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.
Highlights
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder affecting approximately 6% of people over the age of 65 and accounting for 60%–70% of dementia cases (Burns and Iliffe, 2009)
The current study identified a significant correlation between the structural integrity of hippocampo-thalamus and thalamo-posterior cingulate cortex (PCC) fiber pathways and memory in the amnestic mild cognitive impairment (aMCI) cohort which was absent in the healthy controls (HCs) (Figure 4A)
The dynamic nature of thalamo-cortical dialog suggests that abnormalities in default mode network (DMN) operation may best be understood from the perspective of thalamic dysfunction
Summary
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder affecting approximately 6% of people over the age of 65 and accounting for 60%–70% of dementia cases (Burns and Iliffe, 2009). In AD, the first neurofibrillary tangles appear in the parahippocampal regions (Stage I) followed later, and accompanied by cognitive symptoms, in the hippocampus formation (stage III; Braak and Braak, 1991a,b, 1995). This knowledge has reinforced focus on the hippocampus in the context of memory loss in AD but much less well-known and less well-understood are the appearance of tangles and plaques in the thalamic nuclei in parallel with those in the hippocampus. The thalamus, with its dense network of reciprocal interconnections with both hippocampus and PCC, is implicated by association (Vann et al, 2009; Aggleton et al, 2010)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
