thomas Alderson Elizabeth Kehoe Liam Maguire Dervla Farrell Brian Lawlor Rose A. Kenny Declan Lyons Arun L. W. Bokde Damien Coyle |
| author_sort | Thomas Alderson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T11:58:36Z |
| format | Article |
| id | doaj.art-111b961151414533b73b5ef794e53120 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-23T11:58:36Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-111b961151414533b73b5ef794e531202022-12-21T17:48:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652017-11-01910.3389/fnagi.2017.00370294968Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive ImpairmentThomas Alderson0Elizabeth Kehoe1Liam Maguire2Dervla Farrell3Brian Lawlor4Rose A. Kenny5Declan Lyons6Arun L. W. Bokde7Damien Coyle8Intelligent Systems Research Centre, University Ulster, Derry, United KingdomTrinity College Institute of Neuroscience and Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, IrelandIntelligent Systems Research Centre, University Ulster, Derry, United KingdomTrinity College Institute of Neuroscience and Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, IrelandMercer’s Institute for Research on Ageing, St. James’s Hospital, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, IrelandMercer’s Institute for Research on Ageing, St. James’s Hospital, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, IrelandSt. Patrick’s Hospital, Dublin, IrelandTrinity College Institute of Neuroscience and Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, IrelandIntelligent Systems Research Centre, University Ulster, Derry, United KingdomAlzheimer’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.http://journal.frontiersin.org/article/10.3389/fnagi.2017.00370/fulldiffusion MRItractographyeffective connectivityAlzheimer’s diseasemild cognitive impairmentdefault mode network |
| spellingShingle | Thomas Alderson Elizabeth Kehoe Liam Maguire Dervla Farrell Brian Lawlor Rose A. Kenny Declan Lyons Arun L. W. Bokde Damien Coyle Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment Frontiers in Aging Neuroscience diffusion MRI tractography effective connectivity Alzheimer’s disease mild cognitive impairment default mode network |
| title | Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment |
| title_full | Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment |
| title_fullStr | Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment |
| title_full_unstemmed | Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment |
| title_short | Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment |
| title_sort | disrupted thalamus white matter anatomy and posterior default mode network effective connectivity in amnestic mild cognitive impairment |
| topic | diffusion MRI tractography effective connectivity Alzheimer’s disease mild cognitive impairment default mode network |
| url | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00370/full |
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